Preparation and GC‐MS‐Identification of N‐Methyl‐Δ³‐pyrroline

Abstract

The preparation of N-methyl-A 3 -pyrroline by 1) reduction of N-methylpyrrole followed by gc-separation or by 2) condensation of cis-l,4-dichloro-2-butene with methylamine is described. The title compound is identified by GC-MS. Darstellung und GC-MS-Untersuchungen an N-Methyl-A -pyrrolinDie Darstellung von N-Methyl-A 3 -pyrrolin 1) durch Reduktion von NMethylpyrrol mit anschließender gc-Trennung und 2) durch Kondensation von cis-l,4-Dichlor-2-buten mit Methylamin wird beschrieben. Die Titelverbindung wird durch GC-MS identifiziert.In the course of our synthesis of rac. macrostomine (2) 1 ) the last step comprises a Pd/C-catalyzed dehydrogenation of the 3,4-dihydroisoquinoline 1 (solvent: tetralin). 1 lost unexpectedly the N-methylpyrrolidine group under formation of the 1-benzylisoquinoline 3 2) and minor amounts of 2.Later Kapil et al. In order to find out what had happened to the N-methylpyrrolidine moiety during the reaction mentioned above, we connected the reaction vessel containing 1, Pd/C, and tetrar lin to a special trapping device (Fig. 1) for collecting possible volatile components, e. g. N-methylpyrrolidine (4), N-methyl-A 3 -pyrroline (5), and/or N-methylpyrrole (6). For separation and identification of 4-6 we developed a GC-MS-procedure (Fig. 2). 4,5, and 6 proved to be stable under the pertinent conditions provided there is no Pd present (see below).GC-MS-analysis of the volatile components from the dehydrogenation of 1 (Scheme) indicated that a N-methyl- GC-MS-Separation pyrroline (M 4 " = m/z 83) and traces of 4 (M + * = m/z 85) had been formed. The quantity of the N-methylpyrroline was too small for ^-NMR spectroscopy. In the GC-EI-MS of this compound no loss of C 2 H 3 (27 mu) from (M-l) + was observed nor did we find the elimination of H 2 C = CH 2 from M + ' which is reported for molecules containing a A^pyrro-line increment^. So we assumed that N-methyl-A 3 -pyrroline (5) had been generated. For its identification we needed authentic 5.Various methods for the preparation of 5 are reported: Lukes et al.5) reduced 6 with Zn/HCl to a mixture of 5 and 4, which -as we found -contains components with M +> > m/z 85. This mixture was separated by prep. GC. -Tsuchiya® reduced 6 according to Knorr^, but contrary to his finding a mixture of about 68 % 5 and 32 % 4 arose in our hands ( J H-NMR spectroscopy). -Lehn et al. > synthesized N-methyl-A 3 -pyrroline for NMR-experiments without giving experimental details, condensing cisl,4-dichloro-2-butene with methylamine using Bobbitfs general approach 9 ) for N-alkylated A 3 -pyrrolines.After various trials this twofold condensation yielded 60-80 % 5 in our hands (cf. Exp. Part). 5 is extremely volatile, it is identical with the N-methylpyrroline obtained in the dehydrogenation of 1 (GC, MS).In order to find out whether 5 is stable under the conditions used for the dehydrogenation of 1 to 2 and 3, we treated 5 with Pd/C in tetralin at 190 °C and found some 6 besides the educt 5. Tetralin had been dehydrogenated to 1,2-dihydronaphthalene (7) and naphthalene...

Removal of the Pyrrolidine Group by Dehydrogenation of a 4‐Pyrrolidin‐2‐yl‐tetrahydroisoquinoline

“…In order to get some insight into the fate of the pyrrolidine increment the volatile components of the dehydrogenation of 2 to 1 were analyzed by GC-MS: we found Af-methylpyrroline and traces of N-methylpyrrolidine 5 ).…”

“…However, these compounds are hydrogenated and dehydrogenated under these conditions so that no clear-cut view of the cleavage mechanism could be obtained 5 ).…”