Piperideine trimer

The simplest compounds, -pyrroline and -piperideine,donotexistin the monomeric form. Schdpf et al. (29S) described two geometric isomers of J -piperideine trimer and called them a- and -tripiperideines (182). An equilibrium exists between A -piperideine and both trimers which, therefore, react as typical aldehyde ammonia. The trimer rearranges at pH 9-10 in an almost quantitative yield to isotripiperideine (183) which, in turn, is in equilibrium with tetrahydroanabasine (184) and -piperideine. 

The A piperideine trimer hypothesis is supported initially by the equal incorporation of lysine and cadaverine into all three alkaloid fragments13,14 but more significantly by the incorporation of three molecules of A piperideine (1) into lupanine (10) and by the manner of this incorporation label from C-6 appeared at C-2, C-15, and, by inference, C-10, whereas C-2 label appeared at C-17, C-ll, and, by inference, C-6, consistent with the hypothesis (see Scheme 3).19 Further, approximately a third of the label was located at each of the determined sites. 

The dimer of 1-methyl- -pyrroline (39) was obtained by reduction of N-methylpyrrole with zinc and hydrochloric acid (132) and, together with the trimer, by mercuric acetate dehydrogenation of N-methylpyrrolidine (131). J -Pyrroline-N-oxides form dimers in a similar manner (302). Treatment of 1,2-dimethyl-zl -piperideine with formaldehyde, producing l-methyl-3-acetylpiperidine (603), serves as an example of a mixed aldol reaction (Scheme 18). 

Accepting the enthalpies of formation given by Jackman and Packam150 for all three imines results in a value of 40 14 kJ mol 1, considerably lower than experiment148. In principle, clarification of this discrepancy could be achieved by related studies on other 1-azacycloalkenes. However, except for an unsuccessful attempt148 for the corresponding 1-azacyclohexene (alternatively, A1-piperideine or 3,4,5,6-tetrahydropyridine) 65—its trimer fails to monomerize—we do not know of any such study. 

Oxidation of JV-hydroxypiperidine with cupric acetate or potassium ferricyanide gives J1-piperideine 1-oxide (30) in addition to a dimer or trimer.184,185 Dehydrogenation of l-hydroxy-2-phenylpiperidine takes a similar course.189... 

This trimer hypothesis may be extended to related alkaloids, e.g. matrine (12).19 Attractive though this is, it is argued against by the unequal utilization of A1-piperideine (1) units in the construction of this alkaloid skeleton.20... 

Generally speaking, piperideines and pyrrolines exist predominantly in the imine form and not in the tautomeric enamine form A -alkyl analogues have no alternative but to exist as enamines. These cyclic imines are resistant to hydrolytic fission of the C = N bond, in strong contrast with acyclic imines, but nonetheless they are very susceptible to nucleophilic addition at the azomethine carbon. An example of this is that both piperideine and pyrroline exist as trimers formed by the nucleophilic addition of nitrogen of one molecule to the azomethine carbon of a second molecule, etc. 

The two trimeric forms of A -piperideine (2,3,4,5-tetrahydropyridine) have been obtained in excellent yield from l-formyl-2-methoxypiperidine. The reaction of A -piperideine (108) with electron-deficient alkenes gives dimeric products (109) that are notable for their AT-alkylated structures (Scheme 42)." ... 

The principal reaction of chlorine dioxide with N-methylpiperidine (43) is methyl cleavage to produce piperidine the latter is further oxidized rather slow to piperideine, which rapidly trimerizes... 

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