Synthesis of the first representative of the 2,3,6,7-tetrahydro-1H-benzo[d]azonine system from 1-cyanomethyl-2-methyl-1,2,3,4-tetrahydroiso-quinolinium chloride and dimethyl acetylene-dicarboxylate

Abstract

In previous work, we were the first to establish the feasibility of a one-step synthesis of the 1,2,3,6-tetrahydroindeno[2,1-c]azonine [1] and 1,2,3,4,7,12-hexahydroazonino[4,5-b]indole heterocyclic systems [2], which had previously been difficult to obtain, in the reaction of quaternary 2,3-dihydro-1H-indeno-[2,1-c]pyridinium or 1,2,3,4-tetrahydro--carbolinium salts with dimethyl acetylenedicarboxylate (2) in the presence of base. Gimranova [3] has also undertaken an attempt to convert a series of N-(ethoxycarbonylmethyl)-1,2,3,4-tetrahydroisoquinolinium halomethylates by an analogous method into 2,3,4,7-tetrahydro-1H-benzo[d]azonines. However, in this case, the expected products could not be isolated or even detected by HPLC/MS. In the present work, we report the cascade synthesis of the first representative of the tetrahydro-1H-benzo[d]azonine system. This system was formed upon the action of 20% aq. NaOH on a mixture of DMADC 2 and quaternary salt 1 containing a N-cyanomethyl group at 20°C over 20 h and isolated by preparative chromatography in 72% yield. The mass and IR spectral data and elemental analysis results confirmed the chemical formula of diester 3.

Heterocycles from α‐Aminonitriles

“…[64] Starting from similar tetrahydroiso- quinolinium salts 121 in combination with dimethyl acetylenedicarboxylate, the same authors achieved a ring enlargement by three carbon atoms under formation of 2,3,6,7-tetrahydro-1H-benz[d]azonines 124 (Scheme 25). [65] More recently, Lahm et al reported a concise synthesis of polycyclic alkaloids based on the Stevens rearrangement of nitrile-stabilized ammonium ylides derived from spirocyclic ammonium salts. Starting from simple cyclic a-aminonitriles 125, the salts 127 were prepared by double N-alkylation with readily available dibromide 126 (two steps from veratrol and diacetyl).…”

“…Soldatova and co‐workers employed the same sequence for the ring homologation of tetrahydroisoquinolinium salts to tetrahydro‐3‐benzazepines 64. Starting from similar tetrahydroisoquinolinium salts 121 in combination with dimethyl acetylenedicarboxylate, the same authors achieved a ring enlargement by three carbon atoms under formation of 2,3,6,7‐tetrahydro‐1 H ‐benz[ d ]azonines 124 (Scheme ) 65…”