Title of Invention	PROCESS FOR THE PRODUCTION OF CYCLIC DIKETONES
Abstract	The present invention relates to a process for the preparation of compounds of formula (I), wherein the substituents are as defined in claim 1, by reacting a compound of formula (II), either with a chlorination or bromination agent or with a compound of formula (III) CI-SO2R9, R9 being C1-C4alkyl, C1-C4haloalkyl, phenyl or C1-C4alkyl-substituted phenyl, to form the compound of formula (IV), reacting the compound of formula (IV) with a compound of formula (V) M+-O--C(O)-Y, wherein Y is as defined above and M+ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, to form the compound of formula (VI) and treating that compound with a cyanide source in the presence of a base

Title of Invention

PROCESS FOR THE PRODUCTION OF CYCLIC DIKETONES

Abstract

The present invention relates to a process for the preparation of compounds of formula (I), wherein the substituents are as defined in claim 1, by reacting a compound of formula (II), either with a chlorination or bromination agent or with a compound of formula (III) CI-SO2R9, R9 being C1-C4alkyl, C1-C4haloalkyl, phenyl or C1-C4alkyl-substituted phenyl, to form the compound of formula (IV), reacting the compound of formula (IV) with a compound of formula (V) M+-O--C(O)-Y, wherein Y is as defined above and M+ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, to form the compound of formula (VI) and treating that compound with a cyanide source in the presence of a base

Full Text	Process for the production of cyclic diketones The present invention relates to a process for the preparation of cyclic 1,3-diketone derivatives carbonylated in the 2-position. Processes for the preparation of cyclic 1,3-diketones substituted in the 2-position by an arylcarbonyl group are described, for example, in WO/0015615. WO 00/37437, WO 01/66522 and WO 01/94339. The compounds disdosed therein have herbicidal action. Those known processes have the disadvantage, however, that certain cyclic 1,3-diketone starting compounds unsubstituted in the 2-position, especially the bicyclic 1,3-diketone starting compounds, are generally not readily acceessible and their derivatives can usually be prepared only by means of a plurality of laborious synthesis steps and purification procedures. Furthermore, in the known processes the isolation of the end products, especially in the case of 2-benzoyl, 2-pyridycarbonyl and 2-heteroarylcarbonyl derivatives, involves a generally multi-step procedure which is highly laborious. The purity and yield of the cyclic 1,3-diketones prepared using the known processes are therefore often unsatisfactory. The problem of the present invention Is accordingly to make available a novel general process for the preparation of monocyclic and bicyclic 1,3-diketone derivatives, especially 2-benzoyl, 2-isonicotinoyl and 2-nicotinoyl derivatives, which makes It possible to prepare such compounds in high yields and good quality with a simple reaction procedure and little outlay without the above-mentioned disadvantages of the known processes. The present invention accordingly relates to a process for the preparation of compounds of formula 1 wherein Y is an organic substltuent which is so selected that the compound of formula I has a pK value of from 1 to 5; A1 is CR1R2; A2 is oxygen, C(0), SO2 or (CR3R4)n; n is 1 or 2; A3 is CR5R6; a) a compound of formula it wherein A1, A2 and A3 are as defined for formula I, is reacted with a bromine or chlorine source to form a compound of formula III wherein Ai, A2 and A3 are as defined for formula I and X Is chlorine or bromine; b) that compound Is reacted with water to form the compound of formula IV wherein A1, A2 and A3 are as defined for formula I and X is chlorine or bromine; c) that compound is converted, using a compound of formula V M+-O-"C(O)-Y (V), wherein Y is as defined hereinbefore and M+ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, into the compound of formula VI wherein A1, A2, A3 and Y are as defined for formula I, and d) then that compound is treated with a cyanide source in the presence of a base. Especially advantageously, it is possible, using the process according to the invention, to ^ prepare compounds of formula I wherein Y is wherein A4 is CRa1 or =n-(O)p; p is 0 or 1; X3 and X7 are each independently of the other a three- to ten-membered monocyclic or annellated bicyclic ring system which may be aromatic, saturated or partially saturated and may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, the ring isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxy-carbonyl; preferably methoxycarbonyl or ethoxycarbonyl. A heteroaryl group Y substituted at least in the ortho position is to be understood as being especially a 5- or 6-membered aromatic heteroaryl group as defined hereinbefore which is. in addition, substituted once or up to three times by substituents selected from the meanings of Ra1, Ra2, Ras and Ra4 and Ra5 at the nitrogen and/or at the carbon atoms. Using the process according to the invention it is possible, especially advantageously, to prepare the cyclohexanedione herbicides described in WO 00/15615, WO 00/37437, WO 01/66522 and WO 01/94339. Compounds of formula I that are highly suitable for preparation using the process according to the invention are those wherein R1 and R2 are hydrogen; Q is Q1, wherein A4 is GRa1 or N-(O)p; p is 0; bromosuccinimide (NBS), bromo- and chloro-acetamides and alkyl hypohalites. A preferred: bromine source is bromine or NBS, and a preferred chlorine source is chlorine. In the case of bromination it is advantageous for the HBr that is formed to be removed from the reaction The reaction is preferably carried out in the presence of a solvent Suitable solvents are chlorobenzene, hexane, acetonitrile, tetrahydrofuran, methylcyclohexane or CCU and also mixtures thereof; special preference is given to chlorobenzene or CCI4. The temperatures are generally from 0oC to 150°C; preference is given to a range from 80°C to 130°C. Compounds of formula II are known; they are commercially available in some cases or can be prepared by known methods. The compounds of formula 111 wherein A1, A2 and A3 are as defined for formula I and X is either chlorine or bromine, are novel and were developed specifically for the process according to the invention, and the present invention accordingly also relates thereto. An especially valuable intermediate is the compound of formula IlIb Reaction Step b): Reaction Step b) is preferably carried out with acid- or base-catalysis, preferably acid-catalysis. Suitable acids are mineral acids such as sulfuric acid, hydrochloric acid or bromic add or organic acids such as acetic add. Special preference is given to sulfuric acid. As bases there may be used organic or inorganic bases such as, for example, quaternary ammonium hydroxides or sodium hydroxide. For complete conversion at least 2 equivalents of water are used. In a preferred embodiment, first one equivalent of water Is added to the compound of formula III until the monoketone of formula IV wherein A1, A2 and A3 are as defined hereinbefore and X is chlorine or bromine, is formed and then, as a result of the addition of the second equivalent of water, the diketone of formula I Is formed. The selectivity of the reaction can be further Increased using this preferred embodiment In a preferred embodiment of the process according to the invention, some reaction steps are carried out in the form of a one-pot reaction. Very special preference is given to carrying out Reaction Steps c) and d) in the form of a one-pot reaction. It can also be advantageous to carry out the entire reaction (Reaction Steps a), b), c) and d)) in the form of a one-pot reaction, without isolation of intermediates. The possibility of carrying out the process according to the invention in a one-pot reaction constitutes a considerable advantage especially for large-scale application. 57.8 g (88 % of theory) of 4-bromo-bicycloI3.2.1]oct-3-en-2-one are obtained as a 6.3 % solution in dilorobenzene. ylcarbony)oxy)-cyc)ohex-2-en-1 -one are obtained in the form of an orange-brown oil. MS: 373 (M+), 354, 328, 262, 230, 202, 187, 159,139, 109, 95, 59, 45. 1H NMR(CDCl3): 2.10-2.20 (m, 2H). 2.45-2.50 (m, 2H), 2.70-2.75 (m, 2H), 3.35 (s, 3H, CH3O), 3.50 (CH2CH2O), 3.70 (OCH2CH2), 5.00 (s, 2H, arCH2), 6.10 (s, 1H, C=CH), 7.75 (d, 1H, ar. H), 8.30 (d, 1H, ar. H). (s, 3H. OCH3). 3.50 (m, 2H, CH2CH2O), 3.70 {m. 2H, OCH2CH2), 5.00 (s, 2H, ar. CH2), 5.90 (s, 1H, C=CH), 7.75 (d, 1H, ar. H), 8.30 (d, 1H, ar. H). A mixture of 500 mg of 4-Chlorobicyclo[3-2.1]oct-3-en-2-one, 440 mg of ZnCl2, 400 mg of 4-chlorobenzoio acid, 1.05 g of diisopropylethylamine and 5 ml of toluene is stirred at room temperature under a nitrogen atmosphere at reflux temperature for 6 hours. After cooling the reaction mixture is then diluted with dichloromethane and washed with 5 % aqueous sulfuric acid and 5 % aqueous sodium hydroxide. After concentration of the organic phase to e A mixture of 500 mg of 4-chlorobicyclo [3.2.1]oct-3-en-2-one, 440 mg of ZnCI2, 400 mg of 4-benzoic acid, 1.05 g of diisopropylethylamine and 5 ml of toluene is stirred at room temperature under a nitrogen atmosphere at reflux temperature for 8 hours. After cooling, the reaction mixture is then diluted with dichloromethane and washed with 10 % aqueous 1H NMR (CDCl3): 1.65-1.75 (m. 2H), 2.05-2.30 (m, 4H). 3.00 (br t, 1H), 3.10 (br s, 1H), 3.35 (s, 3H, OCH3), 3.50 (m, 2H, CH2CH2O), 3.70 (m, 2H, OCH2CH2), 5.00 (s, 2H, ar. CH2), 5.90 (s, 1H, C=CH), 7.75 (d, 1H, ar. H), 8.30 (d, 1H, ar. H). 1H NMR (CDCl3): 1.70-1.80 (m, 2H), 2.05-2.30 (m, 4H), 2.90 (br s, 1H), 3.15 (br s, 1H), 3.30 (s, 3H, OCH3), 3.40 (m, 2H, CH2CH2O), 3.50 (m, 2H, OCH2CH2), 4.75 (s, 2H, ar. CH2), 7.50 (s, 2H, ar. H). What is claimed is: 1. A process for the preparation of a compound of formula I wherein Y is an organic substituent which is so selected that the compound of formula I has a pK value of from 1 to 5; A1 is CR1R2; A2 is oxygen, C(O), SO2 or (CR3R4)n; n is 1 or2; A3 is CR5R6; wherein A1, A2 and A3 are as defined for formula I, is reacted with a bromine or chlorine source to form a compound of formula HI wherein A1, A2 and A3 are as defined for formula I and X is chlorine or bromine; b) that compound Is reacted with water to form the COMPOUND OF FORMULA IV wherein A1, A2 and A3 are as defined for formula I and X Is chlorine or bromine; c) that compound is converted, using a compound of formula V hr-O-c(O)-Y (V), wherein Y is as defined hereinbefore and M+ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium Ion, into the compound of formula VI wherein A1, A2, A3 and Y are as defined for formula I, and d) then that compound is treated with a cyanide source in the presence of a base. 2. A compound of formula III wherein A1, A2 and A3 are as defined for formula 1 in claim 1 and X is either chlorine or bromine. 3. The compound of formula lllb

Full Text

Process for the production of cyclic diketones
The present invention relates to a process for the preparation of cyclic 1,3-diketone derivatives carbonylated in the 2-position.
Processes for the preparation of cyclic 1,3-diketones substituted in the 2-position by an
arylcarbonyl group are described, for example, in WO/0015615. WO 00/37437,
WO 01/66522 and WO 01/94339. The compounds disdosed therein have herbicidal action.
Those known processes have the disadvantage, however, that certain cyclic 1,3-diketone starting compounds unsubstituted in the 2-position, especially the bicyclic 1,3-diketone starting compounds, are generally not readily acceessible and their derivatives can usually be prepared only by means of a plurality of laborious synthesis steps and purification procedures.
Furthermore, in the known processes the isolation of the end products, especially in the case of 2-benzoyl, 2-pyridycarbonyl and 2-heteroarylcarbonyl derivatives, involves a generally multi-step procedure which is highly laborious. The purity and yield of the cyclic 1,3-diketones prepared using the known processes are therefore often unsatisfactory.
The problem of the present invention Is accordingly to make available a novel general process for the preparation of monocyclic and bicyclic 1,3-diketone derivatives, especially 2-benzoyl, 2-isonicotinoyl and 2-nicotinoyl derivatives, which makes It possible to prepare such compounds in high yields and good quality with a simple reaction procedure and little outlay without the above-mentioned disadvantages of the known processes.
The present invention accordingly relates to a process for the preparation of compounds of formula 1

wherein Y is an organic substltuent which is so selected that the compound of formula I has
a pK value of from 1 to 5;
A1 is CR1R2;
A2 is oxygen, C(0), SO2 or (CR3R4)n;
n is 1 or 2;
A3 is CR5R6;

a) a compound of formula it

wherein A1, A2 and A3 are as defined for formula I, is reacted with a bromine or chlorine source to form a compound of formula III

wherein Ai, A2 and A3 are as defined for formula I and X Is chlorine or bromine;
b) that compound Is reacted with water to form the compound of formula IV

wherein A1, A2 and A3 are as defined for formula I and X is chlorine or bromine;
c) that compound is converted, using a compound of formula V
M+-O-"C(O)-Y (V),
wherein Y is as defined hereinbefore and M+ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, into the compound of formula VI

wherein A1, A2, A3 and Y are as defined for formula I, and
d) then that compound is treated with a cyanide source in the presence of a base.

Especially advantageously, it is possible, using the process according to the invention, to ^
prepare compounds of formula I wherein
Y is
wherein
A4 is CRa1 or =n-(O)p;
p is 0 or 1;

X3 and X7 are each independently of the other a three- to ten-membered monocyclic or annellated bicyclic ring system which may be aromatic, saturated or partially saturated and may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, the ring

isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxy-carbonyl; preferably methoxycarbonyl or ethoxycarbonyl.

A heteroaryl group Y substituted at least in the ortho position is to be understood as being especially a 5- or 6-membered aromatic heteroaryl group as defined hereinbefore which is.

in addition, substituted once or up to three times by substituents selected from the meanings of Ra1, Ra2, Ras and Ra4 and Ra5 at the nitrogen and/or at the carbon atoms.
Using the process according to the invention it is possible, especially advantageously, to prepare the cyclohexanedione herbicides described in WO 00/15615, WO 00/37437, WO 01/66522 and WO 01/94339.
Compounds of formula I that are highly suitable for preparation using the process according
to the invention are those wherein
R1 and R2 are hydrogen;
Q is Q1, wherein A4 is GRa1 or N-(O)p;
p is 0;

bromosuccinimide (NBS), bromo- and chloro-acetamides and alkyl hypohalites. A preferred: bromine source is bromine or NBS, and a preferred chlorine source is chlorine. In the case of bromination it is advantageous for the HBr that is formed to be removed from the reaction

The reaction is preferably carried out in the presence of a solvent Suitable solvents are chlorobenzene, hexane, acetonitrile, tetrahydrofuran, methylcyclohexane or CCU and also mixtures thereof; special preference is given to chlorobenzene or CCI4.
The temperatures are generally from 0oC to 150°C; preference is given to a range from 80°C to 130°C.
Compounds of formula II are known; they are commercially available in some cases or can be prepared by known methods.
The compounds of formula 111

wherein A1, A2 and A3 are as defined for formula I and X is either chlorine or bromine, are novel and were developed specifically for the process according to the invention, and the present invention accordingly also relates thereto. An especially valuable intermediate is the compound of formula IlIb

Reaction Step b):
Reaction Step b) is preferably carried out with acid- or base-catalysis, preferably acid-catalysis. Suitable acids are mineral acids such as sulfuric acid, hydrochloric acid or bromic add or organic acids such as acetic add. Special preference is given to sulfuric acid. As bases there may be used organic or inorganic bases such as, for example, quaternary ammonium hydroxides or sodium hydroxide. For complete conversion at least 2 equivalents

of water are used. In a preferred embodiment, first one equivalent of water Is added to the compound of formula III until the monoketone of formula IV

wherein A1, A2 and A3 are as defined hereinbefore and X is chlorine or bromine, is formed and then, as a result of the addition of the second equivalent of water, the diketone of formula I Is formed. The selectivity of the reaction can be further Increased using this preferred embodiment

In a preferred embodiment of the process according to the invention, some reaction steps are carried out in the form of a one-pot reaction. Very special preference is given to carrying out Reaction Steps c) and d) in the form of a one-pot reaction. It can also be advantageous to carry out the entire reaction (Reaction Steps a), b), c) and d)) in the form of a one-pot reaction, without isolation of intermediates. The possibility of carrying out the process according to the invention in a one-pot reaction constitutes a considerable advantage especially for large-scale application.

57.8 g (88 % of theory) of 4-bromo-bicycloI3.2.1]oct-3-en-2-one are obtained as a 6.3 % solution in dilorobenzene.

ylcarbony)oxy)-cyc)ohex-2-en-1 -one are obtained in the form of an orange-brown oil.
MS: 373 (M+), 354, 328, 262, 230, 202, 187, 159,139, 109, 95, 59, 45.
1H NMR(CDCl3): 2.10-2.20 (m, 2H). 2.45-2.50 (m, 2H), 2.70-2.75 (m, 2H), 3.35 (s, 3H, CH3O), 3.50 (CH2CH2O), 3.70 (OCH2CH2), 5.00 (s, 2H, arCH2), 6.10 (s, 1H, C=CH), 7.75 (d, 1H, ar. H), 8.30 (d, 1H, ar. H).

(s, 3H. OCH3). 3.50 (m, 2H, CH2CH2O), 3.70 {m. 2H, OCH2CH2), 5.00 (s, 2H, ar. CH2), 5.90 (s, 1H, C=CH), 7.75 (d, 1H, ar. H), 8.30 (d, 1H, ar. H).

A mixture of 500 mg of 4-Chlorobicyclo[3-2.1]oct-3-en-2-one, 440 mg of ZnCl2, 400 mg of 4-chlorobenzoio acid, 1.05 g of diisopropylethylamine and 5 ml of toluene is stirred at room temperature under a nitrogen atmosphere at reflux temperature for 6 hours. After cooling the reaction mixture is then diluted with dichloromethane and washed with 5 % aqueous sulfuric acid and 5 % aqueous sodium hydroxide. After concentration of the organic phase to
e
A mixture of 500 mg of 4-chlorobicyclo [3.2.1]oct-3-en-2-one, 440 mg of ZnCI2, 400 mg of 4-benzoic acid, 1.05 g of diisopropylethylamine and 5 ml of toluene is stirred at room temperature under a nitrogen atmosphere at reflux temperature for 8 hours. After cooling, the reaction mixture is then diluted with dichloromethane and washed with 10 % aqueous

1H NMR (CDCl3): 1.65-1.75 (m. 2H), 2.05-2.30 (m, 4H). 3.00 (br t, 1H), 3.10 (br s, 1H), 3.35 (s, 3H, OCH3), 3.50 (m, 2H, CH2CH2O), 3.70 (m, 2H, OCH2CH2), 5.00 (s, 2H, ar. CH2), 5.90 (s, 1H, C=CH), 7.75 (d, 1H, ar. H), 8.30 (d, 1H, ar. H).

1H NMR (CDCl3): 1.70-1.80 (m, 2H), 2.05-2.30 (m, 4H), 2.90 (br s, 1H), 3.15 (br s, 1H), 3.30 (s, 3H, OCH3), 3.40 (m, 2H, CH2CH2O), 3.50 (m, 2H, OCH2CH2), 4.75 (s, 2H, ar. CH2), 7.50 (s, 2H, ar. H).

What is claimed is:
1. A process for the preparation of a compound of formula I

wherein Y is an organic substituent which is so selected that the compound of formula I has
a pK value of from 1 to 5;
A1 is CR1R2;
A2 is oxygen, C(O), SO2 or (CR3R4)n;
n is 1 or2;
A3 is CR5R6;

wherein A1, A2 and A3 are as defined for formula I, is reacted with a bromine or chlorine source to form a compound of formula HI

wherein A1, A2 and A3 are as defined for formula I and X is chlorine or bromine;
b) that compound Is reacted with water to form the COMPOUND OF FORMULA IV

wherein A1, A2 and A3 are as defined for formula I and X Is chlorine or bromine;
c) that compound is converted, using a compound of formula V
hr-O-c(O)-Y (V),
wherein Y is as defined hereinbefore and M+ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium Ion, into the compound of formula VI

wherein A1, A2, A3 and Y are as defined for formula I, and
d) then that compound is treated with a cyanide source in the presence of a base.
2. A compound of formula III

wherein A1, A2 and A3 are as defined for formula 1 in claim 1 and X is either chlorine or bromine.
3. The compound of formula lllb

Documents:

4011-chenp-2006 correspondence others 18-02-2011.pdf

4011-chenp-2006 other patent document 18-02-2011.pdf

4011-CHENP-2006 AMENDED CLAIMS 03-09-2010.pdf

4011-CHENP-2006 AMENDED PAGES OF SPECIFICATION 03-09-2010.pdf

4011-CHENP-2006 CORRESPONDENCE OTHERS 03-09-2010.pdf

4011-CHENP-2006 CORRESPONDENCE OTHERS 06-07-2011.pdf

4011-CHENP-2006 CORRESPONDENCE OTHERS 01-12-2009.pdf

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4011-CHENP-2006 FORM-13.pdf

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4011-chenp-2006 form-3 03-09-2010.pdf

4011-CHENP-2006 OTHER PATENT DOCUMENT 03-09-2010.pdf

4011-CHENP-2006 PETITIONS.pdf

4011-CHENP-2006 POWER OF ATTORNEY 03-09-2010.pdf

4011-chenp-2006-abstract.pdf

4011-chenp-2006-claims.pdf

4011-chenp-2006-correspondnece-others.pdf

4011-chenp-2006-description(complete).pdf

4011-chenp-2006-form 1.pdf

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Patent Number

250859

Indian Patent Application Number

4011/CHENP/2006

PG Journal Number

06/2012

Publication Date

10-Feb-2012

Grant Date

02-Feb-2012

Date of Filing

01-Nov-2006

Name of Patentee

SYNGENTA PARTICIPATIONS AG

Applicant Address

SCHWARZWALDALLEE 215, CH-4058 BASE, SWITZERLAND

Inventors:

#	Inventor's Name	Inventor's Address
1	JACKSON, DAVID, ANTHONY	SYNGENTA HUDDERSFIELD, MANUFACTURING CENTRE, LEEDS ROAD, HUDDERSFIELD, WEST YORKSHIRE HD2 1FF, UK
2	BOWDEN, MARTIN, CHARLES	SYNGENTA HUDDERSFIELD, MANUFACTURING CENTRE, LEEDS ROAD, HUDDERSFIELD, WEST YORKSHIRE HD2 1FF, UK
3	EDMUNDS, ANDREW	SYNGENTA CROP PROTECTION AG, SCHWARZWALDALLEE 215, CH-4058 BASEL, SWITZERLAND
4	BROCKBANK, BEN	SYNGENTA HUDDERSFIELD, MANUFACTURING CENTRE, LEEDS ROAD, HUDDERSFIELD, WEST YORKSHIRE HD2 1FF, UK

PCT International Classification Number

C07D 213/52

PCT International Application Number

PCT/EP05/04681

PCT International Filing date

2005-04-29

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	00765/04	2004-04-30	Switzerland