PREPARATION OF 2-(CHLORO, BROMO OR NITRO)-4-(ALKYL-SULFONYL)BENZOIC ACIDS AND INTERMEDIATES

Abstract: Compounds having structural formula (I), wherein R is chloro, bromo or nitro, are used in the preparation of 2-(chloro, bromo or nitro)-4-(alkyl-sulfonyl) benzoic acid compounds having structural formula (II), wherein R is chloro, bromo or nitro and R<1> is hydrogen or C1-C3 alkyl.

Description: PREPARATION OF 2-(CH 0RO, BROMO OR NITRO)-4-(A KYL- SUIFONYL)BENZOIC ACIDS AND INTERMEDIATES Background of the Invention This invention relates to a process for the preparation of 2-(chloro, bromo or nitro)-4-(alkylsulfonyl)benzoic acids and to inter¬ mediates useful in the process. These 2-(chloro, brαno or nitro)-4-(alkylsulfonyl)benzoic acids are intermediates useful for the preparation of certain 2-(2-chloro, brcrno or nitro)-4-(alkylsulfonyl)benzoy1-1,3-cyclohexanedione herbicides. Ωie 2-(chloro, bromo or nitro)-4-(alkylsulfonyl)benzoic acid is converted to its acid chloride or cyanide and it is reacted with certain 1,3-cyclohex- anediones according to the process of U.S. Patent 4,695,673 or U.S. Pat. 4,708,127. Summary of the Invention One embodiment of this invention is directed tb a process for the preparation of 2-(chloro, bromo or nitro)-4- (alkylsulfonyl)benzoic acids, represented by the following reaction steps: Ω e 2- (chloro, bromo or nitro)-4-(chlorosulfonyl)benzoyl chlo- ride [reactant of Step ( 1 ) ] can be prepared by the following reaction: HEET In the above Reaction Steps (1), (2) and (3), R is chloro, bromo or nitro; R 1 is hydrogen or C1-C3 alkyl, preferably methyl or ethyl, most preferably R 1 is hydrogen; M is hydrogen, sodium, potassium or aπmonium, preferably sodium; and X is chloro, bromo or iodo, preferably chloro. A second embodiment of this invention is the intermediate reac¬ tion product of Reaction Step (3). This 2-(chloro, bromo or nitro)-4- (chlorosulfonyl)benzoyl chloride intermediate has the structural formula SO2CI wherein R is chloro, brcrno or nitro. A third embodiment of this invention is the intermediate reac¬ tion product of Reaction Step (1). This second intermediate has the structural formula wherein R is chloro, bromo or nitro and M is hydrogen, sodium, potassium or ammonium. Detailed Description of the Invention Referring to the three reaction steps under the "Summary of the Invention" section, the following is additionally taught. SUBSTITUTESHEET Tlie process of this invention is depicted by Reaction Steps (1 ) and (2). Step (3) is provided to show a process for the preparation of the intermediate 2-(chloro, bromo or nitro)-4-(chlorosulfonyl)benzoyl chloride which is an embodiment of this invention. Also the intermediate reaction product of Reaction Step (1) is an embodiment of the invention. Generally in Reaction Step (1) the 2-(chloro, bromo or nitro)-4- (chlorosulfonyl)benzoyl chloride reaction product of Reaction Step (3) preferably is reacted with an equimolar amount of a reducing agent, pre- ferably sodium or potassium sulfite, along with a base, preferably an inorganic base, having a sodium, potassium or ammonium cation. Such bases are sodium or potassium hydroxide, sodium or potassiim bicarbonate or aπtnonium hydroxide. Preferably the base is sodium bicarbonate. Generally about 3 or more moles of the base are used, preferably between about 4.0 to 4.5 moles. Ihe reaction preferably should be run at a pH of about 7-9. Ihe reaction is run in water, optionally in the presence of a non-miscible organic solvent. During Reaction Step (1 ), the sulfonyl chloride group is reduced to the sodium, potassium or ammonium salt of the corresponding sulfinate and the acid chloride group is hydrolyzed to the sodium, potas- sium or aπinonium salt of the benzoic acid. Reaction Step (1) is prefer¬ ably run at a temperature above about 0 β C, more preferably between about 20°C to about 100°C, even more preferably between about 30°C to about 75°C and most preferably between about 40°C and about 50 β C. Vtien "R" is nitro, the reaction preferably should be run at a temperature between about 10°C to about 20°C. The reaction at the most preferable temperature or above is very quick and normally takes less than 15 minutes. The reaction product is soluble in the aqueous solvent and nor¬ mally is not isolated. Reaction Step (2) is carried out by adding a mole of the sodium, potassium or aπinonium salt of an ,^-halocarboxylic acid of the structural formula X R1-CH-CCO M SUBSTITUTE SHEET wherein R1 is hydrogen, C1-C3 alkyl, preferably methyl, ethyl or n-propyl, more preferably hydrogen; M is sodium, potassium or aimtonium; and X is chloro, bromo or iodo, preferably chloro, to the aqueous reaction product of Reaction Step (1) . In the alternative, the above salt of an -halo- carboxylic acid can be formed _in situ by adding equal molar amounts of an X-halocarboxylic acid of the structural formula X R1-CH-C00H where ~ 0 and X are as defined with an inorganic base having a sodium, potassium or ammonium cation. Such bases are the sane as defined in Reaction Step (1 ). The reaction is carried to completion by heating the reaction mixture to reflux for about 6-48 hours. The reaction time can be reduced by heating the reaction mixture at higher temperatures under pressure. Generally in Reaction Step (3), the reaction between the benzoic acid reactant and the thionyl chloride is run in conventional equipment using excess thionyl chloride and at least 5 mole percent of the dimethyl- formamide (DMF) catalyst. Preferably, the reaction is run in an inert solvent such as toluene or ethylene dichloride, or excess thionyl chloride can serve as the solvent. Preferably, the reaction is run at a tempera¬ ture between about 50 β C to about 100 β C in the absence of moisture. The reaction product is recovered by conventional techniques such as separat¬ ing solids by filtration and evaporating excess solvent from the filtrate to yield the desired reaction product. As previously recited, an embodiment of this invention is directed to a process for preparing 2,4-disubstituted benzoic acid com¬ pounds having the structural formula 1 wherein R is chloro, brαno or nitro and R^ is hydrogen or C1-C3 alkyl , by SUBSTITUTE SHEET 1 ) reacting a compound having the structural formula C0C1 wherein R is as defined with a reducing agent along with a base, prefer¬ ably an inorganic base, having a sodium, potassium or ammonium cation in an aqueous medium to prepare an intermediate having the structural formula I _ + SO2M wherein R is chloro, bromo or nitro and M is hydrogen, sodium, potassium or ammonium, followed by 2) reacting the intermediate from step (1 ) with a salt having the structural formula X R' _-C'H-COO-M+ wherein X is chloro, brcrno or iodo; R 1 is hydrogen or C1-C3 alkyl and M is sodium, potassium or ammonium, to prepare a salt of a benzoic acid having the structural formula 1 wherein M, R and R^ are as defined and finally acidifying the salt to pre¬ pare the desired product having the structural formula 1 wherein R and R 1 are as defined. The intermediate benzoic acids of Reaction Step (2) can easily be converted to their respective acid chlorides and then to their acid cyanides, if desired, by the following two reactions. First, a mole of oxalyl chloride and a catalytic amount of dimεthylformamide in a suitable solvent such as methylene chloride is heated at a temperature of 20 to 40°C for 1 to 4 hours with a mole of the interπediate benzoic acid. The corresponding benzoic acid cyanide can easily be prepared from the benzoic acid chloride by reaction with cuprous cyanide at a temperature of 50 to 220°C for 1 to 2 hours. _he following series of exaπples teach the synthesis of repre¬ sentative intermediate ccmpounds of this invention and the processes of this invention. The structures of all compounds of the examples and tables were verified by nuclear magnetic resonance (1WR), infrared spec- troscopy (IR) and mass spectroscopy (MS). EXAMPLE 1 2-Chloro-4-(chlorosulfonyl)benzoyl Chloride A 25 milliliter (iriL) round bottom flask equipped with reflux condenser, thermometer, and magnetic stirrer was charged with 3.2 grams (g) [10.0 millimole (mmol)] of the potassium salt of 2-chloro-4-sulfoben- zoic acid (85 wt. % pure), 10 iriL (140 ππvol) of thionyl chloride and 0.03 g (0.5 πmol) of d_unethylfonnanu.de (DMF). After heating for one hour at 60 β C, the cooled reaction mixture was diluted with 10 mL of toluene, filtered and evaporated to afford 2.55 g (100% yield) of 2-chloro-4- (chlorosulfonyl)bεnzoyl chloride as a brown oil. TESHEET EXAMPLE 2 2-Chloro-4-(πethylsulfonyl)benzoic Acid Using Chloroacetic Acid and Sodium Hydroxide SO2CH3 A 250 L round bottom flask equipped with a reflux condenser, thermometer, and magnetic stirrer was charged with 9.2 g (73 mmol) of sodium sulfite, 24.6 g (292 ΠΠDI) of sodium bicarbonate and 80 mL of water. The resulting slurry was heated to 50°C, and 20.0 g (70 mmol) of 2-chloro-4-(chlorosulfonyl)benzoic acid was added over 15 minutes. After heating at 50°C for three hours, chloroacetic acid (10.4 g, 110 πrrol) and 5.7 mL (110 mmol) of 50% aqueous sodium hydroxide were added sequentially to the aqueous solution of 2-chloro-4-sulfinylbenzoic acid, and the reaction mixture heated to reflux. After heating for 19 hours, the reac¬ tion mixture was allowed to cool to ambient temperature and acidified with dilute HCl. The precipitated solids were collected by filtration, washed with dilute HCl and dried to give 17.4 g of 2-chloro-4-(methylsulfonyl)- benzoic acid as a white solid. Ωie solid was assayed at 85% purity, cor¬ responding to an overall yield of 89%. EXAMPLE 3 2-Chloro-4-(methylsulfonyl)benzoic Acid Using the Sodium Salt of Chloroacetic Acid COOH A 100 mL round bottom flask equipped with a reflux condenser, thermometer, and magnetic stirrer was charged with 4.6 g (37 mmol) of sodium sulfite, 12.3 g (146 πmol) of sodium bicarbonate and 40 mL of water. The resulting slurry was heated to 75 β C and 10 g (33 πmol) of 2-chloro-4-(chlorosulfonyl)benzoyl chloride was added slowly. After stirring at 75°C for 2 hours, 6.4 g (55 mol) of the sodium salt of HEET chloroacetic acid was added and the reaction mixture heated at reflux for 21 hours. The cooled reaction mixture was acidified with dilute HCl and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and evaporated to dryness to afford 7.5 g of 2-chloro-4-(methyl- sulfonyl)benzoic acid as a white solid. Ihis material was shown to be 87% pure, representing an 85% overall yield. EXAMPLE 4 2-Brαno-4-(chlorosulfonyl)benzoyl chloride SO2CI A 100 mL round bottom flask equipped with reflux condenser, tem¬ perature controller and magnetic stirrer was charged with 8.8 g (28 πmol) of the potassium salt of 2-broπo-4-sulfobenzoic acid, 21.5 mL (301 mmol) of thionyl chloride, and 0.12 g (1.7 πmol) of DMF. After heating for five hours, the cooled reaction mixture was filtered and evaporated to afford the desired product, 2-bromo-4-( chlorosulfonyDbenzoyl chloride. EXAMPLE 5 2-Brcmo-4- ( ethylsulf onyl ) benzoic Acid COOH SO2CH3 A 50 mL round bottom flask equipped with a reflux condenser, thermometer and magnetic stirrer was charged with 1.6 g (13 πmol) of sodium sulfite, 4.2 g (50 πmol) of sodium bicarbonate and 20 mL of water. The resulting slurry was heated to 75°C and 4.0 g (13 πmol) of 2-brcmo-4- (chlorosulfonyDbenzoyl chloride was added over 30 minutes. After heating at 75 C C for one hour, chloroacetic acid (1.8 g, 19 πrnol) and 1.0 mL (19 iπmol) of 50% aqueous sodium hydroxide were added sequentially to the aqueous solution of 2-bromo-4-sulfinylbenzoic acid, and the reaction mix¬ ture heated to reflux. Additional chloroacetic acid (2.0 g) was added as TE SHEET necessary to drive the reaction to completion. After heating for 16 hours, the reaction mixture was allowed to cool to ambient temperature and acidified with concentrated HCl. The precipitated solids were collected by filtration and dried to give 1.6 g of 2-brσmo-4-(methylsulfonyl)benzoic acid, corresponding to a 46% yield. EXAMPLE 6 2-Nitro-4-(chlorosulfonyl)benzoyl Chloride SO2CI A 250 mL round bottom flask equipped with reflux condenser, thermometer, and magnetic stirrer was charged with 9.0 g (32 πmol) of the potassium salt of 2-nitro-4-sulfobenzoic acid, 10.7 mL (142 mmol) of thionyl chloride, 0.23 g (3.2 πmol) of DMF and 40 mL of toluene. After heating for one hour at 85 β C, the cooled reaction mixture was filtered and evaporated to afford 8.2 g (92% yield) of 2-nitro-4-(chlorosulfonyl)- benzoyl chloride as an amber oil. EXAMPLE 7 2-Nitro-4-( ethylsulfonyl)benzoic Acid COOH SO2CH3 A 100 iriL round bottom flask equipped with a reflux condenser, thermometer and magnetic stirrer was charged with 1.9 g (15 mmol) of sodium sulfite, 5.1 g (60 ΠΠDI) of sodium bicarbonate and 20 L of water. The resulting slurry was cooled to 15 β C and 4.0 g (14 mmol) of 2-nitro-4- (chlorosulfonyDbenzoyl chloride was added over 5 minutes. The reaction mixture was stirred at 15 β C for three hours and then at ambient tempera- ture overnight. After warming to 40°C, 3.1 g (27 mmol) of the sodium salt of chloroacetic acid was added to the aqueous solution of 2-nitro-4-sul- finylbenzoic acid and the reaction mixture heated to reflux. After UBSTITUTE SHEET heating for 7 hours, the reaction mixture was allowed to cool to ambient temperature, diluted with 30 mL of water and washed with 50 L of ethyl acetate. The aqueous layer was acidified with concentrated HCl and extracted with 75 mL of ethyl acetate. The organic solution was concen- trated to afford 3.0 g (87% yield) of 2-nitro-4-(methylsulfonyl)benzoic acid as a pale yellow solid. HEET

Claims: WHAT IS CLAIMED IS: 1 . An intermediate compound having the structural formula wherein R is chloro, bromo or nitro. 2. The compound of Claim 1 vrtierein R is chloro. 3. The compound of Claim 1 wherein R is brcmo. 4. The compound of Claim 1 wherein R is nitro. 5. An intermediate compound having the structural formula wherein R is chloro, brαno or nitro and M is hydrogen, sodium, potassium or ammonium. 6. The compound of Claim 3 wherein R is chloro and M is sodium. 7. The compound of Claim 5 wherein R is brcmo and M is sodium. 8. he compound of Claim 5 wherein R is nitro and M is sodium. 9. A process for preparing 2-(chloro, bromo or nitro)-4-(alkyl- sulfonyl) benzoic acid compounds having the structural formula wherein R is chloro, brcmo or nitro and R 1 is hydrogen or C1-C3 alkyl, comprising 1 ) reacting a compound having the structural formula wherein R is as defined with a reducing agent along with a base in an aqueous medium to prepare a cccnpound having the structural formula wherein R is chloro, bromo or nitro and M is sodium, potassium or anmonium and 2) reacting the prepared cαipound from step (1) with an c -halocarboxylic acid compound having the structural formula X R'-CH-COO M wherein X is chloro, brαno or iodo; R > is hydrogen or C1-C3 alkyl; and M is sodium, potassium or anmonium, to prepare a benzoic acid compound having the structural formula S02CH2R 1 !3 wherein M, R and R> are as defined, and finally acidifying the ccmpound to prepare the desired product having the structural formula COOH 1 & S02CH2R 1 wherein R and R^ are as defined. 10. The process of Claim 9 wherein R is chloro, R 1 is hydrogen, M is sodium and X is chloro. 11. The process of Claim 9 wherein R is nitro, R^ is hydrogen, M is sodium and X is chloro. 12. The process of Claim 9 wherein the cK-halocarboxylic acid ccmpound of step (2) is prepared in situ from about equal molar amounts of an <?(-halocarboxylic acid of the structural formula X . i R'-CH-COOH wherein R1 and X are as defined and a base having sodium, potassium or ammonium as the cation. 13. The process of Claim 9 wherein the base is an inorganic base having a sodium, potassium or anmonium cation.

Inventors: BROWN RICHARD W, BROWN, RICHARD, W.
Applicants: ICI AMERICA INC, ICI AMERICAS INC.
Application year: 1989
Main classification: C07C309
IPC codes: C07C309, C07C313, C07C315, C07C317