Ketone cyclohexyl methyl

Using Figure 17 15 as a guide write a mechanism for the ] Baeyer-Villiger oxidation of cyclohexyl methyl ketone by peroxybenzoic acid J... 

Cyclohexyl methyl ketone gives cyclohexyl acetate, bp 74-77°/23 mm,... 

METHYL KETONES FROM CARBOXYLIC ACIDS CYCLOHEXYL METHYL KETONE... 

The product may be analyzed by use of a gas chromatography column packed with either LAC-728 (diethylene glycol succinate) or Carbowax 20M suspended on Chromosorb P. Using a 2.5-m. LAC-728 column heated to 100°, the submitters found retention times of 9.4 and 13.0 minutes for cyclohexyl methyl ketone and cyclohexyldimethylcarbinol. Less than 1% of the carbinol by-product was present. 

Apart from the reaction of cyclohexanecarboxylic acid with methyllithium, cyclohexyl methyl ketone has been prepared by the reaction of cyclohexylmagnesium halides with acetyl chloride or acetic anhydride and by the reaction of methylmagnesium iodide with cyclohexanecarboxylic acid chloride. Other preparative methods include the aluminum chloride-catalyzed acetylation of cyclohexene in the presence of cyclohexane, the oxidation of cyclohexylmethylcarbinol, " the decarboxylation and rearrangement of the glycidic ester derived from cyclohexanone and M)utyl a-chloroj)ropionate, and the catalytic hydrogenation of 1-acetylcycIohexene. "... 

Scheme 6.3 Reaction scheme for the hydrogenation of acetophenone. AP acetophenone PE 1-phenylethanol CHMK cyclohexyl methyl ketone CHE 1-cyclohexylethanol ST styrene EB ethylbenzene and ECH ethylcyclohexane.

CMK = cyclohexyl methyl ketone, CHE = 1-cyclohexylethanol, EB = ethylbenzene and ECH = ethylcyclohexane). 

Table 6.13 Racemic hydrogenation of acetophenone" initial reaction rate rf, selectivity to products at 100% conversion. Results for the chemical reduction with NaBH4 are included for comparison. PE 1-phenylethanol, CHMK cyclohexyl methyl ketone and CHE 1-cyclohexylethanol. (Reproduced from Reference [34])...

Aliphatic Ketones The asymmetric hydrogenation of simple aliphatic ketones remains a challenging problem. This may be attributed to the difficulty with which the chiral catalyst differentiates between the two-alkyl substituents of the ketone. Promising results have been obtained in asymmetric hydrogenation of aliphatic ketones using the PennPhos-Rh complex in combinahon with 2,6-lutidine and potassium bromide (Tab. 1.11) [36]. For example, the asymmetric hydrogenation of tert-butyl methyl ketone affords the requisite secondary alcohol in 94% ee. Similarly, isopropyl, Butyl, and cyclohexyl methyl ketones have been reduced to the corresponding secondary alcohols with 85% ee, 75% ee, and 92% ee respectively. 

Baeyer-Villiger oxidation of cyclohexyl methyl ketone by peroxybenzoic acid. 

Excellent enantioselectivity was achieved for the transfer hydrogenation of pinacolone by using (S)-25a as a catalyst with 2-propanol in the presence of (CH3)2CHONa to give the S alcohol in >99% ee (Scheme 28) [90], 2,2-Dimethyl-cyclohexanone was reduced with the same catalyst with 98% optical yield. Reduction of cyclohexyl methyl ketone with (S)-25b gave the S alcohol in 66% ee. 

Enantioselective reduction of simple aliphatic ketones is one of the most challenging of the currently unresolved problems in this field. The Rh/4 complex catalyzed the hydrosilylation of 2-butanone with diphenylsilane at 0 °C, which after hydrolysis gave (S)-2-butanol in 56% ee (Scheme 3) [17]. 2-Octanone and 4-phenyl-2-butanone were reduced with diphenylsilane in the presence of the cationic Rh/EtTRAP-H at -50 °C and gave optical yields of 77% and 81%, respectively [12], The cationic Rh/(R,R)-t-Bu-MiniPHOS was also effective for the reduction of 4-phenyl-2-butanone with 1-naphthylphenylsilane at -20 °C, affording the R product in 80% ee [13]. 3-Methyl-2-butanone was reduced using the Rh/4 complex with 76% optical yield [17]. Hydrosilylation of cyclohexyl methyl ketone with the Rh/(R,S)-2 complex followed by hydrolysis afforded the R alcohol in 87% ee [8]. Highly enantioselective hydrosilylation of pinacolone with diphenylsilane at -20 °C was achieved by means of the Rh/4 complex and yielded the desired R product in 95% ee [17]. 

Alkyl aryl ketimines were reduced with up to 99% ee (Scheme 8) [24]. The high enantioselectivity was not affected by the E Z ratio of the imines. For example, a 1.8 1 E Z mixture of the N-propylimine of 4 -methoxy-3-methyIbuty-rophenone was converted to the desired product in 97% optical yield. Hydrosilylation of the N-propylimine of cyclohexyl methyl ketone with a substrate to Ti molar ratio of 2,000 1 was completed to give the product in 98% ee [24]. N-Benzylimine of 2-octanone, a simple aliphatic ketimine, was reduced with 69% optical yield. The reduction of W-benzyl-l-indanimine gave the corresponding amine in 92% ee (Scheme 9) [24]. 

AT-Phenylimine of cyclohexyl methyl ketone was hydrosilylated using PMHS (12 equivalents) as a reducing agent with a slow addition of i-C4H9NH2... 

Another important development is chiral titanocene catalyst using 203 as the catalyst precursor225. The (R, R)-(EBTK)Ti(OR)2 (203) is proposed to generate the active catalyst species, (R, R)-(EBTHI)TiH , upon reaction with n-BuLi (2 equivalents) and polymethyl-hydrosiloxane (PMHS). This chiral Ti-catalyst system is highly efficient for the reactions of aromatic alkyl ketones achieving >90% ee in many cases. In sharp contrast to this, only 24% ee is obtained for the reaction of cyclohexyl methyl ketones. However, the reaction of cyclohexen-l-yl methyl ketone achieved 85-90% ee. Thus, it is extremely important for this chiral Ti-catalyst to have a 7r-system to be effective. 

A general convenient alkyl methyl ketone synthesis, which utilises the /7-keto ester system as an intermediate, involves the acylation of a malonate ester by way of the ethoxymagnesium derivative. Hydrolysis and decarboxylation to the ketone is accomplished by heating in acid solution the synthesis of cyclohexyl methyl ketone is the illustrative example (Expt 5.96). 

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