Amide 2-methylpiperidine

A nitrogen atom at X results in a variable downfield shift of the a carbons, depending in its extent on what else is attached to the nitrogen. In piperidine (45 X = NH) the a carbon signal is shifted by about 20 p.p.m., to ca. S 47.7, while in A-methylpiperidine (45 X = Me) it appears at S 56.7. Quaternization at nitrogen produces further effects similar to replacement of NH by A-alkyl, but simple protonation has only a small effect. A-Acylpiperidines show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 p.p.m., and the mean shift is close to that of the unsubstituted amine (45 X=NH). The nitroso compound (45 X = N—NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 p.p.m.). The (3 and y carbon atoms of piperidines. A- acylpiperidines and piperidinium salts are all upfield of the cyclohexane resonance, by 0-7 p.p.m. 

In only a few instances has enough hydrogen been absorbed to carry the reaction beyond the 2-piperidone stage. Galinovsky (79) obtained 1-methylpiperidine from the reduction of l-methyl-2-pyridone with a 50% ratio of platinum oxide for 42 hr. 3-Methyl-2-pyridone was converted to 3-methyl-2-piperidone in 80% yield by reduction in methyl alcohol in the presence of Raney nickel at 200-240° and 120 atm (80). When the reaction temperature was raised to 280° some of the cyclic amide was reduced to 3-methylpiperidine and further alkylated to 1,3-dimethylpiperidine. 

Piperidine or lithium piperidide and benzyne form N-phenylpiperidine, as expected, but the same product (40-50%) was also obtained unexpectedly from V-methylpiperidine, fluorobenzene, and phenyllithium before the formation of benzyne under these conditions was properly recognized. A series of N-alkylmorpholines gives secondary and tertiary aniline derivatives 213 and 214 when treated with bromobenzene and sodium amide. A route for formation of these products via the ylid 211 is outlined in Scheme 19, in which the formation of 211 is similar to that of 16 in Scheme 2 and the step 212 -+ 213 is similar to the decomposition of 33 in Scheme 5. The final... 

PAs with 2-methylpentamethylenediamine are difficult to prepare by conventional melt condensation methods. Namely, 2-methylpentamethylenediamine can be easily cyclized to methylpiperidine under the liberation of ammonia. Thus one potential amide group is lost and the compound becomes monofunctional and acts as chain stopper. ... 

When a 2.0 equimolar amount of 2-methylpiperidine was used, 30% of naphthamide 3a was consumed, and 30% of 16a was isolated. The reaction conversion was low however, the reaction was very clean, and 70% of unreacted naphthamide was recovered. Fortunately, 16a was obtained as the optically active form in 94% ee. Based on an increase of the amount of lithium amide to 5 eq., all naphthamide 3a was consumed and converted to 16a quantitatively with 81 % ee. These results indicate that the 2.0 equimolar amounts of lithium amide form a stable intermediacy complex with naphthamide 3a, and an extra amount of piperidine must be necessary to obtain product 16 in good yield. The intermediacy enantiomeric complex reacts preferentially with one enantiomer of the racemic peridine. 

Figure 125. Conformational equilibrium in the (i -MTPA amide of (i -2-methylpiperidine.

Thus, in (i -2-methylpiperidine, the resonances for the syn rotamer in the spectra of the (5)- and (R)-MTPA amides should be identified first and the signals due to the axial methyl group at C-2 and the axial proton at C-3 (Figure 126a and b) used to obtain the value. 

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