Abramovitch

A special application of the Japp-Klingemann/Eischer sequence is in the preparation of tryptamines from piperidone-3-carboxylate salts, a method which was originally developed by Abramovitch and Shapiro[2]. When the piperidone is subjected to Japp-Klingemann coupling under mildly alkaline conditions decarboxylation occurs and a 3-hydrazonopiperidin-2-one is isolated. Fischer cyclization then gives 1-oxotetrahydro-p-carbolines which can be hydrolysed and decarboxylated to afford the desired tryptamine. 

NaHC03 H2O, dry (MgS04), filter, evaporate and distil residue. Identified by hydrolysis to the acid and determining the neutralisation equiv (theor 80.0). The acid has m 155-157° efferv [Hauser, Abramovitch and Adams J Am Chem Soc 64 2715 1 942 Bush and Beauchamp J Am Chem Soc 75 2949 1953]. 

A variety of l,2,3,4-tetrahydro-j8-carbolines have been prepared from 3-piperidone phenylhydrazone derivatives. Used initially to obtain pentacyclic derivatives (35) related to the yohimbe alkaloids, this route was later extended to the synthesis of tetracyclic compounds (36). l-Methyl-5,6,7,8-tetrahydro-j8-carboline (37) was prepared in low yield by heating cyclohexanone 2-methyl-3-pyridylhydrazone with zinc chloride, a synthesis probably based on the similar preparation of the tetracyclic compound 38 starting from the corresponding quinolylhydrazine. Abramovitch and Adams extended this approach to the cyclization of cyclohexanone 3-pyri-dylhydrazone (39) itself. The main product was 6,7,8,9-tetrahydro-8-carboline (40), a smaller amount of the j8-isomer (41) also being obtained. This provides a convenient and readily reproducible route to the otherwise difficultly accessible 8-carboline ring system. The favored attack at carbon-2 over carbon-4 of the pyridine nucleus... 

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