Benzene → beta-Phenylisovaleric acid

Temperature

0 °C

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.

1. customwhich produced vigorous bubbling
2. customUpon completion of the bubbling, a capped condenser (i.e. closed system)
3. customplaced in an oil bath at 65° C
4. stirringstirring
5. dissolutiondissolved
6. extractionThe aqueous layer was extracted with diethyl ether three times
7. concentrationThe organic layer was concentrated to 150 mL
8. extractionwas extracted with a saturated sodium hydrogen carbonate solution six times
9. extractionThe acidic aqueous layer was extracted with diethyl ether three times
10. dry with materialthe accumulated organic layer was dried with magnesium sulfate
11. filtrationThe solution was filtered
12. customthe diethyl ether was removed in vacuo

ORD record

ord-771e1bd9caaa4c45bfe4520ecd5d4c80

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07579323B1