Title of Invention

A PROCESS FOR PREPARING A SUBSTITUTED TRIAZOLINONE

Abstract A process for preparing a substituted triazolinone comprising the steps of: a) reacting a thionocarbamate of the following general formula (I) wherein R1 represents an unsubstituted or substituted alkyl, arylalkyl or aryl, and R2 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cyclo-alkyl, cycloalkylalkyl, aryl or arylalkyl, wherein R2 is as defined above; and 20 with hydrazine, hydrazine hydrate, or an acid adduct of hydrazine, to produce a triazolinone intermediate product of the following general formula (II) b) reacting the intermediate product of formula (II) in step a) under pH controlled of from pH 7.0 to pH 9.0 with an alkylating agent of the following general formula (III) R3 - X (III) wherein X represents a halogen, -O-SO2-O-R3, or -O-CO-O-R3, and R3 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, in the presence of a solvent and a base, to produce a substituted triazolinone of the following general formula (IV) wherein R2 and R3 are as defined above.
Full Text F0RM-3A
THE PATENTS ACT, 1970
COMPLETE SPECIFICATION
SECTION 10

TITLE

A PROCESS FOR PREPARING A SUBSTITUTED TRIAZOLINONES



APPLICANT

BAYER CORPORATION, BAYER ROAD, PITTSBURGH, PENNSYLVANIA -15205, USA

The following Specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performed


The present invention relates to a process for preparing substituted triazolinones, which are intermediates in the preparation of herbicidally active compounds (e.g.
known from US 5,534,486). In particular, this invention relates to the alkylation of a non-alkylated tnazolinone intermediate product, wherein the improvement comprises conducting the alkylation reaction under pH controlled conditions. In this context the term "alkylation" represents a generic term and thus, includes the use of alkylat¬ing agents having an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group or an arylalkyl group.
In a preferred embodiment, the invention relates to the preparation of a 5-alkoxy(or aryloxy)-2,4-dihydro-3H-l,2,4-triazol-3-one, and the alkylation of this non-alkylated triazolinone intermediate product to produce a 5-alkoxy(or aryloxy)-4-alkyl-2,4-di-hydro-3H-l,2,4-triazol-3-one.
Triazolinones are well known in the art, as are processes for their preparation and use as herbicides. U.S, Patent 5,708,183 describes a process for the preparation of substituted triazolinones by reacting triazolinethiones with methyl iodide, in the presence of an acid binding agent, and then heating the alkylthiodiazole derivative with hydrogen peroxide in the presence of acetic acid. U.S. Patent 5,912,354[dis-closes a process for the preparation of substituted aminotriazolinones, which in-cludes reacting an oxadiazalinone with hydrazine hydrate in the absence ofia sol- vent. U.S. Patent 5,9l7,050ulescribes a process for the preparation of alkoxytri-azolinones by reacting thioimidodicarboxylic diesters with hydrazine, hydrazine hydrate or an acid adduct of hydrazine, in the presence of a diluent and a basic re¬action auxiliary.
Further, U.S. Patents 5,606,070; 5,599,945; and 5,594,148; each describes a proc¬ess for the preparation of alkoxytriazolinones which includes reacting iminothio-
-2-

carbonic diesters with carbazinic esters, and then subjecting the resultant semicarbazide derivatives to a cyclizing condensation reaction.
However, these prior art processes produce triazolinones in unsatisfactory yield and purity. Thus, there is a need in the art for a process to manufacture substituted triazolinones in high yield and purity.
Accordingly, there is provided a process for preparing a substituted triazolinone comprising the steps of:
a) reacting a thionocarbamate of the following general formula (I)

wherein
R1 represents an unsubstituted or substituted alkyl, arylalkyl or aryl, and
R2 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cyclo-alkyl, cycloalkylalkyl, aryl or arylalkyl,
with hydrazine, hydrazine hydrate, or an acid adduct of hydrazine, to produce a triazolinone intermediate product of the following general formula (II)
- 3 -


wherein R2 is as defined above; and
b) reacting the intermediate product of formula (II) in step a) under pH controlled of from pH 7.0 to pH 9.0 with an alkylating agent of the following general formula (III)
R3-X (III)
wherein
X represents a halogen, -O-SO2-O-R3, or -O-CO-O-R3, and
wherein R2 and R3 are as defined above.
- 4 -
R3 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, in the presence of a solvent and a base, to produce a substituted triazolinone of the following general formula (IV)


The present invention is related to a process for the preparation of a substituted tri-azolinone by the alkylation of a non-alkylated triazolinone intermediate product. In this context, the term "alkylation" is used as a generic term and thus, expressly includes the definition of R provided below. The process includes the reaction of a thionocarbamate of the following general formula (I)

wherein
R represents an unsubstituted or substituted alkyl, arylalkyl or aryl, and
R represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cyclo-alkyl, cycloalkylalkyl, aryl or arylalkyl,
with hydrazine, hydrazine hydrate or an acid adduct of hydrazine, to produce a tri¬azolinone intermediate product of the following general formula (II)

wherein
5

Mo-5445-Foreign Countries
R2 is as defined above.
The intermediate product of the general formula (II) is then reacted under pH con-
5 trolled reaction conditions with an alkylating agent of the following general for-
mula (III)
R3 - X (III)
wherein
10 X represents a halogen, -O-SO2-O-R3, or -O-CO-O-R3, and
R3 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cyclo-alkyl, cycloalkylalkyl, aryl or arylalkyl,
15 in the presence of a solvent and a base, to produce a substituted triazolinone of the
following general formula (IV)

wherein 20
R2 and R3 are as defined above.
In a preferred embodiment of the invention,
25 R represents an alkyl group having 1 to 4 carbon atoms, a benzyl group or a
phenyl group, and
6

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R2 represents an alkyl group, an alkenyl group or an alkynyl group having in
each case up to 6 carbon atoms, and each of which is-unsubstituted or sub¬
stituted by cyano, halogen or C1-C4-alkoxy,
or
5 represents a cycloalkyl group having 3 to 6 carbon atoms or a cycloalkyl-
alkyl group having 3 to 6 carbon atoms in the cycloalkyl moiety and 1 to 4 carbon atoms in the alkyl moiety, each of which is unsubstituted or substi¬tuted by halogen or C1-C4-alkyl, or
10 represents an aryl group having 6 or 10 carbon atoms or an arylalkyl group
having 6 or 10 carbon atoms in the aryl moiety and 1 to 4 carbon atoms in the alkyl moiety, each of which is unsubstituted or substituted by carboxyl, nitro, cyano, halogen, C1-C4-alkyl, C1-C4-halogenoalkyl, C1-C4-alkoxy, C1 C4-halogenoalkoxy or C1-C4-alkoxy-carbonyl, and
15
R3 represents an alkyl, alkenyl or alkynyl, each of which has up to 6 carbon at¬oms and each of which is unsubstituted or substituted by cyano, halogen or C1-C4-alkoxy,
20 or
represents a cycloalkyl having 3 to 6 carbon atoms or a cycloalkylalkyl
having 3 to 6 carbon atoms in the cycloalkyl moiety and 1 to 4 carbon at¬
oms in the alkyl moiety, each of which is unsubstituted or substituted by
25 halogen or C1-C4 -alkyl,
or
represents an aryl having 6 to 10 carbon atoms or an arylalkyl having 6 or
30 10 carbon atoms in the aryl moiety and 1 to 4 carbon atoms in the alkyl
moiety, each of which is unsubstituted or substituted by carboxyl, cyano,
7

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5

nitro, halogen, C1-C4-alkyl, Cj-C4-halogenoalkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy or C1-C4-alkoxy-carbonyl.
More preferably,
R2 represents methyl, ethyl, n- or i-propyl, n-, i-, s-, or t-butyl, each of which is unsubstituted or substituted by cyano, fluorine, chlorine or bromine, meth-oxy or ethoxy,

10 or
represents propenyl, butenyl, propinyl or butinyl, each of which is unsub¬stituted or substituted by cyano, fluorine, chlorine or bromine,
15 or
represents cyclopropyl or cyclopropylmethyl, each of which is unsubsti¬tuted or substituted by fluorine, chlorine, bromine, methyl or ethyl,
or
20

25

represents phenyl or benzyl, each of which is unsubstituted or substituted by cyano, fluorine, chlorine, bromine, methyl, ethyl, trifiuoromethyl, meth-oxy, ethoxy, difluoromethoxy, trifiuoromethoxy, methoxycarbonyl or eth-oxycarbonyl, and
R represents methyl, ethyl, n- or i-propyl or n-, i-, s- or t-butyl, each of which
is unsubstituted or substituted by cyano, fluorine, chlorine or bromine,
methoxy or ethoxy,
8



30

or

Mo-5445-Foreign Countries

represents propenyl, butenyl, propinyl or butinyl, each of which is unsub-
stituted or substituted by cyano, fluorine, chlorine or bromine,
or
5 represents cyclopropyl, cyclobutyl or cyclopropylmethyl, each of which un-
substituted or substituted by fluorine, chlorine, bromine, methyl or ethyl,
or
10 represents phenyl or benzyl, each of which is unsubstituted or substituted
by cyano, fluorine, chlorine, bromine, methyl, ethyl, trifiuoromethyl, meth-oxy, ethoxy, difluoromethoxy, trifluoromethoxy, methoxycarbonyl or eth-oxycarbonyl.
15 Most preferably,
R1 and R2 each represents methyl, n- or i-propyl, and
R represents methyl. 20
The process of the invention may be conducted as a one pot process, without isola¬tion of the intermediate product of formula (II).
The process according to the invention is generally carried out at atmospheric pres-
25 sure. However, it is also possible to conduct the process under elevated or reduced
pressure.
The reaction of a thionocarbamate with hydrazine, hydrazine hydrate or an acid
adduct of hydrazine, is carried out at a temperature of from about -10°C to about
30 95°C, and preferably at a temperature of from about 0°C to about 60°C. Examples
9

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of suitable acid adducts of hydrazine include hydrazine acetate, hydrazine hydro¬chloride, and hydrazine sulfate.
In an embodiment of the invention, the reaction of the thionocarbamate with hy-
5 drazine, hydrazine hydrate or an acid adduct of hydrazine, is carried out in the
presence of a base, a solvent, or mixtures thereof.
Suitable bases include customary inorganic or organic bases or acid acceptors. These include alkali metal or alkaline earth metal acetates, amides, carbonates, bi-
10 carbonates, hydrides, hydroxides, or alkoxides such as, for example, sodium ace-
tate, potassium acetate or calcium acetate, lithium amide, sodium amide, potassium amide or calcium amide, sodium carbonate, potassium carbonate or calcium car¬bonate, sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, lithium hydride, sodium hydride, potassium hydride or calcium hydride, lithium hydrox-
15 ide, sodium hydroxide, potassium hydroxide or calcium hydroxide, sodium
methoxide or potassium methoxide, sodium ethoxide or potassium ethoxide, so¬dium n- or i-propoxide or potassium n- or i-propoxide, sodium n-, i-, s- or t-bu-toxide or potassium n-, i-, s- or t-butoxide, and also basic organic nitrogen com¬pounds such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl
20 diisopropylamine, N,N-dimethyl-cyclohexylamine, dicyclohexylamine, ethyl-di-
cyclohexylamine, N,N-dimethyl-aniline, N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, l,4-diazabicyclo[2.2.2]-octane (DABCO), 1,5-diazabi-
25 cyclo[4.3.0]-non-5-ene (DBN), or l,8-diazabicyclo[5.4.0]-undec-7-ene (DBU).
Suitable solvents include aliphatic, alicyclic or aromatic, unhalogenated or halo-
genated hydrocarbons such as, for example, benzene, toluene, xylene, chloroben-
zene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane,
30 chloroform, carbon tetrachloride; ethers such as diethyl ether, diisopropyl ether,
dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol di-

10

Mo-5445-Foreign Countries
ethyl ether; ketones such as acetone, butanone, or methyl isobutyl ketone; nitriles
such as acetonitrile, propionitrile or butyronitrile; amides such as N,N-dimethyl-
formamide, N,N-dimethylacetamide, N-methyl-formanilide, N-methyl-pyrrolidone
or hexamethylphosphoric triamide; esters such as methyl acetate or ethyl acetate;
5 sulfoxides such as dimethyl sulfoxide; alcohols such as methanol, ethanol, n- or i-
propanol, n-, i-, s- or t-butanol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol mono-ethyl ether; water; and mixtures thereof.
10 Preferred solvents include water, methanol, propanol, and a commercially available
mixture of xylenes containing ethylbenzene, ortho-xylene, para-xylene and meta-xylene.
In an embodiment of the invention, the reaction of a thionocarbamate with hydra-
15 zine hydrate is carried out in a mixture of water and methanol, or a mixture of wa-
ter, propanol, and xylenes.
In another embodiment, a nitrogen flow is maintained through the reaction mixture for the purpose of removing the H2S formed in the reaction.
20
Further, in another embodiment of the invention, benzyl chloride is added to the reaction mixture containing the thionocarbamate and hydrazine, hydrazine hydrate or acid adduct of hydrazine, to improve the purity of the alkylated triazolinone product of formula (IV). The benzyl chloride is added to the reaction mixture at a
25 temperature of from about -10°C to about 95°C, in an amount such that the benzyl
chloride is from about 0.1% to about 10% by mole of the mixture; and preferably from about 3% to about 5% by mole.
In an embodiment of the invention, a base is added to the reaction mixture follow-
30 ing the completion of the reaction between the thionocarbamate and hydrazine, hy-
drazine hydrate or acid adduct of hydrazine. The base is added in an amount such

11

Mo-5445-Foreign Countries

that the pH of the resulting mixture is from about 8.0 to about 12.0. Suitable bases
include alkali metal or alkaline earth metal salts of an acid having a pKa value of 5
or higher. Examples of such bases include alkali metal or alkaline earth metal hy¬
droxides, carbonates, bicarbonates, and alkoxides. In a preferred embodiment, the
5 base is potassium hydroxide.
In the process of the invention, following the completion of the reaction between
the thionocarbamate and hydrazine, hydrazine hydrate or acid adduct of hydrazine,
an alkylating agent is added to the reaction mixture. The alkylation of the interme-
10 diate compound of the formula (II) proceeds with high selectivity on the N atom in
the 4-position. In this context, the terms "alkylation" and "alkylating agent" (for¬mula III) are used as generic terms and thus, expressly include the above definition ofR3.
15 The alkylation reaction is carried out at a temperature of from about -10°C to about
95°C, and preferably at a temperature of from about 20°C to about 70°C. As a re¬sult of adding the alkylating agent, the pH of the reaction mixture decreases to a value of from about 7.0 to about 9.0. The reaction mixture is then maintained at a pH of from about 7.0 to about 9.0, preferably from about 7.5 to about 8.5, and most
20 preferably from about 7.9 to about 8.1, by the addition of a base to the mixture as
necessary.
The reaction time for the alkylation step corresponds to the time that is necessary
for the pH of the reaction mixture to remain stable between 7.0 and 9.0, and pref-
25 erably between 7.5 and 8.5, without the addition of a base.
The base for use in the alkylation step of the present invention includes the con¬
ventional inorganic or organic bases. These include, for example, the hydrides,
hydroxides, amides, alcoholates, acetates, carbonates, or hydrogen carbonates of
30 alkaline earth metals or alkali metals such as, for example, sodium hydride, sodium
amide, sodium methylate, sodium ethylate, potassium tert-butylate, sodium hy-

12

Mo-5445-Foreign Countries
■/
droxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, pptassium carbon-
ft-ate, potassium hydrogen carbonate, sodium hydrogen carbonate,, or ammonium
carbonate, and also basic organic nitrogen compounds such as trimethylamme, tri-
5 ethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethyl-benzylamine, pyri-
dine, l,4-diazabicyclo[2.2.2]-octane (DABCO), l,5-diazabicyclo[4.3.0]-non-5-ene (DBN), or l,8-diazabicyclo[5.4.0]-undec-7-ene (DBU).
Suitable alkylating agents for use in the process of the present invention include
10 compounds of the general formula (III) as defined above. A preferred alkylating
agent is dimethyl sulfate. The alkylation reaction is carried out in the presence of a solvent.
Suitable solvents for use in the alkylation reaction of the present invention include
15 aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons such as, for
example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum
ether, hexane, cyclohexane, dichloromethane, chloroform, tetrachloromethane;
ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene
glycol dimethyl ether or ethylene glycol diethyl ether; ketones such as acetone,
20 butanone, or methyl isobutyl ketone; nitriles such as acetonitrile, propionitrile or
benzonitrile; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-
methylformanilide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; es¬
ters such as methyl acetate or ethyl acetate, sulfoxides such as dimethyl sulfoxide,
alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, s-, or t-butanol, ethyl-
25 ene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol
monomethyl ether, diethylene glycol monoethyl ether; water and mixtures thereof. Preferred solvents include methyl isobutyl ketone, methanol, propanol, water and a commercially available mixture of xylenes containing ethylbenzene, ortho-xylene, para-xylene, and meta-xylene.

13


Mo-5445-Foreign Countries
In an embodiment of the invention, the alkylation reaction; is carried out in the
presence of a mixture of water, methanol and methyl isobutykketone, or a mixture
of water, propanol and xylenes.

5 In another embodiment of the invention, the substituted triazolinone product of the
general formula (IV) is isolated as a hydrate at the end of the alkylation reaction.
Further, in a preferred embodiment, 5-methoxy-4-methyl-2,4-dihydro-3H-l,2,4-tri-azol-3-one (MMT) is produced by methylating 5-methoxy-2,4-dihydro-3H-1,2,4-
10 triazol-3-one (HMT) in a mixture of MIBK, methanol, and water. The molar ratio
of HMT to MIBK is from about 1.0:2.0 to about 1.0:3.5, and preferably about 1.0:2.8. The molar ratio of HMT to methanol is from about 1.0:5.0 to about 1.0:15.0, and preferably about 1.0:9.5. The molar ratio of HMT to water is from about 1.0:3.0 to about 1.0:6.0, and preferably about 1.0:4.8.
15
Moreover, in a preferred embodiment, 5-propoxy-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (PMT) is produced by methylating 5-propoxy-2,4-dihydro-3H-1,2,4-triazol-3-one (HPT) in a mixture of xylenes, propanol, and water. The reaction mixture contains an aqueous phase and an organic phase. The aqueous phase
20 (lower phase) is discarded and the PMT is recovered from the organic phase (upper
phase) at a temperature of 60°C, in the presence of propanol and methanol. The molar ratio of HPT to xylenes is from about 1.0:2.0 to about 1.0:4.0, and preferably about 1.0:3.0. The molar ratio of HPT to propanol is from about 1.0:2.0 to about 1.0:6.0, and preferably about 1.0:4.0. The molar ratio of HPT to water is from
25 about 1.0:3.0 to about 1.0:9.0, and preferably about 1.0:6.1.
Furthermore it may be mentioned that the alkylation step under pH-controlled con¬ditions of the inventive process taken alone is new and based on inventive activity.
14

Mo-5445-Foreign Countries

The invention is further illustrated but is not intended to be limited by the follow¬
ing examples in which all parts and percentages are by weight unless otherwise
specified. x- '* ."


Mo-5445-Foreign Countries

EXAMPLES
Example 1 - The Preparation of HMT
5 To a chilled (i.e., about 0°C) solution containing 399.0 grams (2.68 moles) of N-
methoxycarbonyl-O-methylthionocarbamate (MTC) and 710 grams of methanol, was added 17.8 grams (0.143 mole) of 45% aqueous potassium hydroxide and 40.0 grams of water. At a temperature of about 0°C, 133.8 grams (2.65 moles) of 64% hydrazine hydrate were added to the reaction mixture over a period of about 2
10 hours at a uniform rate. A net subsurface nitrogen flow (to help remove the H2S
formed in the reaction) was maintained through the reaction mixture. The reaction mixture was stirred at a temperature of about 0°C for about 4 hours. The mixture was then heated to a temperature of about 40°C over a time period of about 2 hours. At a temperature of about 40°C, 17.1 grams (0.135 mole) of benzyl chloride
15 were added to the reaction mixture and the mixture was maintained at this tem-
perature for about 1 hour. The reaction mixture was then heated to a temperature of about 50°C over a period of about 1 hour and the mixture was maintained at this temperature for about 2 hours. The reaction mixture contained about 262 grams (2.28 moles, 85% yield based on MTC) of 5-methoxy-2,4-dihydro-3H-l,2,4-tri-
20 azol-3-one (HMT) in a mixture of methanol (MeOH) and water.
At this point, the HMT slurry was either further reacted to produce an 5-alkoxy-4-
methyl-2,4-dihydro-3H-l,2,4-triazol-3-one (e.g., Example 3), or the pure HMT was
isolated from the reaction mixture. To isolate the pure HMT, the reaction mixture
25 was cooled to a temperature of about 0°C, filtered under vacuum and the filter cake
was washed with 2 X 50 ml of cold (about 0°C) methanol. The filter cake was then dried in a vacuum oven at a temperature of about 50°C for about 16 hours to obtain 223.6 grams of HMT (96.5% purity and 70.0% yield based on MTC).

Mo-5445-Foreign Countries

Example 2 - The Preparation of HPT
To a solution containing 587.0 grams (2.86 moles) of N-propexycarbonyl-O-
propylthionocarbamate (PTC) and 240 grams of propanol, was added 280 grams of
5 xylenes (i.e., a commercially available mixture of ethylbenzene, orthb-xylene,
para-xylene and meta-xylene), 70.0 grams of water, and 4.2 grams (0.03 mole) of 45% aqueous potassium hydroxide. The reaction mixture was then cooled to a temperature of about 0°C. At a temperature of about 0°C, 146.0 grams (2.95 moles) of 64% hydrazine hydrate were added to the reaction mixture over a period
10 of about 2 hours at a uniform rate. A net subsurface nitrogen flow (to help remove
the H2S formed in the reaction) was maintained through the reaction mixture. Following addition of the hydrazine hydrate, the reaction mixture was heated to a temperature of about 20°C and stirred for about 3 hours. The mixture was then heated to a temperature of about 50°C over a time period of about 2 hours. The re-
15 action mixture was cooked at a temperature of about 50°C for about 1 hour. The
reaction mixture was then diluted with 525 grams of xylenes. This slurry con¬tained about 348 grams (2.43 moles, 85% yield based on PTC) of 5-propoxy-2,4-dihydro-3H-l,2,4-triazol-3-one (HPT) in a mixture of xylenes, propanol and water.
20 At this point, the HPT was further reacted to produce 5-propoxy-4-methyl-2,4-di-
hydro-3H-l,2,4-triazol-3-one (e.g., Example 4).
Example 3 - Preparation of MMT Hydrate from HMT Slurry
25 To a HMT slurry (e.g., as prepared in Example 1), which contained 262 grams
(2.28 moles) of HMT in a mixture of methanol and water, was added 45% aqueous potassium hydroxide (KOH) solution at a temperature of about 50°C, over a time period of about 30 minutes. The KOH solution was added in an amount such that the pH of the reaction mixture was increased to about 10.0. About 650 grams of
30 methyl isobutyl ketone (MIBK) were then added to the reaction mixture, and the
mixture was cooled to room temperature (i.e., about 25°C). About 446 grams (3.54
17

Mo-5445-Foreign Countries

moles) of dimethyl sulfate were then added to the mixture over a period of about 2
hours, while maintaining the temperature of the mixture from about 25 °C to about
30°C. As the dimethyl sulfate was added, the pH of the reaction'mixture de¬
creased. The pH of the mixture was maintained between about 7.9 and about 8.1
5 by the simultaneous addition of 45% aqueous KOH solution. Following addition
of the dimethyl sulfate, the temperature of the reaction mixture was increased to about 60°C over a time period of about 4 hours, while maintaining the pH between about 7.9 and about 8.1.
10 The reaction mixture was cooked at about 60°C until the pH was stable; i.e., the
point at which the addition of aqueous KOH was not necessary to maintain the pH between about 7.9 and about 8.1.
A fractional distillation of the reaction mixture was then conducted under reduced
15 pressure to remove the methanol, and isolate the 5-methoxy-4-methyl-2,4-dihydro-
3H-l,2,4-triazol-3-one (MMT) product as a hydrate. About 680 grams of water
were added to the residue and heated to a temperature of about 75°C to dissolve the
MMT. The mixture was then cooled to a temperature of about 0°C over a time pe¬
riod of about 4 hours, and stirred for about 1 hour. The resulting two phase slurry
20 was filtered, and then washed with 280 grams of warm MIBK and 280 grams of ice
cold water. The filter cake was dried at room temperature for about 8 hours under a 200 mm vacuum, to obtain 261 grams of MMT hydrate (1.74 moles, purity of 98% as hydrate, and yield of 76% based on HMT).
25 Example 4 - Preparation of PMT Solution in Xylenes from HPT slurry in
Xylenes/Propanol/Water
To a HPT slurry (e.g., as prepared in Example 2), which contained 348 grams (2.43
moles) of HPT in a mixture of xylenes, propanol and water, was added 45% aque-
30 ous potassium hydroxide (KOH) solution at a temperature of about 30°C, over a
time period of about 30 minutes. The KOH solution was added in an amount such
18

Mo-5445-Foreign Countries

that the pH of the reaction mixture was increased to about 10.0. About 480 grams
(3.77 moles) of dimethyl sulfate were then added to the mixture over-a period of
about 2 hours, while maintaining the temperature of the mixture from about 25 °C
to about 30°C. As the dimethyl sulfate was added, the pH of the reaction mixture
5 decreased. The pH of the mixture was maintained between about 7.9 and about 8.1
by the simultaneous addition of 45% aqueous KOH solution. Following addition of the dimethyl sulfate, the temperature of the reaction mixture was increased to about 60°C over a time period of about 4 hours, while maintaining the pH between about 7.9 and about 8.1.
10
The reaction mixture was cooked at about 60°C until the pH was stable; i.e., the point at which the addition of aqueous KOH was not necessary to maintain the pH between about 7.9 and about 8.1. Stirring of the reaction mixture was stopped and the mixture separated into two phases. The aqueous phase (lower phase) was dis-
15 carded and the organic phase (upper phase) was subjected to distillation under re-
duced pressure to remove the methanol, dipropyl ether, propanol and water. The residue, which consisted of crude 5-propoxy-4-methyl-2,4-dihydro-3H-l,2,4-tri-azol-3-one (PMT) in xylenes, was diluted with fresh anhydrous xylenes to adjust its concentration to about 13% with respect to PMT. At this point the PMT solu-
20 tion contained 319 grams (2.03 moles) of PMT in 2455 grams of total solution.
The solvent-free purity of PMT was 82% and the yield was 83.5% based on HPT.
Although the invention has been described in detail in the foregoing for the purpose
of illustration, it is to be understood that such detail is solely for that purpose and that
25 variations can be made therein by those skilled in the art without departing from the
spirit and scope of the invention except as it may be limited by the claims.
19

CLAIM:-
1. A process for preparing a substituted triazolinone comprising the steps of:
a) reacting a thionocarbamate of the following general formula (I)

wherein
R1 represents an unsubstituted or substituted alkyl, arylalkyl or aryl, and
R2 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cyclo-alkyl, cycloalkylalkyl, aryl or arylalkyl,
wherein R2 is as defined above; and
20
with hydrazine, hydrazine hydrate, or an acid adduct of hydrazine, to produce a triazolinone intermediate product of the following general formula (II)


b) reacting the intermediate product of formula (II) in step a) under pH controlled of from pH 7.0 to pH 9.0 with an alkylating agent of the following general formula (III)
R3 - X (III)
wherein
X represents a halogen, -O-SO2-O-R3, or -O-CO-O-R3, and
R3 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, in the presence of a solvent and a base, to produce a substituted triazolinone of the following general formula (IV)

wherein R2 and R3 are as defined above.
2. The process as claimed in claim i wherein the reaction in step (a) and b) is carried out at a temperature of from -10°C to 95°C.
3. The process as claimed in claim 1 wherein the base recited in step b) is selected from the group consisting of hydrides, hydroxides, amides, alcoholates, acetates, carbonates, or hydrogen carbonates of alkaline earth metals or alkali metals.
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Documents:

1151-mum-2000-cancelled pages(12-9-2001).pdf

1151-mum-2000-claims(21-12-2000).doc

1151-mum-2000-claims(21-12-2000).pdf

1151-MUM-2000-CLAIMS(GRANTED)-(23-3-2011).pdf

1151-mum-2000-claims.pdf

1151-mum-2000-correspondence(23-10-2001).pdf

1151-MUM-2000-CORRESPONDENCE(27-4-2011).pdf

1151-MUM-2000-CORRESPONDENCE(5-4-2011).pdf

1151-mum-2000-correspondence(ipo)-(24-01-2002).pdf

1151-MUM-2000-CORRESPONDENCE(IPO)-(25-3-2011).pdf

1151-mum-2000-correspondence(ipo)-(31-10-2000).pdf

1151-mum-2000-correspondence-others.pdf

1151-mum-2000-correspondence-received-ver-120901.pdf

1151-mum-2000-correspondence-received-ver-160301.pdf

1151-mum-2000-correspondence-received-ver-170901.pdf

1151-mum-2000-correspondence-received-ver-211200.pdf

1151-mum-2000-correspondence-received-ver-231001.pdf

1151-mum-2000-descripiton (complete).pdf

1151-mum-2000-description(complete)-(21-12-2000).pdf

1151-MUM-2000-DESCRIPTION(GRANTED)-(23-3-2011).pdf

1151-mum-2000-form 1(21-12-2000).pdf

1151-mum-2000-form 2(21-12-2000).pdf

1151-MUM-2000-FORM 2(COMPLETE)-(21-12-2000).pdf

1151-MUM-2000-FORM 2(GRANTED)-(23-3-2011).pdf

1151-mum-2000-form 2(title page)-(21-12-2000).pdf

1151-MUM-2000-FORM 2(TITLE PAGE)-(GRANTED)-(23-3-2011).pdf

1151-mum-2000-form 3(12-09-2001).pdf

1151-mum-2000-form 3(21-12-2000).pdf

1151-mum-2000-form 3(23-10-2003).pdf

1151-mum-2000-form 3a(2 complete)-(21-12-2000).doc

1151-mum-2000-form 3a(2 complete)-(21-12-2000).pdf

1151-mum-2000-form 5(21-12-2000).pdf

1151-mum-2000-form-1.pdf

1151-mum-2000-form-2.doc

1151-mum-2000-form-2.pdf

1151-mum-2000-form-26.pdf

1151-mum-2000-form-3-ver-110901.pdf

1151-mum-2000-form-3-ver-160301.pdf

1151-mum-2000-form-5.pdf

1151-mum-2000-petition under rule 124(23-10-2001).pdf

1151-mum-2000-power of authority(12-09-2001).pdf

1151-mum-2000-specification(amended)-(12-9-2001).pdf


Patent Number 246959
Indian Patent Application Number 1151/MUM/2000
PG Journal Number 12/2011
Publication Date 25-Mar-2011
Grant Date 23-Mar-2011
Date of Filing 21-Dec-2000
Name of Patentee BAYER CORPORATION
Applicant Address 100 BAYER ROAD, PITTSBURGH, PA-15205 UAS
Inventors:
# Inventor's Name Inventor's Address
1 SHEKHAR V. KULKARNI 6119 PARKHILL, SHAWNEE, KS-66216, USA
2 VIJAY C. DESAI 14005 WEST 55 TERRACE, SHAWNEE, KS-66216. USA
3 VIDYANATHA A. PRASAD 14205 CANTERBURY COURT, LEAWOOD, KS-66224, USA
4 ERIC RIVADENEIRA 8900 WEST 132 STREET, OVERLAND PARK, KS-66213, USA
5 KLAUS JELICH PAUL-EHRLICH-STR. 2,42113 WUPPERTAL, GERMANY.
PCT International Classification Number C07D249/12
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 09/472,482 1999-12-27 U.S.A.