Cyclohexanones, 2-alkyl-5-methyl

Cyclohexanones, 2-alkyl-5 methyl-, 56 Cyclohexene, 34 Cyclohexene, 1,6-dibromo-, 34 CYCLOHEXENE, 3-METHYL-, 101 Cyclohexene, 1-phenyl- [Benzene, (1-eyclohexen-l-yl)-], 106 2-Cyclohexen-l-ol, 2-bromo-, 34 2-Cyclohexen-l-ol, 3-methyl-, 101 2-Cyclohexen-l-one, 2-allyl-3-methyl-[2-Cyclohexen-l-one, 3-methyl-2-(2-piopenyl)-], 55... 

With alkyl methyl ketones (R-CH2,CO,Me) the reaction is complicated by the presence of two alternative sites of oxidation in practice the methyl group appears to be oxidised in preference to the methylene group for reasons which have not been adequately clarified, but in any case the yields are usually poor. Unsubstituted, or symmetrically substituted cyclic ketones possessing of course an a-methylene group, are similarly converted into 1,2-diketones (e.g. the formation of cyclohexane-l,2-dione from cyclohexanone, Expt 5.99, cognate preparation) unsymmetrically substituted cyclic ketones would normally give rise to regioisomers. 

Their stability at low temperature means that lithium enolates are usually preferred, but sodium and potassium enolates can also be formed by abstraction of a proton by strong bases. The increased separation of the metal cation from the enolate anion with the larger alkali metals leads to more reactive but less stable enolates. Typical very strong Na and K bases include the hydrides (NaH, KH) or amide anions derived from ammonia (NaNH2, KNH2) or hexamethyldisilazane (NaHMDS, KHMDS). The instability of the enolates means that they are usually made and reacted in a single step, so the base and electrophile need to be compatible. Here are two examples of cyclohexanone alkylation the high reactivity of the potassium enolate is demonstrated by the efficient tetramethylation with excess potassium hydride and methyl iodide. 

The Stork variation was pioneered by Stork and co-workers in 1963. It entails the reaction of pyrrolidine or morpholine enamine derived from unsymmetrical cyclohexanones with methyl vinyl ketones. The alkylation is directed to the less substituted carbon opposite to the alkylation regioisomer formed by the standard Robinson annulation conditions. Cyclization to the corresponding octalone then occurs. The morpholine enamine is less reactive than the pyrrolidine and hence pyrrolidine enamine has been mostly used for this approach. An example of such annulation is shown in the s mthesis of 8-methyl-2-oxo-A octalone (19). The pyrrolidine enamine of 2-methylcyclo-hexanone is refluxed in benzene with MVK for 24 h followed by the addition of an acetate buffer and reflux for 4 h, and after the reaction is worked up purification gives 19 in 45% yield. 

Photolysis of pyridazine IV-oxide and alkylated pyridazine IV-oxides results in deoxygenation. When this is carried out in the presence of aromatic or methylated aromatic solvents or cyclohexane, the corresponding phenols, hydroxymethyl derivatives or cyclohexanol are formed in addition to pyridazines. In the presence of cyclohexene, cyclohexene oxide and cyclohexanone are generated. 

In 1954 Stork et al. (i) reported that the alkylation of the pyrrolidine enamine of cyclohexanone (5) with methyl iodide followed by acid hydro-I ysis led to the monoalkylated ketone. It was thus obvious that the enamine (7) derived by the loss of proton from the intermediate methylated iminium cation (6) failed to undergo any further alkylation. 

Methyl vinyl sulfone forms 1,2-cycloaddition adducts with aldehydic enamines, both with and without 3 hydrogens (37). Simple alkylation was reported to take place when phenyl vinyl sulfone was allowed to react with cyclohexanone enamines (58,60), but it has recently been shown that phenyl vinyl sulfone also forms cyclobutane adducts (60a). 

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

Bei der elektrochemischen Reduktion von Cycloalkanonen steht i. a. der stereochemi-sche Aspekt (cis/trans axial/aquatorial) im Vordergrund, so z. B. bei der Reduktion der Methyl- und anderer Alkyl-cyclohexanone, substituierter 2-Oxo-bicyclo[2.2.1]heptane und bei Oxo-dekalinen. Mit zumeist Alkoholen als Solvens fallen die entsprechenden cy-clischen sekundaren Alkohole zu 47-60% d.Th. an7-11. 

In this study we examine the generalities in reductive alkylation however, since the subject is vast, we limited ourselves to the interaction of aromatic and aliphatic primary amines and diamines with ketones. The ketones examined include the cyclic ketone, cyclohexanone, and aliphatic ketones such as acetone, and methyl isobutyl ketone (MIBK). We limited our study to sulfided and unsulfided Pt and Pd catalysts supported on activated carbon that were commercially available from Evonik Degussa Corporation. 

The anion of cyclohexanone /V,/V-dimclhyl hydrazone shows a strong preference for axial alkylation.122 2-Methylcyclohexanone N,N-dimethylhydrazonc is alkylated by methyl iodide to give d.v-2,6-dimclhylcyclohcxanone. The 2-methyl group in the hydrazone occupies a pseudoaxial orientation. Alkylation apparently occurs anti to the lithium cation, which is on the face opposite the 2-methyl substituent. 

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