1- Acetyl-2-methylcyclohexene

The purity of the product was determined by the checkers by GLC analysis using the following column and conditions 3-nrn by 1.8-m column, 5% free fatty acid phase (FFAP) on acid-washed chromosorb W (60-80 mesh) treated with dimethyldichlorosilane, 90°C (1 min) then 90° to 200°C (15°C per min). The chromatogram showed a major peak, for methyl 2-methyl-l-cyclohexene-l-carboxylate preceded by two minor peaks for methyl 1-cyclohexene-l-carboxylate and 1-acetyl-2-methylcyclohexene. The areas of the two impurity peaks were 5-6% and 0.5-2% that of the major peak. The purity of the product seems to depend upon careful temperature control during the reaction. The total amount of the two impurities was 14-21% 1n runs conducted at about -15 to -20°C or at temperatures below -23°C. 

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. 

Acetic acid 2-hydroxy-3-oxo-3-phenylpropyl ester 3 - Acetoxy-1 -cyclohexene 17)3-Acetoxy-estr-5(10)-ene-3-one rrara-Cyclohexenyl diacetate 4-Acetyl- 1-Methylcyclohexene 3-(Azidopropenyl)benzene... 

Methylcyclopentene co-ozonolyzed with formaldehyde, acetyl cyanide, or benzoyl cyanide afforded only the normal 1,2,4-trioxolane (secondary ozonide, 88) by contrast, 1-methylcyclohexene co-ozonolyzed with formaldehyde or acetyl cyanide gave no such ozonide, but almost equal amounts of the aldehyde-ozonide 86 and the diozonide 87, as shown in Equation (8) and Table 10. 

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 submitters purified the product by distillation in a Kugelrohr apparatus with an oven temperature of 85-88°C (20 mm) and obtained 3.80-3.85 g (88-89%). The purity of the product was 93-96% according to GLC analysis. The major impurity (2-6%) was l-acetyl-2-methylcyclohexene. 

The photoaddition of an excess of 1-nitrosopiperidine to 3-methylcyclohexene is diastereo-selective and afforded exclusively rran. -2-methyl-6-(l-piperidinyl)cyclohexanone oxime (4) as a mixture of (E)- and (Z)-isomers. The reaction with Ar-nitrosodimethylamine was less efficient and also produced a small amount (2%) of the (E)-trans-regioisomer the major product was separated and reduced to the corresponding 1,2-diamines 5 with slightly different diastereo-selectivity32. The relative ratio of diastereomeric diamines and the relative stereochemistry of the three substituents in the predominant diamine diastereomer were established by HNMR of the. V-acetyl derivative, while those of the minor diastereomer were proposed from mechanistic considerations. The photoaddition of A -nitrosodimethylamine with 4-fer/-butylcyclohex-ene, however, afforded a mixture of diastereomers and regioisomers21,32. 

The nitration of enol acetates with acetyl nitrate is a regiospecific electrophilic addition to the 3-carbon of the enol acetate, followed by a hydrolytic conversion of the intermediate to the a-nitro ketone. With enol acetates of substituted cyclohexanones the stereochemistry is kinetically established. So, 1-acetoxy-4-methylcyclohexene (22) yields the thermodynamically less stable rrans-4-methyl-2-nitrocylo-hexanone (24) in greater proportion cis. trans = 40 60) (equation 8). This mixture can be equilibrated in favor of the thermodynamically more stable cis diastereomer (23) (cis. trans = 85 15). Nitration of 1-ace-toxy-3-methylcyclohexene (25) leads to frans-3-methyl-2-nitrocyclohexanone (26), which is also the thermodynamically more stable isomer (equation 9). No stereoselection occurs in the kinetically controlled nitration with acetyl nitrate of l-acetoxy-5-methylcyclohexene (27 equation 10), but the 1 1 mixture of the 5-methyl-2-nitrocyclohexanones can be equilibrated in favor of the trcms diastereomer (28) (cis trans = 10 90). 2-Alkyl-2-nitrocyclohexanones cannot be prepared in acceptable yields by nitration of the corresponding enol acetates with acetyl nitrate. 

Acetyl-l-methylcyclohexene was synthesized by the method described by Lutz et al. l3) and Fray et al (14) Ninety mmol of SnCU was added to 120 mL of benzene while stirring at 3°C, and then 550 mmol of isoprene was added. The reaction mixture was added to 500 mmol of methyl vinyl ketone over a 15-min period, and then stirred continuously for 2 hr at 5-10°C. The mixture was successively washed with an NaCl aq. solution and KOH aq. solution, and dried with sodium sulfate. After drying, the mixture was evaporated to 31.4 g (a yield of 45.4%). Identification was carried out by GC and GC-MS. The purity of 4-acetyl-1-methylcyclohexene was 96% by GC, containing 4% of 3-acetyl-l-methylcyclohexene. 

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. 

Methylcyclohexene allowed to react at -25° with methyloxocarbonium fluoro-borate in nitromethane 6-acetyl-l-methylcyclohexene. Y 70%. F. e. and reactions s. W. A. Smit et al., Tetrah. Let. 1971, 3101. 

The following Lewis acids are also claimed to be superior to AICI3 Zn(Cu)/CH2l2 (AcCl, CH2CI2, A), by which cyclohexene is converted into acetylcyclohexene in 68% yield (after treatment with KOH/MeOH) ZaCh (AcCl, Et20/CH2Cl2, -75 °C -20 °C), by which 2-methyl-2-butene is converted into a 15 85 mixture of 3,4-dimethyl-4-penten-2-one and 4-chloro-3,4-dimethyl-2-pentanone in quantitative combined yield and SnCU. by which cyclohexene (AcCl, CS2, —5 °C — It) is converted into acetylcyclohexene in 50% yield (after dehydrochlorination with PhNEt2 at 180 C), methylcyclo-hexene (CS2, it) is converted into l-acetyl-2-methylcyclohexene in 48% yield (after dehydrochlorination), and camphene is converted into an acetylated derivative in 65% yield. ... 

Employment of AC2O instead of AcCl is also advantageous in some cases. For example, methylcyclohexene can be converted into 3-acetyl-2-methylcyclohexene in 90% yield by treatment with ZnCl2 (neat AC2O, rt, 12 h). ... 

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