Benzene → beta-Phenylisovaleric acid

Participants

Reaction Conditions

Reaction Steps

3-Methyl-2-butenoic acid (1, 5.10 g, 50.9 mmol) and AlCl3 (20.4 g, 153 mmol) were placed in a one-neck round-bottomed flask. Benzene (50 mL) was added, which produced vigorous bubbling. Upon completion of the bubbling, a capped condenser (i.e. closed system) was attached, the reaction mixture was stirred and placed in an oil bath at 65° C. The pressure in the system was occasionally released. The progress of the reaction was followed by following the loss of starting material by GC. If the reaction was not complete within 1 h, a small quantity of AlCl3 was added and stirring was continued. To the solution was added diethyl ether and the mixture was cooled to 0° C. Slowly conc. HCl and some water were added until all the solid dissolved and the pH was less than 2. The aqueous layer was extracted with diethyl ether three times. The organic layer was concentrated to 150 mL and then was extracted with a saturated sodium hydrogen carbonate solution six times. The combined aqueous layer were acidified with conc. HCl until the pH was less than 2. The acidic aqueous layer was extracted with diethyl ether three times and the accumulated organic layer was dried with magnesium sulfate. The solution was filtered and the diethyl ether was removed in vacuo producing a white solid (8.51 g, 47.7 mmol) in 94% yield, which did not need further purification. mp 55-56° C. 1H-NMR (400 MHz, CDCl3) 10.45 (bs, 1H, CO2H), 7.38 (d, 2H, J=7.2 Hz, H-11 and H-7), 7.32 (t, 2H, J=7.2 Hz, H-10 and H-8), 7.21 (t, 2H, J=7.2 Hz, H-9), 2.65 (s, 2H, H-2), 1.47 (s, 6H, H-5 and H-4); Mass spectrum (EI) 178 (23, M.+), 119 (100, [C9H11]+). For pioneering work to form 2 see: F. J. Eijkman (1908) Chem. Kentr. II, p. 110; or A. Hoffman (1929) J. Am. Chem. Soc. 51:2542.

Provenance & Evidence