Method A. 2-Nitrobenzoic acid derivatives.

A. 2-nitrobenzoate. A 1-L, two-necked, round-bottomed flask equipped with a magnetic stirring bar and a 250-mL dropping funnel is charged with 2-nitrobenzoic acid (33.4 g, 200 mmol) and 200 mL of ethanol. To this solution is added a solution of potassium hydroxide (85%) (13.2 g, 200 mmol, 1.00 equiv) in 200 mL of ethanol dropwise over 2 h. After complete addition, the reaction mixture is stirred for another 1 h at room temperature. A gradual formation of a white precipitate is observed. The resulting solid is collected by filtration through an 10-cm Büchner funnel (fitted with Whatman-1 filter paper, 90 mm), washed sequentially with ethanol, 2 × 50 mL, and 50 mL of cold (0 °C) diethyl ether, transferred to a 500 mL round-bottomed flask, and dried at 1.0 mmHg to provide potassium 2-nitrobenzoate (35.3 g, 86%) as a white powder.
 

B. 4-Methyl-2'-nitrobiphenyl. An oven-dried 500-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, an internal thermometer and a reflux condenser fitted with a nitrogen gas inlet, is charged with potassium 2-nitrobenzoate (22.6 g, 110 mmol, 1.10 equiv), (1,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate (1.25 g, 1.50 mmol, 0.015 equiv) and palladium acetylacetonate (45.7 mg, 0.15 mmol, 0.0015 equiv). After deoxygenating the flask with three alternating vacuum and nitrogen purge cycles, a solution of (12.3 mL, 100 mmol) in 150 mL of anhydrous mesitylene is added. The flask is lowered into an oil bath preheated to 175 °C, so that the internal temperature remains constant at 150 °C. After the reaction mixture is stirred and heated for 16 h, an aliquot checked by GC analysis indicates that the reaction is complete. The heat source is removed and the mixture is allowed to stir for 2 h further while cooling to room temperature. The nitrogen source is removed and any condensate is washed from the condenser into the reaction mixture with 10 mL of ethyl acetate. The mixture is then suction filtered through a 6-cm fritted glass funnel (coarse) containing a 1 cm bed of dry Celite into a 500-mL round-bottomed flask. The filter cake is rinsed with ethyl acetate, 3 × 20 mL. The resulting dark brown filtrate and the washes are concentrated under reduced pressure (23 °C, 20 mmHg). The residue is purified by Kugelrohr distillation at 1.0 mmHg, gradually increasing the oven temperature from 25 °C to 155 °C. The fraction distilling at 155 °C oven temperature contains 4-methyl-2'-nitrobiphenyl (21.1 g, 99%) as a pale yellow oil.
 

Method B. Other ortho-substituted benzoic acids.
 

A. Potassium 2-acetylbenzoate. A 500-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar and a 250-mL dropping funnel is charged with 2-acetylbenzoic acid (16.4 g, 100 mmol) and 100 mL of ethanol. To this solution is added a solution of 85 % potassium hydroxide (6.6 g, 100 mmol, 1.00 equiv) in 100 mL of ethanol dropwise over 1 h. After complete addition, the reaction mixture is stirred for another 1 h at room temperature. The solvent is removed at 60 °C and 20 mmHg on a rotary evaporator to afford the crude product as a foam. The crude product can be crystallized by dissolving it in 17 mL of boiling ethanol, slowly cooling the solution to room temperature, and then carefully layering it with 70 mL of diethyl ether. The biphasic mixture is then allowed to stand for 12 h at room temperature then 24 h at -20 °C. The resulting off-white crystals are collected by filtration through an 8-cm Büchner funnel (fitted with Whatman-1 filter paper, 70 mm), then are washed sequentially with 3 × 25 mL of diethyl ether, are transferred to a 250-mL round-bottomed flask, and are dried at 1.0 mmHg to provide potassium 2-acetylbenzoate (19.2 g, 95%) as colorless crystals.

 

B. 2-Acetyl-4'-methylbiphenyl. An oven-dried 250-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, an internal thermometer and a reflux condenser fitted with a nitrogen gas inlet, is charged with potassium 2-acetylbenzoate (8.9 g, 44 mmol, 1.10 equiv), copper(I) bromide (574 mg, 4.00 mmol, 0.10 equiv), 1,10-phenanthroline (721 mg, 4.00 mmol, 0.10 equiv), palladium acetylacetonate (122 mg, 0.40 mmol, 0.01 equiv), and bis(diphenylphosphino)methane (307 mg, 0.80 mmol, 0.02 equiv). After deoxygenating the flask with three alternating vacuum and nitrogen purge cycles, a solution of 4-bromotoluene (4.92 mL, 40 mmol) in a mixture of 60 mL of anhydrous 1-methyl-2-pyrrolidone and 20 mL of anhydrous quinoline is added. The flask is lowered into an oil bath preheated to 180 °C, so that the internal temperature remained constant at 160 °C. After stirring the reaction mixture for 24 h, the heat source is removed and the reaction mixture is allowed to stir while cooling to room temperature. The nitrogen source is removed and any condensate is rinsed from the condenser into the reaction mixture with 10 mL of ethyl acetate. The reaction mixture is suction filtered through a 6-cm fritted glass funnel (coarse) containing a 1 cm bed of dry Celite into a 250-mL round-bottomed flask. The filter cake is rinsed with ethyl acetate, 3 × 15 mL. The resulting dark brown filtrate and washings are transferred into a 250-mL separatory funnel and are washed with a 1 N aqueous hydrochloric acid solution (1 × 100 mL and 2 × 50 mL). Each aqueous layer is extracted with ethyl acetate, 2 × 35 mL. The combined organic phases are washed with brine (1 × 100 mL), dried over anhydrous magnesium sulfate (2-3 g) and filtered. The solvent is evaporated under reduced pressure (23 °C, 20 mmHg), and the residue is purified by Kugelrohr distillation at 1.0 mmHg, gradually increasing the oven temperature from 25 °C to 130 °C. The fraction distilling at 130 °C oven temperature contains 2-acetyl-4'-methylbiphenyl (6.78 g, 81%) as a pale-green liquid.