Title of Invention

"A 3-(N-OXY-IMINO)-1-ARYLPYRAZOLE COMPOUND"

Abstract The present invention relates to a 3-(n-oxy-imino)-l-arylpyrazole compound of general formula (I) formula (I) and compositions and derivatives thereof. These compounds are found to be generally safe systemic insecticides for control of arthropod, nematode, helminth or protozoan pests.
Full Text Field of the invention
The present invention relates to a 3-(N-oxy-imino)-l-arylpyrazole compound. It relates to their unexpected and useful systemic insecticidal activity. The invention particularly pertains to compositions of said compounds and method, using said compounds, for the control of arthropod, nematode, helminth or protozoan pests. In particular to the application of said compounds or compositions in agricultural methods of use, particularly as pesticides, for controlling arthropods, especially insects by systemic action. The invention also relates to 1-arylpyrazole hydrazones.
Description of the Related Art
The control of insects nematodes or helminths by means of active material having a 1-arylpyrazole group therein has been described by many patents or patent application such as International Patent Publication No. WO 93/06089 (and the equivalent U.S. Patent No. 5,451,598),WO 94/21606 and WO 87/03781 as well as in European Patent Publication Numbers 0295117, 659745, 679650, 201852 and 412849, German Patent No. DE 19511269 and U.S. Patent No. 5,232,940. Other compounds are disclosed in WO 92/13451, 20 August 1992, to Schering Agrochemicals Ltd., which describes 5-chloro-l-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(4,5-dicyano-lH-imidazol-2-yl)-3-hydroxyiminomethyl lH-pyrazole as an intermediate, also with activity against a single species Lucilia, sericata, sleep blow fly. This Schering reference appears to be the only reference describing 1-arylpyrazole-oxime compounds as insecticides. It is an object of the present invention to provide new pesticidal compounds of the 1-arylpyrazole family together with processes for their preparation. A second object of the present invention is to provide pesticidal compositions and pesticidal methods of use of the pesticidal pyrazole compounds against arthropods especially insects, plant nematodes, or helminth or protozoan pests,


particularly in agricultural or horticultural crops, forestry, veterinary medicine or livestock husbandry, or in public health.
A third object of the present invention is to provide very active compounds, with broad spectrum pesticidal activity, as well as compounds with selective special activity, e.g.. aphicidal. miticidal. foliar insecticidal. soil insecticidal and nematicidal. systemic, antifeeding or pesticidal activity via seed treatment.
A fourth object of the present invention is to provide compounds with substantially enhanced and more rapid activity, especially against insects and more particularly insects in their larval stages.
A fifth object of the present invention is to provide compounds with greatly improved (greater and faster) penetration into pest species when topically applied and thus provide enhanced movement of the compounds to the pesticidal site(s) of action within the pest.
Another object of the present invention is to provide compounds with high activity and improved safety to the user and the environment.
These and other objects of the invention shall become readily apparent from the detailed description of the present invention. These objects are met in whole or in part by the instant invention.
This invention describes novel pesticidal compositions
and methods including systemic chemical compositions and
methods for treating plants with the compositions having
pesticidal, including insecticidal or nematocidal systemic
activity of the following formula (I):

(Formula Removed)

wherein:
X is-S(0)mR6orR7
Y is hydrogen, C-3 to C-6 alkenyl, alkynyl, formyl, alkylcarbony]
cycloalkylcarbonyl, halocycloalkyl carbonyl, optionally
substituted aroyl, arylalkylcarbonyl,
a l k y l s u l l o n y l . arylsulfonyl. haloalkylcarbonyi. aminoalkylcarbonyl.
alky laminoalkylcarbonyl. dialkylaminoalkylcarbonyl. alkoxyalkylcarbonyl.
aryloxyalkylcarbonyl. alkylthioalkylcarbonyl. alkylsulfonylalkylcarbonyl.
aryhhioalkylcarbonyl. N-alkylcarbamoyl. X-arylcarbamoyl. Xalkyhhiocarbamoyl.
X-arylthiocarbamoyl. alpha-hydroxyarylalkylcarbonyl.
hydroxyalkylcarbonyl, carboxyalkylcarbonyl. alkoxycarbonylalkylcarbonyl. -
P(=0)(O-Alkyl)2,
-P(=S)(O-alkyl)2. -P(=O)(S-alkyl)2, -P(=S)(S-alkyl)2? trialkylsilyl.
alkylcarbonylaminoalkylcarbonyl. alkylcarbonyloxyalkylcarbonyl, aryl.
pyridinyl. pyrimidinyl. -C(=0)S-alkyl, -C(=O)S-aryl. -C(=0)S-alkylaryl.
alkoxvalkoxvcarbonvl. alkvlthioalkoxvcarbonvl. alkvlsulfonvlalkoxvcarbonvl. r * f f * * • •• f * *
arylthioalkoxycarbonyl, alkoxycarbonyl. aryloxycarbonyl ajid
aryloxycarbonylalkylcarbonyl; or alkyl or haloalkyl. optionally subsututed by
alkoxy. alkoxycarbonyl. carboxy. cyano. aminocarbonyl. alkylaminocarbonyl.
dialkylaminocarbonyl, alkylthio. nitro. alkylsulfmyl. alkylsulfonyl.
alkylcarbonyl. amino. alkylamino. dialkylamino. hydroxy. alkylcarbonylamino
or alkylcarbonyloxy:
Z is hydrogen. halogen.-C (0) R7 , -S (0) nRs , -C(0)OR9- alkyl. haloalkyl. -ORg.
-N=C(Rio)(Ri l). alkenyl. hydrazino. alkylthiocarbonyl. IH-pyrrol-l-yl or
IH-pyrazol-l-yl.
-CHO. -CH=NOH. amino. RjoNH-or R^R^N-:
R! is hydrogen, alkyl or-XRi5Ri6:
R2 is hydrogen or halogen;
R3 and R5 are hydrogen, halogen or alkyl:
R4'is halogen, haloalkyl. haloalkoxy. RiyS(0)p-or SFs:
R6 is alkyl or haloalkyl. alkenyl or haloalkenyl. alkynyl or haloalkynyl or cycloalkyl
having 3 to 5 carbon atoms:
Ry is alkyl or haloalkyl;
Rg is R? or phenyl:
R9 and RIO are hydrogen, alkyl or haloalkyl;
R! i is alkyl. haloalkyl. alkoxy. or a phenyl group which is optionally substituted by
one or more groups selected from hydroxy. halogen, alkoxy, cyano. Ry or
-S(0)qR?:
Rl2- R l 3 and R 4 . which are identical or different, are R7S(O)r. formyl. alkynyl,
alkoxycarbonyl. alkylthiocarbonyl or aroyl; or alkyl. C-3 to C-6 alkenyl or
-C(0 ) a l k y l h e r em the a l k y l and alkenyl portions arc optionally substituted by
one or more R] $: or R j 3 and l\\4 are joined so as together to form a divalent
radical having 4 to 6 atoms in the chain, this divalent radical being alkylene.
alkyleneoxyalkylene or alkyleneaminoalkylene. preferably to form a
morpholine. pyrrolidine. piperidine or piperazine ring:
R.15 and R]g are independently hydrogen or alkyl;
R l 7 represents haloalkyl;
RlS is cyano. nitro. alkoxy. haloalkoxy. -C(0)R7. RsS(O)s-. -C(O)OR9.
aminocarbonyl. alkylaminocarbonyl, dialkylaminocarbonyl. halogen, hydroxy.
aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyh
m. n. p. q, r and s represent zero, one or two;
M is C-halo, C-CH}. C-CH2F, C-CH2C1. C-N02, or N;
geometric isomers, tautomeric forms and pesticidally acceptable salts thereof.
By the term "pesticidally acceptable salts" is meant salts the anions and
cations of which are known and accepted in the art for the formation of pesticidally
acceptable salts. Preferably such salts are water soluble. Suitable acid addition salts
formed from compounds of formula (I) containing an amine group, include salts with
inorganic acids for example hydrochlorides. phosphates, sulfates and nitrates, and
salts with organic acids for example acetates. Suitable salts formed from
compounds of formula (I) containing a carboxylic acid group, include alkali metal (for
example sodium or potassium) salts, ammonium salts and organic amine (for example
diethanolamine or morpholine) salts.
Compounds of formula (I) wherein RI represents -NR15R16 in which R16
represents hydrogen and RIS represents hydrogen or alkyl may exist in tautomeric
forms as shown in formulae (la) and (Ib). Such tautomerism is well known as is
described in S.Patai (The Chemistry of Functional Groups: Amidines and Imidates,
Vol 2, 1991, pages 276-277). It will be understood that all such tautomeric forms are
embraced by the present invention.
R.
(la)
Unless otherwise specified alkyl. alkoxy and alkylthio groups have from one to six
(preferably one to four) carbon atoms, alkenyl groups have from two to six (preferably
two to four) carbon atoms and alkvnyl groups have from three to six (preferably three
or four) carbon atoms; such groups are straight- or branchedchain.
Cycloalkyl groups have from 3 to 8 carbon atoms,
preferably 5
to 7 carbon atoms. By the term "aryl" is meant mono or polycyclic aromatic moieties,
preferably including phenyl. pyridyl. pyrimidinyl. furyl and naphthyl groups. It shall
be understood that the rings formed by the divalent alkvlene radicals which include
the nitrogen atoms to which they are attached are generally 5, 6 and 7 membered
rings. In the instant invention, some words are used in a specific sense:
The term "aminocarbonyl" means a carbamoyl radical, that is. a radical of the formula
-C(0)NH2- Similarly, the term "alkylaminocarbonyl" means an alkylcarbamoyl
radical, that is. a radical of the formula -C(0)-NH-alkyl; and the term
"dialkylaminocarbonyl" means a dialkylcarbamoyl radical, that is. a radical of the
formula -C(O)-N(alkyl): in which the alkyl moieties can be the same or different. The
term "aminosulfonyl" means a sulfamoyl iadical. that is. -S02NH2- Similarly, the
term "alkylaminosulfonyl" means an alkylsulfamoyl radical, that is, a radical of the
formula -SCbNH-alkyl: while the term "dialkylaminosulfonyl" means a
dialkylsulfamoyl radical, which has the formula
-S02N(alkyl)2 wherein the alkyl moieties can be the same or different.
The term "halo" before the name of a radical means that this radical is partially
or completely halogenated. that is to say, substituted by F. Cl. Br, or I, in any
combination, preferably by F or Cl. The term "halogen" means F, Cl, Br or I. When
the name of any substituent is repeated, it keeps the same meaning unless otherwise
specified. The term "aroyl" designates a carbonyl aromatic radical, that is, aryl-C(O)-,
which is preferably a benzoyl optionally substituted by one or more alkyl, alkoxy or
halogen groups.
Compounds in u h i c h 7. is ammo. RpNH-or R p R N - a r e preferred.
Compounds in u h i c h X is -S(O)mR(-, are preferred.
R! is preferably ammo or hydrogen:
R(3 is preferably alkyl: especially preferred are methyl and ethyl:
R3 and Rs are preferably hydrogen:
R4 is preferably haloalkyl. haloalkoxy or SF5: especially preferred is trifluorotnethyl.
M is preferably C-halo. or N.
Y is preferably hydrogen or alkoxycarbonyl.
Preferred phenyl groups or pyridyl groups comprising the R2 to Rs and M
radicals in formula (I) are: 2.6-dichloro-4-trifluoromethylphenyl; 2,6-dichloro-4-
trifluoromethoxyphenyl; 2-bromo-6-chloro-4-trifluoromethylphenyl; 2-bromo-6-
chloro-4-trifluoromethoxyphenyh 2.6-difluoro-4-trifluoromethylphenyl; 2-chloro-4-
trifiuoromethylphenyl; 3-chloro-5-trifluoromethyl-2-pyridinyl; 3-chloro-5-
trifluoromethoxy-2-pyridinyl: 2-bromo-6-fluoro-4-difluoromethylphenyl; 2-chloro-6-
fluoro-4-trifluoromethylphenyl; 2.6-dibromo-4-trifluoromethylphenyl: 2.6-dibromo-4-
trifluoromethoxyphenyl: and 2.6-dichloro-4-pentafluorothiophenyl.
A preferred class of compounds of formula (I) are those wherein:
X is -S(0)mR6:
Y is hydrogen; alkyl having 1 to 4 carbon atoms (including linear, branched and
cyclic) optionally substituted by aminocarbonyl. alkylsulfonyl, alkoxy.
alkoxycarbonyl. alkylcarbonyl. cyano or nitro; C-3oi"C-4 alkenyl; C-3 to C-5
alkynyl; alkylcarbonyl; optionally substituted aroyl; arylalkylcarbonyl;
alkylsulfonyl; alkoxycarbonylalkylcarbonyl; haloalkylcarbonyl;
N-alkylcarbamoyl; alkoxycarbonyl; ar'loxycarbonyl; alkoxyalkylcarbonyl;
alpha-hydroxyarylalkylcarbonyl: hydroxyalkylcarbonyl; aminoalkylcarbonyl;
-C(=O)S-alkyl and trialkylsilyl:
Z is amino. R12NH-. , halogen or methyl;
R! is hydrogen, methyl, amino or methylamino;
R 2 s F . Cl. BrorH;
R} and R5 are hydrogen:
R4 is CF3, CF3O. CHF2- CF3S(O)p, CF2C1. CFCh . CF2C1O, CFChO, Cl, Br, or F;
Rg is methyl or ethyl optionally substituted by F. Cl or Br;
MisCCl. CF, CBr, orN:
Rl2- R-13 and R]4 are CF3S(0)p, alkynyl or alkoxycarbonyl:
or alkyl. C-3 to C-6 alkenyl or -C(O)alkyl wherein the alkyl and alkenyl portions are
optionally substituted by one or more Rig; and
is cyano. nitro. alkoxy. huloalkoxy. - C O . R(sS(O)s-. -C(O)ORq.
aminocarbonyl. alkylaminocarbonyl. dialkylaminocarbonyl. halogen. hydroxy.
aminosulfonyl. alky laminosulfonyl or dialkylaminosult'onyl.
A further preferred class of compounds of formula ( I ) are those wherein:
Y represents hydrogen: a C\ to C} alkyl group optionally substituted by cyano. carbamoyl.-
carboxy. alkoxycarbonyl. alkylthio. alkylsulfinyl or alkylsulfonyl; trialkylsilyl: acetyh
propionyl substituted by alkoxycarbonyl; benzoyl optionally substituted by alkyl:
alkoxycarbonyl: or N-alkylcarbamoyl;
Z represents amino, Rj^NH-. Rp,Ri4N-. -CHO. -CH=NOH, halogen or methyl;
R! represents hydrogen, methyl, amino or methylamino:
R2 represents chlorine, bromine or hydrogen;
R} and RS represent hydrogen:
R4 represents CF3 or OCF};
R5 represents optionally halogenated methyl or ethyl;
Ry represents CF3;
Rj2- R-13 and R j 4 represent alkynyl; or methyl or ethyl optionally substituted by RgS(0)s-,
cyano or aminocarbonyl;
Rg represents alkyl or phenyl; and
M represents C-C1. C-Br or N.
According to another aspect of the invention, Y may be a
sugar moiety; preferably Y is a
ring containing 4, 5. or 6 carbon atoms and which is interrupted by one oxygen atom, the carbon
atoms being substituted by one or more hydroxy groups, one or more
CH2OH groups or one or more OC(0)alkyl groups.
The instant invention also provides arylpyrazoles of the following formula (I
Y 1 is hydrogen, substituted or unsubstituted alkyl. substituted or unsubstiiuted
alkem 1. substituted or unsubstituted a l k n l . substituted or unsubstituted ury]
-C(O)R27- -C(S)R27- cyano or nitro:
R]9 is hydrogen, alkyl. haloalkyl. or -N'R;4R35:
R2Q is -S(0)bR36 or R37:
R2i is hydrogen, halogen. -C(0)R3g. -S(O)CR39. alkyl. haloalkyl. -OR4Q-
-N=C(R4i)(R42), alkenyl. -NR43R44. IH-pyrrol-l-yl. IH-pyrazol-l-yl. or
-CH=NOH;
R22 • R23 and R25 are independently selected from hydrogen, halogen or alkyl;
R24 is halogen, haloalkyl. haloalkoxy. -S(0)dR45 or SF5;
R26 is hydrogen or substituted or unsubstituted alkyl;
R27 is hydrogen, substituted or unsubstituted alkyl of C\ to C20- substituted or
unsubstituted aryl. -OR4g . -NR4yR4g. or -SR49;
R2S is substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
R29 and R3Q are independently selected from alkoxy and thioalkoxy:
R3j. R32 and R33 are independently selected from alkyl. haloalkyl and aryl;
R34 and R35 are independently selected from hydrogen or substituted or
unsubstituted alkyl:
R36 is alkyl. alkenyl. alkynyl. or C3-C cycloalkyl each of which is optionally
substituted by one or more halogens:
is alkyl or haloalkyl;
is hydrogen, alkyl, haloalkyl, alkoxy or thioalkoxy:
R39 is alkyl, haloalkyl or aryl;
R40 and R4] are independently selected from hydrogen, alkyl and haloalkyl;
R42 is alkyl. haloalkyl, alkoxy or phenyl each of which is optionally substituted by
one or more groups selected from hydroxy, halogen, alkoxy. -CM, alkyl,
-S(0)ealkyl;
R43 and R44 are independently selected from hydrogen. NH2. -S(0)fR5Q,
-C(0)R5i, substituted or unsubstituted alkyl, substituted or unsubstituted
alkenyl and alkynyl: or R43 and R44 may form together a divalent alkylene
radical which may be interrupted by one or more heteroatoms, preferably
selected from oxygen, nitrogen and sulfur;
R45 is haloalkyl;
R45 and R49 are independently selected from substituted or unsubstituted alkyl and
substituted or unsubstituted arvl;
R and R are mdcpcndcniK selected from hydrogen, substituted or unsubsutuied
a l k l and substituted or unsubstituted aryl; or R.47 and may form together
a divalent a l k y l e n e radical which may be interrupted by one or more
hcteroatoms preferably selected from oxygen, nitrogen and sulfur;
R is substituted or unsubstituted aikyl;
R ] is hydrogen, alkyl. haloalkyl. an.'!, alkenyl. -OR52- -SR53- or -NR54R-55:
R2 and Rs3 are independently selected from alkyl and haloalkyl;
R54 and R55 are independently selected from hydrogen, alkyl. haloalkyl and aryl;
a. b. c. d. e and f independently represent zero, one or two;
MI is C-halo. C-CHj. C-CHoF. C-CI-bCl. C-NCn, or N;
or a geometric isomer, tautomeric form or pesticidally acceptable
salt thereof. Compounds of formula (I bis) wherein R19
represents -NR3,R35 in which R34 represents hydrogen and R35
represents hydrogen or alkyl may exist in tautomeric forms. It
will be understood that all such tautomeric forms are embraced by
the present invention.
A preferred group of compounds of formula (I bis) are those with one or more
of the following features wherein:
Y] is hydrogen, alkyl. or -C(O)R27-
R9 is hydrogen or Nth;
R20 is -S(0)bR36:
R is halogen;
RT} and R25 are hydrogen;
R24 is haloalkyl;
R27 is alkyl or O-alkyl; or
M is C-halo.
Another preferred group of compounds of formula (I bis) are those wherein:
A is -NR26-;
YI is hydrogen, alkyl. or -C(0)R2y:
Rj9 is hydrogen or NHo:
R20 is -S(0)bR36;
R22 is halogen;
R 3 and R25 are hydrogen;
R 4 i s haloalkyl;
R27 is alkyl or O-alkyl; and
M is C-halo.
In the compounds of formula ( I bis), preferably by the term "substituted" is
meant by one or more of the following substituents: halogen, hydroxy. alkylthio.
cyano. carboxy. -C(O)alkyl. -C(0)Oalkyl. -QCMNtK -C(0)NHalkyl.
-C(O)N(alkyl)2. aryl. nitro. azido. amino.alkylamino. dialkylamino. alkylsulfenyl.
alkylsulfmyl. alkylsulfonyl. aryloxy. arylthio. alkylcarbonylamino. alkylcarbonyloxy. •
or aryloxycarbonyl.
Among the compounds of general formula (I) or (I bis) are the following
particularly preferred compounds, which provide particularly useful control of insect
species by systemic action. The compound numbers are for reference purposes only.
1) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-1Hpyrazole-
3-carboxaldehyde oxime
2) l-[2.6-Dichloro-4-(trifluoromethynphenyl]-5-ethylamino-4-methylsulfinyl-
1 H-pyrazole-3-carboxaldehyde oxime
3) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfmyl-
1 H-pyrazole-3-carboxaldehyde oxime
4) 5-Amino-1-[2.6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde oxime
5) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyr)phenyl]-4-ethylsulfmyl-lHpyrazole-
3-carboxaldehyde oxime
6) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-
1 H-pyrazole-3-carboxaldehyde oxime
7) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-difluoromethylthio-lHpyrazole-
3-carboxaldehyde oxime
8) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-lHpyrazole-
3-carboxaldehyde oxime
9) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-
1 H-pyrazole-3-carboxaldehyde O-(methyl)oxime
10) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde 0-(acetyl)oxime
11) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde 0-(2-methylbenzoyl)oxime
12) 5-Amino-l-[2r6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde 0-(methoxycarbonyl)oxime
13) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lHpyrazole-
3-carboxaldehyde 0-[2-(ethoxycarbonyl)propionyl]oxime
14) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1 H-pyrazole-3-
carboxaldehyde 0-(acetyl)oxime
1 5 ) 5-Amino-l-[2.6-dichloro-4-(tritluoromethyl)phenyl]-4-methylthio-lHpyrazole-
3-carboxaldehyde 0-( methoxycarbonyl loxime
16) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-lHpyrazole-
3-carboxaldehyde oxime
17) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyr)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde 0-(methyl)oxime
18) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lHpyrazole-
3-carboxaldehyde 0-(~N"-methylcarbamoyl)oxime
19) 5-Amino-1 -[2.6-dichloro-4-(trifluoromeihyl)phenyl]-4-methylsulfmyl-1Hpyrazole-
3-carboxaldehyde O-(carboxymethyl)oxime
20) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lH-pyrazole-3-
carboxaldehyde oxime
21) 5-Amino-1-[2.6-dichloro-4-(trifluoromethynphenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde O-(tert-butyldimethylsilyl)oxime
22) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-
trifluoromethylthio-1 H-pyrazole-3-carboximidamide
23) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-X-hydroxy-5-
hydroxyiminomethyl-4-trifluoromethylthio-l H-pyrazole-3-carboximidamide
24) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lHpyrazole-
3-carboxaldehyde 0-(isopropyl)oxime
25) 5-Amino-1 -[2.6-dichloro-4-( trifluoromethyl)phenyl]-4-methylsulfmyl-1Hpyrazole-
3-carboxaldehyde O-(ethoxycarbonylmethyl)oxime
26) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyDphenyl]-4-methylsulfinyl-lHpyrazole-
3-carboxaldehyde 0-(aminocarbonylmethyl)oxime
27) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lHpyrazole-
3-carboxaldehyde 0-[2-(ethylsulfonyl)ethyl]oxime
28) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde O-(2-cyanoethyl)oxime
29) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-lHpyrazole-
3-carboxaldehyde oxime
30) l-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde oxime
31) 1 -[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-1Hpyrazole-
3-carboxaldehyde oxime
32) 5-Amino-l-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde oxime
331 l-[2.6-Dichloro-4-(tritluoromethyl)phenyl]-4-ethylthio-5-methyl-lH-pyrazole-
3-carboxaldehyde oxime
34) 1 -[2.6-Dichloro-4-( trifluoromethyl )phenyl]-4-ethylsulfiny 1-5-methy [-1Hpyrazole-
3-carboxaldehyde oxime
35) 1 -[2-Chloro-4-(trifluorometh\i)phenyl]-5-[2-ethylsulfonyl(ethylamino]-4-
methylsulfmyl-lH-pyrazole-3-carboxaldehyde oxime
36) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-dimethylamino-4-methylthio-
1 H-pyrazole-3-carboxaldehyde oxime
37) 5-Amino-l-[2.6-dichloro-4-(trifluoromethoxy)phenyl]-4-ethylsulfinyl-lHpyrazole-
3-carboxaldehyde oxime
38) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl-lHpyrazole-
3-carboxaldehyde oxime
39) 3-Acetyl-5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-
-IH-pyrazole oxime
40) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfinyl-
1 H-pyrazole-3-carboximidamide
41) 5-Amino-l-[2.6-dichloro-4-(tritluoromethyl)phenyl]-X-methoxy-4-trifluoromethylsulfmyl-
1 H-pyrazole-3-carboximidamide
42) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfinyl-
1 H-pyrazole-3-carboximidamide
43) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-X-hydroxy-4-ethylthio-lHpyrazole-
3-carboximidamide
44) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-
1 H-pyrazole-3-carboximidamide
45) 5-Amino-l-[2.6-dichloro-4-(trifluoromethoxy)phenyl]-N-hydroxy-4-methylsulfinyl-
1 H-pyrazole-3-carboximidamide
46) 5-Amino-1 -[2.6-dichloro-4-(trifluorometh\pl)phenyl]-N-hydroxy-4-methylsulfony
1-1 H-pyrazole-3-carboximidamide
47) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylthio-
1 H-pyrazole-3-carboximidamide
48) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfonyl-
1 H-pyrazole-3-carboximidamide
49) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-
methylsulfmyl-1 H-pyrazole-3-carboximidamide
50) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-X-methoxy-N'-rnethyl-
4-methylsulfmy 1-1 H-pyrazole-3-carboximidamide
51) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-
(2-fluoroethylsultlnyl)-l H-pyrazole-3-carboximidamide
52) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-
(2-fluoroethylsulfonyl)-lH-pyrazole-3-carboximidamide
53) 5-Amino-l-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-ethylsulfmyl-Nhydroxy-
lH-pyrazole-3-carboximidamide
54) 5-Amino-l-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfmyl-Nhydroxy-
1 H-pyrazole-3-carboximidamide
55) l-[2.6-Dichloro-4-(trifluoromethyl)phen\i]-N-hydroxy-5-methylamino-4-
methylsulfmyl-lH-pyrazole-3-carboximidamide
56) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-N-hydroxy-4-
methylsulfinyl-1 H-pyrazole-3-carboximidamide
57) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyr)ethylamino]-
N~-hydroxy-4-methylsulfinyl-l H-pyrazole-3-carboximidamide
58) 5-[2-(Cyano)ethylamino]-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-Nhydroxy-
4-methylsulfmyl-l H-pyrazole-3-carboximidamide
59) 5-(Aminocarbonylmethylamino)-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-
N-hydroxy-4-methylsulfmyl-l H-pyrazole-3-carboximidamide
60) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-5-[2-
(phenylsulfonyl)ethylamino]-N-hydroxy-l H-pyrazole-3-carboximidamide
61) 5-Amino-l-[2.6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-Nhydroxy-
1 H-pyrazole-3-carboximidamide
62) l-[2-Bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-
methylsulfmyl-N-hydroxy-1 H-pyrazole-3-carboximidamide
63) 5-Amino-l-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-Nhydroxy-
1 H-pyrazole-3-carboximidamide
64) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfmyl-5-[2-
(methylsulfinyl)ethylamino]-N-hydroxy-1 H-pyrazole-3-carboximidamide
65) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-
(methylsulfinyl)ethylamino]-N-hydroxy-l H-pyrazole-3-carboximidamide
66) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-
(ethylsulfmyl)ethylamino]-N-hydroxy-l H-pyrazole-3-carboximidamide
67) l-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-5-[(prop-2-
ynyl)amino]- N-hydroxy-1 H-pyrazole-3-carboximidamide
68) 5-Amino-l-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-
1 H-pyrazole-3-carboximidamide.
Other compounds of formula ( I ) or ( I bis) that are provided by the instant
invention include:
69) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-Namino-
1 H-pyrazole-3-carboximidamide:
70) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N"-
(isopropylcarbonyl)amino-l H-pyrazole-3-carboximidamide:
71) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyr)phenyl]-4-methylsulfmyl-N-(nheptylcarbonyOamino-
1 H-pyrazole-3-carboximidamide:
72) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(ethoxycarbonyl)amino-l H-pyrazole-3-carboximidamide:
73) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)pheny l]-4-
trifluoromethylsulfinyl-N-amino-1 H-pyrazole carboximidamide:
74) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-amino-
1 H-pyrazole carboximidamide:
75) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
trifluoromethylsulfinyl-N-acetylamino-1 H-pyrazole carboximidamide:
76) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(lmethylethenylcarbonylamino)-
1 H-pyrazole carboximidamide:
77) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-(tenbutylcarbonylamino)-
1 H-pyrazole carboximidamide:
78) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-(2-
methylethenylcarbonylamino)-1 H-pyrazole carboximidamide:
79) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(ethylcarbonylamino)-1 H-pyrazole carboximidamide;
80) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(propylcarbonylamino)-1 H-pyrazole carboximidamide;
81) 5-Amino-1 -[2.6-dichloro-4-( trifluoromethyl)phenyl]-4-methylsulfinyl-N-( 1 -
ethylpropylcarbonylamino)-1 H-pyrazole carboximidamide;
82) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(butylcarbonylamino)-l H-pyrazole carboximidamide;
83) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(pentylcarbonylamino)-1 H-pyrazole carboximidamide:
84) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(hexylcarbonylamino)-l H-pyrazole carboximidamide;
85) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfmyl-Nacetylamino-
1 H-pyrazole carboximidamide;
86) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-Nchloroacetylamino-
1 H-pyrazole carboximidamide:
87) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(tridecylcarbonylamino)-l H-pyrazole carboximidamide:
88) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-(npropoxycarbonylamino)-
1 H-pyrazole carboximidamide:
89) 5-Amino-1 -[2.6-dichloro-4-( trifluoromethyl)phenyl]-4-methylsulfmyl-N-( 1.1-
dimethylpropyloxycarbonylamino)-! H-pyrazole carboximidamide:
90) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-niethylsulfinyl-N-
(tertbutyloxycarbonylamino)-l H-pyrazole carboximidamide:
91) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(acetyloxy) -1 H-pyrazole carboximidamide:
92) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfmyl-N-
(acetyloxy) -1 H-pyrazole carboximidamide:
93) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(ethylcarbonyloxy) -1 H-pyrazole carboximidamide:
94) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methy Isulfmyl-N-
(propylcarbonyloxy) -1 H-pyrazole carboximidamide:
95) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(2-
methylethenylcarbonyloxy) -1 H-pyrazole carboximidamide:
96) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(benzoyloxy) -1 H-pyrazole carboximidamide:
97) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-
N-(acetyloxy)-! H-pyrazole carboximidamide:
98) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-
(acetyloxy)-1 H-pyrazole carboximidamide;
99) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(heptylcarbonyloxy) -1 H-pyrazole carboximidamide;
100) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-
(heptylcarbonyloxy) -1 H-pyrazole carboximidamide;
101) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-
(acetyloxy)-1 H-pyrazole carboximidamide;
102) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-
(heptylcarbonyloxy) -1 H-pyrazole carboximidamide;
103) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
trifluoromethylsulfmyl-N-(acetyloxy)-l H-pyrazole carboximidamide;
104) l-[2.6-Dichloro-4-(trifluoromethyliphenyl]-5-tbrmylamino-4-ethylsulfenyl-X-
(acety loxy)-1 H-pyrazole carboximidamide:
105) 5-Amino-l-[2,6-dichloro-4-(trifluoromethyliphenyl]-4-methylsulfmyl-N-
(hexylcarbonyloxy) -1 H-pyrazole carboximidamide:
106) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(pentylcarbonyloxy) -1 H-pyrazole carboximidamide:
107) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(butylcarbonyloxy) -1 H-pyrazole carboximidamide:
108) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-
(cyclopentylcarbonyloxy) -1 H-pyrazole carboximidamide;
109) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(cyclopentylcarbonyloxy) -IH-pyrazole carboximidamide:
110) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methy lsulfinyl-N-(tertbutylcarbonyloxy)
-1 H-pyrazole carboximidamide;
111) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-(isopropylcarbonyloxy)
-1 H-pyrazole carboximidamide;
112) l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfmyl-N-
(acety loxy )-l H-pyrazole carboximidamide:
113) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(chloroacetyloxy)-l H-pyrazole carboximidamide:
114) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-N-
(bromoaceiyloxy)-1 H-pyrazole carboximidamide:
115) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(lethylpropylcarbonyloxy)-
1 H-pyrazole carboximidamide:
116) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-[(3-
acetyloxy)phenylcarbonyloxyj-1 H-pyrazole carboximidamide;
117) 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoro
methylsulfonyl-lH-pyrazole-3-carboximidamide;
118) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoro
methylsulfenyl-lH-pyrazole-3-carboximidamide;
119) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-
(methoxycarbonylamino)-4-methylsulfmyl-lH-pyrazole-3-carboxaldehyde
hydrazone;
120) 5-Amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-
(methylsulfonylamino)-4-methylsulfinyl-lH-pyrazole-3-carboxaldehyde
hvdrazone:
1 2 1 ) 5-Amino-l-[2.6-dichloro-4-(tritluorometh\1)phenyl]-\-amino-4-eth\lsulfmyl'
1 H-pyrazole-3-carboxaldehyde hydrazone:
122) 5-Amino-l-[2.6-dichloro-4-(trirluoromethyl)phenyl]-N-amino-4-
trifluoromethylsulfenyl-1 H-pyrazole-3-carboxaldehyde hydrazone:
123) 5-Amino-l-[2.6-dichloro-4-(trifiuoromethyl)phenyl]-N-amino-4-
methylsulfenyl-1 H-pyrazole-3-carboximidamide:
124) 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N"-(furylcarbonylamino)-
4-methylsulfmyl-1 H-pyrazole-3-carboximidamide: or
125)
DETAILED DESCRIPTION OF THE INVENTION
METHODS OR PROCESSES OF SYNTHESIS
The compounds of formula (I) can be prepared according to the manufacturing
processes described in International Patent Publications Nos. WO 94/21606 and
\VO 93/06089 or International Patent Publication No. WO 87/03781 as well as in
European Patent Publication No. 0295117 and Hatton et al U.S. Patent No. 5.232.940.
Those skilled in the art will choose the proper initial reactant in these known methods
and adapt these known methods to the said reactant so as to obtain the corresponding
desired products. It is understood that in the description of the following processes the
sequences for the introduction of the various groups on the pyrazole ring may be
performed in a different order and that suitable protecting groups may be required as
will be apparent to those skilled in the art.
In the following description of processes when symbols appearing in formulae
are not specifically defined, it is to be understood that they are "as defined above" in
accordance with the first definition of each symbol in the specification.
According to a further feature of the present invention compounds of general
formula (I) wherein Po. R3- R4- R. M. X. Y and Z are as defined above and R1
represents amino (namely compounds of formula ( l a ) or db) in u h i c h represents
hydrogen), may be prepared by the reaetion of a compound of formula ( I I ) :
in which Y is defined above. The reaction is generally performed using an acid salt of
compound (III) for example the hydrochloride salt and in the presence of a base for
example pyridine or an alkali metal carbonate (such as sodium carbonate) or an alkali
metal acetate (such as sodium acetate) or ammonium acetate in a solvent such as
methanol and-'or water at a temperature from 0°C to 100°C.
According to a further feature of the present invention compounds of general
formula (I) wherein R2- R3- R. Rf. M. X. Y and Z are as defined above and Rj
represents amino may be prepared by the reaction of a compound of formula (IV):
wherein R represents alkyl. with a compound of formula (III) in which
Y is defined above. The reaction is generally performed using an using an acid salt of
compound (III) for example the hydrochloride salt and optionally in the presence of a
base for example pyridine or an alkali metal carbonate (such as sodium carbonate) or
an alkali metal acetate (such as sodium acetate) or ammonium acetate in a solvent
such as methanol and or water at a temperature from 0°C to 100°C.
According to a further feature of the present invention compounds of general
formula ( I ) wherein R^. R}. R4- R. M. X. Y and Z are as defined above and RI
represents alkylamino or dialkylamino may be prepared by the reaction of the
corresponding compound of formula (I) wherein R1 represents amino with an
alkylating agent preferably of formula R-hal where R represents alkyl and hal is
chloro. bromo or iodo. The reaction is usually carried out in the presence of a strong
base such as potassium t-butoxide or sodium hydride in a solvent such as
tetrahydrofuran at a temperature from 0°C to 100°C.
According to a further feature of the present invention compounds of general
formula (I) wherein R2- R3- . M. X. Y and Z are as defined above and R
represents hydrogen or alkyl may be prepared by the reaction of a compound of
in which Rj represents hydrogen or alkyl with a compound of formula (III) in which
Y is defined above and using the same conditions as employed in the reaction of
compounds of formula (II) with compounds of formula (III) above.
According to a further feature of the present invention compounds of general
formula (I) wherein Ro. R3- R4- R^. M. X and Z are as defined above, Rj represents
hydrogen or alkyl. and Y is defined above with the exclusion of hydrogen, formyl.
aryl. pyridinyl and pyrimidinyl (the exclusions being for chemical reasons only), may
be prepared by reaction of the corresponding compound of formula (I) wherein Y
represents hydrogen with an appropriate alkylating or acylating reagent or Michael
acceptor generally in the presence of a base for example triethylamine in an inert
solvent such as dichloroethane at a temperature of from 0°C to 100°C.
According to a further feature of the present invention compounds of general
formula (I) wherein Z represents R^NH- or R^R^N- in which Rj2, Rj3 and/or
R14 represent - C ( O ) a l k y l optionally substituted b\ one or more may be prepared
by the of the corresponding compound wherein Z represents ammo,
according to methods described in one or more oflnternational Publications No. W ()
94 21606. WO 93 06089 and WO 87 03781. European Patent Publication No.
0295117 and Hatton et al U.S. Patent No. 5.232.940.
For the synthesis of 5-alkylamino and dialkylamino compounds wherein Z
represents R 1 2 N H - o r - i n which R . R a n d R)4 represent alkyl o r C-3 t o
C-6 alkenyl optionally substituted by R18. including the cyclic amino compounds
(i.e.. the compounds in which R3 and R4 are joined together) of formula (I), three
basic methods are appropriate. The first method includes direct alkylation of
precursor compounds of formula (I) in which Z represents amino with alkylating
agents. The second method involves a two-step sequence, with formation of the
imino ethers, followed by a reduction. The third method of preparation is through a
conjugate addition, e.g.. a Michael-type addition.
The compounds o f formula (I) wherein Z represents R H - o r R R N R j 3
in which R J T . RH and/or R j 4 are R7S(0)r. formyl. alkynyl. alkoxycarbonyl.
alkylthiocarbonyl or aroyl. and R-j and r are defined above can be prepared by
methods described in one or more oflnternational Publications No. WO 94/21606,
WO 93/06089 and WO 87/03781. European Patent Publication No. 0295117 and
Hatton et al U.S. Patent No. 5,232.940.
The compounds of formula (I) in which Z represents hydrogen, halogen, -
S(0)nRg. -C(0)R7. -C(O)OR9- alkyl. haloalkyl, -N=C(Rio)(R] l)- alkylthiocarbonyl
and amino. R^NH-or R^R^N- may be prepared by methods described in one or
more oflnternational Publications Numbers WO 94/21606. WO 93/06089 and WO
87/03781. European Patent Publication Numbers EP 0295117, EP 511845, EP 403309
and EP 403300. and Hatton et al U.S.Patent No. 5,232.940, and German Patent
Publication No. DE 19511269.
According to a further feature of the present invention compounds of general
formula (I) wherein Z represents ORg may be prepared by methods described in US
Patent Numbers 5.047.550 and 4.918.085.
According to a further feature of the present invention compounds of formula
(I) in which the substituent Z is hydrazino. IH-pyrrol-l-yl or IH-pyrazol-l-yl may be
prepared according to the procedures described in EP 0352944.
The synthesis of higher oxidation states of the compounds of formula (I), i.e.,
compounds in which m is 1 or 2, can be achieved by oxidation of the corresponding
compounds in which m is 0 or 1. In general sulfinyl and
sulfonyl compounds can be prepared from sulfenyl and sulfinyL
compounds.
Intermediates of formula ( I I ) may be prepared by known methods ( see for
example the above listed references).
Certain compounds of formula ( I I ) are novel and as such constitute a further
feature of the invention.
Intermediates of formula (IV) wherein R represents alkyl may be prepared by
the reaction of compounds of formula (II) with an alcohol of formula ROH where R is
alkyl. The alcohol is usually employed in excess as the solvent but a co-solvent such
as tetrahydrofuran may be present. The reaction is generally carried out in the
presence of a base such as sodium alkoxide at a temperature of from 0°C to 100°C.
Intermediates of formula (V) wherein Rj represents hydrogen or alkyl may be
prepared by known methods for example as described in WO 8703781 and EP
295117. For example where Rj represents hydrogen by the reaction of the
corresponding compound of formula (II) with diisobutylaluminium hydride, and
where Rj represents alkyl by the reaction of the corresponding compound of formula
(II) with an organometallic reagent of formula RjQ in which Q represents for example
Mg-Cl or lithium in an inert solvent such as tetrahydrofuran.
Compounds of formula (IV) are novel and as such constitute a further feature
of the invention.
Certain compounds of formula (V) are novel and as such constitute a further
feature of the invention.
Intermediates of formula (III) are known or may be prepared by known
methods.
According to a further feature of the present invention compounds of general
formula (I bis) in which RJQ is amino may be prepared by the reaction of a compound
of formula (II bis):
with a compound of formula (III bis):
(III bis)
in which Y, is as defined above for Y. The reaction is
generally performed using an acid salt of a compound of
formula (III bis) for example the hydrochloride salt and in
the presence of a base for example pyridine or an alkali metal carbonate (such as
sodium carbonate) or an alkali metal acetate (such as sodium acetate) or ammonium
acetate in a solvent such as methanol and or water at a temperature from 0°C to
100°C.
According to a further feature of the present invention compounds of general
formula (1 bis) wherein R JQ is amino may be prepared by the reaction of a compound
wherein R represents alkyl. with a compound of formula (III bis). The reaction is
generally performed using an using an acid salt of a compound of formula (III bis), for
example the hydrochloride salt, and optionally in the presence of a base (for example
pyridine or an alkali metal carbonate such as sodium carbonate) or an alkali metal
acetate (such as sodium acetate or ammonium acetate) in a solvent such as methanol
and/or water and generally at a temperature from 0°C to 100°C.
According to a further feature of the present invention compounds of general
formula (I bis) wherein Rjg represents NR34R35 and wherein one or both or of R34
and R}5 are substituted or unsubstituted alkyl may be prepared by the reaction of the
corresponding compound of formula (I) wherein Rj9 represents amino with an
alkylating agent formula R-hal where R represents alkyl and hal is chloro, bromo or
iodo. preferably iodo. The reaction is usually carried out in the presence of a strong
base such as potassium t-butoxide or sodium hydride in a solvent such as
tetrahydrofuran at a temperature from 0°C to 100°C.
According to a further feature of the present invention compounds of general
formula (I bis) with the above definitions wherein RJQ represents hydrogen or alkyl
may be prepared by the reaction of a compound of formula (V bis):
in which Rjg represents hydrogen or alkyl with a compound of formula (III bis)
defined above and using the same conditions as employed in the reaction of
compounds of formula (II bis) with compounds of formula (III bis) above.
According to a further feature of the invention, compounds of formula (I bis)
wherein yx is -s (o) aR28/ -P(0)R29R30 . -P(S)R29R3Q. -Si(R31KR32XR-33).
-C(0)R27- -C(S)R27- cyano or nitro may be prepared by reaction of a compound of
formula (I bis) wherein \'\ is hydrogen, with sulfenylating. sulfinylating. sulfonating
phosphorylating. thiophosphorylating. silylating. acylating or thioacylating reagent,
respectively, generally in the presence of a base such as triethylamine or sodium
carbonate and generally in a solvent at a temperature generally in the range -100 to
100=C.
According to a further feature of the invention for the synthesis of 5-
alkylamino and dialkylamino compounds of formula (I bis) wherein R21 represents
R43NH- or R43R44N- in which R43 and R44 represent substituted or unsubstituted
alkyl or substituted or unsubstituted C-3 or C-6 alkenyl three basic methods are
appropriate. The first method includes direct alkylation of precursor compounds of
formula (I bis) in which R represents amino with alkylating agents. The second
method involves a two-step sequence, with' formation of the imino ethers, followed
by a reduction. The third method of preparation is through a conjugate addition, e.g..
a Michael-type addition.
The compounds of formula (II bis) wherein R2, R3, R4, R. and M are the
above described substituents can be prepared by methods described in one or more of
the following: WO 94/21606. WO 93/06089. WO 87/03781. WO 97/22593:
European Patent Publications EP 0295117. EP 0511845. EP 0403309. EP 0403300,
EP 352944. EP 780378: U.S. Patents 5.232.940. 5,047.550. 4.918.085: German Patent
Publication No. 19511269: or bv methods known to the skilled in the art.
The synthesis of higher oxidation states of the compounds of formula (I bis),
i.e.. compounds in which a. b. c. d. e or fare 1 or 2. can be achieved by oxidation of
the corresponding compounds in which those variable are is 0 or 1.
Intermediates of formula (II bis) may be prepared by known methods ( see for
example the above listed references).
REPRESENTATIVE COMPOUNDS OF THE INVENTION
The compounds of TABLE 1 are illustrative of some of the preferred
compounds of general formula (I) wherein R3 and R5 represent hydrogen and can be
prepared by the herein described methods or processes of synthesis, by the appropriate
selection of reactants. conditions and procedures, which are commonly known and
apparent to one skilled in the art. In Table 1 Me means methyl. Et means ethyl and
where subscripts are omitted they should be present, for example CH2 means CH2 (Table Removed)
DESCRIPTION OF THE PREFERRED EMBODIMENTS
DETAILED EXAMPLES OF COMPOUND SYNTHESIS
The following EXAMPLES 1 to 17 and REFERENCE EXAMPLES 1 to 24
illustrate detailed methods of synthesis and the physical properties of representative
pesticidal compounds of formula (I) (and their chemical intermediates) according to
the invention. These example compounds and others prepared in a similar manner,
following the detailed procedures or other methods or processes herein described, are
shown in Tables 2. Additionally, one or more spectroscopic analyses (IR. H1 or F19
NMR. MS. etc.) have been performed on each compound for characterization and
confirmation of the chemical structure. In the following Tables Me means methyl. Et
means ethyl. 2-Tolyl means 2-methylphenyl and C2H means ethynyl.
EXAMPLE 1
A mixture of 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfmyl-lH-pyrazole-3-carboxaldehyde (2.74g). hydroxylamine hydrochloride
(0.99g) and pyridine (1.68g) was stirred in methanol at 46° C for 2.8 hours,
evaporated, washed (water) and crystallized from ethanol to give 5-amino-l-[2.6-
dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lH-pyrazole-3-carboxaldehyde
oxime (T.74g) as a white solid m.p.219-221° C (decomposition). Compound 1
In a manner similar to that employed above, the following compounds shown in
Table 2 were also prepared.
EXAMPLE:
A mixture of 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
trirluoromethylthio-1 H-pyrazole-3-carboxaldehyde (0.66g). methoxyamine
hydrochloride (0.2g) and pyridine was stirred at room temperature for 26 hours.
Pyridine \vas evaporated and the residue dissolved in ethyl acetate;acetonitrile.
washed with 1% aqueous HC1. dried (MgS04) and evaporated.. The residue was
purified by silica gel column chromatography. eluting with hexane/ethyl acetate, to
give 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-lHpyrazole-
3-carboxaldehyde 0-methyloxime (0.3g) as a white solid m.p. 129-131.5° C.
Compound 9.
EXAMPLE 3
Acetyl chloride (0.27ml) was added to a solution of 5-amino-l-[2.6-dichloro-
4-(trifluoromethyl)phenyl]-4-methylsulfmyl-1 H-pyrazole-3-carboxaldehyde oxime
(1 .Og) and triethylamine (0.56ml) in tetrahydrofuran at 0°C and the mixture stirred for
1 hour. The solvent was evaporated and the residue chromatographed on silica gel
eluting with 3:1 dichloromethane/ethyl acetate to give 5-amino-l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-methylsulfmyl-1 H-pyrazole-3-carboxaldehyde 0-
(acetyl)oxime (0.83g)as an orange solid m.p.130-134° C. Compound 10.
In a manner similar to that employed above the following compounds shown
in Table 3 were also prepared.
EXAMPLE 4
A mixture of 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime (1.38g). 30% hydrogen peroxide
(1.38ml) sodium tungstate dihydrate (0.17g) in methanol/acetic acid was stirred at
20°C overnight, then at 50°C for 4 hours, and again at 20 °C overnight. Water was
added and the solid filtered, water-washed and dried to give 5-amino-l-[2,6-dichloro-
4-(trifluoromethyl)phenyl]-4-methylsulfonyl-lH-pyrazole-3-carboxaldehyde oxime
(0.93g) m.p.209.5-211°C (decomposition). Compound 16.
EXAMPLE 5
A solution of 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)-phenyl]-4-
methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime (0.15g) in ethanol was added to
a solution of sodium ethoxide (0.025g)in ethanol at 20 °C. followed by iodomethane
(0.023ml). The reaction was monitored by HPLC and over the next 24 hours three
additional equivalents of iodomethane were added. The reaction mixture was then
concentrated and partitioned between dichloromethane and water. The organic layer
was water-washed, dried (MgS04) and concentrated. This was then combined with
crude product from another identical preparation and chromatographed on a silica gel
column, eluting with hexane/ethyl acetate, to give 5-amino-l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-methylsulfmyl-lH-pyrazole-3-carboxaldehydeO-
(methyl)oxime (0.06g)as a yellow solid m.p.80°C. Compound 17.
EXAMPLE 6
A mixture of 5-amino-1 -[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime (1.5g). methyl isocyanate
(0.705g). and dibutyltin diacetate (2 drops) was stirred in dichloromethane at 20°C in
a sealed bottle for 2 days. The mixture was partitioned between water and
dichloromethane. the organic layer dried (Na2S04) and evaporated and the residue
crystallized from ethyl acetate/hexane to give 5-amino-l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-methylsulfinyl-1 H-pyrazole-3-carboxaldehyde 0-(Nmethylcarbamoyl)
oxime C1.22g) m.p.l46-147°C.
Compound 18.
EXAMPLE 7
A mixture of 5-amino-1 -[2.6-dichloro-4-(trifluoromethy 1 )phenyl]-4-
methylsulfinyl-lH-pyrazole-3-carboxaldehyde (5.15g) and carboxymethoxylamine
hemihydrochloride (5.83g) was stirred at 20°C in pyridine methanol for 17 hours.
The methanol was evaporated and the residue water-washed and subjected to flash
column chromatography on silica gel. eluting with acetic acid/ ethyl acetate (1:9) to
give 5-amino-1- [2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lHpyrazole-
3-carboxaldehyde 0-(carboxymethyl)oxime (1.44g). Mass spectrometric
analysis of the product indicated a molecular weight of 458. Compound 19.
EXAMPLE 8
Ten-butyl nitrite (1.25g) was added to 5-amino-1-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime
(2.0g) in tetrahydrofuran and stirred for 4.5 hours. After evaporation the resulting
orange solid was triturated with carbon tetrachloride to give l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime
(0.24g) m.p.239-240°C. Compound 20.
EXAMPLE 9
A solution of tert-butyldimethylsilyl chloride (0.8g) in N.Ndimethylformamide
(DMF) was added to a stirred solution of 5-amino-1-[2.6-
dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-pyrazole-3-carboxaldehyde
oxime (2.0g) in (DMF). followed by dropwise addition of a solution of imidazole
(0.72g) in DMF during 7-minutes. The mixture was heated at 50°C for 3.5-hours and
then held at 20 °C for 18 hours. The mixture was diluted (water), extracted (methyl
ten-butyl ether) and the organic phase washed in turn with NaHCOs solution, 5% HC1
solution and with NaHCO} solution, dried (MgS04), filtered and evaporated. The
residue was purified by flash chromatography on silica gel to give 5-amino-1- [2.6-
dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lH-pyrazole-3-carboxaldehyde
0-(tert-butyldimethylsilyl)oxime (0.76g)as a light yellow solid m.p.150-154°C.
Compound 21.
EXAMPLE 10
To a stirred solution of l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-4-
trifluoromethylthio-lH-pyrazole-3-carbonitrile (3.0g) in ethanol was added a solution
of hydroxylamine hydrochloride (0.46g) and sodium carbonate (0.9g) in water. After
1 hour the mixture was poured into water, extracted (ethyl ether), dried (sodium
sulfate) and evaporated. Purification by column chromatography on silica gel gave 1-
[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-trifluoromethylthiolH-
pyrazole-3-carboximidamide (0.255g). m.p.72-75°C. Compound 22.
The following compounds shown in Table 4 were prepared in a similar manner.
EXAMPLE 11
A mixture of l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-rbrmyl-4-
trifluoromethylthio-lH-pyrazole-3-carbonitrile (l.Og). hydroxylamine hydrochloride
(0.48g) and sodium acetate trihydrate (0.94g) in ethanol \vas heated under reflux for
one hour. After cooling to 20°C the mixture was concentrated and partitioned
between water and ether. The organic phase was washed (brine), dried (magnesium
sulfate) and evaporated to give l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-Nhydroxy-
5-hydroxyiminomethyl-4-trifluoromethylthio-lH-pyrazole-3-
carboximidamide (0.5g). m.p.68-72°C. Compound 23.
EXAMPLE 12
A suspension of sodium ethoxide (0.34g) in ethanol was added to a stirred
solution of 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboxaldehyde oxime (2.0g) in ethanol. 2-Iodopropane (1ml) was then
added and the mixture stirred overnight at 20°C and evaporated. The residue (in
dichloromethane) was water-washed, dried (magnesium sulfate). concentrated and
purified by chromatography on silica gel to give 5-amino-1-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-methylsulfmyl-lH-pyrazole-3-carboxaldehyde 0-
(isopropyl)oxime (0.35g). m.p.l28-130°C. Compound 24.
By proceeding in a similar manner the following compounds were also prepared:
5-amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-l-H-pyrazole-3-
carboxaldehyde 0-(ethoxycarbonylmethyl)oxime. Compound 25. m.p.l27-128°C ;
and
5-amino-1 -[2.6-di.chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1 -H-pyrazole-
carboxaldehyde O-(carbamoylmethyl)oxime. Compound 26. m.p.165-167°C .
EXAMPLF P
In a manner similar to that employed in Example 12 an ethanol solution of 5-
amino-1 -[2.6-dichloro-4-(trifluoromethyl )phenyl]-4-methylsulfinyl-1 H-pyrazole-3-
carboxaldehyde oxime was reacted with sodium ethoxide and ethyl vinyl sulfone to
give 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lHpyrazole-
3-carboxaldehydeO-[2-(ethylsulfonyl)ethyl]oxime. m.p.144-
148°C.Compound27.
EXAMPLE 14
In a manner similar to that employed in Example 12 an ethanol solution of 5-
amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lH-pyrazole-3-
carboxaldehyde oxime was reacted with sodium ethoxide and acrvlonitrile to give 5-
amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-pyrazole-3-
carboxaldehyde 0-(2-cyanoethyl)oxime. Compound 28. as the 85 percent (by weight)
component of a mixture containing 8 percent of the oxime starting material. Mass
spectrometric analysis of the product indicated the following: MS nv'e = 453 (M~).
EXAMPLE 15
30% Hydrogen peroxide solution (0.32ml) was added to a solution of l-[2.6-
dichloro-4-(trifluoromethyDphenyl]-5-methyl-4-methylthio-lH-pyrazole-3-
carboxaldehyde oxime (O.Sg) in trifluoroacetic acid at 20°C. The reaction solution
was partitioned between water and dichloromethane and the organic layer dried
(magnesium sulfate). evaporated and flash-chromatographed on silica gel. eluting
with dichloromethane/ethyl acetate (3:1) to give l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-lH-pyrazole-3-carboxaldehyde
oxime (0.29g). m.p.210-214°C. Compound 30 and l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-lH-pyrazole-3-carboxaldehyde
oxime (0.2g). m.p.211-212°C. Compound 31.
EXAMPLE 16
To a stirred solution of -
metriylsulfmyl-lH-pyrazoleO-carboximidic acid methyl ester ( l . O g ) in anhydrous
methanol was added anhydrous methoxvlamine hvdrochloride (0.2g). After 4 hours at
20 °C. the mixture was evaporated and dichloromethane and water added. The
organic layer was dried (MgS04 ). evaporated and chromatographed on a florisil
column, eluting with 3:1 dichloromethane/ethyl acetate to give 5-amino-l-[2.6-
dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-[H-pyrazole-3-
carboximidamide(0.28g).m.p.l40-145°C.Compound 49. By proceeding in a similar
manner the following compounds were prepared:5-amino-l-[2.6-dichloro-4-
(trifluoromethyl)pheny l]-N-methoxy-4-trifluoromethylsulfmyl-1 H-pyrazole-3-
carboximidamide. m.p.!69-170°C. Compound 41. : and
5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-
trifluoromethylsulfmyl-1 H-pyrazole-3-carboximidamide. m.p.222-224°C. Compound
40.
EXAMPLE 17
A solution of 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-
4-methylsulfinyl-lH-pyrazole-3-carboximidamide (0.5g) in anhydrous THF was
stirred at 0-5°C and potassium tert-butoxide (0.13g) and iodomethane (0.081ml)
added. After three hours further potassium tert-butoxide (0.068g) and iodomethane
(0.08ml) were added at 0-5° C. The mixture was stirred at this temperature for 16
hours, evaporated and the residue purified by chromatography on silica gel eluting
with 3:1 dichloromethane/ethyl acetate to give 5-amino-l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-N-methoxy-N'-methyl-4-methylsulfmyl-lH-pyrazole-3-
carboximidamide (0.13g). m.p.l39-142°C. Compound 50.
EXAMPLE 18
A mixture of 5-amino-3-cyano-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfmyl-lH-pyrazole (550 g). anhydrous hydrazine (700 g) in absolute ethanol
(1.55 L) was stirred at ambient temperature for four hours. Water (6.5 L) was added
and the precipitate filtered and washed with water. After 12 hours another batch of
precipitate was filtered. All solids were combined to provide 568 g of Compound 69
as a white solid, m.p. 210°C.
In a similar manner the following compounds were prepared:
Compound 73 m.p. 170°C;
Compound 74 m.p. 193°C.
EXAMPLE 19
The mixture of Compound 69 (1.0 g) and acetic anhydride(327 mg) in pdioxane
( 1 0 ml) was stirred at room temperature for 2 days. The mixture was
evaporated and the residue washed with hexane with small amount of ethyl acetate
and the suspension filtered to give 1.08 g of Compound 75. m.p 230°C.
Compound 85 was synthesized using a similar procedure.
EXAMPLE 20
The mixture of Compound 69 (0.2 g) and propionic anhydride (0.07 ml) in
tetrahydrofuran (5 ml) was stirred at room temperature for 6 days. The mixture wras
evaporated and the residue purified by silica gel chromatography to give 70mg of
Compound 79. m.p. 155-162°C.
In a similar manner the following compounds were prepared:
EXAMPLE 21
The mixture of Compound 69 (0.2 g) and di-t-amyldicarbonate (0.13 ml) in
tetrahydrofuran (4.5 ml) was stirred at room temperature for 5 days. The mixture was
evaporated and the residue purified by silica gel chromatography to give 20 mg (0.038
mmol) of Compound 89. m.p. 95-98°C.
The following compounds were synthesized with the similar procedure using
an appropriate dicarbonates: Compound 88. m.p. 135°C. Compound 90. m.p. 155°C.
Compound 72. m.p. 196°C.
EXAMPLE 22
To a suspension of 5-amino-3-cyano-l-(2,6-dichloro-4-
trifluoromethylphenyl)-4-methylsulfinylpyrazole (20g) inmethanol (120ml) was
added hydroxylamine hydrochloride ( 3.99g). followed by addition of triethylamine
(8.0 ml). The mixture was stirred at room temperature overnight then evaporated. The
residue was partitioned between water and ethyl acetate. The organic layer was
washed with water, followed by wash with brine. The organic layer was dried over
anhydrous sodium sulfate. The solution was concentrated by evaporation of solvent. A
precipitate was formed and collected by filtration. The solid was washed with small
amount of ethyl acetate to give Compound 44 (16.1 g). m.p. 225-226°C.
REFERENCE EXAMPLE 1
Diisobutylaluminum hydride ( 1M in toluene. 391ml) was added dropwise
during 1.5 hours to 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfmyl-3-carbonitrile (50g) in dry THF at -20° C. The partially evaporated
mixture was then quenched by addition to acetonitrile/water at 0-5° C. Aluminum
salts were filtered, the filtrate evaporated and the residue extracted with
dichloromethane. The extract was dried (MgS04), and evaporated to give 5-amino-l-
[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-pyrazole-3-
carboxaldehyde (47.Ig).
By proceeding in a similar manner the following compounds shown in Table 5
were also prepared.
(a) 25.0 cm x 4.6 mm SUPELCOSIL LC-18 Column. Eluant: MeCN/H2O (3:l)at
one ml/minute.
(b) used \vithout purification in the next stage
REFERENCE EXAMPLE 2
A 1.4 M solution of methyllithium (31ml) in ethyl ether was added to a stirred
solution of 5-bromo-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1Hpyrazole-
minutes and allowed to warm to 0°C over 3-hours. After receding to -65°C. methyl
iodide (3.06ml) in THF was added over 3 minutes, the mixture warmed to -20°C over
1.5 hours, and then partitioned between aqueous ammonium chloride and
dichloromethane. The organic phase was dried (magnesium sulfate). evaporated and
purified by flash chromatography on silica gel eluting with hexane/methyl tertbutylether
to give l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthiolH-
pyrazole-3-carbonitrile (6.2g) having a purity of 90.7 area percent by HPLC..
By proceeding in a similar manner the following compound was also prepared:
l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-5-methyl-l-H-pyrazole-3-
carbonitrile m.p.79-S2°C..
REFERENCE EXAMPLE 3
30% Hydrogen peroxide (1.82ml) was added to a stirred solution of 1-[2.6-
dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-lH-pyrazole-3-
carbonitrile (6.2g) in methanol. containing i-PrOHT-hS catalyst (5.31ml) described
by Drabowicz. et al (above) at 0-5° C. The mixture was allowed to warm to 20°C
over 17 hours. Additional hydrogen peroxide (5.46 ml) was added in three portions
over the next 24 hours, along with the catalyst (5ml). After stirring for a further 60
hours water was added to give l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-
methylsulfmyl-lH-pyrazole-3-carbonitrile (6.72 g) as a yellow oil (91.7% area purity
by HPLC) having a retention time of 3.61 minutes on a 25.0 centimeter by 4.6
millimeter SUPELCOSIL LC-18 column, eluting with CHsCN / H20 (3:1) solvent at
1 ml minute..
By proceeding in a similar manner the following compounds were also
obtained:
l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-methyl-l-H-pyrazole-3-
carbonitrile. m.p.109-115°C;
5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)sulfinyl]-l-Hpyrazole-
3-carbonitrile. m.p. 182-183°C;
l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylsulfinyl)ethylamino]-4-
ethylsulfmyl-lH-pyrazole-3-carbonitrile. m.p. 106-108 °C. from l-[2,6-dichloro-4-
(trifluoromethyl)phenyl]-5-[2-(methylthio)ethylamino]-4-ethylsulfinyl-lH-pyrazole-
3-carbonitrile;
l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylsulfinyl)ethylamino]-4-
methylsulfinyl-lH-pyrazole-3-carbonitrile. m.p. 114-116 °C. from l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-5-[2-(methylthio)ethylamino]-4-methylsulfinyl-lH-pyrazole-
3-carbonitrile:
l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsuifinyhethyIamino]-4-
ethylsulfmyl-lH-pyrazole-3-carbonitrile. m.p. 138-140 °C. from l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-5-[2-(ethylthio)ethylamino]-4-ethylsulfinyl-lH-pyrazole-3-
carbonitrile:
5-amino-l-[3-chloro-5-(trifluoromethyl)pyrid-2-yl]-4-ethylsulfmyl-lH-pyrazole-3-
carbonitrile. m.p.150-152 °C: and
5-amino-l-[2.6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-pyrazole-3-
carbonitrile. m.p.165-166 °C.
REFERENCE EXAMPLE 4
90% Tertiary-butyl nitrite (27.9ml) was slowly added to a stirred solution of 5-
amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-lH-pyrazole-3-
carbonitrile (49.8g) in bromoform (600ml) at 0-5°C. The mixture was stirred for three
hours whilst warming to 20°C evaporated and re-evaporated after addition of
hexane/ethyl acetate (1:1) to give 5-bromo-l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-ethylthio-1 H-pyrazole-3-carbonitrile (32.65g). showing
93.3 area % purity by HPLC and with a retention time of 11.26 minutes on a 25.0 cm
by 4.6 mm SUPELCOSIL LC-18 column, eluting with CHsCN/FhO (3:1) solvent at
1 ml/minute.
By proceeding in a similar manner the following compound was prepared:
5-bromo-1 -[2.6-dichloro-4-( trifluoromethyl)phenyl]-4-methylthio-1 H-pyrazole-3-
carbonitrile. m.p. 134-140 °C.
REFERENCE EXAMPLE 5
Ozone was bubbled through a solution of l-(2.6-dichloro-4-
trifluoromethylphenyl)-5-(E-2-methoxycarbonylethenyl)-4-trifluoromethylthio-lHpyrazole-
3-carbonitrile (36.6g) in dichloromethane at -78°C for 3 hours. The intensely
blue solution was decolorized with oxygen gas. then treated with dimethylsulfide (19
ml) and allowed to warm to 20°C during 14 hours The mixture was then washed with
water, dried (magnesium sulfate), filtered and evaporated to give l-(2.6-dichloro-4-
trifluoromethylphenyl)-5-formyl-4-trifluoromethylthio-1 H-pyrazole-3-carbonitrile as
white crystals (30.7g). m.p.90°C.
REFERENCE EXAMPLE 6
1.8-Diazabicyclo-[5.4.0]-undec-7-ene (13 ml) was added to a solution of 5-(2'-
bromo-2'-carbomethoxy)ethyl-l-(2.6-dichloro-4-trifluoromethylphenyl)-4-
trifluoromethylthio-1 H-pyrazole-3-carbonitrile (45g) in toluene and stirred for 0.5
hour. The mixture was diluted ( e t h y l acetate), and washed with water, hydrochloric
acid solution, saturated sodium hydrogen carbonate solution and brine. The organic
phase was dried (magnesium sulfate). concentrated and triturated with cold pentane to
give l-(2.6-dichloro-4-tritluoromethylphenyl)-5-(E-2-methoxycarbonylethenyl)-4-
trifluoromethylthio-lH-pyrazole-3-carbonitrile as a white solid (36.6 g). m.p.90°C.
REFERENCE EXAMPLE 7
A solution of 5-amino-1 -(2.6-dichloro-4-trifluoromethylphenyl)-4-
trifluoromethylthio-lH-pyrazole-3-carbonitrile (lOOg) in acetonitrile was added
dropwise to a mixture of methyl aery late (430 ml), copper (II) bromide (80 g) and
90% tert-butylnitrite (51 ml) in acetonitrile at 0°C. warmed to 20°C and stirred for 12
hours. The mixture was diluted (ether), washed (water), dried (magnesium sulfate)
and concentrated. Trituration with hexane gave 5-(2'-bromo-2'-carbomethoxy)ethyll-(
2.6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-lH-pyrazole-3-
carbonitrile as a white solid (72.7g) m.p.l22°C.
REFERENCE EXAMPLE 8
To a stirred suspension of 5-amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-
4-methylsulfinyl-lH-pyrazole-3-carbonitrile (5.0g) in anhydrous methanol was added
a 25% ww solution of sodium methoxide (8.95ml) in methanol. at 20 °C. The
mixture was stirred for 16-hours. cooled to 0 °C and diluted with ice-cold anhydrous
methanol. Carbon dioxide was passed into the solution for 15-minutes until a pH of 8
was attained. The precipitate was filtered off. washed (ethyl acetate) and evaporated to
give 5-amino-1-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-lHpyrazole-
3-carboximidic acid methyl ester (3.65s). ^H NMR (CDC13) in ppm:
8.34(s.lH). 7.79(s.2H). 5.1 l(brs.2H). 3.93(s.3H). 2.94(s.3H). By proceeding in a
similar manner the following compound was prepared:5-Amino-l-[2,6-dichloro-4-
(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-lH-pyrazole-3-carboximidic acid
methyl ester, m.p. 179-180 °C.
REFERENCE EXAMPLE 9
To a stirred solution of 4.4'-dithiobis [5-amino-3-cyano-l-{2.6-dichloro-4-
(trifluoromethyl)phenyl}-lH-pyrazole (l.Og) in methanol was added sodium
borohydride (0.03g). After 7-minutes l-bromo-2-fluoroethane (0.05ml) was added.
Five funher portions of sodium borohydride (0.15g) and l-bromo-2-fluoroethane
(0.25ml) were added over 5 hours. The mixture was evaporated, dichloromethane and
water added and the organic phase dried (MgS04) and re-evaporated to give 5-amino-
1-[2.6-dichloro-4-( tritluorometh\ 1 iphenyl]-4-[2-( tluoroethyl ithioj-1 H-pyrazole-3-
carbonitrile (1.09g). m.p. 130-13 1.5° C. By proceeding in a similar manner the
following compound was obtained:
5-amino-l-[2.6-dichloro-4-(tritluoromethoxy)phenyl]-4-ethylthio-lH-pyrazole-3-
carbonitrile. m.p.!27-128°C. 4.4'-Dimiobis [5-amino-3-cyano-l-{2.6-dichloro-4-
(trifluoromethoxy)phenyl|-lH-pyrazole used above may be prepared in a similar
manner to 4.4'-dithiobis [5-amino-3-cyano-l-[2.6-dichloro-4-
(trifluoromethyl)phenyl}-lH-pyrazole as described in French Patent Application
Numbers 8816710 and 8913371.
REFERENCE EXAMPLE 10
In a manner similar to that of Example 15. 5-amino-l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)thio]-lH-pyrazole-3-carbonitrile was
oxidized with hydrogen peroxide in trifluoroacetic acid solution to give 5-amino-l-
[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)sulfonyl]-lH-pyrazole-3-
carbonitrile. m.p.l92-193°C By proceeding in a similar manner the following
compounds were prepared:
5-amino-l-[2-bromo-6-chloro-4-(trifluoromethynphenyl]-4-methylsulfinyl-lHpyrazole-
3-carbonitrile. m.p.l50-151°C. 5-amino-l-[2.6-dichloro-4-
(trifluoromethoxy)phenyl]-4-methylsulfinyl-lH-pyrazole-3-carbonitrile. m.p.137-
138°C. 5-amino-l-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lHpyrazole-
3-carbonitrile. m.p.l46-147°C.
REFERENCE EXAMPLE 11
A mixture of l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-5-
amino-lH-pyrazole-3-carbonitrile (5.0g). trimethyl onhoacetate (100ml) and ptoluenesulfonic
acid (0.2g) in toluene was heated to 145CC for 2 hours and then at
130CC with distillation of the methanol.. The mixture was evaporated and the residue
purified by column chromatography using 20% ethyl acetate in hexane to give l-[2.6-
dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[l-(methoxyethylene)amino]-
lH-pyrazole-3-carbonitrile (3.3 Ig) m.p.164 to 165°C.
REFERENCE EXAMPLE 12
To a suspension of l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfinyl-5-[l-(methoxyethylene)amino]-lH-pyrazole-3-carbonitrile (6.0g) in
methanol was added sodium borohydride (0.79g) in three portions over 15 min. at
20°C then stirred under nitrogen for 45 mins..After evaporation the residue was
purified by column chromatography on silica gel using 15°o ethyl acetate in
methylene chloride to give l-[2.6-dichloro-4-(trifluoromethyl)phenyll-4-
methylsulfinyl-5-ethylamino-lH-pyrazole-3-carbonitrile ( l . l g ) . m.p.130-
131:C(decomp.).
By proceeding in a similar manner was prepared:
l-[2.6-dichloro-4-(trifluoromethyl)phen\-l]-5-methylamino-4-methylsulfinyl-lHpyrazole-
3-carbonitrile. m.p. 147-150° C (decomposition).
By proceeding in a similar manner out replacing sodium borohydride with
sodium cyanoborohydride was prepared:
1 -[2-bronio-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-ethylamino-1Hpyrazole-
3-carbonitrile. m.p.l25-126.5°C.
REFERENCE EXAMPLE 13
A solution of 5-amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfinyl-lH-pyrazole-3-carbonitrile (4.92g) in triethyl orthoformate (100ml)
was heated under reflux for two hours, then stirred at 20°C for 16 hours and
evaporated. Trituration with boiling hexane gave l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-5-[(ethoxymeth\-lene)amino]-4-methylsulfmyl-lH-pyrazole-
3-carbonitrile (4.05g). m.p.93-95° C. By proceeding in a similar manner the following
compound was prepared:
l-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-[l-(methoxyethylene)amino]-4-
methylsulfmyl-lH-pyrazole-3-carbonitrile. This was used directly in the next stage.
REFERENCE EXAMPLE 14
To a suspension of 35% potassium hydride in oil (0.7g) in dry N.Ndimethylformamide
(DMF) was added a solution of 5-amino-1-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-(methylsulfinyl)-lH-pyrazole-3-carbonitrile (lO.Og) in dry
DMF dropwise at 4°C over 10 minutes. After stirring for 20 minutes, vinyl ethyl
sulfone (3.13g) in dry DMF was added during 5 hours at 4°C. The mixture was
stirred overnight under nitrogen with warming to 20°C. Ammonium chloride was
added at 4°C. and the mixture extracted (ethyl acetate), washed twice with water,
dried (sodium sulfate) and evaporated. Crystallization from ethyl
acetate/methanol/hexane gave 1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-
(ethylsulfonyl)ethylamino]-4-(methylsulfmyl)-1 H-pyrazole-3-carbonitrile (4.08g),
m.p.!31-132°C. By proceeding in a similar manner the following compounds were
prepared:
1 -[2.6-dichloro-4-( trifluoromethyl )phenyl]-5-[2-( cyanoethyl )aminc]-4-
(methylsulfmyl)-1 H-pyrazole-3-carbonitrile. m.p.55o7:C: 1 -[2.6-dichloro-4-
(trifluoromethyl)phenyl]-4-methylsulfmyl-5-[2-(phenylsultbnyl)ethylamino]-lHpyrazoIe-
3-carbonitrile. m.p.!38-139:C: and
l-[2-chloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyr)ethylamino]-4-
methylsulfmyl-lH-pyrazole-3-carbonitrile.m.p.l39-140°C.
REFERENCE EXAMPLE 1 5
To a solution of 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfinyl-1 H-pyrazole-3-carbonitrile (0.5g) in acetonitrile was added 2-
bromoacetamide (0.18g) in water and calcium carbonate (0.13g). The mixture was
heated under reflux for 1.5 hours, cooled to 25°C and a solution of sodium hydroxide
(0.05g) in water added. This was then heated under reflux for one hour, evaporated
and the residue purified by preparative thin-layer chromatography eluting first with
20% methanol in dichloromethane to give l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-
4-methylsulfinyl-5-[(aminocarbonylmethyl)amino]-l H-pyrazole-3-carbonitrile
(O.OS9g). m.p.155-157°C.
REFERENCE EXAMPLE 16
To a suspension of 5-amino-l-[2.6-dichloro-4-(trifluoromethynphenyl]-4-
methylsulfinyl-1 H-pyrazole-3-carbonitrile (2g) in toluene was added methyl
magnesium bromide (7ml of a 1.4M solution in toluene/THF). The mixture was
stirred at 20°C (1 hr.) and neutralised with saturated ammonium chloride solution.
The organic layer was dried (sodium sulfate). evaporated and the residue purified by
chromatography using 40% ethyl acetate in hexane to give 3-acetyl-5-amino-l-[2.6-
dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfmyl-1 H-pyrazole (0.68g), m.p.
166°C.
REFERENCE EXAMPLE 17
To a suspension of 35% potassium hydride in oil (1.4g) in dry N.Ndimethylforrnamide
(DMF) was added a solution of l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-5-amino-4-(ethylsulfmyl)-lH-pyrazole-3-carbonitrile (5.0g)
in dry DMF at 4°C and stirred for 40 min. 2-Chloroethyl methyl sulfide (1.39g) was
added at 4°C and the stirred mixture allowed to warm to 20°C over 40 minutes, then
heated to 50°C for 4 hours and at 20°C for 3 days. Ammonium chloride solution and
ethyl acetate were added and the organic layer dried (sodium sulfate). evaporated and
purified by column chromatography using 80% methyl t-butyl ether in hexane to give
l-[2.6-dichloro-4-(trifluoromethyl )phenyl]-5-[[-2-(methylthio)ethyl]amino]-4-
(ethylsultlnyl)-lH-pyrazole-3-carbonitrile(0.26g). m.p.l26-127:C.
By proceeding in a similar manner there were prepared:
l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-[-2-(methylthio)ethylamino]-4-
methylsulfmyl-lH-pyrazole-3-carbonitrile. m.p.l 11-113°C. l-[2.6-dichloro-4-
(trifluoromethyl)phenyl]-5-[-2-(ethylthio)ethylamino]-4-ethylsulfinyl-lH-pyrazole-3-
carbonitrile. m.p.27.5-29=C. l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylsulfinyl-5-(2-propynyl)amino-lH-pyrazole-3-carbonitrile. m.p. 140-141°C
REFERENCE EXAMPLE 18
Sulfuryl chloride (1.48g) was added to methyl disulfide (3.16g) in methyl tbutyl
ether and stirred for 5 hours to give methyl sulfenyl chloride. This was added
dropwise over 5 minutes to a solution of 5-amino-l-[2-bromo-6-chloro-4-
(trifluoromethyl)phenyl]-lH-pyrazole-3-carbonitrile (4.0g) heated under reflux in
methyl t-butyl ether under nitrogen. After 1 hour the cooled mixture was washed in
turn with water, sodium bicarbonate solution and water, dried (sodium sulfate) and
evaporated. Purification by chromatography on silica gel eluting with hexane/ethyl
acetate (9:1) gave 5-amino-l-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-
methylthio-lH-pyrazole-3-carbonitrile (3.15g). m.p.l7S-1802C._ By proceeding in a
similar manner the following compound was prepared:
5-amino-l-[3-chloro-5-(trifluoromethyl)pyrid-2-yl]-4-ethylthio-lH-pyrazole-3-
carbonitrile.
REFERENCE EXAMPLE 19
Step 1
Bromine (0.5 ml) was added over 10 minutes to a stirred solution of sodium
thiocyanate (1.7 g) in anhydrous methanol at -65° C. A solution of 5-amino-l-(2-
chloro-4-(trifluoromethyl)phenyl]-l-H-pyrazole-3-carbonitrile (1.5 g) in anhydrous
methanol was added over 10-minutes and the stirred mixture allowed to warm to 20°
C over 16-hours. After pouring into water the precipitate was collected and dried to
give 5-amino-l-[2-chloro-4-(trifluoromethyl)phenyl]-4-thiocyanato-lH-pyrazole-3-
carbonitrile (1.64 g). HPLC (C-18 column, eluting with 3:1 CH3CN/H20 at 1.0
ml/min.) showed the compound as a peak of 86.6% area at 5.11 minutes.
Step 2
lodomethane (0.7 ml) was injected into a stirred suspension of 5-amino-l-[2-
chloro-4-(trifluoromethyl)phenyl]-4-thiocyanato-lH-pyrazole-3-carbonitrile (1.64 g),
in methanol at 4° C. A 10% aqueous solution of sodium hydroxide (2.8 ml) was
added and the reaction mixture stirred tor 1 hour at 4° C . poured into water and
extracted with dichloromethane and ethyl acetate. The dried (Na:S04 combined
organic phase was evaporated and purified by flash-chromatography on silica gel
eiuting with 4:1 hexane ethyl acetate to give, after trituration with
hexane dichloromethane. 5-amino-l-[2-chloro-4-(trifluoromethyl)phenyl]-4-
methylthio-lH-pyrazole-3-carbonitrile (0.4 g). m.p.l29-132°C.
By proceeding in a similar manner as step 1 above there was obtained:
A) 5-amino-l-[2.6-dichloro-4-(trifluoromethoxy)phenyl]-4-thiocyanato-
IH-pyrazole. which was used in Step 2 with iodomethane to give 5-amino-l-[2.6-
dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-lH-pyrazole-3-carbonitrile. m.p.
147-148°C.
B) 5-amino-!-[2.6-dibromo-4-(trifluoromethyl)phenyl]-4-thiocyanato-lHpyrazole-
3-carbonitrile. which was used directly in step 2 with iodoethane and
methanol as solvent to give the 5-amino-l-[2.6-dibromo-4-(trifiuoromethyl)phenyl]-4-
methylthio-lH-pyrazole-3-carbonitrile. m.p. 21 1-214°C .
REFERENCE EXAMPLE 20
A suspension of 5-amino- 1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]- 1 Hpyrazole-
3-carbonitrile (9.8gi and N-iodosuccinimide (8.87g) was heated at reflux in
carbon tetrachloride for 3.5 hours, cooled and washed with sodium bisulfite solution.
NaOH solution and water. The dried (magnesium sulfate) solution was evaporated and
purified by chromatography on silica gel eiuting with dichloromethane to give 5-
amino- 1 -[2.6-dichloro-4-( trifluoromethyl )phenyl]-4-iodo- 1 H-pyrazole-3-carbonitrile
(4.0g). m.p.212-214°C.
REFERENCE EXAMPLE 21
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-iodo-lH-pyrazole-3-
carbonitrile (1.96g) was stirred with dimethylformamide dimethyl acetal (10ml) at 20
°C for 2 hours, then excess ice' water added and the solid filtered and oven-dried to
give l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-iodo-5-N-
(dimethylaminomethyleneamino)-l H-pyrazole-3-carbonitrile (1.53g), m.p. 177-1 80
REFERENCE EXAMPLE 22
Activated cadmium was prepared by washing cadmium with hydrochloric acid
(10%). water, ethanol and ether and dry-ing. Dibromodifluoromethane (317.2g) in dry
N.N'-dimeihylformamide (DMF) was added during 1 hour to a mixture of activated
cadmium 212.5g) in dry DMF initially at 0-5°C and \vhen initiated at below 35°C
with stirring under nitrogen. Hexamethylphosphoramide (11.dry) was added followed
by copper ( I ) bromide ( I G S . f g i and. after 15 minutes. l-[2.6-dichloro-4-
critluoromethyl)phenyl]-4-iodo-5-N-(dimethylaminomethy!eneamino)-lH-pyrazole-
3-carbonitrile (lOO.Og) and the mixture heated at 75°C for 2 hours. The cooled
mixture was filtered (celitei. concentrated, diluted (.water) and filtered. The product
was washed (hot water) to give l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-N-
(dimethylaminomethyleneamino)-4-trifluoromethyl-lH-pyra2ole-3-carbonitrile
(80.9g). m.p. 156-157.5°C.
REFERENCE EXAMPLE 23
A solution of l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-5-X-
(dimethylaminomethyleneamino )-4-trifluoromethyl-1 H-pyrazole-3-carbonitrile
(120.5g) in tetrahydrofuran and hydrochloric acid (6N) was heated at reflux for 24
hours, concentrated and filtered. The solid was mixed with dichloromethane and
filtered to give 5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-trifiuoromethyl-
1 H-pyrazole-3-carbonitrile (SS.2g). m.p. 191-193°C.
REFERENCE EXAMPLE 24
A solution of 5-amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-
methylthio-1 H-pyrazole-3-carbonitrile (l.Og) in tetrahydrofuran was added to
anhydrous sodium hydride (0.13g) stirred under nitrogen in tetrahydrofuran at 4°C.
After 2 hours iodomethane (0.34ml) was added and the mixture stirred at 20°C
overnight and treated with ammonium chloride solution. Extraction (ethyl acetate).
drying (sdium sulfate) and evaporation was followed by chromatography on silica gel
eluting with ethyl acetate dichloromethane (1:9) to give l-[2.6-dichloro-4-
(trifluorometh\-l)phenyl]-5-dimethylamino-4-methylthio-lH-p\Tazole-3-carbonitrile
(0.5g). m.p.H8-119°C.
MITICIDE. INSECTICIDE. APHICIDE. AND NEMATICIDE USE
The following representative test procedures, using compounds of the
invention, were conducted to determine the pesticidal use and activity of compounds
of the invention against: mites: certain insects, including aphids. two species of
caterpillar, a fly. and three species of beetle larvae (one foliar feeding and two root
feeding): and nematodes. The specific species tested were as follows:
GENUS. SPECIES COMMON NAME (ABBREVIATION)
Tetranychus urticae twospotted spider mite TSM
Aphis nasiurtii buckthorn aphid BA
Spodoptera eridania southern armyworm SAW
Epiiachna variveti Mexican bean beetle MBB
Musca domestics housefly HF
Diabrotica u. howardi southern corn rootworm SCRW
Diabrotica virgifera western corn rootworm WCRW
Meloidogyne incognita southern root-knot nematode SRKN
Aphis gossypii cotton aphid CA
Schizaphis graminum greenbug (aphid) GB
Heliothis virescens tobacco budworm TBW
Foimulations:
The test compounds were formulated for use according to the following
methods used for each of the test procedures.
For mite, aphid, southern armyworrn. Mexican bean beetle, and tobacco
budworm tests, a solution or suspension was prepared by adding 10 mg of the test
compound to a solution of 160 mg of dimethylformamide. 838 mg of acetone. 2 mg of
a 3:1 ratio of Triton X-172 : Triton X-152 (respectively, mainly anionic and nonionic
low foam emulsifiers which are each anhydrous blends of alkylaryl polyether alcohols
with organic sulfonates). and 98.99 g of water. The result was a concentration of 100
ppm of the test compound.
For housefly tests, the formulation was initially prepared in a similar manner
to the above, but in 16.3 g of water with corresponding adjustment of other
components, providing a 200 ppm concentration. Final dilution with an equal volume
of a 20° o by weight aqueous solution of sucrose provided a 100 ppm concentration of
the test compound. When necessary, sonication was provided to insure complete
dispersion.
For southern and western corn rootworm tests, a solution or suspension was
prepared in the same manner as that used for the initial 200 ppm concentration for
housefly. Aliquots of this 200 ppm formulation were then used by dilution with water
according to the required test concentration.
For southern root-knot nematode and systemic tests for southern armyworrn.
cotton aphid, tobacco budworm and greenbug. a stock solution or suspension was
prepared by adding 15 mg of the test compound to 250 mg of dimethylformamide.
1250 mg of acetone and 3 mg of the emulsifier blend referenced above. Water was
then added to provide a test compound concentration of 150 ppm. When necessary,
sonication was provided to insure complete dispersion.
For tobacco buduorm contact tests, a stock solution was prepared by
dissolving the compound in acetone and then further diluted to pro\ ide the required
serial dilution concentrations.
Test Procedures:
The above formulated test compounds were then evaluated for their pesiicidal
activity at the specified concentrations, in ppm (parts per million) by weight,
according to the following test procedures:
Twospotted spider mite: Leaves infested with adult and nymphal stages of the
two-spotted spider mite, obtained from a stock culture were placed on the primary
leaves of two bean plants growing in a 6 cm. peat pot. A sufficient number of mites
(150-200) for testing were transferred to the fresh plants within a period of twentyfour
hours. The potted plants (one pot per compound) were placed on a revolving
turntable and sprayed, sufficient to wet the plants to runoff, with 100 ml of the 100
ppm test compound formulation by use of a DeYilbiss spray gun set at 40 psig. air
pressure. As an untreated control. 100 ml of the \vater-acetone-DMF-emulsifier
solution, containing no test compound, were also sprayed on infested plants. A
treated control with a commercial technical compound, either dicofol or hexythiazox.
formulated in the same manner, was tested as a standard. The sprayed plants were
held for six days, after which a mortality count of motile forms was made.
Twospotted spider mite fovicide t e s t ) : Eggs were obtained from adults of the
twospotted spider mite from a stock culture. Heavily infested leaves from the stock
culture were placed on uninfested bean plants. Females were allowed to oviposit for a
period of about 24 hours, after which the leaves of the plant were dipped into a
solution of TEPP (tetraethyl diphosphate) in order to kill the motile forms and prevent
additional egg laying. This dipping procedure, which was repeated after the plants
dried, did not affect the viability of the eggs. The potted plants (one pot per
compound) were placed on a revolving turntable and sprayed, sufficient to wet the
plants to runoff, with 100 ml of the 100 ppm test compound formulation by use of a
DeVilbiss spray gun set at 40 psig. air pressure. As an untreated control. 100 ml of
the water-acetone-DMF-emulsifier solution, containing no test compound, were also
sprayed on infested plants. A treated control with a commercial technical compound.
typically demeton. formulated in the same manner, was tested as a standard. The
sprayed plants were held for seven days, after which a mortality count of egg forms
was made along with notations on residual activity on hatched larvae.
Buckthorn or cotton aphid: Adult and nymphal stages of buckthorn or cotton
aphid were reared on potted dwarf nasturtium or cotton plants, respectively. The
potted plants tone pot per compound tested) infested with 100-150 aphids. were
placed on a revolving turntable and sprayed with 100 ml of the 100 ppm test
compound formulation by use of a DeYilbiss spray gun set at 40 psig air pressure. As
an untreated control. 100 ml of a water-acetone-DMF-emulsifier solution, containing
no test compound, were also sprayed on infested plants. A treated control with a
commercial technical compound, malathion or cyhalothrin. formulated in the same
manner, was tested as a standard. After spraying, the pots were stored for one day on
buckthorn aphid or three days for cotton aphid, after which the dead aphids were
counted.
Southern armvworm: Potted bean plants, were placed on a revolving turntable
and sprayed with 100 ml of the 100 ppm test compound formulation by use of a
DeYilbiss spray gun set at 40 psig air pressure. As an untreated control. 100 ml of a
water-acetone-DMF-emulsifier solution, containing no test compound, were also
sprayed on plants. A treated control with a commercial technical compound, either
cypermethrin or sulprofos. formulated in the same manner, was tested as a standard.
\Vhen dry. the leaves were placed in plastic cups lined with moistened filter paper.
Five randomly selected second instar southern armyworm larvae were introduced into
each cup which was closed and held for five days. Larvae which were unable to move
the length of the body, even upon stimulation by prodding, were considered dead.
Tobacco bud worm: Potted cotton plants were placed on a revolving turntable
and sprayed with 100 ml of the 100 ppm test compound formulation by use of a
DeYilbiss spray gun set at 40 psig air pressure. As an untreated control. 100 ml of a
water-acetone-DMF-emulsifier solution, containing no test compound, were also
sprayed on plants. A treated control with a commercial technical compound, either
cypermethrin or sulprofos. formulated in the same manner, was tested as a standard.
When dry. the leaves were placed in plastic dishes containing a piece of filter paper
and a moistened dental wick. One randomly selected second instar tobacco budworm
larva was then introduced into each cup which was closed and held for five days.
Larvae unable to move the length of their body, even upon stimulation by prodding,
were considered dead.
Mexican bean beetle: Potted bean plants were placed on a revolving turntable
and sprayed with 100 ml of the 100 ppm test compound formulation, sufficient to wet
the plants to runoff, by use of a DeYilbiss spray gun set at 40 psig air pressure. As an
untreated control. 100 ml of a water-acetone-DMF-emulsifier solution, containing no
test compound, were also sprayed on plants. A treated control with a commercial
technical compound, either cypermethrin or sulprofos. formulated in the same
manner, was tested as a standard When dry. the leaves were placed in plastic cups
lined with moistened filter paper. Five randomly selected second instar Mexican bean
beetle larvae were introduced into each cup which was closed and held for five days.
Larvae which were unable to move the length of the body, even upon stimulation by
prodding, were considered dead.
House fly: Four to six day old adult house flies were reared according to the
specifications of the Chemical Specialties Manufacturing Association (Blue Book.
McN'air-Dorland Co.. N.Y. 1954: pages 243-244. 261) under controlled conditions.
The flies were immobilized by anesthetizing with carbon dioxide and twenty five
immobilized individuals, males and females, were transferred to a cage consisting of a
standard food strainer and a wrapping-paper-covered surface. Ten ml of the 100 ppm
test compound formulation were added to a souffle cup containing an absorbent cotton
pad. As an untreated control. 10 ml of a \vater-acetone-DMF-emulsiller-sucrose
solution, containing no test compound, were applied in a similar manner. A treated
control with a commercial technical compound, malathion. formulated in the same
manner, was tested as a standard. The bait cup was introduced inside the food strainer
prior to admitting the anesthetized flies. After 24 hours, flies which showed no sign
of movement on stimulation were considered dead.
Southern or western corn rootworm: Into a jar containing 60g of sandy loam
soil was added 1.5 ml of an aqueous formulation consisting of an aliquot of the 200
ppm test compound formulation, diluted with water as appropriate for the final soil
concentration of the test compound. 3.2 ml of water and five pregerminated corn
seedlings. The jar was shaken thoroughly to obtain an even distribution of the test
formulation. Following this, twenty corn rootworm eggs (or optionally ten first instar
larvae in the case of \VCR\V) were placed into a cavity, which was made in the soil.
Vermiculite (1 ml), used optionally in the case of WCRW tests, and water (1.7ml)
were then added to this cavity. In a similar manner, an untreated control was prepared
by application of the same size aliquot of a water-acetone-DMF-emulsifier solution,
containing no test compound. Additionally, a treated control with a commercial
technical compound (selected typically from terbufos. fonofos. phorate. chlorpyrifos.
carbofuran. isazophos. or ethoprop). formulated in the same manner was used as
needed as a test standard. After 7 days, the living rootworm larvae were counted
using a well known "Berlese" funnel extraction method.
Southern root-knot nematode: Infected roots of tomato plants, containing egg
masses of southern root-knot nematode. were removed from a stock culture and
cleaned of soil by shaking and washing with tap water. The nematode eggs \vere
separated from the root tissue and rinsed with water. Samples of the egg suspension
were placed on a fine screen over a receiving bowl, in which the water level was
-54 -
adjusted to be in contact with the screen. From the bowl, juveniles were collected on
a fine screen. The bottom of a cone-shaped container was plugged with coarse
vermiculite and then filled to .within 1.5 cm of the top with about a 200 ml volume of
pasteurized soil. Then into a hole made in the center of the soil in the cone was
pipetted an aliquot of the 150 ppm test compound formulation. A treated control with
a commerical technical compound, fenamifos. formulated in a similar manner, was
tested as a standard. As an untreated control, an aliquot of a water-acetone-DMFemulsifier
solution, containing no test compound, was applied in a similar manner.
Immediately after treatment of the soil with the test compound there were added to the
top of each cone 1000 second stage juvenile southern root-knot nematodes. After 3
days, a single healthy tomato seedling was then transplanted into the cone. The cone,
containing the infested soil and tomato seedling, was kept in the greenhouse for 3
weeks. At the termination of the test, roots of the tomato seedling were removed from
the cone and evaluated for galling on a rating scale relative to the untreated control as
follows:
1- severe galling, equal to untreated control
3- light galling
4- very light galling
5- no galling, ie. complete control
These results were then converted to an ED} or EDf value (effective dose to
provide a 3 or 5 gall rating).
Southern armyworm on tomato - systemic evaluation: This test was conducted
in conjunction with the southern root-knot nematode evaluation (discussed below).
The tomato plants, grown in the soil (at an initial compound test screening rate of 6.6
ppm soil concentration or about 150 ppm solution concentration) for nematode
evaluation, were then utilized for evaluation of a compound's uptake via roots and
subsequent systemic transport to the tomato foliage. At the termination of the
nematode test. 21 days after treatment, the tomato foliage was excised, placed into a
plastic container, and infested with second instar larvae of southern armyworm. After
about 5 days, the larvae were examined for percent mortality.
Cotton aphid and tobacco budworm (on cotton') and greenbug and tobacco
budworm (on sorghum) - systemic evaluation: A 7.0 ml aliquot of the 150 ppm
nematode test solution was applied to deliver the equivalent of 10.0 ppm soil
concentration dose as a drench to 6 cm pots containing cotton and sorghum plants.
The cotton plants were previously infested with cotton aphids about two days before
treatment and greenbug one day before treatment. After holding the plants about three
days, the plants were rated for aphid activity. Again at six days, the plants were rated
tor aphid activity and the cotton aphids and greenbugs were counted and mortality
as assessed. Portions of the cotton and sorghum foliage were excised, placed in
separate plastic containers, and infested with second instar larvae of lobacco
budworm. The potted plants were dipped in sulfotepp to kill the remaining aphids and
returned to the greenhouse for regrowth. Thirteen days after treatment, the remaining
foliage was excised and fed to tobacco budworms. Mortality was assessed six days
after infestation.
Cotton aphid and southern armywoim (on cotton) and greenbug and southern
army worm 'on sorghurrn - systemic evaluation: A stock solution or suspension was
prepared to deliver 5 ml of a 20 ppm soil concentration dose (and subsequent
dilutions) as a drench to 6 cm pots containing cotton and sorghum plants. The cotton
plants were previously infested with cotton aphids about two days before treatment
and greenbug one day before treatment. After holding the plants about three days, the
plants were rated for aphid activity. Again at six days, the plants were rated for aphid
activity and the cotton aphids and greenbugs were counted and mortality was
assessed. Portions of the cotton and sorghum foliage were excised, placed in separate
plastic containers, and infested with second instar larvae of southern armyworms. The
potted plants were dipped in sulfotepp to kill the remaining aphids and returned to the
greenhouse for regrowth. Thirteen days after treatment the remaining foliage was
excised and fed to southern armyworm. Mortality was assessed six days after
infestation.
Cotton aphid and southern armyworm (on cotton and oats^ - seed treatment
evaluation: Technical material was applied to the seed of oats and cotton by placing
the compound and the seed in an appropriate sized jar and rolling the jar on a ball
mill. Assay of the material applied to the seed was by weight. Seed was then planted.
When germinated and emerged, the plants were infested at the appropriate intervals
with host insects. Mortality was assessed on those insects.
Tobacco budworm • contact evaluation: The following topical application
method provides an assessment of contact toxicity of a compound to tobacco
budworm larvae. The test compound solution at sequential two-fold dilution
concentrations from 10 down to 0.16 ug'ul was applied by a microinjector in
replicated 1 ul portions to the dorsum of approximately 20 mg tobacco budworm
larvae. This is equivalent to applied doses of 500 down to 8 ug'g body weight. An
acetone treated control, without any test compounds, was also applied. A treated
control with a commercial technical compound, cypermethrin or thiodicarb. also in
acetone was used as a standard. The treated larvae were placed, individually, in
separate plastic petri dishes containing an untreated cotton leaf and a moist dental
the percent mortality was rated
All of the Compound Numbers
activity in one or more of the a
activity in the systemic tests.
METHODS AND COMPOSIT
The present invention p
arthropods at a locus, especiall
ground portions of plants. Con
application or by application b
plant roots or plant seeds with
portions of the plants. Such sy
reside not only at the point of
by translocation from one side
untreated leaf. Examples of the
controlled by the arylpyrazole
(piercing-sucking). Hemiptera
.
to 118 of the invention showed
bove evaluatuion methods;with particularly
invention is especially appropriate for aphids and thrips.
rovides a method for the systemic control of
y some insects or mites which feed on the above
rol of such foliar pests may be provided by direct foliar
• for example soil spray or granule application to the
subsequent systemic translocation to the above ground
temic activity includes the control of insects which
pplication but at a remote pan of the plant for example
of a leaf to the other or from a treated leaf to an
classes of insect pests which may be systemically
of the invention include the Homoptera order
order tpiercing-sucking), and Thysanoptera order. The
As is evident from the
provides pesticidally active ar
the control of a number of pes
or mites: plant nematodes or.
formula (I) or (I bis) o
advantageously employed
in practical uses, tor example.
veterinary medicine or livesto
forward, whenever the term a
arylpyrazoles of formula ( I ) an
"arylpyrazole of formula (I )
acceptable salt thereof.
The present invention
locus which comprises the tre umem of the locus (e.g.. by application or
administration) with an effective amount of an arylpyrazole of'formula (I)
or (I bis) or a
toregoing pesticidal uses. the present invention
Ipyrazoles and methods of use of said arylpyrazoles for
species which includes: arthropods, especially insects
selminth or protozoan pests. The arylpyrazoles of
' pesticidally acceptable salts thereof thus are
in agricultural or horticultural crops, forestry,
k husbandry, or in public health. From this point
rylpyrazoles of formula (I)" is used this term embraces
d their pesticidally acceptable salts. The term
mbraces a arylpyrazole of formula (I) and a pesticidally
therefore provides a method of control of pests at a
pesticidally acceptable salt tr
defined. The locus includes,
field, structure, premises, for
the like) where the pest residi
ereof, wherein the substituent groups are as hereinbefore
for example, the pest itself or the place (plant, animal.
est, orchard, waterway, soil, plant or animal product, or
or feeds.
The arylpyrazoles of this invention may in addition be used to control soil
insects, such as corn rootworm. termites (especially for protection of structures), root
maggots, wireworms. root weevils, stalkborers. cutworms, root aphids. or grubs.
They may also be used to provide activity against plant pathogenic nematodes. such as
root-knot, cyst, dagger, lesion, or stem or bulb nematodes. or against mites. For the
control of soil pests, for example corn rootworm. the arylpyrazoles are advantageously
applied to or incorporated at an effective rate into the soil in which crops are planted
or to be planted or to the seeds or growing plant roots.
In the area of public health, the arylpyrazoles are especially useful in the
control of many insects, especially filth flies or other Dipteran pests, such as
houseflies. stableflies. soldierflies. homilies, deerflies. horseflies, midges, punkies.
blackflies. or mosquitoes.
Arylpyrazoles of the invention may be used in the following applications and
on the following pests including arthropods, especially insects or mites, nematodes. or
helminth or protozoan pests:
In the protection of stored products, for example cereals, including grain or
flour, groundnuts, animal feedstuff's, timber or household goods, e.g. carpets and
textiles, arylpyrazoles of the invention are useful against attack by arthropods, more
especially beetles, including weevils, moths or mites, for example Ephestia spp. (flour
moths). Anthrenus spp. (carpet beetles). Tribolium spp. (flour beetles). Sitophilus spp.
(grain weevils) or Acarus spp. (mites).
In the control of cockroaches, ants or termites or similar arthropod pests in
infested domestic or industrial premises or in the control of mosquito larvae in
waterways, wells, reservoirs or other running or standing water.
For the treatment of foundations, structures or soil in the prevention of the
attack on building by termites, for example. Reticulitermes spp.. Heterotermes spp..
Coptotermes spp..
In agriculture against adults, larvae and eggs of Lepidoptera (butterflies and
moths), e.g. Heliothis spp. such as Heliothis virescens (tobacco budworm). Heliothis
armigera and Heliothis zea. Against adults and larvae of Coleoptera (beetles) e.g.
Anthonomus spp. e.g. grandis (cotton boll weevil). Leptinotarsa decemlineata
(Colorado potato beetle). Diabrotica spp. (corn rootworms). Against Heteroptera
(Hemiptera and Homoptera) e.g. Psylla spp.. Bemisia spp.. Trialeurodes spp.. Aphis
spp.. Myzus spp.. Megoura viciae. Phylloxera spp.. N'ephotettix spp. (rice leaf
hoppers). N'ilaparvata spp..
Against Diptera e.g. Musca spp.. Against Thysanoptera such as Thrips tabaci.
Against Orthoptera such as Locusta and Schistocerca spp.. (locusts and crickets) e.g.
Gryilns spp.. and Ac'neta spp. for example. Blatta orientalis. Peripianeta americana.
Blarelia germanica. Locusta migratoria mieraiorioides, and Schistocerca gregaria.
Against Collembola e.g. Periplaneta spp. and Blattela spp. (roaches). Against Isoptera
e.g. Coptotermes spp. (termites).
Against arthropods of agricultural significance such as Acari (mites) e.g.
Tetranvchus spp.. and Panonychus spp..
Against nematodes which attack plants or trees of importance to agriculture,
forestry or horticulture either directly or by spreading bacterial, viral, mycoplasma or
fungal diseases of the plants. For example root-knot nematodes such as Meloidogyne
spp. (e.g. M. incognita).
In the field of veterinary' medicine or livestock husbandry or in the
maintenance of public health against arthropods, helminths or protozoa which are
parasitic internally or externally upon vertebrates, particularly warm-blooded
vertebrates, for example domestic animals, e.g. cattle, sheep, goats, equines. swine.
poultry, dogs or cats, for example Acarina. including ticks (e.g. Ixodes spp..
Boophilus spp. e.g. Boophilus microplus. Rhipicephalus spp. e.g. Rhipicephalus
appendiculatusOrnithodorus spp. (e.g. Omithodorus moubata) and mites (e.g.
Damalinia spp.): Diptera (e.g. Aedes spp.. Anopheles spp.. Musca spp.. Hypoderma
spp.): Hemiptera.: Dictyoptera (e.g. Periplaneta spp.. Blatella spp.): Hymenoptera: for
example against infections of the gastro-intestinal tract caused by parasitic nematode
worms, for example members of the family Trichostrongylidae: in the control and
treatment of protozoa! diseases caused by. for example. Eimeria spp. e.g.
Trypanosoms cruzi. Leishaminia spp.. Plasmodium spp.. Babesis spp..
Trichomonadidae spp.. Toxoplasma spp. and Theileria spp..
In practical use for the control of arthropods, especially insects or mites, or
nematode pests of plants, a method, for example, comprises applying to the plants or
to the medium in which they grow an effective amount of a arylpyrazole of the
invention. For such a method, the active arylpyrazole is generally applied to the locus
in which the arthropod or nematode infestation is to be controlled at an effective rate
in the range of about 5 g to about 1 kg of the active arylpyrazole per hectare of locus
treated. Under ideal conditions, depending on the pest to be controlled, a lower rate
may offer adequate protection. On the other hand, adverse weather conditions,
resistance of the pest or other factors may require that the active ingredient be used at
higher rates. The optimum rate depends usually upon a number of factors, for
example, the type of pest being controlled, the type or the growth stage of the infested
plant, the row spacing or also the method of application. More preferably an effective
rate range of the active arylpyrazole is from about 50g Tia to about 400 g;ha.
When a pest is soil-borne, the active arylpyrazole generally in a formulated
composition, is distributed evenly over the area to be treated t ie. for example
broadcast or band treatment) in any convenient manner and is applied a: rates from
about 5 to about 1kg ai ha. preferably from about 50 to about 250 g ai ha. When
applied as a root dip to seedlings or drip irrigation to plants the liquid solution or
suspension contains from about 0.075 to about 1000 mg ai 1. preferably from about 25
to about 200 mg ai 1. Application may be made, if desired, to the field or cropgrowing
area generally or in close proximity to the seed or plant to be protected from
attack. The active component can be washed into the soil by spraying with water over
the area or can be left to the natural action of rainfall. During or after application, the
formulated arylpyrazole can. if desired, be distributed mechanically in the soil, for
example by ploughing, disking, or use of drag chains. Application can be prior to
planting, at planting, after planting but before sprouting has taken place, or after
sprouting.
The arylpyrazoles of the invention and methods of control of pests therewith
are of particular value in the protection of field, forage, plantation, glasshouse,
orchard or vineyard crops, of ornamentals, or of plantation or forest trees, for
example: cereals (such as wheat or rice), cotton, vegetables (such as peppers), field
crops (such as sugar beets, soybeans or oil seed rape), grassland or forage crops (such
as maize or sorghum), orchards or groves (such as of stone or pit fruit or citrus).
ornamental plants, flowers or vegetables or shrubs under glass or in gardens or parks,
or forest trees (both deciduous and evergreen) in forests, plantations or nurseries.
They are also valuable in the protection of timber (standing, felled, converted.
stored or structural) from attack, for example, by sawflies or beetles or termites.
They have applications in the protection of stored products such as grains,
fruits, nuts, spices or tobacco, whether whole, milled or arylpyrazoleed into products,
from moth, beetle, mite or grain weevil attack. Also protected are stored animal
products such as skins, hair, wool or feathers in natural or converted form (e.g. as
carpets or textiles) from moth or beetle attack as well as stored meat, fish or grains
from beetle, mite or fly attack.
Additionally, the arylpyrazoles of the invention and methods of use thereof are
of particular value in the control of arthropods, helminths or protozoa which are
injurious to. or spread or act as vectors of diseases domestic animals, for example
those hereinbefore mentioned, and more especially in the control of ticks, mites, lice.
fleas, midges, or biting, nuisance or myiasis flies. The arylpyrazoles of the invention
are particularly useful in controlling arthropods, helminths or protozoa which are
present inside domestic host animals or which feed in or on the skin or suck the blood
or the animal, for which purpose they may be administered orally. parenterally.
percutaneously or topically.
Furthermore, arylpyrazoles of the invention may be useful for coccidiosis. a
disease caused by infections from protozoan parasites of the genus Eimeria. It is an
important potential cause of economic loss in domestic animals and birds, particularly.
those raised or kept under intensive conditions. For example, cattle, sheep, pigs or
rabbits may be affected, but the disease is especially important in poultry, particularly
in chickens. Administration of a small amount of a arylpyrazole of the invention.
preferably by a combination with feed is effective in preventing or greatly reducing
the incidence of coccidiosis. The arylpyrazoles are effective against both the cecal
form and the intestinal forms. Furthermore, the arylpyrazoles of the invention may
also exert an inhibiting effect on oocytes by greatly reducing the number and
sporulation of those produced. The poultry disease is generally spread by the birds
picking up the infectious organism in droppings in or on contaminated litter, ground.
food, or drinking water. The disease is manifested by hemorrhage, accumulation of
blood in the ceca. passage of blood to the droppings, weakness and digestive
disturbances. The disease often terminates in the death of the animal, but the fowl
which survive severe infections have had their market value subtantiallv reduced as a
result of the infection.
The compositions hereinafter described for application to growing crops or
crop growing loci or as a seed dressing may. in general, alternatively be employed for
topical application to animals or in the protection of stored products, household
goods, property or areas of the general environment. Suitable means of applying the
arylpyrazoles of the invention include:
to growing crops as foliar sprays, dusts, granules, fogs or foams or also as
suspensions of finely divided or encapsulated compositions as soil or root treatments
by liquid drenches, dusts, granules, smokes or foams: to seeds of crops via application
as seed dressings by liquid slurries or dusts:
to animals infested by or exposed to infestation by arthropods, helminths or
protozoa, by parenteral. oral or topical application of compositions in which the active
ingredient exhibits an immediate and. or prolonged action over a period of time against
the arthropods, helminths or protozoa, for example by incorporation in feed or suitable
orally-ingestible pharmaceutical formulations, edible baits, salt licks, dietary
supplements, pour-on formulations, sprays, baths, dips, showers, jets, dusts, greases,
shampoos, creams, wax smears or livestock self-treatment systems;
to the environment in general or to specific locations where pests may lurk.
including stored products, timber, household goods, or domestic or industrial
premises, as sprays, fogs, dusts, smokes, wax-smears, lacquers, granules or baits, or in
tricklefeeds to waterways, wells, reservoirs or other running or standing water:
to domestic animals in feed to control fly larvae feeding in their feces:
In practice, the arylpyrazoles of the invention most frequently form pans of
compositions. These compositions can be employed to control: arthopods. especially
insects or mites: nematodes: or helminth or protozoan pests. The compositions may
be of any type known in the an suitable for application to the desired pest in any
premises or indoor or outdoor area or by internal or external administration to
vertebrates. These compositions contain at least one arylpyrazole of formula (I) or a
pesticidally acceptable salt thereof, such as described earlier, as the active ingredient
in combination or association with one or more other compatible components which
are for example, solid or liquid carriers or diluents, adjuvants, surface-active-agents,
or the like appropriate for the intended use and which are agronomically or
medicinally acceptable. These compositions, which may be prepared by any manner
known in the an. likewise form a pan of this invention.
These compositions may also contain other kinds of ingredients such as
protective colloids, adhesives. thickeners, thixotropic agents, penetrating agents, sprayoils
(especially for acaridical use), stabilizers, preservative agents (especially mold
preservatives), sequestering agents, or the like, as well as other known active
ingredients with pesticidal propenies (particularly insecticidal. miticidal. nematicidal.
or fungicidal) or with propenies regulating the growth of plants. More generally, the
arylpyrazoles employed in the invention may be combined with all the solid or liquid
additives corresponding to the usual techniques of formulation.
Compositions, suitable for applications in agriculture, horticulture, or the like
include formulations suitable for use as. for example, sprays, dusts, granules, fogs.
foams, emulsions, or the like.
The effective use doses of the arylpyrazoles employed in the invention can
vary within wide limits, particularly depending on the nature of the pest to be
eliminated or degree of infestation, for example, of crops with these pests. In general.
the compositions according to the invention usually contain about 0.05 to about 95%
(by weight) of one or more active ingredients according to the invention, about 1 to
about 95% of one or more solid or liquid carriers and. optionally, about 0.1 to about
50% of one or more other compatible components, such as surface-active agents or
the like.
In the present account, the term "carrier" denotes an organic or inorganic
ingredient, natural or synthetic, with which the active ingredient is combined to
facilitate its application, for example, to the plant, to seeds or to the soil. This carrier
is therefore generally inert and it must be acceptable (for example, agronomically
acceptable, particularly to the treated plant).
The carrier may be a solid, for example, clays, natural or synthetic silicates,
silica, resins, waxes, solid fertilizers (for example ammonium salts), ground natural
minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite. montmorillonite.
bentonite or diatomaceous earth, or ground synthetic minerals, such as silica, alumina,
or silicates especially aluminium or magnesium silicates. As solid carriers for
granules the following are suitable: crushed or fractionated natural rocks such as
calcite. marble, pumice, sepiolite and dolomite: synthetic granules of inorganic or
organic meals: granules of organic material such as sawdust, coconut shells, corn
cobs, com husks or tobacco stalks: kieselguhr. tricalcium phosphate, powdered cork,
or absorbent carbon black: water soluble polymers, resins, waxes: or solid fertilizers.
Such solid compositions may. if desired, contain one or more compatible wetting.
dispersing, emulsifying or colouring agents which, when solid, may also serve as a
diluent.
The carrier may also be liquid, for example: water: alcohols, particularly
butanol or glycol. as well as their ethers or esters, particularly methylglycol acetate:
ketones. particularly acetone, cyclohexanone. methylethyl ketone.
methylisobutylketone. or isophorone: petroleum fractions such as paraffmic or
aromatic hydrocarbons, particularly xylenes or alkyl naphthalenes: mineral or
vegetable oils: aliphatic chlorinated hydrocarbons, particularly trichloroethane or
methylene chloride: aromatic chlorinated hydrocarbons, particularly chlorobenzenes:
water-soluble or strongly polar solvents such as dimethylformamide. dimethyl
sulphoxide. or X-methylpyrrolidone: liquefied gases: or the like or a mixture thereof.
The surface-active agent may be an emulsifying agent, dispersing agent or
wetting agent of the ionic or non-ionic type or a mixture of such surface-active agents.
Amongst these are e.g.. salts of polyacrylic acids, salts of lignosulphonic acids, salts
of phenolsulphonic or naphthalenesulphonic acids, polycondensates of ethylene oxide
with fatty alcohols or fatty acids or fatty esters or fatty amines, substituted phenols
(particularly alkylphenols or arylphenols). salts of sulphosuccinic acid esters, taurine
derivatives (particularly alkyltaurates). phosphoric esters of alcohols or of
polycondensates of ethylene oxide with phenols, esters of fatty acids with polyols. or
sulphate, sulphonate or phosphate functional derivatives of the above arylpyrazoles.
The presence of at least one surface-active agent is generally essential when the active
ingredient and'or the inert carrier are only slightly water soluble or are not water
soluble and the carrier agent of the composition for application is water.
Compositions of the invention may further contain other additives such as
adhesives or colorants. Adhesives such as carboxymethylceilulose or natural or
synthetic polymers in the form of powders, granules or lattices, such as arabic gum.
polyvinyl alcohol or polyvinyl acetate, natural phospholipids. such as cephalins or
lecithins, or synthetic phospholipids can be used in the formulations. It is possible to
use colorants such as inorganic pigments, for example: iron oxides, titanium oxides or
Prussian Blue: organic dyestuffs. such as alizarin dyestuffs. azo dyestuffs or metal
phthalocyanine dyestuffs: or trace nutrients such as salts of iron, manganese, boron.
copper, cobalt, molybdenum or zinc.
Compositions containing arylpyrazoles of formula (I), or pesticidally
acceptable salts thereof, which may be applied to control arthropod, plant nematode.
helminth or protozoan pests, may also contain synergists (e.g. piperonyl butoxide or
sesamex). stabilizing substances, other insecticides, acaricides. plant nematocides.
anthelmintics or anticoccidials. fungicides (agricultural or veterinary as appropriate,
e.g. benomyl and iprodione). bactericides. arthropod or vertebrate attractants or
repellents or pheromones. deodorants, flavouring agents, dyes, or auxiliary therapeutic
agents, e.g. trace elements. These may be designed to improve potency, persistence.
safety, uptake where desired, spectrum of pests controlled or to enable the
composition to perform other useful functions in the same animal or area treated.
Examples of other pesticidally-active arylpyrazoles which may be included in.
or used in conjunction with the compositions of the present invention are: acephate.
chlorpyrifos. demeton-S-methyl. disulfoton. ethoprofos. fenitrothion. fenamiphos.
fonofos. isazophos. isofenphos. malathion. monocrotophos. parathion. phorate,
phosalone. pirimiphos-methyl. terbufos. triazophos. cyfluthrin. cypermethrin,
deltamethrin. fenpropathrin. fenvalerate. permethrin. tefluthrin. aldicarb. carbosulfan.
methomyl. oxamyl. pirimicarb. bendiocarb. teflubenzuron. dicofol. endosulfan.
lindane. benzoximate. cartap. cyhexatin. tetradifon. avermectins. ivermectins,
milbemycins. thiophanate, trichlorfon. dichlorvos. diaveridine or dimetriadazole.
For their agricultural application, the arylpyrazoles of the formula (I), or
pesticidally acceptable salts thereof, are therefore generally in the form of
compositions, which are in various solid or liquid forms.
Solid forms of compositions which can be used are dusting powders (with a
content of the arylpyrazole of formula (I), or a pesticidally acceptable salt thereof,
ranging up to 80%). wettable powders or granules (including water dispersible
granules), particularly those obtained by extrusion, compacting, impregnation of a
granular carrier, or granulation starting from a powder (the content of the arylpyrazole
of formula (I), or a pesticidally acceptable salt thereof, in these wettable powders or
granules being bemeen about 0.5 and about 80%). Solid homogenous or
heterogenous compositions containing one or more arylpyrazoles of formula ( I ) , or
pesticidally acceptable salts thereof, for example granules, pellets, briquettes or
capsules, may be used to treat standing or running water over a period of time. A
similar effect may be achieved using trickle or intermittent feeds of water dispersible
concentrates as described herein.
Liquid compositions, for example, include aqueous or non-aqueous solutions
or suspensions (such as emulsifiable concentrates, emulsions, flowables. dispersions,
or solutions) or aerosols. Liquid compositions also include, in particular, emulsifiable
concentrates, dispersions, emulsions, flowables. aerosols, wertable powders (or
powder for spraying), dry flowables or pastes as forms of compositions which are
liquid or intended to form liquid compositions when applied, for example as aqueous
sprays (including low and ultra-low volume) or as fogs or aerosols.
Liquid compositions, for example, in the form of emulsifiable or soluble
concentrates most frequently comprise about 5 to about 80° o by weight of the active
ingredient, while the emulsions or solutions which are ready for application contain.
in their case, about 0.01 to about 20% of the active ingredient. Besides the solvent.
the emulsifiable or soluble concentrates may contain, when required, about 2 to about
50° o of suitable additives, such as stabilizers, surface-active agents, penetrating
agents, corrosion inhibitors, colorants or adhesives. Emulsions of any required
concentration, which are particularly suitable for application, for example, to plants.
may be obtained from these concentrates by dilution with water. These compositions
are included within the scope of the compositions which may be employed in the
present invention. The emulsions may be in the form of water-in-oil or oil-in-water
type and they may have a thick consistency.
The liquid compositions of this invention may. in addition to normal
agricultural use applications be used for example to treat substrates or sites infested or
liable to infestation by arthropods (or other pests controlled by arylpyrazoles of this
invention) including premises, outdoor or indoor storage of processing areas,
containers or equipment or standing or running water.
All these aqueous dispersions or emulsions or spraying mixtures can be
applied, for example, to crops by any suitable means, chiefly by spraying, at rates
which are generally of the order of about 100 to about 1.200 liters of spraying mixture
per hectare, but may be higher or lower (eg. low or ultra-low volume) depending upon
the need or application technique. The arylpyrazoles or compositions according to the
invention are conveniently applied to vegetation and in particular to roots or leaves
having pests to be eliminated. Another method of application of the arylpyrazoles or
compositions according to the invention is by chernigation. that is to say. the addition
of a formulation containing the active ingredient to irrigation water. This irrigation
may be sprinkler irrigation for foliar pesticides or it can be ground irrigation or
underground irrigation for soil or for systemic pesticides.
The concentrated suspensions, which can be applied by spraying, are prepared
so as to produce a stable fluid product which does not settle (fine grinding) and
usually contain from about 10 to about 75° b by weight of active ingredient, from
about 0.5 to about 30% of surface-active agents, from about 0.1 to about 10% of
thixotropic agents, from about 0 to about 30% of suitable additives, such as antifoaming
agents, corrosion inhibitors, stabilizers, penetrating agents, adhesives and. as
the carrier, water or an organic liquid in which the active ingredient is poorly soluble
or insoluble Some organic solids or inorganic salts may be dissolved in the carrier to
help prevent settling or as antifreezes for water.
Thewettable powers (or powder for spraying) are usually prepared so that they
contain from about 10 to about 80% by weight of active ingredient, from about 20 to
about 90° o of a solid carrier, from about 0 to about 5% of a wetting agent, from about
3 to about 10% of a dispersing agent and. when necessary, from about 0 to about 809 b
of one or more stabilizers and or other additives, such as penetrating agents,
adhesives. ami-caking agents, colorants, or the like. To obtain these wettable
powders, the active ingredient! s) isiare) thoroughly mixed in a suitable blender with
additional substances which may be impregnated on the porous filler and is(are)
ground using a mill or other suitable grinder. This produces wettable powders, the
wettability and the suspendability of which are advantageous. They may be
suspended in water to give any desired concentration and this suspension can be
employed very advantageously in particular for application to plant foliage.
The "water dispersible granules (\VG)" (granules which are readily dispersible
in water) have compositions which are substantially close to that of the wettable
powders. They may be prepared by granulation of formulations described for the
wettable powders, either by a wet route (contacting finely divided active ingredient
with the inert filler and a little water, e.g. 1 to 20% by weight, or with an aqueous
solution of a dispersing agent or binder, followed by drying and screening), or by a
dry route (compacting followed by grinding and screening).
The rates and concentrations of the formulated compositions may vary
according to the method of application or the nature of the compositions or use
thereof. Generally speaking, the compositions for application to control arthropod.
plant nematode. helminth or protozoan pests usually contain from about 0.00001% to
about 95%. more particularly from about 0.0005% to about 50% by weight of one or
more aryIpyrazoles of formula ( I) . or pesticidally acceptable sa!:s thereof, or of total
active ingredients (that is to say the arylpyrazole of formula (1). or a pesticidally
acceptable salt thereof, together with: other substances toxic to arthropods or plant
nematodes. anthelmintics. anticoccidials. synergists. trace elements or stabilizers I.
The actual compositions employed and their rate of application will be selected to
achieve the desired effect( s) by the farmer, livestock producer, medical or veterinary
practitioner, pest control operator or other person skilled in the art.
Solid or liquid compositions for application topically to animals, timber,
stored products or household goods usually contain from about 0.00005% to about
90%. more particularly from about 0.001% to about 10%. by weight of one or more
arylpyrazoles of formula (I I or pesticidally acceptable salts thereof. For
administration to animals orally or parenterally. including percutaneously solid or
liquid compositions, these normally contain from about 0.1% to about 90% by weight
of one or more arylpyrazoles of formula (I) or pesticidally acceptable salts thereof.
Medicated feedstuffs normally contain from about 0.001% to about 3% by weight of
one or more arylpyrazoles of formula ( I ) or pesticidally acceptable salts thereof.
Concentrates or supplements for mixing with feedstuffs normally contain from about
5% to about 90%. preferably from about 5% to about 50%. by weight of one or more
arylpyrazoles of formula ( I ) or pesticidally acceptable salts thereof. Mineral salt licks
normally contain from about 0.1% to about 10% by weight of one or more
arylpyrazoles of formula (I i or pesticidally acceptable salts thereof.
Dusts or liquid compositions for application to livestock, goods, premises or
outdoor areas may contain from about 0.0001% to about 15%. more especially from
about 0.005% to about 2.0%. by weight, of one or more arylpyrazoles of formula (I)
or pesticidally acceptable salts thereof. Suitable concentrations in treated waters are
between about 0.0001 ppm and about 20 ppm. more particularly about 0.001 ppm to
about 5.0 ppm. of one or more arylpyrazoles of formula (I), or pesticidally acceptable
salts thereof, and may be used therapeutically in fish farming with appropriate
exposure times. Edible baits may contain from about 0.01% to about 5%. preferably
from about 0.01% to about 1.0%. by weight, of one or more arylpyrazoles of formula
(I) or pesticidally acceptable salts thereof.
When administered to vertebrates parenterally. orally or by percutaneous or
other means, the dosage of arylpyrazoles of formula (I), or pesticidally acceptable
salts thereof, will depend upon the species, age. or health of the vertebrate and upon
the nature and degree of its actual or potential infestation by arthropod, helminth or
protozoan pests. A single dose of about 0.1 to about 100 mg. preferably about 2.0 to
about 20.0 mg. per kg body weight of the animal or doses of about 0.01 to about 20.0
mg. preferably about . 1 to about 5.0 mg. per kg body weight of the animal per day.
for sustained medication, are generally suitable by oral or parerueral administration.
By use of sustained release formulations or devices, the daily doses required over a
period of months may be combined and administered to animals on a single occasion.
The following composition EXAMPLES 2A - 2M illustrate compositions for .
use against arthropods, especially mites or insects, plant nematodes. or helminth or
protozoan pests which comprise, as active ingredient, arylpyrazoles of formula (I), or
pesticidally acceptable salts thereof, such as those described in preparative examples.
The compositions described in EXAMPLES 2A - 2M can each be diluted to give a
sprayable compositon at concentrations suitable for use in the field. Generic chemical
descriptions of the ingredients (for which all of the following percentages are in
weight percent), used in the composition EXAMPLES 2A - 2M exemplified below.
are as follows:
Trade Name Chemical Description
Ethylan BCP N'onylphenol ethylene oxide condensate
Soprophor BSU Tristyrylphenol ethylene oxide condensate
Aryian CA A 70° o w'v solution of calcium dodecylbenzenesulfonate
Solvesso 150 Light C]Q aromatic solvent
Aryian S Sodium dodecylbenzenesulfonate
Darvan N'o2 Sodium lignosulphonate
Celite PF Synthetic magnesium silicate carrier
Sopropon T36 Sodium salts of polycarboxylic acids
Rhodigel 23 Polysaccharide xanthan gum
Bentone 38 Organic derivative of magnesium montmorillonite
Aerosil Microfme silicon dioxide
EXAMPLE 2A
A water soluble concentrate is prepared with the composition as follows:
Active ingredient 7%
Ethylan BCP 10%
N-methylpyrrolidone 83%
To a solution of Ethylan BCP dissolved in a portion of N-methylpyrrolidone is
added the active ingredient with heating and stirring until dissolved. The resulting
solution is made up to volume with the remainder of the solvent.
EXAMPLE B
An emulsifiable concentrate lEOis prepared with the composition as follows:
Active ingredient 25° oi max)
Soprophor BSU 10%
Arylan CA 5° o
X-methylpyrrolidone 50%
Solvesso 150 10%
The first three components are dissolved in X-methylpyrrolidone and to this is
then added the Solvesso 150 to give the final volume.
EXAMPLE 2C
A wettable powder (\VP) is prepared with the composition as follows:
Active ingredient 40%
ArylanS 2%
Dai-van Xo2 5%
Celite PF 53%
The ingredients are mixed and ground in a hammer-mill to a powder with a
panicle size of less than 50 microns.
EXAMPLE 2D
An aqueous-fiowable formulation is prepared with the composition as follows:
Active ingredient 40.00° o
EthylanBCP 1.00%
Sopropon T360. 0.20%
Ethylene glycol 5.00°o
Rhodigel 230. 0.15%
Water 53.65%
The ingredients are intimately mixed and are ground in a bead mill until a
mean particle size of less than 3 microns is obtained.
EXAMPLE 2E
An emulsiflable suspension concentrate is prepared with the composition as
follows:
Active ingredient 30.0%
EthylanBCP 10.0%
Bentone 38 0.5%
Solvesso 150 59.5° o
The ingredients are intimately mixed and ground in a beadmill until a mean
panicle size of less than 3 microns is obtained.
EXAMPLE 2F
A water dispersible granule is prepared with the composition as follows:
Active ingredient 30%
DarvanNo2 15%
Arylan S 8%
Celite PF 47%
The ingredients are mixed, micronized in a fluid-energy mill and then
granulated in a rotating pelletizer by spraying with water (up to 10%). The resulting
granules are dried in a fluid-bed drier to remove excess water.
EXAMPLE 2G
A dusting ponder is prepared with the composition as follows:
Active ingredient 1 to 10° o
Talc powder-superfine 99 to 90° o
The ingredients are intimately mixed and further ground as necessary to
achieve a fine powder. This powder may be appplied to a locus of arthropod
infestation, for example refuse dumps, stored products or household goods or animals
infested by. or at risk of infestation by. arthropods to control the arthropods by oral
ingestion. Suitable means for distributing the dusting powder to the locus of
arthropod infestation include mechanical blowers, handshakers or livestock self
treatment devices.
EXAMPLE 2H
An edible bait is prepared with the composition as follows:
Active ingredient 0.1 to 1.0° o
Wheat flour 80° o
Molasses 19.9tol9°o
The ingredients are intimately mixed and formed as required into a bait form.
This edible bait may be distributed at a locus, for example domestic or industrial
premises, e.g. kitchens, hospitals or stores, or outdoor areas, infested by arthropods.
for example ants, locusts, cockroaches or flies, to control the arthropods by oral
ingestion.
EXAMPLE 21
A solution formulation is prepared with a composition as follows:
Active ingredient 15%
Dimethyl sulfoxide 85%
The active ingredient is dissolved in dimethyl sulfoxide with mixing and or
heating as required. This solution may be applied percutaneously as a pour-on
application to domestic animals infested by arthropods or. after sterilization by
filtration through a polytetrafluoroethvlene membrane (0.22 micrometer pore size), by
parentera! injection, at a rate of application of from 1.2 to 12 nil of solution per 100 ki
of animal body weight.
EXAMPLE 2J
A wettable powder is prepared with the composition as follows:
Active ingredient 50° b
EthylanBCP 5°o
Aerosil 5°o
Celite PF 40%
The Ethylan BCP is absorbed onto the Aerosil which is then mixed with the
other ingredients and ground in a hammer-mill to give a wettable powder, which may
be diluted with water to a concentration of from 0.001% to 2°o by weight of the active
arylpyrazole and applied to a locus of infestation by arthropods, for example.
dipterous larvae or plant nematodes. by spraying, or to domestic animals infested by.
or at risk of infection by arthropods, helminths or protozoa, by spraying or dipping, or
by oral administration in drinking water, to control the arthropods, helminths or
protozoa.
EXAMPLE 2K
A slow release bolus composition is formed from granules containing the
following components in varying percentages similar to those described for the
previous compositions) depending upon need:
Active ingredient
Density agent
Slow-release agent
Binder
The intimately mixed ingredients are formed into granules which are
compressed into a bolus with a specific gravity of 2 or more. This can be
administered orally to ruminant domestic animals for retention within the reticulorumen
to give a continual slow release of active arylpyrazole over an extended period
of time to control infestation of the ruminant domestic animals by arthropods,
helminths or protozoa.
EXAMPLE 2L
A slow release composition in the form of granules, pellets, brickettes or the
like can be prepared with compositions as follows:
Active ingredient 0.5 to 25°-o
Polyvinyl chloride 75 to 99.5° o
Dioctyl phthalate (plasticizer)
The components are blended and then formed into suitable shapes by meltextrusion
or molding. These composition are useful, for example, for addition to
standing water or for fabrication into collars or eartags for attachment to domestic
animals to control pests by slow release.
A water dispersible granules isprepared with, the composition follows:
Active ingredient S5'":(max)
Polyvinylpyrrolidone 5%
Anapulgiie clay 6°o
Sodium lauryl sulfate 2°o
Ghcerine 2°o
The ingredients are mixed as a 45° o slurry with water and wet milled to a
panicle size of 4 microns, then spray-dried to remove water.





WE CLAIM
1 A 3-{N-oxy-imino)-l-arylpyrazole compound having the
formula





(Formula Removed)

wherein:
Xis-S(O)mR6orR7-
Y is hydrogen, C-3 to C-6 alkenyl. alkynyl. formyl, alkylcarbonyl.
cycloalkylcarbonyl, halocycloalkyl carbonyl, (optionally substituted aroyl, arylalkylcarbonyl,
alkylsulfonyl. arylsulfonyl, haloalkylcarbonyl. aminoalkylcarbonyl. alkylaminoalkyicarbonyl. dialkylaminoalkylcarbonyl. alkoxyalkylcarbonyl, aryloxyatkylcarbonyl. alkykhioalkylcarbony], alkylsulfonylalkylcarbonyl. arylthioalkylcarbonyl.
N"-aIkylcarbamoyl: N'-arylcarbamoyl, N-alkylthiocarbamoyl. N:-arylthiocarbamoyl. alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl. carboxyalkylcarbonyl, alkoxycarbonylalkyicarbonyl, -P(=O)(O-Alky 1)2, -P(=S)(O-alkyl)2, -P(=O)(S-alkyl)2, -PC=S)(S-alkyl)2, trialkylsilyl, alkylcarbonylaminoalkylcarbony!, alkylcarbonyloxyalkylcarbonyl, aryl, pyridinyl, pyrimidinyl. -C(=O)S-alkyl, -C(=O)S-ary[, -C(=O)S-alkyIaryk alkoxyalkoxycarbonyl. alkylthioalkoxycarbonyl, alkylsulfonylalkoxycarbonyl, arylthioalkoxycarbonyl. alkoxj'carbonyl, aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkyl both of which are unsubstituted or substituted by alkoxy, alkoxycarbonyl, carboxy, cyano, aminocarbonyl. alkylaminocarbonyl, dialkylarriinocarbonyl, alkylthio, nitro, alkylsulfinyl. alkylsulfonyl, alkylcarbonyl, amino, alkylamino, dialkylamino, hydroxy, alkylcarbonyJamino or alkylcarbonyloxy; Z is hydrogen, halogen, -c (o)R,, -S(O)nRg, -C(O)OR9, alkyl. haloalkyl, -OR9, -N=C(R10)(Rl l)- alkenyl. hydrazine alkylthiocarbonyl. 1H-pyrrol-l-yl or 1 H-pyrazol-1 -yl, -CHO. -CH=NOH. amino, R12NH-or R13R14N-;


R1 is hydrogen. alkyl or-NR15R R10,:
R2 is hydrogen or halogen:
R3 and R5 arc hydrogen, halogen or alkyl; ..
R4 is halogen, haloalkyl. haloalkoxy. R1 7SiO1p-or SF5:
R6 is alkyl or haloalkyl. alkenyl or haloalkenyl. alkynyl or haloalkynyl or cycloalkyl
having 3 to 5 carbon atoms:
R7 is alkyl or haloalkyl:
RS is R7 or phenyl:
R9 and R10 are hydrogen, alkyl or haloalkyl:
Rl1 is alkyl. haloalkyl. alkoxy, or a phenyl group which is unsubstituted or-
substituted by one or more groups selected from hydroxy, halogen, alkoxy, cyano. R7 or -S(O)qR7: Rl2- Rl 3 and R14. which are identical or different, are R7S(O)r. formyl. alkynyl, alkoxycarbonyl. alkylthiocarbonyl or aroyl; or alkyl. C-3 to C-6 alkenyl or -C(O)alkyl wherein the alkyl and alkenyl portions are unsubstituted or
substituted by one or more R18:or
R21 and R22 are joined so as together to form a divalent radical
having 4 to S atoms in
the chain, this divalent radical being alkylene. alkyleneoxyalkylene or
alkyleneaminoalkylene: R] 5 and R16 are independently hydrogen or alkyl; Rl 7 is haloalkyl: R18 is cyano. nitro, alkoxy, haloalkoxy, -C(O)R7, R8S(O)s-, -C(O)OR9.
aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl. halogen, hydroxy.
aminosulfonyl. alkylaminosulfonyl or dialkylaminosulfonyl: m, n, p, q, r and s are independently of one another zero, one or two;
M is C-halo. C-CH3. C-CH2F. C-CH2Cl. C-N'O2. or N;
or a geometric isomer, tautomeric form or pesticidally acceptable salt thereof.
2. A 3-(N-oxy-imino)-l-arylpyrazole compound as claimed in
claim 1, in which X is -S(O)mR6:
Y is hydrogen; alkyl having 1 to 4 carbon atoms, cycloalkyl having up to 4 carbons both of which are unsubstituted or substituted by aminocarbonyl. alkylsulfonyl, alkoxy. alkoxycarbonyl, alkylcarbonyl. cyano or nitro; c-3 or c-4 alkenyl; C-3 to C-5 alkynyl; alkylcarbonyl: unsubstituted or substituted aroyl: arylalkylcarbonyl; alkylsulfonyl; alkoxycarbonylalkylcarbonyl; haloalkylcarbonyl; N-alkylcarbamoyl: alkoxycarbonyl; aryloxycarbonyl;

alkoxyalkylcarbonyl: alpha-hydroxyarylalkylcarbonyl: hydroxyalkylcarbonyl: aminoalkylcarbonyl: -C(=O)S-alkyl and trialkylsilyl: Z is amino. R12NH-. R13R14N-. halogen or methyl: Rl is hydrogen, methyl, amino or methylamino: R2 is F. Cl. Br or H: R3 and R5 are hydrogen:
R4 is CF3. CF3O. CHF2. CF3S(O)p. CF2Cl. CFCh . CF2ClO. CFCbO. Cl. Br. or F: R6 is methyl or ethyl optionally substituted by F. Cl or Br; M is CC1. CF. CBr. or X: R12- R13 and R14 are CF3S(O)r: alkynyl or alkoxycarbonyl; or alkyl. C-3 to C-6
alkenyl or -C(O)alkyl wherein the alkyl and alkenyl portions are unsubstiruted or substituted by one or more R18- and Rl g is cyano. nitro. alkoxy. haloalkoxy. -C(O)R7, R85(O)5. -C(O)OR9-
aminocarbonyl. alkylaminocarbonyl. dialkylaminocarbonyl. halogen, hydroxy, aminosulfonyl. alkylaminosulfonyl or dialkylaminosulfonyl.
3. A 3-(N-oxy-imino)-l-arylpyrazole compound as claimed in
claim 1 i, which is
5-Amino-l-[2.6-dichloro-4-(trifluororneihyl)phenyl]-4-meth}lsulfinyl-lH-pyrazole-3-carboxaIdehyde oxime:
l-p.6-DichIoro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxirne:
l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1 H-pyrazole-3-carboxaldehyde oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromeihyl)phenyl]-4-ethylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime:
5-Axnino-l-[2.6-dichloro-4-(trifluoromethynphenyl]-4-trifluoromethylthio-1 H-pyrazole-3-carboxaIdehyde oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-difluoromethylthio-lH-pyrazole-3-carboxaldehyde oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-lH-pyrazole-3-carboxaldehyde oxime:
5-Amino-l-[2.6-dichloro-4-(trinuoromethyl)phenyl]-4-trifluoromethylthio-1 H-pyrazole-3-carboxaldehyde O-(methyl)oxime;

5-Amino-l-[2.6-dichloro-4-nrifluoromethyl)pheny|]-4-methylsulfinyl-lH-
pyrazole-3-carboxaldehyde 0-{acety] loxime:
5-Amino-1 -[2.6-dichIoro-4-( trifluoromethyl )phenyl]-4-meihylsulfinyl-1H-
pyrazoleo-carboxaldehyde O-(2-methylbenzoyl)oxime:
5-Amino-1 -[2.6-dichIoro-4-(trifluoromethyl)phenyl]-4-methylsulfiny 1-1H-
pyrazole-3-carboxaldehyde O-(methoxycarbonyl)oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phcnyl]-4-methylsulfinyl-lH-
pyrazoIe-3-carboxaldehyde O-[2-(ethoxycarbonyl)propionyl]oxime;
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methy!thio-lH-
pyrazole-3-carboxaldehyde O-(aceryl)oximc:-
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-lH-
pyrazole-3-carboxaldehyde O-(methoxycarbonyl)oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-lH-
pyrazole-3-carboxaIdehyde oxime;
5-Amino-l-[2.6-dichloro-4-(trifluoromcthyl)phenyl]-4-methylsulfinyl-1H-
pyrazole-3-carboxaldehyde O-(methyl)oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-
pyrazole-3-cafboxaIdehyde O-(X-methylcarbamoyl)oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyI]-4-mcthylsulfmyl-lH-
pyrazole-3-carboxaldehyde O-(carboxymethyl)oxime:
l-[2.6-Dich!oro-4-(trifluoromethyl)pheny]]-4-methylsulfinyl-lH-pyrazoIe-3-
carboxaldchyde oxime:
5-Amino-l -[2.6-dichloro-4-(trifluoromethyl)phenyL]-4-methylsulfinyl-1H-
pyrazole-3-carboxaldehyde O-(ten-butyldimethylsilyl)oxime;
l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-
trifluoromethylthio-lH-pyrazole-3-carboximidamidc:
1 -[2.6-DichIoro-4-(irifluorometh\i)phenyl]-N-hydroxy-5-
hydroxyiminomethyl-4-trifluoromcthyIthio-lH-pyrazole-3-carboximidamide;
5-Amino-l -[2,6-dichloro-4-(trifluoromethyl)phcnyl]-4-mcthylsulfxnyl-1H-
pyrazole-3-carboxa]dehyde O-(isopropyI)oxime;
5-Amino-l-[2.6-dichloro-4-(trifluoromcthyl)phcnyl)-4-methyIsulfinyl-lH-
pyrazole-3-carboxaldehyde O-(ethoxycarbonylmethyl)oximc;
5-Amino-l-[2,6-dichloro-4-(trifluoromcthyl)phcnyl]-4-mcthylsulfiny I-1H-
pyrazoIc-3-carboxaldehyde O-(aminocarbonylmethyl)oxime:
5-Amino-l-[2.6-dich]oro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-lH-
pyrazole-3-carboxaldehydc O-[2-(ethylsulfonyi)ethyl]oxime;

5-Amino-1 -[2.6-dichloro-4-(tritluoromethyl )phenyl]-4-methylsulfinyl-1H-
pyrazole-3-carboxaldehyde O-(2-cyanoethy!loxime:
l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-lH-
pyrazoIe-3-carboxaldehyde oxime;
l-[2.6-Dichloro-4-(trifluoromethy|)phenyl]-5-methyl-4-methylsulfinyl-lH-
pyrazole-3-carboxaldehyde oxime:
l-[2.6-Dichloro-4-(tritluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-lH-
pyrazole-3-carboxaldehyde oxime;
5-Amino-1 -[3-chloro-5-( trifluoromethy1)-2-pyridiny l]-4-methylsulfmyl-1H-
pyrazole-3-carboxaldehyde oxime:
l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethyIthio-5-methyl-lH-pyrazole-
3-carboxaldehyde oxime;
l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-methyl-lH-
pyrazole-3-carboxaldehyde oxime:
l-[2-Chloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethyiamino]-4-
methylsulfinyl-lH-pyrazole-3-carboxaldehyde oxime;
l-[2.6-Dich!oro-4-(trifluoromethyI)phen}i]-5-dimethylamino-4-methylthio-
1 H-pyrazole-3-carboxaldehyde oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethoxy'jphenyl]-4-ethylsulfiny 1-1H-
pyrazole-3-garboxaldehyde oxime:
5-Amino-1 -[2.6-dichloro-4-(Trifluoromemyl)phenyl]-4-trifluoromethyI-1H-
pyrazole-3-carboxaldehyde oxime:
3-Aceiyl-5-amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-
-1 H-pyrazole oxime:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoro-
methylsulfinyl-1 H-pyrazole-3-carboximidamide;
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-trifluoro-
methylsulfinyl-lH-pyrazole-3-carboximidamide:
5-Amino-l-[2,6-dichloro-4-(trifluoromethyI)phenyl]-N-hydroxy-4-ethyIsulfinyl-
lH-pyrazole-3-carboximidamide;
5-Amino-l-[2.6-dich!oro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylthi6-
lH-pyrazole-3-carboximidamide:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyi]-N-hydroxy-4-memyl-
sulfinyl-1 H-pyrazole-3-carboximidamide;
5-Amino-l-[2.6-dichIoro-4-(trifluoromethoxy)phenyl]-N-hydroxy-4-methyI-
sulfinyl- lH-pyrazole-3-carboximidamide;
5-Amino-l-[2.6-dichIoro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methyI-

sulfonyl-1 H-pyrazok-3-carboximidarnide:
5-Amino-l-[2.6-dich]oro-4-(irif!uoromeihyl)pheny|]-N-hydroxy-4-methyl-thio-lH-pyrazole-3-carboximidamide:
5-Amino-I-[2.6-dichloro-4-ftrifluoromethyI)phenyI]-N-hydroxy-4-ethyl-
sulfonyl-1 H-pyrazole-3-carboximidamide:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-N'-methoxy-4-
methyIsuIfinyi-lH-pyrazole-3-carboximidamide:
5-Amino-l-[2.6-dichloro-4-(trifluoromethyr)phenyl]-N-methoxy-N'-methyl-
4-methylsulfinyl-lH-pyrazole-3-carboximidamide:
5-Amino-l-[2.6-dichloro-4-(trifluoromcthyl)phenyl]-N"-hydroxy-4-
[2-(fluoroethyl)sulfinyl]-1 H-pyrazole-3-carboximidamide:
5-Amino-l-[2.6-dich]oro-4-(trifluoroniethy|)phenyl]-N-hydroxy-4-
[2-(fluoroethyl)sulfonyl]-1 H-pyrazole-3-carboximidamide:
5-Amino-l-[3-chloro-5-(trifluoromcthyl)-2-pyridinyl]-4-ethylsulfinyl-N-
hydroxy-1 H-pyrazole-3-carboximidamide:
5-Amino-l-[3-chloro-5-('trifluoromethyl)-2-pyridinyl]-4-methylsuIfinyl-N-
hydroxy-lH-pyrazole-3-carboximidarhide:
l-[2.6-Dichloro-4-(trifluoromethy|)phenyl]-N-hydroxy-5-methylamino-4-
meihylsulfinyI-lH-pyrazole-3-carboximidamide;
l-[2.6-Dichloro-4-itrifluoromethyl)phenyl]-5-ethylamino-N-hydroxy-4-
mcthylsulfinyl-lH-pyrazolc-3-carboximidamide:
l-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-
N-hydroxy-4-methylsulfinyl-lH-pyrazole-3-carboximidamide:
5-[2-(Cyano)ethylamino]-l-[2.6-dichloro-4-(trifluoromethyl)phcnyl]-N-
hydroxy-4-mcthylsuIfmyl-lH-pyrazole-3-carboximidamide:
5-(Aminocarbonylmethylamino)-l-[2.6-dichloro-4-(trifluorornethyl)phenyl]-
N-hydroxy-4-methYlsulfinyl-1H-pyrazole-3-carboximidamide;
]-[2.6-Dichloro-4-(trifluoromethyl)phenyl]-4-mcthy!sulfinyl-5-[2-
(phenylsulfonyl)cthylamino]-N-hydroxy-lH-pyrazo!c-3-carboximidamide:
5-Amino-l-[2.6-dibromo-4-(trifluoromcthy])phenyl]-4-methylsulflnyl-N-
hydroxy-1 H-pyrazole-3-carboximidamide;
l-[2-Bromo-6-chloro-4-(trifluoromethyl)phcnyl]-5-ethylamino-4-
methylsulfinyl-N-hydroxy-l H-pyrazole-3-carboximidamide;
5-Amino-l-[2-bromo-6-chIoro-4-(rrifluoromethyl)phcny|]-4-methyIsulfinyl-
N-hydroxy-lH-pyrazole-3-carboximidamide;

l-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-
(rflethylsulfLnyl)ethylamino]-N-hydroxy-lH-pyra2ole-3-carboximidamide;
l-[2,6-Dichloro-4-(trifluoromethyl)phenyI]-4-methylsulfinyl-5-[2-
(methyIsulfinyl)ethylamino]-N-hydroxy-lH-pyrazole-3-carboximidaiiiide;
l-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-
(ethylsulfinyl)ethylamino]-N-hydroxy-1 H-pyrazole-3 -carboximidamide;
l-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[(prop-2-
ynyl)amino]-N-hydroxy-lH-pyrazo]e-3-carboximidamide; and
5-Amino-l-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
hydroxy-1 H-pyrazole-3 -carboximidamide.
4. A 3-(N-oxy-imino)-l-arylpyrazole compound as claimed in
claim 1, wherein the compound of formula (I) is:
5-Amino-l-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(acetyloxy)-lH-pyrazole carboximidamide;
5-Amino-l-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-(acetyloxy)-lH-pyrazole carboximidamide;
5-Amino-l-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethylcarbonyloxy)-lH-pyrazole carboximidamide; 5-Amino-l-[2,6-dichloro-4-(trifIuoromethyl)phenyl]-4-methylsulfinyl-N-(propylcarbonyloxy-1 H-pyrazole carboximidamide;

5-Amino-l-[2.6-dichloro-4-(trifluo-romethyIiphenyl]-4-methylsulfiny|-N'-(2-
methylethenylcarbonyloxy) -1 H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichloro-4-(trinuoromethyl)phenyl]-4-methyIsulfinyl-N-
(benzoyloxyl-1 H-pyrazole carboximidamide: l-[2.6-Dich]oro-4-(trifluoromethyl)phcnyl]-5-methylarnino-4-methylsulfiny!-N-
(acetyloxy)-1 H-pyrazole carboximidamide; 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-X-(acetyloxy)-
1 H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichIoro-4-(trifluoromethyl)phenyl]-4-meihylsulfinyl-X-
(heprylcarbonyloxy) -1 H-pyrazole carboximidamide: 5-Arnino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-
(heprylcarbonyloxy) -1 H-pyrazole carboximidamide: 5-Amino-1 -[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-X-Caceryoxy)-'
1 H-pyrazole carboximidamide; 5-Amino-l-[2.6-dichloro-4-(trifluoromethynphenyl]-4-methylsulfenyl-X-
(heptylcarbonyloxy) -1 H-pyrazole carboximidamide: 5-Ajnino-l-[2.6-dichloro-4-(trifluoromethyl)pheny]]-4-trifluoromethylsulfinyl-N-
(aceryloxy)-l H-pyrazole carboximidamide: l-[2.6-DichIoro-4-ftrifluoromethyl)phenyl]-5-formylamino-4-ethylsulfenyl-N-
(acetyloxy)-lH-pyazolc carboximidamide; 5-Amino-1-[2.6-dichIoro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
fhexylcarbonyloxy) -1 H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(pentylcarbonyloxy)-1 H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichloro-4-(irifluoromethyl)phenyl]-4-methylsulfinyl-N-
(butylcarbonyloxy) -1 H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichloro-4-(trif]uoromethyl)phenyl]-4-methylsulfenyl-N-
(cyclopentylcarbonyloxy) -1 H-pyrazole carboximidamide; 5-Amino-]-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-
(cyclopentylcarbonyloxy) -1 H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ten-butylcarbonyloxy) -1 H-pyrazole carboximidamide;
5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methyIsuliinyl-N-(iso-propylcarbonyloxy) -1 H-pyrazole carboximidamide:
l-[2.6-DichIoro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfinyI-N-(acetyloxy)-l H-pyrazole carboximidamide;

5-Amino-l-[2.6-dichloro-4-(trinuoromethyI1phenyl]-4-meihylsulrlnyl-N-
(chloroacetyloxy)-l H-pyrazole carboximidamide: 5-Amino-1-[2.6-dichloro-4-{trifluoromcthyl;phenyl]-4-rnethylsulfinyl-N-
(bromoacetyloxy)-]-1H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichloro-4-(trifluororncthy])phenyl]-4-rnethylsulfinyl-N-(l-
ethylpropylcarrxmyloxyVl H-pyrazole carboximidamide: 5-Amino-l-[2.6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-[(3-
acetyloxy)phenylcarbonyloxy]-1 H-pyrazole carboximidamide; 5-Amino-l-[2.6-dichloro-4-('trifluoromethyl)phenyl]-N'-hydroxy-4-trifluoro
methylsulfonyl-lH-pyrazole-3-carboximidamide; or 5-Amino-l-[2.6-dichloro-4-Ctrifluoromcthyl)phenyl]-N-hydroxy-4-trifluoro
methylsulfenyl-lH-pyrazole-3-carboximidamide.
5. A process for preparing a 3-(N-oxy-imino)-l-arylpyrazole compound of formula I in which Ri represents amino comprises reacting a compound of Formula (IT)




(Formula Removed)
with a compound of formula (111)

(Formula Removed)
wherein R2, R3, R4, R5, M, X, Y and Z are defined in claim 1.
6. A 3-(N-oxy-imino)-l-arylpyrazole compound of formula I as claimed in any of the preceding claims as and when used for the preparation of the pesticidal composition along with agriculturally acceptable carrier.


Documents:

3776-DEL-1997-Abstract-(06-10-2008).pdf

3776-DEL-1997-Abstract-(16-12-2008).pdf

3776-del-1997-abstract.pdf

3776-DEL-1997-Claims-(06-10-2008).pdf

3776-DEL-1997-Claims-(10-07-2008).pdf

3776-DEL-1997-Claims-(16-12-2008).pdf

3776-del-1997-claims.pdf

3776-DEL-1997-Correspondence-Others-(06-10-2008).pdf

3776-DEL-1997-Correspondence-Others-(10-07-2008).pdf

3776-DEL-1997-Correspondence-Others-(18-07-2008).pdf

3776-del-1997-correspondence-others.pdf

3776-DEL-1997-Description (Complete)-(06-10-2008).pdf

3776-DEL-1997-Description (Complete)-(16-12-2008).pdf

3776-del-1997-description (complete)-10-07-2008.pdf

3776-del-1997-description (complete).pdf

3776-DEL-1997-Drawings-(06-10-2008).pdf

3776-DEL-1997-Form-1-(06-10-2008).pdf

3776-DEL-1997-Form-1-(10-07-2008).pdf

3776-DEL-1997-Form-1-(16-12-2008).pdf

3776-del-1997-form-1.pdf

3776-del-1997-form-13.pdf

3776-del-1997-form-18.pdf

3776-DEL-1997-Form-2-(06-10-2008).pdf

3776-DEL-1997-Form-2-(10-07-2008).pdf

3776-DEL-1997-Form-2-(16-12-2008).pdf

3776-del-1997-form-2.pdf

3776-DEL-1997-Form-3-(10-07-2008).pdf

3776-del-1997-form-4.pdf

3776-DEL-1997-Form-5-(06-10-2008).pdf

3776-del-1997-form-6.pdf

3776-DEL-1997-GPA-(10-07-2008).pdf

3776-DEL-1997-GPA-(18-07-2008).pdf

3776-del-1997-gpa.pdf

3776-DEL-1997-Others-Document-(10-07-2008).pdf

3776-del-1997-petition -others.pdf

3776-DEL-1997-Petition-137-(10-07-2008).pdf

3776-DEL-1997-Petition-138-(10-07-2008).pdf

abstract.jpg


Patent Number 232907
Indian Patent Application Number 3776/DEL/1997
PG Journal Number 13/2009
Publication Date 27-Mar-2009
Grant Date 21-Mar-2009
Date of Filing 24-Dec-1997
Name of Patentee RHONE-POULENC AGROCHIMIE
Applicant Address 14-20 RUE PIERRE BAIZET, B.P. 9163 LYON 09M 69263 LYON CEDEX 09, FRANCE.
Inventors:
# Inventor's Name Inventor's Address
1 DAVID TREADWAY MANNING 102 SUMMERWINDS DRIVE, CARY, NORTH CAROLINA 27511, U.S.A.
2 JENNIFER PHILLIPS RT. 3, 220B, APEX, NORTH CAROLINA 27502, U.S.A.
3 PATRICK LOWDER 3532, PEACH HAVEN COURT, RALEIGH, NORTH CAROLINA 27607, U.S.A.
4 PETER WYATT NEWSOME 101 CREEKS EDGE, CHAPEL HILL, NORTH CAROLINA 27516, U.S.A.
5 NICHOLAS CH. RAY 6725 SIX FORKS ROAD, B-2 RALEIGH, NORTH CAROLINA 27615, U.S.A.
6 ALAIN CHENE LA CERISAIE 92, AVENUE PASTEUR, 69370 SAINT DIDIER AU MONT D'OR, FRANCE.
7 TAI-TEH WU 200 COLLINSON DRIVE, CHAPEL HILL, NORTH CAROLINA 27514, U.S.A.
PCT International Classification Number A01N 043/56
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 08/946,375 1997-10-07 U.S.A.
2 60/033888 1996-12-24 U.S.A.