Effect of solvents on the reactivity of carbonyl compounds in Michael and C-alkylation reactions

Summary

• 1. When boiled in methanol solution with methyl iodide, the sodium derivative of 2-methyl-1,3-cyclo-hexanedione (III) gives 2,2-dimethyl-1,3-cyclohexanedione (IV) in 46% yield.

• 2. When boiled for four hours with methyl iodide in aqueous methanol, the potassium derivative of 3-methyltetronic acid (VII) gives 3,3-dimethyltetronic acid (VIII) in 27% yield.

• 3. The potassium derivative of Hagemann's ester (X) reacts vigorously with methyl iodide in dry tert-butyl alcohol at room temperature with formation of ethyl 2,3-dimethyl-4-oxo-2-cyclohexene-1-carboxylate (XI) in 77% yield. Further methylation of Hagemann's ester under the same conditions gives the dimethyl derivative (XII), hydrolysis of which gives 2,3,3-dimethyl-4-oxo-1-cyclohexene-1-carboxylic acid (XIII).

• 4. Reaction of methyl 5-oxo-6-heptenoate (XIX) with 2-methyl-3-oxocyclohexanecarbonitrile (XX) in tert-butyl alcohol in presence of potassium tert-butoxide, followed by hydrolysis and cyclization of the reaction product (XXI), gives the bicyclic dicarboxylic acid (XXII).

• 5. Unlike the strongly enolized (acidic) derivatives of 1,3-cyclohexanedione and tetronic acid, which undergo Michael and C-alkylation reactions more readily in aqueous solvents, neutral carbonyl compounds such as cyclohexanone generally react more readily in nonaqueous solvents such as dry tert-butyl alcohol.