TC-1782

cf. Yakugaku Zasshi 83(11),1067-72(1963).The cyclization of substituted 2-aminophenethylpyridinium salts (I) by the Pschorr reaction gave the title compounds (II), which on catalytic reduction with PtO₂ and H in EtOH gave hexahydrobenzo[a]quinolizines (III).2-Nitro-4,5-methylenedioxyphenethyl bromide (IV) was prepared in 72% yield by adding 1.8 ml. HNO₃ (d. 1.42) in 2 ml. AcOH to 1.8 g. 4,5-methylenedioxyphenethyl bromide (IVa) in 10 ml. AcOH at room temperature, m. 45-8° [(iso-Pr)₂O-petr. ether].2-Nitro-4,5-dimethoxyphenethyl chloride (V) was similarly prepared (86.5%), m. 111-12°.A solution of 1.2 g. IV, 5 ml. AcOH, and 15 ml. Ac₂O was shaken with 50 mg. Pt.₂ and H to give 42% 2-acetamido-4,5-methylenedioxyphenethyl bromide (VI), m. 171-2° (EtOH).Similarly was prepared 89.5% 2,4,5-AcNH(MeO)₂C₆H₂CH₂CH₂Cl (VII), m. 156-7° (EtOH).From 2.18 g. VI, 0.9 g. pyridine, and 50 ml. dry PhMe refluxed 15 hrs. was obtained 86.5% VIIIb, m. 274-5° (decomposition) (EtOH).Similarly, from 1.28 g. VII was obtained 83% VIIId, m. 262° (decomposition) [picrate m. 181-2° (EtOH)], and from 1 28 g. VII and 5.3 ml. picoline, 1.45 g. of the Me analog (VIIIf) was obtained, m. 250-1° (decomposition).A mixture of 1.125 g. VIIIb and 10% HCl was heated 3 hrs. on a steam bath to yield 89.5% Ib, m. 257° (decomposition) (EtOH).Similarly were prepared Id, 85%, m. 253-3.5° (decomposition) (MeOH-Et₂O) [dipicrate m. 194-5.5° (decomposition)], and If, 86.5% [dipicrate m. 198-9° (aqueous AcOH)].To a suspension of 0.89 g. Ib in 4.5 ml. 20% HCl was added 0.21 g. NaNO₂ in 3 ml. H₂O at 0.5°.After 10 min., the mixture was warmed slowly to 70-80° to complete the decomposition of the diazonium compound, cooled, neutralized with 10% Na₂CO₃, and treated with solid KI to give 83.6% IIc (EtOH).From VIIIb was prepared, without isolation of the intermediate Ib, the hydrate of IIb; picrate m. 227.5-8.5° (Me₂CO).VIIIc, m. 267-8° (decomposition), was prepared by addition of saturated aqueous KI to VIIIb.Treatment of VIIIc with AgCl in 50% EtOH gave VIIIa, m. 270° (decomposition) (EtOH).Hydrolysis, diazotization, and decomposition of 0.4 g. VIIIa gave 0.18 g. IIa, m. 278-9° (decomposition) (EtOH-EtOAc).To cold (0-3°) diazotized Id (0.66 g.) was added fresh Gattermann Cu until N evolution ceased.The filtered solution was evaporated, the residue extracted with EtOH, the EtOH extracts evaporated, the residue dissolved in H₂O, KI added, and the solution extracted with CHCl₃ to give 0.37 g. IIe, m. 241-2.5° (H₂O); picrate m. 202-4° (aqueous EtOH).Similarly, from 1.3 g. If was prepared 0.85 g. IIg; picrate m. 174-5° (aqueous EtOH).Reduction of 0.12 g. IIa in 5 ml. 95% EtOH over 20 mg. PtO₂ with H gave 70% IIIa, m. 254-6° (EtOH-iso-PrOH); picrate m. 198-9° (decomposition) (EtOH); HClO₄ salt m. 231-3° (EtOH).Iodide IIe was converted into the chloride IId and reduced catalytically to give IIId.2-Amino-1-(3,4-methylenedioxyphenethyl)pyridinium bromide (IX), m. 212-13.5° (EtOH), was prepared in 2.7 g. yield by refluxing 3.25 g. IVa and 2.0 g. 2-aminopyridine in 30 ml. EtOH 6 hrs.; picrate m. 175-7°.The failure of IX to undergo Pschorr cyclization was attributed to the predominance of the tautomeric pyridoneimine form X.