Synthesis of spinacine and spinacine derivatives: crystal and molecular structures of N^π-hydroxymethyl spinacine and N^α-methyl spinaceamine

Abstract

The natural amino acid L-Spinacine (4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid) has been synthesized following a new pathway which gives a chemically and optically pure product with an excellent yield. The crystal structures of a synthetic intermediate, N^π-hydroxymethyl-spinacine, and a spinacine derivative, N^α-methyl-spinaceamine, have been investigated through X-ray diffraction: Spi(πMeOH)·H₂O, monoclinicP2 _i,a=8.571(1),b=6.682(1),c=8.588(1) Å, and β=94.67(1)^o. Spm(αMe)·2HCl·H₂O, triclinicP l,a=7.492(4),b=10.799(3),c=7.040(2) Å, α=91.88(2), β=98.36(3) and γ=73.34(3)^o. Spi(πMeOH) crystallizes with a water molecule and displays a zwitterionic character. The carboxylate group is in equatorial position and forms a short electrostatic interaction of 2.618(2) Å between one of its oxygens and the protonated nitrogen of the tetrahydropyridine ring. The crystal packing is assured by strong O−H−−−O, O−H−−−N, N−H−−−N intermolecular hydrogen bonds and C−H−−−O close contacts. The biprotonated compounds Spm(αMe) crystallizes with two Cl⁻ anions and a water molecule. The positive charge on the imidazole ring is delocalized on the conjugated moiety N=C−N. The crystal is built up by clusters formed by two biprotonated Spm(αMe) molecules, four Cl⁻ anions and two water molecules linked together by hydrogen bonds.