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Title:
PROCESS FOR THE PREPARATION OF 2-NITRO SUBSTITUTED BENZOIC ACIDS
Document Type and Number:
WIPO Patent Application WO/2007/099450
Kind Code:
A3
Abstract:
The present invention relates to a process for the preparation of 2-nitro substituted benzoic acids of formula (I), wherein the (O)PSO2R1substituent(s) is in the 3-, 4- and/or 5-position, R1 represents a straight- or branched-chain alkyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms; n is zero or an integer from one to three; and p is zero or 1; said process comprising the oxidation of the corresponding compound of formula (II) wherein R1, n and p are as hereinbefore defined, and q is zero, 1 or 2, provided that when p is 1, q is not zero, with hydrogen peroxide in the presence of an acid and a catalyst.

Inventors:
LEGRAS PAUL GEORGE (US)
Application Number:
PCT/IB2007/000534
Publication Date:
November 22, 2007
Filing Date:
February 28, 2007
Export Citation:
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Assignee:
SYNGENTA PARTICIPATIONS AG (CH)
LEGRAS PAUL GEORGE (US)
International Classes:
C07C51/285; C07C57/30; C07C57/42; C07C309/29; C07C317/32
Domestic Patent References:
WO2004058698A12004-07-15
WO2003099774A12003-12-04
WO2002067913A12002-09-06
Foreign References:
US2907792A1959-10-06
EP0710647A11996-05-08
Other References:
DATABASE BEILSTEIN [online] BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002442122, accession no. brn 3343989
Attorney, Agent or Firm:
ANDREWS, Christopher, John (Intellectual Property DepartmentP.O. Box 3538,Jealott's Hill International Research Centr, Bracknell Berks RG42 6YA, GB)
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Claims:
Claims

1. A process for the preparation of 2-nitro substituted benzoic acids of formula (I)

wherein the (O) P SO 2 R 1 substituent(s) is in the 3-, 4- and/or 5-position,

R 1 represents a straight- or branched-chain alkyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms; n is zero or an integer from one to three; and p is zero or 1; said process comprising the oxidation of the corresponding compound of formula

(II)

wherein R 1 , n and p are as hereinbefore defined, and q is zero, 1 or 2, provided that when p is 1, q is not zero, with hydrogen peroxide in the presence of an acid and a catalyst.

2. A process according to claim 1, wherein R 1 is a straight chain alkyl group containing up to four carbon atoms.

3. A process according to claim 2, wherein R 1 is methyl.

4. A process according to any preceding claim, wherein n is one or two.

5. A process according to claim 4, wherein n is one.

6. A process according to any preceding claim, wherein p is zero.

7. A process according to any preceding claim, wherein q is 1 or 2.

8. A process according to claim 7, wherein q is 2. 5

9. A process according to any preceding claim, wherein at least one of the substituents (O) P SO 2 R 1 of formula (I) and (O) p S(O) q R 1 of formula (II) is in the 4- (para) position.

10 10. A process according to any preceding claim, wherein the acid concentration is greater than 70%v/v.

11. A process according to any preceding claim, wherein the acid is sulphuric acid.

15 12. A process according to any preceding claim, wherein the catalyst is a transition metal catalyst.

13. A process according to claim 12, wherein the transition metal catalyst is selected from the group consisting of sodium tungstate, sodium molybdate or copper powder, or a

,20 transition metal catalyst containing a cation selected from the group consisting of copper (I), copper (II), iron (II), iron (III), chromium (III), zinc (II), cobalt (II), silver(II), or the lanthanide cation cerium (IV).

14. A process according to claim 13, wherein the catalyst is selected from the group 25 consisting of sodium tungstate, sodium molybdate, copper powder, copper(I)chloride, copper(II)sulphate, copper(II)acetate, iron(II)chloride, iron(III)chloride, chromium(III)chloride, zmc(π)chloride., cobalt(II)sulphate, silver(II)oxide and cerium(rV)sulphate.

30 15. A process according to any preceding claim, wherein the catalyst loading is within the range of 0.1mol% and 3mol%.

16. A process according to any preceding claim, wherein the concentration of hydrogen peroxide is within the range of 30% to 75%.

17. A process according to any preceding claim, wherein the reaction is carried out at elevated temperature.

18. A process according to claim 13, wherein the reaction is carried out at a temperature of from 3O 0 C to 100 0 C.

19. A process according to any preceding claim, wherein the reaction is carried out at atmospheric pressure.

20. A process for the preparation of a compound of formula (IA)

said process comprising the oxidation of a compound of formula (IIA)

with hydrogen peroxide in the presence of an acid and a catalyst.

Description:

PROCESS

The present invention relates to a novel process for the preparation of 2-nitro substituted benzoic acids.

2-Nitro-4-methylsulphonyl benzoic acid (NMSBA) is an important intermediate in the preparation of mesotrione (2-(4-methylsulphonyl-2-nitrobenzoyl)cyclohexane-l,3- dione), a selective herbicide highly effective in the control of weeds in crops, in particular corn. NMSBA is currently prepared from 2-nitro-4-methylsulphonyltoluene (NMST) by an oxidation reaction using nitric acid. The reaction is run under pressure at high temperature using reactants aggressive to plant equipment. Further nitration produces species that have reduced thermal stability so careful control is required to achieve safe operation. It is therefore an object of the present invention to provide an alternative process for the preparation of 2-nitro substituted benzoic acids.

Accordingly, the present invention provides a process for the preparation of 2- nitro substituted benzoic acids of formula (I)

wherein the (O) P SO 2 R 1 substituent(s) is in the 3-, 4- and/or 5-position,

R 1 represents a straight- or branched-chain alkyl group containing up to six carbon atoms which is optionally substituted by one or more halogen atoms; n is zero or an integer from one to three; and p is zero or 1; said process comprising the oxidation of the corresponding compound of formula

(II)

wherein R 1 , n and p are as hereinbefore defined, and q is zero, 1 or 2, provided that when p is 1, q is not zero, with hydrogen peroxide in the presence of an acid and a catalyst.

Suitably R 1 is a straight chain alkyl group containing up to four carbon atoms, preferably methyl.

Suitably n is one or two, preferably 1.

Suitablyp is zero.

Suitably q is 1 or 2, preferably 2.

Suitably at least one of the substituents (O) P SO 2 R 1 of formula (I) and (O) p S(O) q R 1 of formula (II) is in the 4- (para) position.

One particularly preferred embodiment of the present invention is a process for the preparation of a compound of formula (IA)

said process comprising the oxidation of a compound of formula (IIA)

with hydrogen peroxide in the presence of an acid and a catalyst. The reaction is carried out in acid as the solvent and suitably the acid concentration is greater than 70%v/v, preferably greater than 80%v/v. The preferred acid is sulphuric acid. During the reaction it may be necessary to add further acid at the same or higher concentration, in order to maintain the acid at the desired concentration due to dilution which may occur on addition of the hydrogen peroxide.

A number of different catalysts may be used, but generally the catalyst is a transition metal catalyst. Catalysts containing transition metals include e.g. sodium tungstate or sodium molybdate, copper powder, copper (I) e.g. copper(I)chloride, copper (II) e.g. copper(II)sulphate or copper(II)acetate, iron (II) e.g. iron(II)chloride, iron (III) e.g. iron(iπ)chloride, chromium (III) e.g. chromium(III)chloride, zinc (II) e.g. zmc(ϋ)chloride, cobalt (II) e.g. cobalt(II)sulphate, silver(II) e.g. silver(ϋ)oxide, and the lanthanide cerium (IV) e.g. cerium(IV)sulphate may also be used. Preferred catalysts

include: sodium tungstate, sodium molybdate, copper powder, copper(I)chloride, copper(II)sulphate, copper(II)acetate, iron(II)chloride, iron(III)chloride, chromium(III)chloride, zinc(II)chloride, cobalt(II)sulphate, silver(II)oxide and cerium(TV)sulphate; more preferred include: sodium tungstate, sodium molybdate, copper(II)sulphate, chromium(HI)chloride, zinc(II)chloride and cerium(IV)sulphate; most preferred include: sodium tungstate, sodium molybdate and copper(II)sulphate.

The catalyst loading is suitably within the range of 0.1mol% and 3mol%.

The concentration of hydrogen peroxide used is suitably within the range of 30% to 75% and preferably 50%. Suitably 4 to 8 mol of hydrogen peroxide is used per mol of compound of formula (II), and preferably 5 to 7 mol. One skilled in the art will realise that where the oxidation state of the sulphur atom is increased during the process, a commensurate amount of extra hydrogen peroxide is required.

The reaction is suitably carried out at elevated temperature, for example 30°C to 100°C, preferably 50°C to 75°C. The reaction is suitably carried out at atmospheric pressure.

The process will now be described in more detail with reference to the following examples which are illustrative and not limiting of the invention.

Example 1

Catalyst Evaluation in Reactive Systems Screening Tool CRSST) reactor The solution of NMST in the solvent (80% sulphuric acid) was placed in the

RSST reactor and the catalyst was added. The RSST reactor was placed in its steel container and lmol/mol hydrogen peroxide was added quickly with a syringe at ambient temperature. The RSST container was sealed and pressured to 30psig with nitrogen. The heating and monitoring sequence was started to bring the reaction to the set temperature. Temperature and pressure were monitored over 1 hour. The results are shown in Table 1.

Table 1

Example 2

Catalyst Evaluation in Glass Laboratory Reactor

Sulphuric acid was added to a small amount of water separately to prepare the required strength sulphuric acid solution. This solution was placed in a jacketed reactor that was fitted with a turbine agitator, thermometer and a tube for addition of hydrogen peroxide. 2-nitro-4-methylsulphonyltoluene (NMST) was added to the sulphuric acid solution and heating was started, with stirring, to bring the reaction mass to the required reaction temperature. The catalyst was added and stirred until in solution. Hydrogen peroxide (35% w/w) was fed to the reactor in aliquots of 1 mol/mol NMST per hour via a syringe pump. Samples were removed after each addition for analysis by HPLC.

The results for evaluation using 80% sulphuric acid solvent at 75 0 C are shown in Table 2.

Table 2: Percent yield of NMSBA for the specified hydrogen peroxide charge for various catalysts