L-Acetyl-2-methylcyclohexene

The purity of the product was determined by the checkers by GLC analysis using the following column and conditions 3-nm 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 rain). 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 l-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% in runs conducted at about -15 to -20°C or at temperatures below -23°C. 

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 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. ... 

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 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. 

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