Hydrochloric Acid → 4,4-Dimethyl-6-hydroxymethyl-2-cyclohexen-1-one

Temperatur

0 °C

To a solution of diisopropylamine (7.27 g, 7 mmol) in anhydrous tetrahydrofuran (THF) was added drop wise a hexane solution (1.62 mol/l) of n-butyllithium (44.4 ml, 70 mmol) at −78° C. The solution was warmed to 0° C. and stirred for 1 hr at this temperature. After thus prepared lithium diisopopylamide solution was again cooled to −78° C., 4,4-dimethyl-2-cyclohexen-1-one (7.5 g, 60 mmol) was added dropwise and stirring was continued for 1 hr. Then, gaseous formaldehyde, generated by a thermal decomposition of paraformaldehyde (5 g) over an oil bath, was blown through the solution with a gentle stream of dry nitrogen gas and the reaction mixture was stirred for 2 hr. After standing over night at room temperature, 1N hydrochloric acid was added until the solution became weak acid. The solvent was removed and the residue was extracted with ether. After drying over anhydrous sodium sulfate and removal of the solvent, a mixture of 4,4-dimethyl-6-methylene-2-cyclohexen-1-one and 4,4-dimethyl-6-hydroxymethyl-2-cyclohexen-1-one was obtained (7.03 g). This mixture (3.0 g) was treated in reflxing benzene for 2 hr in the presence of catalytic amount of anhydrous p-toluenegulfonic acid and molecular sieve 3A (4 g). The solution was neutralized with 1N sodium bicarbonate and washed with brine. After drying over anhydrous sodium sulfate and removal of the solvent, crude 4,4-dimethyl-6-methylene-2-cyclohexen-1-one (Yoshixol) was obtained (2.35 g, overall yield 68%). The analytical sample was available. 2-cyclohexen-1-one was obtained (2.35 g, overall yield 68%). The analytical sample was available after purification by column chromatography or kugelrohr distillation but yield was much lowered. This NMR analysis of Yoshixol is following: IR(neat): 1670(C═O), 1620(C═C) cm-1. 1H NMR (60 MHZ, CCL4), d1.15 (s, 6H, C(CH3)2), 2.57 (bs, 2H, CH2), 5.20, 5.93 (2m, 2H, CH2=), 5.87 (d, J=10, 1H, 2-H), 6.63 (d, J=10 Hz, 3-H).

1. stirringstirring
2. waitwas continued for 1 hr
3. stirringthe reaction mixture was stirred for 2 hr
4. waitAfter standing over night at room temperature
5. customThe solvent was removed
6. extractionthe residue was extracted with ether
7. dry with materialAfter drying over anhydrous sodium sulfate and removal of the solvent
8. additiona mixture of 4,4-dimethyl-6-methylene-2-cyclohexen-1-one

ORD-Eintrag

ord-60b3f0e2802d4ec6a669fb38cf9a78a7

Quelldatensatz

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07605183B2