3-Cyclohexyl-4-methyl- - acyl

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). 

This reaction was first reported by Nenitzescu in 1931. It is the formation of an a,p-unsaturated ketone directly by aluminum chloride-promoted acylation of alkenes with acyl halides. Therefore, it is known as the Darzens-Nenitzescu reaction (or Nenitzescu reductive acylation), or Nenitzescu acylation. Under such reaction conditions, Nenitzescu prepared 2-butenyl methyl ketone from acetyl chloride and 1-butene and dimethylacetylcyclohex-ene from acetyl chloride and cyclooctene. However, in the presence of benzene or hexane, the saturated ketones are often resolved, as supported by the preparation of 4-phenyl cyclohexyl methyl ketone from the reaction of cyclohexene and acetyl chloride in benzene, and the synthesis of 3- or 4-methylcyclohexyl methyl ketone by refluxing the mixture of cycloheptene and acetyl chloride in cyclohexane or isopentane. This is probably caused by the intermolecular hydrogen transfer from the solvent. In addition, owing to its intrinsic strain, cyclopropyl group reacts in a manner similar to an oleflnic functionality so that it can be readily acylated. It should be pointed out that under various reaction conditions, the Darzens-Nenitzescu reaction is often complicated by the formation of -halo ketones, 3,)/-enones, or /3-acyloxy ketones. This complication can be overcome by an aluminum chloride-promoted acylation with vinyl mercuric chloride, resulting in a high purity of stereochemistry. ... 

A number of nonnatural amino acids were resolved into individual enantiomers on 0-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSPby Peter and coworkers [48,90,113,114] after derivatization with Sanger s reagent, chloroformates (DNZ-Cl, FMOC-Cl, Z-Cl), Boc-anhydride, or acyl chlorides (DNB-Cl, Ac-Cl, Bz-Cl). For example, the four stereoisomers of P-methylphenylalanine, P-methyltyrosine, P-methyltryptophan, and P-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid could be conveniently resolved as various A-derivatives [113]. The applicability spectrum of cinchonan carbamate CSPs comprises also P-amino carboxylic acid derivatives, which were, for example, investigated by Peter et al. [114]. A common trend in terms of elution order of DNP-derivatized P-amino acids was obeyed in the latter study On the utilized quinine carbamate-based CSP, the elution order was S before R for 2-aminobutyric acid, while it was R before S for the 3-amino acids having branched R substituents such as wo-butyl, iec-butyl, tert-butyl, cyclohexyl, or phenyl residues. 

Hoft reported about the kinetic resolution of THPO (16b) by acylation catalyzed by different lipases (equation 12) °. Using lipases from Pseudomonas fluorescens, only low ee values were obtained even at high conversions of the hydroperoxide (best result after 96 hours with lipase PS conversion of 83% and ee of 37%). Better results were achieved by the same authors using pancreatin as a catalyst. With this lipase an ee of 96% could be obtained but only at high conversions (85%), so that the enantiomerically enriched (5 )-16b was isolated in poor yields (<20%). Unfortunately, this procedure was limited to secondary hydroperoxides. With tertiary 1-methyl-1-phenylpropyl hydroperoxide (17a) or 1-cyclohexyl-1-phenylethyl hydroperoxide (17b) no reaction was observed. The kinetic resolution of racemic hydroperoxides can also be achieved by chloroperoxidase (CPO) or Coprinus peroxidase (CiP) catalyzed enantioselective sulfoxidation of prochiral sulfides 22 with a racemic mixmre of chiral hydroperoxides. In 1992, Wong and coworkers and later Hoft and coworkers in 1995 ° investigated the CPO-catalyzed sulfoxidation with several chiral racemic hydroperoxides while the CiP-catalyzed kinetic resolution of phenylethyl hydroperoxide 16a was reported by Adam and coworkers (equation 13). The results are summarized in Table 4. 

A first hint comes from the fact that the carbonyl carbon of the acyl substituent in IV may be the a carbon of the enol ether moiety in I. In fact, the vinyl ether would be converted into a methyl ketone by breakage of the bond between the acetal carbon and the endocyclic oxygen. In that case, the resulting oxycarbenium ion would serve as a linking position for the carbocyclization that eventually affords the cyclohexyl ring of IV. 

The 209D diastereomer (+ )-590 has also been made by Comins and Zhang (Scheme 78) 466,467). After 77-acylation of the 4-methoxypyridine 591 with (1 S,2R,4S)-4-isopropyl-2-( 1 -methyl-1 -phenylethyl)cyclohexyl chloroformate, the resulting pyridinium salt was intercepted with hexylmagnesium chloride to give the optically active enaminone 592. Removal of the chiral auxiliary and A -alkylation with (Z)-l,3-diiodopropene yielded 593, thereby setting the scene for a novel anionic... 

Nakamiya strain of Japanese encephalitis virus in mice [201]. Thiobarbiturates of type (XLIV, R = C11H23 to C18H37) are claimed to have antiviral activity, especially against influenza [202]. In a related patent the allyl substitution is extended to include Ci-Cg derivatives, which may be alkyl, alkenyl, chloroalkenyl, cyclohexyl or cyclohexenyl [203]. 5-Butyl-5-ethyl-barbituric acid and the 1-methylbutyl analogue (pentobarbitone), as well as two thiouracil derivatives, were found to have a direct virucidal action in vitro on poliomyelitis viruses in monkey testicular and kidney cultures [204]. Among a series of 5-halo, 5-acyl, 5-benzylidene, and 5-phenylcarbamoyl derivatives of 1-H, 1-methyl, and 1-phenylbarbituric acids, the sodium salt... 

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