Papaverine methiodide, reduction

On treatment of N-methylpapaverine, formed by the lithium aluminum hydride reduction of papaverine methiodide with phosphoric acid, N-methylpavine is formed which is identical with the racemic alkaloid argemonine. This reaction was used for the synthesis of the alkaloid (-h)-coreximine (268) (174) and similar compounds containing the proto-berberine grouping in the molecule (269,270). 

Reduction of papaverine methiodide with tin and hydrochloric acid produces, in addition to laudanosine, A -methylpavine formed through cyclization of the transitory 1,4-dihydroisoquinolinium intermediate. Recent syntheses in... 

Racemic laudanosine, C2iH27N04 (LXXV), can be easily prepared in excellent yield by reduction of papaverine methiodide (7.33, 1S4) or methosulfate (1S5) wdth sodium borohydride in aqueous methanol. L-( + )-Laudanosine has been obtained in the sodium-liquid ammonia fission of tetramethylmagnolamine (mp 90°-91° [a] -1-83.4 in EtOH) (136). A dimorphic form of racemic laudanosine methiodide of higher melting point (228.5°-229.5° low mp form, 218°-221°) was prepared by methylation of ( )-i r-norlaudanosine hydriodide with methyl sulfate (137). Under specific conditions the methiodide can be reverted to the original base as when it is boiled with ethanolamine (138) or by the action of lithium aluminum hydride in tetrahydrofuran (139). 

The reduction of papaverine methiodide has been facilitated by the use of new reagents. Its reduction (or of a similar salt) with sodium borohydride in aqueous methanol is now the best method for the production of racemic laudanosine (167) (Section III, F). If pyridine is employed as a solvent 1,2-dihydro-iV-methylpapaverine also is obtained in good yields (166). The 1,2-dihydro derivative is the main product when lithium aluminum hydride is employed although the tetrahydro compound is probably formed in small amounts (169). Polarographic reduction of papaverine and 3,4-dihydropapaverine in aqueous tetra-methylammonium hydroxide gave half-wave potentials of — 1.92 V and — 1.62 V, respectively (170). 

Racemic pseudolaudanine, C20H25NO3 (CXLIII Ri = H R2 = R3 = R4 = CH3) [mp 119°-120° methiodide, mp 211°-213°], has been prepared with improved yields by employing sodium borohydride in the reduction of the chloride CXLVI obtained by fusion of papaverine hydrochloride 123). 

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