NZ202747A - The preparation of 5-(2-halo-4-trifluoromethyl-phenoxy)-2-nitrobenzoic acid derivatives - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £02747 202747 Priority Date(s): Complete Specification Filed: Class: Ce.l .C2 .£<?.? .< /«■? fao Publication Date: P.O. Journal, No: tea/fog#, v^j NEW ZEALAND PATENTS ACT, 1953 No.: Date: COMPLETE SPECIFICATION THE PREPARATION OF CERTAIN DIPKENYL ETHERS ESPECIALLY (i1-TP.IFLUOROMETII¥LPIIENOX¥) AM©-5- (2-HALO-4-TRIFLUORO- MEHTYLPHENOXY)-2-NITROBENZOIC ACID AND SALTS AND ESTERS AND AMIDES i/W'e, ROHM AND HAAS COMPANY, a Corporation organised and existing under the laws of Delaware, United States of America, of Independence Mall West, Philadelphia, Pennsylvania 19105, United States of America, hereby declare the invention for which &,/ we pray that a patent may be granted to coe/us, and the method by which it-is to be performed, to be particularly described in and by the following statement:- , (followed by la) 202747 - la - THE PREPARATION OF CERTAIN DIPHENYL ETHERS ESPECIALLY 5-(2-HALO-4-TRIFLUOROMETHYLPHENOXY)-■2-NITROBENZOIC ACID AND SALTS AND ESTERS AND AMIDES This invention concerns the preparation of certain diphenyl ethers especially 5-(2-halo-4-trifluoromethyl-phenoxy)-2-nitrobenzoic acid and salts and esters and amides.

This invention concerns more particularly a stepwise synthesis for preparing diphenyl ethers having the configuration which is currently believed to afford the most active and selective herbicides known. In this configuration the diphenyl ether has a 4-trifluoromethyl substituents, a 2-halo substituent and a 4'-nitro substituent.

The search for better and more economical methods for preparing these highly active herbicides is a continuing one. Some routes are described in U.S. Patent Nos. 3,862,209; 4,031,131 and 4,262,152. Problems also exist in the stability of trifluoromethylphenol under basic conditions [see Jones, R.G., J.A.C.S., 69, 2346-50 (I947fj . The reduction of decomposition of trifluoromethylphenol and provision of a substantially pure, isomer-free compound is highly desirable.

Known processes for the preparation of these compounds yield the desired active product together with herbicidally inactive impurities especially isomers.

These inactive impurities are toxicologically disadvantageous.

EP-A-19388 and EP-A-3416 disclose the reaction of an unsubstituted p-trifluoromethylphenol with an alkyl-5--chloro-2-nitrobenzoate. However neither exemplifies such a reaction wherein the p-trifluoromethylphenol is free from any further substituent.

According to this invention there is provided a process for preparing a trifluoromethyl substituted diphenyl ether of the Formula (III) given below wherein 2 JUL 1936, 202747 (A) a compound of the formula CF r@- OH is reacted in the presence of an inorganic base in a polar solvent with a compound of the formula: c°2r Xl \2/ no, (II) to form a compound of the formula: if.

(I) co2r wherein X1 is halo and R is hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, carbalkoxyalkyl, cyanoalkyl, alkoxyalkyl, haloalkyl, alkali metal cation, alkaline earth metal cation, quaternary ammonium cation, amino, or mono-R amino or di-R amino; and then 202747 (B) this compound (I) is reacted with a halogenating agent in the presence of a Friedel-Crafts catalyst to form a compound of the formula: (III) no2 wherein X is halo and R is as defined above.

An important feature of the reactions of this invention is the formation and use of compound (I) wherein the trifluoromethylphenoxy moiety is free of halogen which is subsequently added.

A flow diagram for the process according to this invention is as follows: Step A 3 + X1 Base Polar Solvent (I) •/ \J2Jut-msj C1 a %i) C 1 202747 Step A is preferably carried out at a temperature of 25 to 90°C and for 1 to 18 hours.

Step B ^ ^ Halogenating Agent ^ Catalyst NO, (III) Step B is carried out in the presence of a Friedel-Crafts catalyst and preferably at a temperature of 50° to 130°C and for 0.5 to 10 hours.

Step C (If desired) (III) Hydrolysis (in the presence of base) Step D (if NO, NO, (IV) (V) -p; E W> % "2JULI986S 202747 wherein M is an alkali metal cation or alkaline earth metal cation.

The condensation step, Step A, may employ inorganic bases such as sodium carbonate, potassium carbonate, sodium hydride, sodium hydroxide, potassium hydroxide, lithium hydroxide, Grignard reagents, lithium alkyls or any other base which will form the free anion of the phenol. The preferred base is potassium carbonate. This reaction is conducted using a polar solvent, such as, dimethyl sulfoxide, sulfolane, dimethylformamide, hexamethyl phosphoramide, tetramethyl-urea, tetramethylethylene diamine and the like. Dimethyl ; sulfoxide is the preferred solvent. The reaction may be conducted at a temperature in the range of from 25° to 90°C with the range of from 50° to 80°C being more preferred and 70°C being most preferred. The reaction may be carried out for a period of time within 1 to 18 hours, and within 2 to 3 hours being most preferred for completing the reaction.

Gas-liquid chromatography shows that this process can be operated so that only the desired product is obtained and yields of over 80% may be obtainable.

The halogenation step, Step B, can be so operated as to yield, out of five possible isomers, only the single desired product.(mono-halogenated compound III with halogen at the 2-position). While only chlorinating agents have been employed, it is believed that other halogenating agents could be equally effective such as fluorinating or iodinating agents.

Halogenating agents which can be employed include gaseous chlorine, sulfuryl chloride, N-chlorosuccinimide, tert-butyl hypochlorite, hydrogen chloride plus oxidizing agents (e.g. perchlorate) with gaseous chlorine being the preferred chlorinating agent. 202747 The Friedel-Crafts catalyst employed in Step B preferably comprises ferric chloride and/or aluminium chloride. The reaction time may be quite short, from 0.5 to 10 hours, at a temperature from 50° to 130°C. The reaction is preferably run for no more that 3 hours at 70°C. A solvent may optionally be employed although, in general, none is needed. Solvents which could be used include chlorinated solvents such as o-dichloro-benzene, perchloroethylene or ethylene dichloride.

The product (compound III) may be employed directly as a herbicide or may be converted to other herbicides by hydrolysis of the ester, salt or amide to the free acid which can be converted to other esters, alkali metal or alkaline earth metal salts or to various . amine salts as desired.

The following is a description of the various substituents, X, X1, and R. X and X1 are halo, for example, chloro, bromo, fluoro, or iodo.

R may be one of the following: hydrogen, alkyl, such as lower alkyl of from 1 to 5 carbon atoms, alkenyl, such as lower alkenyl of from 2 to 6 carbon atoms, alkynyl, such as lower alkynyl of from 2 to 6 carbon atoms, hydroxy-alkyl such as hydroxy (C^ to C^)-alkyl, carboxyalkyl such as carboxy (C^ to C^)-alkyl, carbalkoxyalkyl, such as carbo (C^ to C^)-alkoxy (C^ to C^)-alkyl, cyanoalkyl such as, cyano (C^ to C^)-alkyl, alkoxyalkyl, such as (C^ to C,_)-alkoxy (C^ to C^)-alkyl, haloalkyl such as halo (C to Cg.)-alkyl, a cation derived from an alkali + + + metal or an alkaline earth metal such as Na , K , Li , Ca++, Mg++, quaternary ammonium cations or amino, mono-and di-R amino where R is as defined above. jNote: 1) When R is hydrogen, two equivalents of base must be employed; 2) R cannot be hydroxylmethy1; and 3) for the halogenation, R is preferably (C^ to C^)-alkyl7j 0> -2JULJ986 ;> 20274 Examples of processes according to the invention are given below for illustrative purposes only.

Example 1 - (2 - C h 1 o r o - 4 -1 r i f 1uoromethylphenoxy) - 2 - n i t r o b e n z o i c 5 acid and its Sodium Salt Step A - Me thy1 5-(4-trifluoromethylphenoxy)-2-n itro-benzoate 4-trifluoromethylphenol (0.22 g, 1.36 mmol), powdered potassium carbonate (0.185 g, 1.34 mmol), and 10 methyl 5-chloro-2-nitrobenzoate (0.288 g, 1.34 mmol) were heated at 70°C under a nitrogen atmosphere in 3 ml of dimethyl sulfoxide. After 50 minutes, an aliquot was quenched in methanolic HC1. (By gas chromatography, the reaction was 45% complete). After 18 hours (overnight), 15 the reaction mixture was cooled to room temperature, diluted with water, and extracted with ether. The organic extracts were shaken with brine, dried (MgSO^) and concentrated to afford methyl 5-(4-trifluoromethylphenoxy)-2-nitrobenzoate in 85% yield. Gas chromatography showed 20 no starting phenol remained.

Step B - Methyl 5-(2-chloro-4-trifluoromethylphenoxy) -2-nitrobenzoate Methyl 5-(4-trifluoromethylphenoxy)-2-nitrobenzoate was stirred with a catalytic amount of ferric chloride. 25 The reaction mixture was heated to 70°C under a continuous stream of chlorine gas. After 2.5 hours, the mixture was taken up in ether, shaken with water and the organic phase was dried over MgSO^. The. ether was evaporated to afford methyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate 30 NMR (CDC13) £ 8.2-7 (m,6) 4.0 (2,3). TLC (40% ether/ hexane) R^^. 4. GL was unable to detect the presence of any impurity. The yield of desired product was quantitative 2027 4 Step C - 5-(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid and its Sodium Salt Methyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate (0.06 mole) was dissolved in methanol (20 g) and a solution of 50% aqueous sodium hydroxide (0.120 mole) was added dropwise beginning at 25°C. The rate of addition was adjusted so as to control the exothermic reaction at less than or equal to 52°C. By this method the sodium salt of 5-(2-chloro-4-trifluoromethylphenoxy ) -2-nitrobenzoic acid was generated in situ. Treatment with 6 M HC1 to pH 1 in water (100 ml) afforded the free acid which was extracted into ethylene chloride. ; The ethylene chloride layer was decanted and concentrated under vacuum to afford 5-(2-chloro-4-trifluoromethylphenoxy) -2-nitrobenzoic acid.

By standard chemical methods 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid can be converted to agronomically acceptable alkali and alkaline earth metal salts by reaction with one equivalent of an appropriate metal hydroxide or to agronomically acceptable amine salts by combining the acid with one equivalent of the appropriate amine. Solutions of the acid salts or free salts can be obtained depending upon reaction conditions. One method for illustrative purposes only to isolate the sodium salt is described below.

Example 1A - Sodium 5-(2-ChToro-4-trifluoromethylphenoxy) -2-nitrobenzoate -(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid (3.0 g, 0.0083 mole) was dissolved in isopropyl alcohol (20 ml) and a solution of 50% aqueous sodium hydroxide (0.644 g, 0.0083 mole) was added dropwise and the reaction mixture stirred for 1 hour before removing the solvent and water under vacuum at 0.2 mm overnight to afford 2.8 g of sodium -(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate.

By following substantially the same procedure as described above the following compounds were prepared: example x r 2 CI -C2H5 3 CI -C3k7 4 F -CH3 Br -CH2CN 6 ci -ch2ch=ch2 7 ci -ch2 c=ch 8 f -ch2cooch3 9 ci -ch2cooh ci -ch2ch2c1 11 ci -ch2oc2h5 12 ci -n(c2h5)2 13 ci -k 14 CI -CH(CH3)C02CH3 202747

Claims (5)

WHAT WE CLAIM IS:

1. A process for preparing a trifluoromethyl substituted diphenyl ether of the formula (III) given below characterised in that (A) a compound of the formula CF. O oh is reacted in the presence of an inorganic base in a polar solvent with a compound of the formula: ^-<C02R xl-\Oy^0: (ii) to form a compound of the formula: CF. (I) co2r wherein X1 is halo and R is hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, carbalkoxyalkyl, cyanoalkyl, alkoxyalkyl, haloalkyl, alkali metal cation, alkaline earth metal cation, quaternary ammonium cation, amino, or mono-R amino or di-R amino,- and then /«' yv «<\ a - 11 - 202747 (B) this compound (I) is reacted with a halogenating agent in the presence of a Friedel-Crafts catalyst to form a compound of the formula: O x I N02 (HI) wherein X is halo and R is as defined above.

2. A process as claimed in Claim 1 wherein reaction (A) is carried out at 25° to 90°C for 1 to 18 hours.

3. A process as claimed in Claim 1 or 2 wherein reaction (B) is carried out at 50° to 130°C for 0.5 to 10 hours. - 12 - 802747

4. A process as claimed in any preceding claim wherein compound (III) is hydrolyzed in the presence of base to form: (IV) wherein M is an alkali metal cation or alkaline earth metal cation and X is halo.

5. A process as claimed in Claim 4 wherein compound (IV) is hydrolysed in the presence of acid to form: (V) wherein X is halo. y't *;-2 JUL1986;- 13 -;202747;6• A process as claimed in Claim 4 or 5 wherein;X is CI and M is Na.;7 . A process as claimed in any one of Claims 1 to 5 which comprises reacting 4-trifluoromethylphenol with methyl 5-chloro-2-nitrobenzoate and potassium carbonate in dimethyl sulfoxide followed by treating the compound (I) obtained with chlorine gas in the presence of ferric chloride to form an ester (III) , then hydrolysing the ester (III) with aqueous base to form sodium 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate.;S. A process as claimed in Claim 7 wherein the sodium 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate is reacted with inorganic acid to form 5 —(2 — chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid.;9. A process as claimed in any one of Claims 1 to 5 whenever performed substantially as hereinbefore described with particular reference to any one of the foregoing Examples.;10. A trifluoromethyl substituted diphenyl ether, whenever prepared by a process as claimed in any one of Claims 1 to 9.;n;\?20 T'.-r;*, jlwf : \Y C:; i. - - - - 7 y rri.1 i// ^ rV -2JU11986 \9