Methylcyclohexene, acetylations, acetyl chloride

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

Epoxyketone 60 has also been prepared by hydroxyselenation of 4-acetyl-1-methylcyclohexene with phenylselenium chloride and water, oxidation of the selenide to selenoxide with buffered aqueous oxone, and elimination of the se-lenoxide in the same pot to provide the epoxide [80]. Control of the conditions was essential to prevent epimerization of the ketone. This route has little to recommend it given the expense and toxicity of the reagents, the moderate yield, and the problems with epimerization. 

Acetyl-n-valeric acid has been prepared by the oxidation of 1-methylcyclohexene with potassium permanganate 5 by the oxidation of 2-methylcyclohexanone with chromic oxide and sulfuric acid 6 by the reaction of methylzinc iodide on the ethyl ester of adipic acid chloride and saponification of the ethyl ester of 5-acetyl-w-valeric acid so obtained 7 by the saponification of the ethyl ester of diacetylvaleric acid 2 and through the hydrolysis of ethyl a-acetyl-6-cyanovalerate with boiling 20% hydrochloric acid.3... 

The previously unknown (+ )-(lS,2S,4R)-isodihydrocarveol (157) has been made from (+ )-limonene epoxide (158) as a component of a mixture of isomers, either with lithium in ethylamine or with the stoicheiometric amount of lithium aluminium hydride. Dihydrocarveol (159) has been synthesized from 4-acetyl-1-methylcyclohexene by conventional means.A method that is said to convert allyl alcohols into the corresponding chlorides without allyl rearrangement has been applied to carveol. The chloride was indeed obtained, but since the rotations of the compounds were not recorded it is unfortunately impossible to draw any conclusions about rearrangement. An ingenious synthesis of pure stereoisomers of carvomenthone-9-carboxylic acids involves a [2 -I- 2]-type cycloaddition of an ynamine to 2-methylcyclohex-5-enone (160). This leads... 

In contrast to the aromatic counterpart, very few works have been devoted to the mechanism of the aliphatic Friedel-Crafts acylation. Several mechanisms have been proposed to explain the reaction of 1-methylcyclohexene in acetic acid with zinc chloride catalyst that exclusively gives the 6-acetyl-l-methylcyclohexene. Early discussions by Deno suggest a carbo-cation intermediate. Finally, the observations by Beak of a product isotope effect in the absence of a corresponding kinetic isotope effect in the series of deuterated cyclenes is compelling evidence for a reaction intermediate, such as carbocation species. In the meantime, H.M.R. Hoffmann observed that the acylation of various olefins with acetyl hexachloroantimonate in methylene chloride in the presence of hindered amines affords 8,T-unsaturated ketones. He suggested that the non-conjugated enone is formed via an ene reaction. 

---