Title of Invention

FUNGICIDAL 2-METHOXYBENZOPHENONES

Abstract Substituted benzophenone compounds are disclosed, having the formula: The compounds are useful as fungicides having high systemicities.
Full Text This invention relates to certain benzophenone compounds, a
process for their preparation, compositions containing such compounds, a
method for combating a fungus at a locus comprising treating the locus
with such compounds and their use as fungicides.
Food production relies upon a variety of agricultural technologies to
ensure the growing population's dietary needs remain affordable,
nutritious and readily available on grocery store shelves. Fungicides are
one of these agricultural technologies which are available to the world
community. Fungicides are agrochemical compounds which protect crops
and foods from fungus and fungal diseases. Crops and food are
constantly threatened by a variety of fungat organisms, which, if left
uncontrolled, can cause ruined crops and devastated harvests.
In particular, ascomycetes, the causative agent for powdery mildew
diseases are an ever-present threat especially to cereal and fruit crops.
However, applications of fungicidal agents at disease control rates can
cause phytotoxic damage to the target plants.
The compounds of the present invention are disclosed in a general
formula of European patent ("EP") application EP 0 727 141, which
published on August 21, 1996, The EP application discloses compounds
having activity against phytopathoc enic fungi, but relatively low
systemicity.
There is no disclosure in the EP application of substituted
benzophenones, wherein the first phenyl group is substituted by a
methoxy group in the 2-position and by a halogen atom or an alkyl group
in the 6-position and the second phenyl group is substituted by three
alkoxy groups and one methyl group.


The present invention provides a compound of formula

wherein
R1 represents a halogen atom or an alkyl or haloalkyl group
R2 represents a hydrogen or halogen atom, or an alkyl, haloalkyl, alkoxy or
nitro group; or R1 and R2 together represent a group of formula
-CH=CH-CH=CH-,
R3 and R4 each independently represent an optionally substituted alkyl
group; and
n is an integer from 0 to 3.
The compounds combine relatively excellent selective fungicidal activities
in various crops with comparably high systemicities
It is an object of the present invention to provide highly systemic
fungicidal compounds.
It is also an object of the invention to provide methods for
controlling an undesired fungus by contacting said plants with a
fungicidally effective amount of the compounds.
It is another object of the invention to provide selective fungicidal
compositions containing the compounds as active ingredients.
These and other objects and features of the invention will be more
apparent from the detailed description set forth hereinbelow, and from the
appended claims.

It has surprisingly been found that the compounds of formula I

in which R1 through R4 and n have the meaning given above combine
relatively excellent fungicidal activity against phytopathogenic fungi, in
particular those that cause powdery mildew diseases and have
comparably high systemicity.
In general terms, unless otherwise stated, as used herein the term
halogen atom may denote a bromine, iodine, chlorine or fluorine atom,
and is especially a bromine, chlorine or fluorine atom, in particular a
bromine or chlorine atom.
Optionally substituted moieties may be unsubstituted or have from
one up to the maximal possible number of substituents. Typically, 0 to 2
substituents are present. Each optionally substituted group independently
is substituted by one or more halogen atoms or nitro, cyano, cycloalkyl,
preferably C3-6 cycloalkyl, cycloalkenyl, preferably C3-6 cycloalkenyl,
haloalkyl, preferably C1-6 haloalkyl, halocycloalkyl, preferably C3-6
halocycloalkyl, alkoxy, preferably C1-6 alkoxy, haioalkoxy, preferably C1-6
haloalkoxy, phenyl, halo- or dihalo-phenyl or pyridyl groups.
In general terms, unless otherwise stated herein, the terms alkyl
and alkoxy as used herein with respect to a radical or moiety refer to a
straight or branched chain radical or moiety. As a rule, such radicals have
up to 10, in particular up to 6 carbon atoms. Suitably an alkyl or alkoxy
moiety has from 1 to 6 carbon atoms, preferably from 1 to 5 carbon atoms.
A preferred alkyl moiety is the methyl, ethyl, n-propyl, isopropyl or n-butyl
group.
In general terms, unless otherwise stated herein, the term haloalkyl
as used herein with respect to a radical or moiety refers to a straight or

branched chain radical or moiety being substituted by one or more
halogen atoms As a rule, such radicals have up to 10, in particular up to 6
carbon atoms. Suitably haloalkyl moieties are fluoroalkyl moieties having
from 1 to 6 carbon atoms, preferably from 1 or 2 carbon atoms. The
fluoroalkyl groups include alkyl groups in which one or more, in particular
all hydrogen atoms have been replaced by fluorine. A preferred fluoroalkyl
moiety is represented by the formula -(CH2)m-(CF2)n-Y, in which m is 0, 1
or 2, n is 1, 2, 3, 4 or 5 and Y represents a hydrogen or fluoro atom.
Particularly preferred is the difluoromethyl, trifluoromethyl, 2,2,2-
trifluoroethyl, pentafluoroethyl, or n-heptafluoropropyl, group.
The invention especially relates to compounds of the general
formula I in which any alkyl part of the groups R1 through R4, which may
be straight chained or branched, contains up to 10 carbon atoms,
preferably up to 9 carbon atoms, more preferably up to 6 carbon atoms,
and in which each optionally substituted group independently is
substituted by one or more halogen atoms or nitiro, cyano, cycloalkyl,
preferably C3-6 cycloalkyl, cycloalkenyl, preferably C3-6 cycloalkenyl,
haloalkyl, preferably C1-6 haloalkyl, halocycloalkyl, preferably C3-6
halocycloalkyl, alkoxy, preferably C1-6 alkoxy, haloalkoxy, preferably C1-6
haloalkoxy, phenyl, or pyridyl groups, in which the phenyl moiety is
optionally substituted by one or two substituents selected from halogen
atoms, cyano, C1-6 alkyl and C1-6 alkoxy groups.
The invention especially relates to compounds of the general
formula I in which R1 represents a halogen atom in particular chlorine, a
straight-chained or branched C1-10 alkyl, in particular a straight-chained
C1-3 alkyl group, most preferably being a methyl group being unsubstituted
or substituted by at least one optionally substituted phenyl group, or a
straight-chained or branched C1-10 fluoroalkyl, in particular a straight-
chained C1-3 fluoroalkyl group, most preferably being a trifluoromethyl
group.
The invention especially relates to compounds of the general
formula I in which R2 represents a hydrogen or halogen atom, in particular

a chlorine, bromine or iodine atom, a nitro, a C1-10 alkyl or a C1-10 haloalkyl
group, most preferred being a hydrogen, chlorine or bromine atom or a
trifluoromethyl group. If R2 is different from hydrogen, it is most preferred
attached in the ortho-position to radical R1.
The invention especially relates to compounds of the general
formula I in which R3 and R4 each independently represent an optionally
substituted straight-chained or branched C1-5 alkyl, in particular a straight-
chained C1-3 alkyl group, most preferably an unsubstituted or substituted
methyl group. This methyl group is preferably unsubistituted or substituted
by a phenyl group which is unsubstituted or substituted by one to five,
preferably one or two halogen atoms or C1-4 alkyl or C1-4 alkoxy groups.
The benzophenone compounds according to formula I are oils,
gums, or crystalline solid materials and possess valuable fungicidal
properties. For example, they can be used in agriculture, or related fields
such as horticulture and viticulture, for the control of phytopathogenic
fungi, especially ascomycetes, in particular powdery mildew diseases
such as those caused by Blumeria (Erysiphe, qraminis, Erysiphe
cichoracearum, Podosphaera ieucotricha, Uncreula necator and the like.
Said benzophenone compounds possess a high fungicidal activity over a
wide concentration range and may be used in agriculture without harmful
phytotoxic effects.
Moreover, the compounds according to the invention show
enhanced curative and residual control of fungi and fungal diseases such
as cereal, cucumber, apple and grape powdery miloew, and improved
foliar systemicity compared with conventional fungicides.
Useful results in terms of control of phytopatho 'enic fungi are
obtained with a compound as defined in formula I wherein
R1 represents a chloro atom or a methyl or trifluoromethyl group:
R2 represents a hydrogen, chloro or bromo atom or trifluoromethyl group;
R3 represents a C1-5 alkyl group;

R4 represents a C1-6 alkyl group or a benzyl group being optionally
substituted by one or more halogen atoms or one or more C1-4 alkyl or
alkoxy groups; and
n is 0 or 2, in particular 0.
If R2 represents CI, Br or CF3, it is preferably attached to the
benzene ring in the ortho-position with respect to radical R1.
Furthermore preferred are those compounds of formula I, wherein
at least one of the radicals R1 and R2 represents a trifluoromethyl group
In particular the compounds of formula lA are preferred

in which
R1 represents a chloro atom or a methyl or triffluoromethyl group,
R2 represents a hydrogen, chloro or bromo atom or a methyl or
trifluoromethyl group, and
R' represents a hydrogen atom or a C1-4 alkyl or a phenyl group being
optionally substituted by one or more fluorine atoms or one or more C1-4
alkyl groups.
In particular the compounds of formula IB are preferred:

in which


R1 represents a hydrogen atom or a C1-4 alkyl or a phenyl group being
optionally substituted by one or more fluorine atoms or one or more C1-4
alkyl groups
Especially good results in terms of control of phytopathogenic fungi
are obtained by using, forexample, the following compounds of formula I:
6,6'-dimethyl-2,2',3,4'-tetramethoxy-benzophenone,
6,6'-dimethyl-3'-pentoxy-2,2',4'-trimethoxy-benzophenone,
5-bromo-6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
5-chloro-6,6-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
5-iodo-6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
6-chloro-6'-methyl--2,2',3',4'-tetramethoxy-benzophenone,
5-bromo-6-chloro-6'-methyl--2,2',3',4'-tetramethoxy-benzophenone,
6-chloro-5,6'-dimethyl--2,2',3',4'-tetramethoxy-benzophenone,
2'-n-butoxy-6-chtoro-6'-methyl-2,3',4'-trimethoxy-benzophenone,
2'-n-butoxy-6-chloro-5,6'-dimethyl-2,2',3'-trimethoxy-benzophenone
6-chloro-2'-(2-fluorobenzyloxy)-6'-methyl-2,3',4'-trimethoxy-
benzophenone,
6-chloro-2'-(4-fluorobenzyloxy)-6'-methyl-2,3',4'-trimethoxy-
benzophenone,
5-bromo-6,6'-dimethyl-3'-n-pentyloxy-2,2 ,4'-trimethoxy-benzophenone
6-chloro-6'-methyl-2'-n-pentyloxy-2,3',4'-trimethoxy-benzophenone,
6-chloro-2'-(3-methylbutyloxy)-6'-methyl-2,3',4'-trimethoxy-benzophenone,
2'-benzyloxy-6-chloro-6'-methyl-2,3',4'-trimethoxy-benzophenone,
6-chloro-2'-(3-methylbenzyloxy)-6'-methyl-2,3',4'-trimethoxy-
benzophenone,
6-chloro-2'-(4-methylbenzyloxy)-6'-methyl-2,3',4'-trimethoxy-
benzophenone,
6-chloro-2-difluoromethoxy-6'-methyl--2,3',4'-trimethoxy-benzophenone,
1-(6-methyl-2,3,4-trimethoxybenzoyl)-2-methoxynaphthalene,
1-(6-methyl-2,3,4-trimethoxybenzoyl)-2-difluoromethoxynaphthalene,
5-chloro-6,6'-dimethyl-3'-ethoxy-2,2',4'-trimethoxy-benzophenone,
5-chloro-6,6'-dimethyl-3'-n-propyloxy-2,2',4'-trimethoxy-benzophenone,

6,6'-dimethyl-2,2',3',4'-etramethoxy-5-trifluoromethyl-benzophenone,
6'-methyl-2,2',3',4'-tetramethoxy-6-trifiuoromethyl-benzophenone,
5-bromo-6'-methyl-2,2',3',4'-tetramethoxy-6-trifluoromethyl-
benzophenone.
The present invention further provides a process (A) for the
preparation of a compound of formula I, wherein n is 0, which comprises
treating a compound of the general formula II

wherein R1, R2, R3 and R4 have the meaning given above and X
represents a fluoro or chloro atom, with gin alkali methylate, preferably
sodium methylate.
Another possibility for the preparation of the compounds of formula
I is a process (B) which comprises the steps of
(a) reacting a compound of formula III,

wherein R1, R2 and n have the meaning given above and Y represents a
leaving group, in particular a chloro atom or a hydroxy group, with
compound of formula IV,


wherein R3 has the meaning given for claim 1; in the presence of a Lewis
acid (Y= leaving group) or a dehydrating agent (Y - OH), preferably
phosphorous pentoxide or POC!3; and
(b) optionally treating the resulting benzophenone of formula I,
wherein R4 represents a methyl group, with a compound of formula V,
R4-O-Met (V)
wherein R4 represents an optionally substituted alkyl group, being different
Trorn methyl, and met aenotes an alkayl metal atom preferably sodium,
The compounds of formula III, wherein R2 represents a halogen
atom, are preferably obtained by a process (C) which comprises the steps
of
(a) reacting a compound of formula VI,

wherein R1 and n have the meaning given for claim 1 and R" represents a
hydrogen atom or an alky! group, with a halogenating agent,
(b) optionally hydrolyzing the resulting halogenated alkyl
benzoate (R" = alkyl), and
(c) optionally treating the resulting halogenated benzoic acid
with thionyl chloride.
The compounds of formula I, wherein R2 represents a
trifluoromethyl group are preferably obtained by treating a compound of
formula I, wherein R2 represents a halogen atom, with trtfluoroacetate in
the presence of a copper salt at elevated temperatures
The starting materials of formulae II, IV, V and VI are known
products, the starting materials of formula III are partly known and partly
novel products.
Accordingly, the invention provides novel intermediate of formula
IIIA


wherein R1 represents an alkyl group, in particular a methyl group and R2
represents a bromo atom or a trifluoromethyl group.
The starting materials of formulae II, IV, V and VI may be prepared
according to established methods or routine adaptations thereof.
Substituents which are not compatible with the selected reaction
conditions may be introduced after formation of the benzophenone. They
may be generated by known methods such as subsequent derivatization
or substitution of a suitable group or by cleaving off a suitable protecting
group.
The reaction between the 2-halobenzophenone of formula II and
the alkali metal methylate is preferably carried out in the oresence of a
solvent, such as ethers like tetrahydrofuran, diethylether, tert-butyl-
methylether or dimethoxyethane or methanol or in mixtures of these
solvents. The molar ratio between formula II and the alkali metal methylate
is preferably in the range of 0.3 to 1.9 at a temperature between 25 and
120 ºC.
The Friedel Crafts reaction between formula III and IV is effected in
the presence of a Lewis acid catalyst according to well-established
procedures (Y = CI). Suitable catalysts include FeCI3, AICI3) SnCl4, ZnCI2,
TiCI4, SbCI5 and BF3, which may be in a molar equivalent amount (based
on the benzoyl chloride of formula III). However, it is also possible to use
lesser amounts of catalyst at elevated temperatures, suitably under reflux
temperatures, preferred catalysts under these conditions being FeCI3, l2,
ZnCI2, iron, copper, strong sulphonic acids such as F3CSO3H, and acidic
ion exchange resins such as Amberlyst® 15 and Nafion®. The preferred
catalyst is FeCI3 in a 0.001 to 0.2 molar ratio at a temperature of about 50
to 180°C. The reaction can be carried out in a solvent inert under the

reaction conditions, for example ethylene or methylene chloride, benzene,
octane, decane or solvent mixtures, or in the absence of solvent,
conveniently by employing one of the reactants in excess, e. g. in the
range of 1:5 to 5:1. If AlCI3 is being used, the motor ratio is preferably in
the range of 0.5 to 2 and the suitable solvents are e.g. dichloromethane or
ethylenechloride at a temperature usually between -10 and 70°C.
In another preferred process according to the invention the benzoic
acid of formula III (Y = OH) is reacted with a compound of formula IV in
the presence of phosphorous pentoxide at temperatures of about 0 to 50
°C, preferably at room temperature or in the presence of POCI3 at
temperatures of about 50 to 150°C preferably under reflux.
The halogenation of the benzoate of formula VI is preferably carried
out in the presence of an inert solvent. Preferred halogenating agents are
for example sulfuryl chloride, bromine and N-halo-succinimide. If R1
represents a halogen atom highly polar solvents such as alcohols or
carboxylic acids, in particular acetic acid are preferred. If R1 represents an
alkyl group, in particular a methyl group, apolar solvents such as
tetrachloromethane are preferred. If the reaction is carried out with
bromine at a temperature between 0 and 40 °C, preferably at room
temperature, the halogenation takes place predominately in the ortho-
position with respect to radical R1
In a preferred embodiment the compounds of formula III, in which
R2 represents a bromo atom are prepared by reacting a compound of
formula VI, wherein R1 represents an alkyl group, n is 0, and R" represents
a hydrogen atom, with bromine. This bromination step is preferably carried
out in the presence of a polar, protic solvent, such as an aliphatic alcohol
or an aliphatic carboxylic acid in particular acetic acid. The bromination
may be carried out advantageously in the presence of a weak base or a
buffer system, such as sodium acetate or sodium carbonate.
One embodiment of the process of the instant invention is a
process wherein bromine is employed in an amount selected from a value

in the range between 1.0 to 1.5, in particular 1.05 to 1.2 molar equivalents
with respect to starting compound of formula VI.
The reaction between the compound of formula VI and bromine is
as a rule carried out at a temperature sufficient to optimally convert the
compound of formula VI to the compound of formula III. This term
represents a temperature sufficiently high to maintain the conversion, but
also sufficiently low to avoid decomposition of the starting material and the
product. The reaction is carried out preferably at temperatures between 0
°C and 40 °C, in particular at ambient temperature.
The reaction between the compound of formula VI and bromine is
as a rule carried out at a length of time sufficient to optimally convert the
compound of formula VI to the compound of formula II). This term
represents a period of time sufficiently long to convert the maximum
amount of the starting material to the compound of formula III. The
reaction is carried out preferably at reaction time between 1 and 40 hours,
in particular between 5 and 24 hours.
The transformation of a compound ot formula I, wherein R2
represents a halogen atom, into a compound of formula I, wherein one of
R2 represents a trifluoromethyl group, is carried out analogously to J.
Chem. Soc. Perkin Trans. PT1 (1988) N4, page 924 Preferably sodium
trifluoroacetate is reacted with the halogen compound in the presence of a
copper salt, preferably copper-(j) hatides, in particular copper-(l) iodide. As
a rule the reaction is carried out in a high-boiling polar aprotic solvent such
as 1-methyl-2-pyrrolidone. The reaction is carried out preferably at
temperatures between 120 °C and 200 ºC, in particular between 150 °C
and 170 °C.
The reaction between tne compound formula I, R1 represents a
halogen atom, and sodium trifluoroacetate is as a rule carried out at a
length of time sufficient to optimally to transform the halogen compound
into a trifluoromethyl compound. This term represents a period of time
sufficiently long to convert the maximum amount of the starting material to
the compound of formula I, wherein R2 represents a trifluoromethyl group.

The reaction is carried out preferably at a reaction time between 40 and
140 hours, in particular between 60 and 100 hours.
The kprocesses described above and below can analogously be
applied to other staring compounds, if desired.
Due to excellent plant toleration, the compounds of formula I may
be used in cultivation of all plants where infection by the controlled fungi is
not desired, e.g. cereals, vegetables, legumes, apples, vine. The absence
of target crop phototoxicity at fungus control rates is a feature of the
present invention.
Accordingly the invention further provides a tungicida! composition
which comprises a carrier and, as active ingredient, at least one
compound of formula I as defined above. A method of making such a
composition is also provided which comprises bringing a compound of
formula i as delned above into association with at least one carrier. Such
a composition may contain a single compound or a mixture of several
compounds of the present invention. It is also envisaged that different
isomers or mixtures of isomers may have different levels or spectra of
activity and thus compositions may comprise individual isomers or
mixtures of isomers.
A composition according to the invention preferably contains from
0.5% to 95% by weight (w/w) of active ingredient.
A carrier in a composition according to the invention is any material
with which the active ingredient is formulated to facilitate application to the
locus to be treated, which may for example be a plant, seed or soil, or to
facilitate storage, transport or handling, A carrier may be a solid or a liquid,
including material which is normallya gas butwhich has been
compressed to form a liquid.
The compositions may be manufactured into e.g. emulsion
concentrates, solutions, oil in water emulsions, wettable powders, soluble
powders, suspension concentrates, dusts, granules, water dispersible
granules, micro-capsules, gels and other formulation types by well-
established procedures. These procedures include intensive mixing

and/or milling of the active ingredients with other substances, such as
filters, solvents, solid carriers, surface active compounds (surfactants), and
optionally solid and/or liquid auxilaries and/or adjuvants. The form of
application such as spraying, atomizing, dispersing or pouring may be
chosen like the compositions according to the desired objectives and the
given circumstances.
Solvents may be aromatic hydrocarbons, e.g. Solvesso® 200,
substituted naphthalenes, phthalic acid esters, such as dibutyl or dioctyl
phthalate, aliphatic hydrocarbons, e.g. cyclohexaneor paraffins, alcohols
and glycols as well as their ethers and esters, e.g. ethanol, ethyleneglycol
mono-and dimethyl ether, ketones such as cyclohexanone, strongly polar
solvents such as N-methyl-2-pyrro!idone, or γ-butyrolactone, higher alkyl
pyrrolidones, e.g. n-octylpyrrolidone or cyclohexylpyrrolidone, epoxidized
plantoil esters, e.g. methylated coconut or soybean oil ester and water.
Mixtures of different liquids are often suitable
Solid carriers, which maybe used for dusts, wettable powders,
water dispersible granules, or granules, may be mineral fillers, such as
calcite, talc, kaolin, montmorillonite or attapulgile. The physical properties
may be improved by addition of highly dispersed silica gel or polymers.
Carriers for granules may be porous material, e.g. pumice, kaolin,
sepiolite, bentonite; non-sorptive carriers may be calcite or sand.
Additionally, a multitude of pre-granulated inorganic or organic materials
may be used, such as dolomite or crushed plantrestdues.
Pesticidal compositions are often formulated and transported in a
concentrated form which is subsequently diluted by the user before
application. The presence of small amounts of a carrier which is a
surfactant facilitates this process of dilution. Thus, preferably at least one
carrier in a composition according to the invention is a surfactant. For
example, the composition may contain at two or more carriers, at least one
of which is a surfactant.
Surfactants may be nonionic, anionic, cationic or zwitterionic
substances with good dispersing, emulsifying and wetting properties

depending on the nature ofthe compound according to general formula I
to be formulated. Surfactants may also mean mixtures of individual
surfactants.
The compositions of the invention may for example be formulated as
wettable powders, water dispersible granules,dusts, granules, solutions,
emulsifiable concentrates, emulsions, suspension concentrates and
aerosols. Wettable powders usually contain 5 to 90% w/w of active
ingredient and usually contain in addition to solid inert carrier, 3 to10%
w/w of dispersing and wetting agents and, where necessary, 0 to 10% w/w
of stabilizer(s) and/or other additives such as penetrants or stickers. Dusts
are usually formulated as a dust concentrate having a similar composition
to that of a wettable powder but without a dispersant, and may be diluted
in the field with further solid carrier to give a composition usually
containing 0.5to 10% w/w of active ingredient Water dispersible granules
and granules are usually prepared to have a size between 0.15 mm and
2.0 mm and may be manufactured by a variety of techniques. Generally,
these types of granules will contain 0.5 to 90% w/w active ingredient and 0
to 20% w/w of additives such as stabilizer, surfactants, slow release
modifiers and binding agents. The so-called "dry flowables" consist of
relatively small granules having a relatively high concentration of active
ingredient. Emulsifiable ooncentrates usually contain, in addition to a
solvent or a mixture of solvents, 1 to 80% w/v active ingredient, 2 to 20%
w/v emulsifiers and 0 to 20% w/v of other additives such as stabilizers,
penetrants and corrosion inhibitors. Suspension concentrates are usually
milled so as to obtain a stable, non-sedimenting flowable product:and
usually contain 5 to 75% w/v active ingredient 0.5 to 15% w/v of
dispersing agents, 0.1 to 10% w/v of suspending agents such asprotective
colloids and thixotropic agents, 0 to 10% w/v of other additives such as
defoamers, oorrosion inhibitors, stabilizers, penetrants and stickers, and
water or an organic liquid in which the active ingredient is substantially
insoluble; certain organic solids or inorganic salts may be present

dissolved in the formulation to assist in preventing sedimentation and
crystalization or as antifreeze agents for water.
Aqueous dispersions and emulsions, for example compositions
obtained by diluting the formulated product according to the invention with
water, also lie within the scope of the invention
Of particular interest in enhancing the duration of the protective
activity of the compounds of this invention is the use of a carrier which will
provide slow release of the pesticidal compounds into the environment of
a plant which is to be protected,
The biological activity of the active ingredient can also be increased
by including an adjuvant in the spray dilution. An adjuvant is defined here
as a substance which can increase the biological activity of an active
ingredient but is not itself significantly biologically active. The adjuvant can
either be included in the formulation as a coformulant a carrier, or can be
added to the spray tank together with the formulation containing the active
ingredient.
As a commodity the compositions may preferably be in a
concentrated form whereas the end user generally employs diluted
compositions, The compositions may be diluted to a concentration down to
0.001% of active ingredient. The doses usuaify are m the range torn 0.01
to 10 kg a.i./ha.
Examples of formulations according to the invention are:
Emulsion Concentrate (EC)
Active Ingredient Compound of Example 6 30 % (w/v)
Emulsifier(s) Atlox® 4856 B / Atlox® 4858 B 1) 5 % (w/v)
(mixture containing calcium alkyl aryl
sulfonate, fatty alcohol ethoxylates and light
aromatics / mixture containing calcium alkyl
aryl sulfonate, fatty alcohol ethoxylates and
light aromatics}
Solvent ShellsoI® A 2) to 1000 ml
(mixture of C9 - C10 aromatic hydrocarbons)

Suspension Concentrate (SC)
Active Ingredient Compound of Example 6 50 % (w/v)
Dispersing agent Soprophor® FL 3) 3 % (w/v)
(polyoxyethylene polyaryl phenyl ether
phosphate amine salt)
Antifoaming agent Rhodorsil® 422 3) 0.2 %
(nonionic aqueous emulsion of (w/v)
polydimethylsiloxanes)
Structure agent Kelzan® S 4) 0.2 %
(Xanthan gum) (w/v)
Antifreezing agent Propylene glycol 5 % (w/v)
Biocidal agent Proxel®; 5) 0.1%
(aqueous dipropytene glycol solution (w/v)
containing 20% 1,2-benisothiazolin-3-one)
Water to 1000 ml
Wettable Powder (WP)
Active Ingredient Compound of Example 6 60 % (w/w)
Wetting agent Atlox® 4995 1) 2 % (w/w)
(polyoxyethylene alkyl ether)
Dispersing agent Witcosperse® D-60 6) 3 % (w/w)
(mixture of sodium salts of condensed
naphthalene sulfonic acid and
alkylarylpolyoxy acetates
Carrier / Filler Kaolin 35 % (w/w)
Water Dispersible Granules (WG)
Active Ingredient Compound of Example 6 50 % (w/w)
Dispersing / Witcosperse® D-450 6) 8 % (w/w)
Binding agent (mixture of sodium salts of condensed
naphthalene sulfonic acid and alkyl
sulfonates)
Wetting agent Morwet® EFW 6) 2 % (w/w)

(formaldehyde condensation product)
Antifoaming agent Rhodorsil® EP 6703 3) 1 % (w/w)
(encapsulated silicone)
Disintegrant Agrimer® ATF 7) 2 % (w/w)
(cross-linked homopolymer of N-vinyl-2-
pyrrolidone)
Carrier / Filler Kaolin 35 % (w/w)
available from ICI Surfactants
2)
available from Deutsche Shell AG
3)
available from Rhodia former (Rhdne-Poulenc)
available from Kelco Co.
5)
available from Zeneca
6)
available from Witco
from International Speciality Products
The compositions of this invention can also comprise other
compounds having biological activity, e.g. compounds having similar or
complementary pesticidal activity or coimpounds having plant growth
regulating, fungicidal or insecticidal activity, These mixtures of pesticides
can have a broader spectrum of activity than the compound of general
formula I alone. Furthermore, the other pesticide can have a synergistic
effect on the pesticidal activity of the compound of general formula I.
The other fungicidal compound can be, for example, one which is
capable of combating diseases of cereals (e.g. wheat) such as those
caused by Erysipha, Puccinia, Sepforia, Gibberella and Helminthosporium
spp., seed and soil borne diseases and downy and powdery mildews on
vines and powdery mildew and scab on apples etc. These mixtures of
fungicides can have a broader spectrum of activity than the compound of
general formula I alone.
Examples of the other fungicidal compounds are anilazine,
azoxystrobin, benalaxyl, benomyl, binapacryl, bitertanol, blasticidin S,
Bordeaux mixture, bromuconazole, bupirimate, captafol, captan,


carbendazim, carboxin, carproparnid, chlorbenzthiazon, chlorothalonil,
chlozolinate, copper-containing compounds such as copper oxychloride,
and copper sulfate, cycloheximide, cymoxanil, cypofuram, cyproconazole,
cyprodinil,, dichlofluanid, dichione, dichloran, diclobutrazol, dicloymet
diclomezine, diethofencarb, difenoconazole, diflumetorim, dimethirimol,
dimethomorph, diniconazole, dinocap, ditslimfoc, dithianon, dodcmorph,
dodine, edifenphos, epoxiconazole, etaconazole, ethirimol, etridiazole,
famoxadone, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid,
fenpicionil, fenpropidin, fenpropimorph, fentin, fentin acetate, fentin
hydroxide, ferimzone, fluazinam, fludioxonil, flumetover, fluquinconazole,
flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium,
fuberidazole, furalaxyi, furametpyr, guazatine, hexaconazole, imazalil
iminoctadine, ipconazole, iprodione, isoprothiolane, kasugamycin, kitazin
P, kresoxim-methyl, mancozeb, maneb, mepanipyrim, mepronil,
metalaxyl, metconazole, methfuroxam, myclobutanil, neoasozin, nickel
dimethyldithiocarbamate, nitrothalisopropyl, nuarimol, ofurace, organo
mercury compounds, oxadixyl, oxycarboxin. penconazole, pencycuron,
phenazineoxide, phthalide, polyoxin D, polyram, probenazole, prochloraz,
procymidione, propamocarb, proptconazole, propineb, pyrazophos,
pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, quinomethionate.
quinoxyfen, quintozene, spiroxamine, SSF-126, SSF-129, streptomycin,
sulfur, tebuconazole, tecioftalame, tecnazene, tetraconazole,
thiabendazole, thifluzannide, thiophanate-methyl, thiram, tolclofosmethyl,
tolylfluanid, triadimefon. triadimenol, thazbutil, triazoxide, tricyclazole,
tridemorph, triflumizole, triforine, triticonazole, validamycin A, vinclozolin,
XRD-563, zarifamid, zineb, ziram
In addition, the co-formulations according to the invention may
contain at least one benzophenone of formula I and any of the following
classes of biological control agents such as viruses, bacteria, nematodes,
fungi, and other microorganism which are suitable to control insects,
weeds or plant diseases or to induce host resisitance in the plants.
Examples of such biological control agents are: Bacillus thuringiensis,

Verticillium lecanii, Autographies californica NPV, Beauvaria bassiana,
Ampelomyces quisqualis, Bacilis subtilis, Pseudomonas fluorescens,
Steptomyces griseoviridis and Trichoderma hazianum.
Moreover, the co-formulations according to the invention may
contain at least one benzophenone of formula ! and a chemical agent that
induces the systemic acquired resistance in plants such as for example
nicotinic acid or derivatives thereof, 2,2-dichloro-3,3-
dimethyicyclopropyicarboxyiic acid or BION.
The compounds of general formula I can be mixed with soil, peat or
other rooting media for the protection of the plants against seed-borne,
soil-borne or foliar fungal diseases,
The invention still further provides the use as a fungicide of a
compound of the general formula I as defined above or a composition as
defined above, and a method for combating fungus at a locus, which
comprises treating the locus, which may be for example plants subjectto
or subjected to fungal attack, seeds of such plants or the medium in which
such plants are growing or are to be grown, with such a compound or
composition.
The present invention is of wide applicability in the protection of crop
and ornamental plants against fungal attack. Typical crops which may be
protected include vines, grain crops such as wheat and barley, rice, sugar
beet, top fruit, peanuts, potatoes, vegetables and tomatoes. The duration
of the protection is normally dependent on the individual compound
selected, and also a variety of external factors, such as climate, whose
impact is normally mitigated by the use of a sutable formulation.
The following examples further illustrate the present invention, it
should be understood, however, that the invention is not limited solely to
the particular examples given below.

Example 1
Preparation of 6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone
1A 2-Methoxy-6-methylbenzoic acid
A mixture of ethyl 2-rnethoxy-6-methylbenzoate (5.0 g, 25 mmol), water
(10 ml), methanol (40 ml) and sodium hydroxide (2.1 g, 50 mmol) is
heated under reflux with stirring. The reaction mixture is. diluted with water
(150 ml) and acidified with concentrated hydrochloric acid. The solid
material is collected by filtration, washed with water and dried yielding
dark yellow crystals, 2 1 g, mp 136 ºC.
1B 2-Methoxy-6-methylbenzoyl chloride
A mixture of 1A (1.7 g, 10.2 mmol) and thionyl chloride (2 ml) is heated
under reflux for 1 hour. The mixture is concentrated and the resulting
benzoylchloride is used without further purification.
1C 6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone
A mixture of 3,4,5-trimethoxytoluene (1.86 g; 10.2 mmol), 1B (10.2 mmol),
aluminium chloride (1.33 g, 10 mmol) and dichloromethane (20 ml) is
stirred at 0° C. The reaction sets up at 0 °C with formation of hydrogen
chloride. Subsequently, the reaction mixture is stirred for another 4 hours
at room temperature. A mixture of dilute hydrochloric acid and ethyl
acetate (1:1 v/v; 100 ml) is then slowly added at 0 °C. The organic phase
is concentrated and the residue is recrystallized from methanol. The solid
material is collected by vacuum fraction, three times washed with
methanol/water (3:1 v/v; 100 ml each) and dried yielding white crystals,
1.0 g (30.3%), mp 84°C.
Example 2
Preparation of 6,6'-dimethyl-2'-n-butoxy-2,3',4'-trimethoxy-benzophenone
A mixture of n-butanol (5 ml) and sodium hydride (60 % in oil, 10 mmol) is
stirred until the formation of H2 gas ceases. A mixture of 1C (0.7 g, 2,2

mmol) and dimethoxyethane (15 ml) is added to the resulting reaction
mixture. Subsequently, the reaction mixture is heated under reflux with
stirring for 24 hours. A mixture of water and ethyl acetate (1 1 v/v; 100 ml)
is then slowly added at room temperature. The organic phase is
separated, concentrated and the residue is purified by column
chromatography (petrol ether: ethyl acetate, 95:5 v/v) yielding the pure
product as a yellow oil, 0.2 g, (24.4 %).
Example 3
Preparation of e-chloro-2'-pentyloxy-6'-methyl-2,3',4'-trimethoxy-
benzophenone
A mixture of sodium methylate in methanol (5.4 mol/l, 19.6 mmol), 2,6-
dichloro-3',4'-dimethoxy-6'-methyl-2'-pentyloxy-benzophenone (obtained
according to EP 0 727 141, 2.69 g, 6.5 mmol) and dimethoxyethane (20
ml) is heated to 80 °C with stirring for 24 hours. A mixture of water and
ethyl acetate (1:1 v/v; 100 ml) is then slowly added at room temperature.
The organic phase is separated and concentrated and the residue is
purified by column chromatography (dichloromethane) yielding the pure
product as a yellow oil, 0.52 g, (19.7 %).
Example 4
Preparation of 5-bromo-6-chloro-6'-methyl-2,2'3',4'-tetramethoxy-
benzophenone
4A Ethyl 5-bromo-6-chloro-2-methoxybenzoate
A mixture of ethyl 6-chloro-2-methoxybenzoate (1.8 g, 8.4 mmol), bromine
(1.41 g, 8.8 mmol) and acetic acid (5 ml) is stirred at room temperature for
24 hours. The reaction mixture is poured into water and extracted with
ethyl acetate. The organic phase is separated and concentrated and the
residue is purified by column chromatography (petrol ether: ethyl acetate,
95:5 v/v) yielding the pure product as a yellow oil, 1.7 g, (69 %).

4B 5-Bromo-6-chloro-2-methoxybenzoic acid
A mixture of 4A (1.7 g, 5,8 mmol), water (10 ml), ethanol (20 ml) and
sodium hydroxide (0.5 g, 12.5 mmol) is heated under reflux with stirring.
The reaction mixture is diluted with water (80 ml) and acidified with
concentrated hydrochloric acid The solid material is collected by filtration,
washed with water and dried yielding white crystals, 1.3 g (85 %), mp 186-
188 ºC.
4C 5-Bromo-6-chioro-2methoxybenzoyl chloride
A mixture of 4B (1.2 g, 4.6 mmol), dichloromethane (15 ml) and oxalyl
chloride (1 ml) is stirred at room temperature for 2 hours. The mixture is
concentrated and the resulting benzoylchloride is used without further
purification.
4D 5-bromo-6-chloro-6'-methyl-2)2'3',4*-tetramethoxy-benzophenone
A mixture of 3,4,5-trimethoxytoluene (0.83 g; 4.6 mmol), 4C (4.6 mmol),
aluminium chloride (0.62 g, 4.6 mmol) and dichloromethane (20 ml) is
stirred at room temperature for 3 hours. A mixture of water and ethyl
acetate (1:1 v/v; 50 ml) is then added The organic phase is concentrated
and the residue is crystallized from diisopropytether and recrystallized
from methanol. The solid material is collected by vacuum filtration, washed
with water and dried yielding yellow crystals, 0 7 g, (35.4 %) mp 87-88 °C.
Example 5
Preparation of 5-(0'-methyl-2,3',4'-tramethoxybenzoyl)-2-

methoxynaphthalene
5A Methyl (2-methoxynaphth-1-yl)-carboxylate
A mixture of 2-hydroxynaphth-1-ylcarboxylic acid (18.82 g, 100 mmol),
sodium hydroxide (8.8 g, 220 mmol), dimethylsulfate (31.5 g, 250 mmol)
and water (200 ml) is heated to 70 °C with stirring for 20 hours.
Subsequently, the reaction mixture is cooled to room temperature and

extracted with ethyl acetate twice. The combined organic phases are
concentrated and the residue is used without further purification
5B Methyl (2-methoxynaphth-1-yl)-carboxylic acid
A mixture of crude 5A (10.5 g, 48 mmol), water (100 ml), methanol (150
ml) and sodium hydroxide (12 g, 300 mmol) is heated under reflux with
stirring. The reaction mixture is extracted with diethylether twice. The
aqueous reaction mixture is filtered and acidified with concentrated
hydrochloric acid. The solid material is collected by filtration, washed with
water and dried yielding yellow crystals, 9.45 g (97.4 %), mp 175-176 ºC.
5C 1 -(6'-methyl-2',3' ,4'-trimethoxybenzoyl)-2 -methoxynaphthalene
A mixture of 5B (2.02 g, 10 mmol), 3,4,5-trimethoxytoluene (1.82 g, 10
mmol), P2O5 (10.0 g) and dichloromethane is stirred at room temperature
for 16 hours. Subsequently, the dichloromethane is distilled off and the
residue is diluted with ethyl acetate. The organic phase is washed with
water and concentrated. The residue is purified by column
chromatography (petrol ethers.ethyl acetate, 8:2 v/v) and recrystallized
from petrol ether: diisopropylether (1:1 v/v). The solid material is collected
by vacuum filtration, washed with cold petrol ether: diisopropylether (1:1
v/v) and dried, yielding white crystals, 0.9 g, (24.6 %) mp 72 °C.
Example 6
Preparation of 5-bromo-6,6'-dimethyl-2,2'3',4'-tetrannethoxy-
benzophenone
6A Ethyl 5-bromo-a-methyl-2-methoxybenzoate
A mixture of ethyl 6-methyl-2-methoxybenzoate (8.4 g, 43.2 mmol),
bromine (6.9 g, 43.2 mmol) and tetrachloromethane (170 ml) is stirred at
room temperature for 60 hours. The reaction mixture is poured into water
and extracted with ethyl acetate. The organic phase is separated and
concentrated. The crude product is obtained as a yellow oil, 10.3 g (87 %)
and is used without further purification.

6B 5-Bromo-6-methyl-2-methoxybenzoic acid
A mixture of 6A (9.8 g, 34.1 mmol), water (40 ml), ethanol (80 ml) and
sodium hydroxide (2.7 g, 68.3 mmol) is heated under reflux with stirring for
42 hours. The reaction mixture is diluted with water (80 ml), acidified with
concentrated hydrochloric acid and extracted with dichloromethane. The
organic phase is separated and concentrated. The solid material is
collected by filtration, washed with water and dried yielding off-white
crystals, 5.4 g (61 %), mp 81-83 CC.
6C 5-bromo-6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone
A mixture of 6B (24 g, 10 mmol), 3,4,5-trimethoxytoluene (1.82 g; 10
mmol), P2O5 (10.0 g) and dichloromethane (150 ml) is stirred at room
temperature for 16 hours. Subsequently, the dichloromethane is distilled
off and the residue is diluted with ethyl acetate. The organic phase is
washed with water and concentrated. The residue is purified by column
chromatography (petrol ether: ethyl acetate, 8:2 v/v) and recrystallized
from diisopropyiether. The solid material is collected by vacuum filtration,
washed with cold petrol ethers diisopropylether (1:1 v/v) and dried,
yielding white crystals, 2.2 g (54 % ), mp 89-91 ºC.
Examples 7-62
Using essentially the same procedures described hereinabove for
Examples 1to 8 and employing standard derivanzation techniqes where
appropriate, the following compounds are prepared and shown in Tables I
and II:







Example 63
Preparation of 5-bromo-6,6'-dimethvl-2,2'3',4'-tetrarnethoxy-
benzophenone
63A 6-methy!-2-methoxybenzoic acid
A mixture of ethyl 6-methyl-2-methoxybenzoate (642.0 g, 3.3 mol), water
(2.5 I), ethanol (4.0 () and sodium hydroxide (270 g, 6.6 mol) is heated
under reflux with stirring for 20 hours. Subsequently, ethanol is distilled off
and the reaction mixture is diluted with water, acidified with concentrated
hydrochloric acid. The solid material is collected by vacuum filtration,
washed with water and dried yielding off-white crystals, 460.0 g (83.9 %).

63B 5-Bromo-6-methyl-2-methoxybenzoic acid
A mixture of bromine (102 mi, 2,0 mol) and acetic acid (225 ml) is added
to a mixture of 63A (304.0 g, 1.8 mol),), sodium acetate (164.0 g, 2.0 mol)
and acetic acid (3.0 I) at a temperature of 10 to 15 °C. The reaction
mixture is stirred at room temperature for 16 hours. The solid material is
collected by vacuum filtration, washed with water and dried yielding off-
white crystals 321.0 g (72.6. %), mp 81-83 °C.
63C 5-bromo-6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone
63B (240 g, 1.0 mo!) is reacted with 3,4,5-trimethoxytoluene (182 g; 1.0
mol) in the presence of P2O5 (1.0 kg) and dichioromethane as described in
Example 6 yielding white crystals, 220 g (54 % ), rnp 89-91 ºC.
The sequence of the saponification (with sodium hydroxide) and
bromination steps described above in Examples 63A and 63B,
respectively, are reversed in Examples 6B and 6A, above.
The bromination described in Examples 63B and 6A is with the free acid
and ester, respectively. The reaction conditions also differ, such as
Example 63B which uses a polar protic solvent (acetic acid) and a
buffering salt (sodium acetate). Example 6A uses a non-polar aprotic
solvent (tetrachioromethane).
Example 64
Preparation of 6,6'-dimethyl-2,2'3',4'-tatramethoxy-5-trifluoromethyl-
benzophenone
A mixture of 63C (6.15 g, 0.015 mol), sodium tnfiuoroacetate (9 52 g, 0.07
mol), copper-(l) iodide (13.37 g, 0.07 mol) and 1-N-methy)-2-pyrrolidinone
(100 ml) is heated to 160°C for 118 hours. The reaction mixture is cooled
to room temperature and diluted with ether and water The organic phase
is separated and concentrated and the residue is purified by column

chromatography (petrol ether: ethyl acetate, 95:5 v/v) yielding the pure
product as white crystals, 1.3 g, (22 %) having a melting point of 95-96 °C.
Example 65
Preparation of 6'-methyl-2,2',3',4'-tetramethoxy-6-trifluoromethyl-
benzophenone
65A 2-methoxy-6-trif!uoromethylbenzoic acid
A mixture of potassium methylate in methanol (15 ml, 15 %) and 2-fluoro-
6-trifiuoromethylbenzoic acid (2.08 g, 0.01 mol) is heated to reflux with
stirring for 40 hours. Upon cooling to room temperature water is added.
The reaction mixture is filtered and the filtrate is acidified with
concentrated hydrochloric acid. The solid material is collected by filtration,
washed with water and dried yielding white crystals, 1.4 g (64 %), mp 130-
131 ºC.
65B 6'-methyl-2,2',3',4'-tetramethoxy-6-trifluoromethyl-benzophenone
65A (1.38 g, 0.00625 mol) is reacted with 3.4,5-trimethoxytoluene (1.14 g;
0.00625 mol) in the presence of P2O5 (5.0 g) and dichloromethane (100
ml) as described in Example 6 yielding white crystals, 1.68 g (69.8 % ), mp
69-70 °C.
Example 66
Preparation of 5-chloro-6,6'-dimethyl-3'-ethoxy-2,2',4'-
trimethoxybenzophenone
66A 5-chloro-6,6'-dimethyl-3'-propionyloxy-2,2',4'-
trimethoxybenzophenone
5-Chloro-2-methoxy-6-methylbenzoic acid (6.00 g, 0.03 mol) is reacted
with 3,5-dimethoxy-4-propionyloxytoluene (6.73 g; 0.03 mol) in the
presence of P2O5 (18.0 g) and dichloromethane (200 ml) as described in
Example 6 yielding white crystals, 6,65 g (56.4 % ), mp 150-151 °C.

66B 5-chioro-6,6'-dimethyl-3'-hydroxy-2,2',4'-trimethoxybenzophenone
A mixture of 66A (6.65 g), potassium carbonate (7.0 g), water (50 ml) and
methanol (100 ml) is heated to reflux for 3 hours. Upon cooling to room
temperature water is added The reaction mixture is filtered and the filtrate
is acidified with concentrated hydrochloric acid. The solid material is
collected and used without further purification
66C 5-chloro-6,6'-dimethyl-3'-ethoxy-2,2',4'-trimethoxybenzophenone
A mixture of 66B (1.15 g), potassium carbonate (1.0 g), diethylsulfate
(0.54 g) and acetonitrile (20 ml) is heated to reflux for 3 hours. Upon
cooling to room temperature water is added. The solid material is collected
and the residue is re-crystallized from methanol yielding white crystals,
1.07 g (85.6 % ), mp 131-132 CC.
Example 67
Preparation of 6,6'-dimethyl-5-fluoro-2,2',3',4'-tetramethoxybenzophenone
67A-2-tert-butyl-4-fluoromethylphenol
A mixture of 4-f!uoro-3-methy!phenol (12.60 g, 0.1 mol), tert-butylchloride
(25 ml) and FeCl3 is heated to reflux for 16 hours. The excess of tert-
butylchloride is distilled off and the residue is purified by column
chromatography (petrol ether: ethyl acetate, 95:5 v/v) yielding the pure
product as a yellow oil, 15.3 g (84 %).
67B 6-bromo-2-tert-butyl-4-fIuoro-5-methylphenol
A mixture of 67A (0.91 g), tetrachioromethane (20 ml). N-
bromosuccinimide (0.89 g) and AICI3 is stirred at ambient temperature for
3 days. The reaction mixture is filtered and concentrated. The obtained
yellow oil (1.25 g) is used without further purification.
67C 2-bromo-4-fluoro-3-methyipheno)
A mixture of 67B (18.5 g), benzene (120 ml) and AICI3 (6.5 g) is heated to
reflux for 5 hours. The reaction mixture is cooled to room temperature and

diluted with ethyl acetate and water. The organic phase is separated and
concentrated. The residue is purified by column chromatography (petrol
ether: ethyl acetate, 95:5 v/v) yielding the pure product as white crystals
9.0 g, (62 %).
67D 2-bromo-6-fluoro-3-methoxytoluene
A mixture of 67C (9.0 g), potassium carbonate (6 g), dimethylsulfate (6 g)
and acetonitrile (150 ml) is heated to reflux for 1 hour. The reaction
mixture is cooled to room temperature, diluted with water and extracted
with diethyl ether twice. The organic phase is separated and concentrated
and the residue (9.0 g) is used without further purification.
67E 3-fluoro-6-methoxy-2-methylbenzoic acid
A solution of n-butyliithium in hexane (18.1 ml, 2.5 mol/l) is slowly added
to a mixture of 67D (9.0 g) and tetrahydrofuran (90 ml) at -78°C. The
resulting reaction mixture is saturated with carbon dioxide at -78ºC and
allowed to warm up to ambient temperature. The reaction mixture is
poured into water, acidified and extracted with diethylether twice. The
organic phase is extracted with an aqueous solution of sodium hydroxide
(5 %). The aqueous extract is acidified and extracted with diethylether
twice. The organic phase is dried and concentrated. The residue (3.9 g)
is used without further purification.
67F 6,6'-dimethyl-5-fluoro-2,2',3',4'-tetramethoxybenzophenone
67E (3.9 g, 0.021 mol) is reacted with 3,4,5-trimethoxytotuene (3.85 g;
0,021 mnl) in the presence of P2O5 (12 0 g) and dichloromethane (150
ml) as described in Example 6 yielding white crystals, 0.34 g, mp 58°C.

Biological Investigations
A Foliar Systemicity
Wheat Powdery Mildew (WPM):
HOST: Wheat (Triticum aestivum L.) variety Kanzler
PATHOGEN: Blumeria (Ervsiphe) graminis DC, f.sp. tritioi E. Marchal
TEST PROCEDURE:
1. Wheat seed (8/pot) is planted in 8 cm diameter plastic pots in the
greenhouse.
2. When the primary leaf is fully expanded, the plants are cut back to
four in each pot of which two are marked with a permanent marker 5
cm below the leaf tip on the upper leaf surface. Thus there are two
band-treated and two untreated plants in each pot.
3. A pipette is used to apply 5 μl of the formulated compound in a band
on the lower leaf surface opposite the mark The application band
should cover the whole leaf width. After application, the plants are not
moved until the bands are dry (half an hour or so later).
4. After treated plants have dried, they are moved to the greenhouse
and kept there for 2 days to allow for movement of the compounds.
The plants are maintained with bottom watering.
5. Two days after application, the plants are inoculated by dusting them
with powdery mildew conidia in the greenhouse. Evaluations are
typically made 7 - 8 days after inoculation.
Evaluation
Three types of compound movement are assessed by evaluating disease
in three areas of each band-treated leaf.
Translaminar movement: The percent disease area is assessed for the
translaminar band area (marked area of the upper leaf surface directly
opposite where band was applied on the lower leaf surface; width of band
approximately 5 mm). Translaminar disease control is then calculated
using the following formula:


Distal movement and proximal movement: The distal and proximal
disease-free zones on the upper leaf surface are measured in mm. The
distal direction is from the band toward the leaf apex sand the proximal
direction is from the band toward the leaf base. The percent of the
disease-free zone relative to the entire distance between the band and
leaf apex or base is calculated. If disease is noticeably lighter in the distal
or proximal area this is also noted.
FORMULATION AND CONTROLS:
1. The compounds are formulated in a solvent/surfactant system
consisting of 5% acetone and 0.05% Tween 20 in deionized water.
Formulated compounds are prepared using deionized water.
Compounds are typically tested at 400 ppm.
2. Two kinds of controls are included:
Plants band-treated with the solvent/surfactant solution and inoculate 1
(Solvent Blank)
Untreated plants which are inoculated (Inoculated Control).
The results of this evaluation are shown inTable Ill


The following compounds, which are known from EP 0 727 141 have been
used as standards:
Standard1 2,6-dichloro-6'-methyl-2,3',4'-trimethoxybenzophenone
Standard2 2',3',4'-trimethoxy-2,6,6'-trimethylbenzophenone
B-1 Comparison of the fungicidal activity of the 2-methoxy-
benzophenones to a 2,6-dichloro- and 2,6-dimethyl-benzophenone
Test diseases:
(a) Wheat Powdery Mildew (WPM):
HOST. Wheat (Triticum aestivum L) variety Kanzler
PATHOGEN, Blumeria (Erysiphe) graminis DC. f.sp. tritici E. Marchal
(b) Barley Powdery Mildew (BPM):
HOST: Barley (Hordeum vulqare L.) variety Golden Promise
PATHOGEN: Blumeria (Erysiphe) graminis DC. f.sp. hordei E. Marchal
TEST PROCEDURE:
This test is a zero day protectant test for control of wheat and barley
powdery mildews.
1. Wheat or barley seed (approximately 8-10/pot) is planted in 6 cm
diameter plastic pots and maintained in the greenhouse.
2. When the primary leaf is fully expanded, formulated test
compounds are sprayed with a single nozzle overhead track
sprayer at a rate of 200 I/ha.
Plants are then allowed to air-dry.
3. Inoculation follows about three hours after compound application.
Plants are set up on greenhouse benches with bottom watering
mats and inoculated by dusting them with conidia from powdery
mildew infected plants (stock cultures at an age of 10-14 days).

4. Disease on the primary leaf as percent leaf area with disease
symptoms/signs is evaluated about 7 days after inoculation. The
tips and bases of the leaves are excluded from the evaluation.
Percent disease control is then calculated by the following formula:

FORMULATION, REFERENCE COMPOUNDS AND CONTROLS:
1. Technical compounds are formulated in a solvent/surfactant system
consisting of 5% acetone and 0.05% Tween 20 in deionized water.
Compounds are dissolved in acetone prior to addition of the water;
the Tween 20 can be added through either the acetone or the
water. Dilutions are made using the solvent/surfactant system.
Test compounds are typically tested over a range of concentrations
covering several orders of magnitude and then ED values are
calculated for comparison of compounds.
Formulated compounds are prepared using deionized water.
2. Two kinds of controls are included:
Plants treated with the solvent/surfactant solution and inoculated
(Solvent Blank).
Untreated plants which are inoculated (Inoculated Control).
The results of this evaluation are shown in Table IV.
Table IV Fungicidal activity of 2-methoxybenzophenones
(ED90 values)
Comparison of the fungicidal activity of the 2-methoxy-benzophenones to
a 2,6-dichioro-and 2,6-dimethyi benzophenone
Results are from 0 day protectant tests in which all analogs were tested
side-by-side.


Compounds applied as technical material formulated in 0.5% acetone 0.05%
Tween 20 water
B-2 Comparison of the curative and residual fungicidal activity
of the 2-methoxy-benzophenones to a 2,6-dichloro- and 2.6-dimethyl-
benzophenone
Test diseases:
(a) Wheat Powdery Mildew (WPM);
HOST. Wheat (Triticum aestivum L ) variety Kanzler
PATHOGEN: Blumeria (Erysiphe) graminis DC. f.sp. tritici E. Marchal
(b) Cucumber Powdery Mildew (QPM):
HOST: Cucumber (Cucumis sativus L ) variety Bush pickle
PATHOGEN: Erysiphe cichoracearum DC
TEST PROCEDURE:
This test procedure is for curative and residual control of powdery mildew
diseases.
1. Wheat seed (approximately 8-10/pot) or cucumber seed (1 seed /
pot) is planted in 6 cm diameter plastic pots and maintained in the
greenhouse.

2. When the primary leaf (wheat) or the cotyledons (cucumber) is/are
fully expanded, formulated test compounds are sprayed with a
single nozzle overhead track sprayer at a rate of 200 I/ha.
Plants are then allowed to air-dry.
3. Inoculation precedes treatment by 2 or 3 days in the case of
curative evaluations and follows treatment by 3 or 4 days in case of
residual evaluatio ns. For inoculation, plants are set up on
greenhouse benches with bottom watering mats and inoculated by
dusting them with conidia from powdery mildew infected plants
(stock cultures at an age of 10-14 days). Between inoculation and
treatment for curative evaluations and between treatment and
inoculation for residual evaluations, plants are maintained in the
greenhouse with bottom watering.
4. Disease on the primary leaf (wheat) or on the cotyledons
(cucumber) as percent leaf area with disease symptoms/signs is
evaluated about 7 days after inoculation. In the case of wheat, the
tips and bases of the leaves are excluded from the evaluation.
Percent disease control is then calculated by the following formula:

FORMULATION, REFERENCE COMPOUNDS AND CONTROLS;
1. Technical compounds are formulated in a solvent/surfactant system
consisting of 5% acetone and 0.05% Tween 20 in deionized water.
Compounds are dissolved in acetone prior to addition of the water;
the Tween 20 can be added through either the acotone or the
water. Dilutions are made using the solvent/surfaciant system
Formulated compounds are prepared using deionized water.
2 Two kinds of controls are included:
Plants treated with the solvent/surfactant solution and inoculated
(Solvent Blank),
Untreated plants which are inoculated (Inoculated Control)

The results of this evaluation are shown in Tables V and VI:




WE CLAIMS
1. A compound of formula I:

wherein
R1 represents a halogen atom or an alky! group or haloalkyl group;
R2 represents a hydrogen or haJogen atom, or an alkyl, haloalkyl, alkoxy or
nitro group; or R1 and R2 together represent a group of formula
-CH=CH-CH==CH-;
R3 and R4 each independently represent an optionally substituted alkyI;
and
n is an integer from 0 to 3.
2. A compound as claimed in claim 1, wherein
R1 represents a chloro atom or a methyl or trifluoromethyl group;
R2 represents a hydrogen, chloro or bromo atom or a trifluoromethyl
group;
R3 represents a C1-5 aikyi group,
R4 represents a C1-5 alkyl group or benzyl group, being optionally
substituted by at least one halogen atom, or C1-4 alkyl or alkoxy group; and
n is 0.

3. A compound as claimed in claim 1 being selected from the
group consisting of
6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
6,6'-dimethyl-3'-pentoxy-2.2',4'-trimethoxy-benzophenone,
5-bromo-6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
5-chloro-6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
5-iodo-6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
5-chloro-6'-methyl-2,2',3',4'-tetramethoxy-benzophenone,
5-bromo-6-chloro-6'-methyl-2,2',3',4'-tetramethoxy-benzophenone,
6-chloro-5,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone,
2'-butoxy-6-chloro-6'-methyl-2,3',4'-trimethoxy-benzophenone,
2'-butoxy-6-chfcro-5,6'-dimethyl-2,2',3'-tetramethoxy-benzophenone,
6-chloro-2'-(2-fluorobenzyloxy)-6'-methyl-2,3',4'-trimethoxy-beinizophenone,
6-chloro-2'-(4-fluorobenzyloxy)-6'-methyl-2.3',4'-trimethoxy-benzophenone,
5-bramo-6,6'-dimethyl-3'-pentyloxy-2,2',4'-trimethoxy-benzophenone
6-chloro-6'-methyl-2'-pentyloxy-2,3',4'-trimethoxy-benzophenone,
5-chlono-2'-(3-methyibutyloxy)-6'-methyl2,3',4'-trimethoxy-benzophenone,
2'-benzyloxy-6-chloro-6'-methyl2,3',4'-trimethoxy-benzophenone,
6-chloro-2'-(3-methylbenzyloxy)-8'-methyl-2,3',4'-trimethoxy-benzophenone,
6-chloro-2'-(4-methylbenzyloxy)-6'-melhyl-2,3',4'-trimethoxy-benzophenone,
6-chloro-2-dlfluoromethoxy-6'-methyl-2,3',4'-trimethoxy-benzophenone,
1-(6'-methyl-2,3',4'-trimethoxybenzoyl)-2-methoxynaphthalene,
1-(6'-methyl-,2',3',4'-trimethoxybenzoyl)-2-difIuoromethoxynaphthalene,
5-chloro-6,6'-dimethyl-3'-ethoxy-2,2',4'-trimethoxy-benzophenone,
5-chloro-6,6'-dimethyl-3'-n-propyloxy-2,2,4'-trimethoxy-benzophenone,
6,6'-dimethyl2,2,3',4'-tetramethoxy-5-trifluoromethyl-benzophenone,
5'-fliethyl-2.2',3',4'-tetramethoxy-6-trifluoromethyl-benzophenone,
5-bromo-6':-methyl-2,2',3',4-tetramethoxy-6-trifluoromethyl-benzophenone.
4. A process for the preparation of the compound as claimed in claim 1
wherein n is 0, which comprises reacting a compound of formula II;


wherein R1, R2, R3 and R4 are as defined in, claim 1, and X
represents a fluoro or chloro atom, with an alkali methanolate.
5. A process for the preparation of the compound as claimed in claim 1, which comprises
(a) reacting a compound of formula III:

wherein R1, R2 and n are as defined in, claim 1, and Y represents a chloro
atom, with a compound of formula IV:

wherein R3 is as defined in, claim 1, in the presence of a Lewis acid selected
from the group consisting of FeCl3, A!C!3, SnCl4. ZnCl2, TICl4, SbCI5. BF3, l2, iron,
copper, F3CSO3H, and acidic Ion exchange resins; and
(b) optionally treating the product obtained in step a) with a compound of formula
V:

wherein R4 represents an optionally substituted alkyl or aryl group wfth the pro-
viso that the alkyl group Is not methyl, and Met denotes an alkali metal atom.

A process for the preparation of the compound as claimed in claim 1, which comprises
(a) reacting a compound of formula III:

wherein R1, R2 and n are as defined in, claim 1, and Y represents a hydroxy
group, with a compound of formula IV:

wherein R3 is as defined in, claim 1, in tbs presence of a dehydrating agent se-
lected from the group consisting of phosphorus pentoxide and POCI3; and
(b) optionally treating the product obtained in step a) with a compound of formula
V:

wherein R4 represents an optionally substituted alkyl or aryl group with the pro-
vfso that the alkyl group is not methyl, and Met denotes an alkali metal atom.

7. A process for the preparation of a compound of formula III

wherein R1 represents a halogen atom or an afkyl group or haloalkyl group, R2
represents bromine, n is an integer from 0 to 3, and V represents an alkoxy group
or a hydroxy group,
which comprises reacting a compound of formula VI

where R1 and n are as described above and wherein R" represents a hydrogen
atom or an alkyl group, with bromine in the presence of a polar protic solvent.
8. A process for the preparation of a compound of formula III

wherein R1 represents a halogen atom or an alkyl group or ha!oa!kyl group, R2
represents bromine, n is an integer from 0 to 3, and Y represents an chlorine or a
hydroxy group,
which comprises

a) reacting a compound of formula VI

where R' and n are as described above and wherein R" represents a hydrogen
atom or an alkyl group, with bromine in the presence of a polar protic solvent,
b) if R" is alky!, hydrolyzing the resulting brominated alkyl benzoate, and
c) optionally treating the resulting brominated alkyl benzoic acid with thionyl chlo-
ride.
9. The process as claimed in claim 7 or 8, wherein R1 is an alkyl group, n is 0, and
R" represents a hydrogen atom.
10. The process as claimed in claim 7 or 8. wherein the polar protic solvent is se-
lacted from an aliphatic acid and an aliphatic alcohol.
11. The process as claimed in claim 7 or 8, wherein the polar protic solvent is acetic
acid.
12. A compound having the formula (IIIA)

wherein R1 represents an alkyl group.

13. A composition which comprises a fungicidally effective amount of at least one
compound as claimed in claim 1, and a carrier.
14. A composition as claimed in claim 13 for combating fungus or a fungal plant disease
at a locus.
15. A composition as claimed in claim 14 wherein the fungal plant disease is
ascomycetes,
16. A composition as claimed in claim 14 wherein the fungus is a member of she
subgroup Erysiphalcs.
17. A composition as claimed in claim 16 wherein the fungus is selected from Blumerio
(Etysiphe) graminis, Erysiphe cichoracearum, Podosphaera leucotrricha or Uncinula
necator.

Substituted benzophenone compounds are disclosed, having the formula:
The compounds are useful as fungicides having high systemicities.

Documents:

1472-CAL-1998-CORRESPONDENCE.pdf

1472-CAL-1998-FORM 27.pdf

1472-CAL-1998-FORM-27.pdf

1472-cal-1998-granted-abstract.pdf

1472-cal-1998-granted-assignment.pdf

1472-cal-1998-granted-claims.pdf

1472-cal-1998-granted-correspondence.pdf

1472-cal-1998-granted-description (complete).pdf

1472-cal-1998-granted-examination report.pdf

1472-cal-1998-granted-form 1.pdf

1472-cal-1998-granted-form 18.pdf

1472-cal-1998-granted-form 2.pdf

1472-cal-1998-granted-form 3.pdf

1472-cal-1998-granted-form 5.pdf

1472-cal-1998-granted-gpa.pdf

1472-cal-1998-granted-reply to examination report.pdf

1472-cal-1998-granted-specification.pdf

1472-cal-1998-granted-translated copy of priority document.pdf


Patent Number 226410
Indian Patent Application Number 1472/CAL/1998
PG Journal Number 51/2008
Publication Date 19-Dec-2008
Grant Date 17-Dec-2008
Date of Filing 19-Aug-1998
Name of Patentee AMERICAN CYANAMID COMPANY
Applicant Address FIVE GIRALDA FARMS, MADISON, NEW JERSEY
Inventors:
# Inventor's Name Inventor's Address
1 JUERGEN CURTZE RHEINGAUBLICK 6, D-65366, GEISENHEIM
2 KARL-OTTO STUMM AM SONNERBERG 8, D-55459, ASPISHEIM
3 GUIDO ALBERT VOLXHEIMER STRASSE 4, D-55546, HACKENHEIM
4 GUNTHER REICHERT HOCHSTRASSE 7, D-55270, HACKENHEIM
5 WERNER SIMON IN DER LIEHWIESE 29, D-55595, HUEFFELSHEIM
6 HENRY VAN TUYL COTTER EISENACHERSTRASSE 49, D-55218, INGELHEIM
7 ANNEROSE EDITH ELISE REHNIG RATHENAUSTRASSE 11, D-55218, INGELHEIM
8 GERD MORSCHHAEUSER INGELHEIMER STRASSE 77, D-55435, GAU-AIGESHEIM
9 ANDREAS WALDECK UFERSTRASSE 17, D-55262, HEIDESHEIM
PCT International Classification Number N/A
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 08/914,966 1997-08-20 U.S.A.
2 08/953,048 1997-10-17 U.S.A.
3 09/103887 1998-06-24 U.S.A.