Methylcyclopentanone

Fifty grams (0.31 mole) of /J-methyladipic acid (p. 195) is placed in a distillation apparatus and heated gently for about 5-6 hours. Distillation begins when the temperature of the reaction mixture has remained at 312° for about 1 hour. Most of the material distils at 319-324° (thermometer in the liquid), leaving only a small black residue. The distillate is shaken with excess dilute aqueous ammonia, and the upper organic layer is separated and dried over anhydrous calcium chloride. Distillation gives 23 g. (75%) of the ketone boiling at 143-144.5°/756-764 mm., ng 1.433. 

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Identify the thermodynamie enolate for each system shown above (2-pentanone enolate A and B 2-methylcyclopentanone enolate A and B decalinone enolate A and B). Also, compare eleetrostatic potential maps for eaeh pair of enolates. What struetural and/or electronic features, if any, appear to dictate which enolate is favored ... 

The addition of 2-nitropropene to the chiral imlne derived from 2-methylcyclopentanone and fS -Tphenylethylamine gives the adduct in high regio- and stereoselectivity fEq 471 The product is converted to a chiral 1,4-diketone via the Nef reaction... 

As observed with cyclohexanones, the diastereoselectivity of the addition reaction of trimeth-ylaluminum to 2-methylcyclopentanone depends on the stoichiometry of the reactants. Thus, addition of one equivalent of trimcthylaluminum proceeds via preferential tram attack whereas, due to the "compression effect , addition of an excess of the reagent leads to the formation of the equatorial alcohol via predominant attack from the cis side (Table 3)6. In contrast to the addition reactions with trimethylaluniinum, no reversal of the diastereoselectivity upon change of reagent stoichiometry was observed in the addition of triphenylaluminum to 2-methylcyclopentanone6. Even with an excess of the aluminum reagent trans attack predominates. However, the diastereoselectivity is lower than with the use of an equimolar amount of the reactants. 

The syn TS is favored by about 1 kcal/mol, owing to reduced eclipsing, as illustrated in Figure 1.4. An experimental study using the kinetic enolate of 3-(/-butyl)-2-methylcyclopentanone in an alkylation reaction with benzyl iodide gave an 85 15 preference for the predicted cis-2,5-dimethyl derivative. 

The two established Hnls, those from L. usitatissimum and P. amygdalus, have found biocatalytic applications for the production of (i )-cyanohydrins. The former of these Hnls is the least widely applied, the natural substrates being acetone cyanohydrin or (i )-2-butanone cyanohydrin (Table 1) [28]. Although an improved procedure for the purification of this enzyme has been reported [27] it is still only available in limited quantities (from 100 g of seedlings approximately 350 U of enzyme are obtained). It was found that this enzyme transforms a range of aliphatic aldehyde and ketone substrates [27], the latter of which included five-membered cyclic (e.g. 2-methylcyclopentanone) and chlorinated ketone substrates. In contrast, attempts to transform substituted cyclohexanones and 3-methylcyclopentanone failed and it was even found that benzaldehyde deactivated the enzyme. 

In the Clemmensen reduction of 1,4-cyclohexanedione, all the products isolated from the reduction of 2,5-hexanedione were found in addition to 2,5-hexanedione (20%) and 2-methylcyclopentanone (6%). The presence of the two latter compounds reveals the mechanism of the reduction. In the first stage the carbon-carbon bond between carbons 2 and 3 ruptured, and the product of the cleavage, 2,5-hexanedione, partly underwent aldol condensation, partly its own further reduction [927], The cleavage of the carbon-carbon bond in 1,4-diketones was noticed during the treatment of 1,2-diben-zoylcyclobutane which afforded, on short refluxing with zinc dust and zinc chloride in ethanol, an 80% yield of 1,6-diphenyl-1,6-hexanedione [75<5]. 

In work which remains unpublished, Wenkert has succeeded in cleverly transforming 2-methylcyclopentanone into isocomene The key elements of his strategy (Scheme LXXXIII) are the acid-catalyzed ring expansion of methoxycyclopropane 747 to 748 and the regiospecific homologation of the cyclobutanone to 749. Unfortunately, the Wolff-Kishner reduction of this penultimate intermediate affords both 731 and its epimer. 

The regioselectivity of the enolization can be controlled in a similar way for cyclic ketones. Typical examples are the enolization of 2-methylcyclopentanone (6)5 and 2-methylcyclohex-anone (7)9, u. 

Reaction of 3,3-disubstituted-l,4-pentadiene 92 with a primary amine under cyclohydrocarbonylation conditions yielded cyclopenta[. ]pyrrole 96 as the predominant product accompanied by a small amount of cyclopentanone 95 (Scheme 15). This unique reaction is proposed to proceed through a cascade hydrocarbonylation-carbonylation process. The first hydrocarbonylation of 92 and the subsequent carbocyclization formed cyclopentanoylmethyl-Rh complex 93. If 93 immediately reacts with molecular hydrogen, 2-methylcyclopentanone 95 is formed. However, if CO insertion takes place faster than the hydrogenolysis, cyclopentanoylacetyl-Rh complex 94 is generated, which undergoes the Paal-Knorr condensation with a primary amine to yield cyclopenta[. ]pyrrole 96. ... 

Hydrocarbonylation of 1,4-dienes.3 Hydrocarbonylation of 1,4-pentadiene catalyzed by Co2(CO)8 results in 2-methylcyclopentanone as the only cyclic product. As expected, a gem-dimethyl group at C3 enhances the tendency to form cyclo-pentanones. Thus hydrocarbonylation of the 1,4-diene 1 leads to the tetramethyl-cyclopentanone 2 with a marked preference for the cw-isomer. The reaction has... 

The same process was used to obtain 4 from 2 and methyl acrylate, and to obtain 5 and 6 from the imine of 2-methylcyclopentanone. 

Unsymmetrical ketones can yield two different enolates, and in some cases the one that is the less stable thermodynamically is formed faster.148 Scheme 24 illustrates the example of 2-methylcyclopentanone. When this ketone is added slowly to excess f-butyllithium, the proton is removed preferentially from the less substituted carbon. If excess ketone is added, it can serve as a proton donor to allow equilibrium to be established, and nearly all the enolate is then the more highly substituted one.149 It may be possible in some cases to take advantage of such a selective formation of one of two possible enolates in synthesis. A more general procedure is to use a compound in which the desired position is activated... 

In addition to acyclic ketones, dolichoderine ants in the genus Azteca generate an alarm signal with 2-methylcyclopentanone (xxxi),cis-l-acetyl-2-methylcyclopentane (XXXII), and 2-acetyl-3-methylcyclopentene (XXXIII) (128). That some ant species utilize aromatic compounds as alarm pheromones is demonstrated by the identification of methyl 6-methyl salicylate (XXXIV) in the... 

The rates for the methylation of cyclopentanone and for the proton abstraction from 2-methylcyclopentanone were significantly increased by a factor of 7500 and 5, respectively, when six equivalents of HMPA were added to the reaction. Using 31P, 7Li and 13C NMR spectroscopy, Suzuki and Noyori found that the tetrasolvated Dy dimer was exclusively generated from the tetrameric (T0,4) and dimeric (D0,4) tetrasolvated lithium amine-free enolate of cyclopentanone (0.16 M in THF, —100 °C, ratio 2/3)275. Kinetic analysis gave a first-order reaction in dimer and HMPA for the reaction with a modulation for free HMPA33, and a first-order reaction in dimer for deprotonation, independent of HMPA. Possible transition state structures for alkylation and proton abstraction are drawn in Scheme 85. 

Hydrocarbonylation of 1,4-dienes. 1,4-Dienes bearing two substituents at C, undergo hydrocarbonylation catalyzed by Co2(CO)n to give 2-methylcyclopentanones as the main product (equation I). ... 

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