Synthesis of Chiral Imidazole Derivatives as Purine Precursors

Abstract

From commercially available chiral building blocks, we have developed methods for the syntheses of imidazole derivatives that contain a chiral alkyl substituent at ring atom. These compounds are suitable for further transformation into Nalkyl purine derivatives.

Isomorphism in Two (E)-1-(4-Halophenyl)-N-[1-(4-Methylphenyl)-1H-Imidazol-4-yl]Methanimines (Halide = Cl, Br)

“…Preparation of Compounds 1-(4-Methylphenyl)-4-nitroimidazole was reduced in a current of hydrogen under atmospheric pressure at room [2,3], the resulting amine, was not worked out but immediately treated with aromatic aldehydes. The addition of a catalytic amount of acetic acid caused the precipitation of the corresponding Schiff's bases in good yields.…”

“…The presence of the nitro group, essential for the reaction mentioned, becomes not only unnecessary but it can interfere with the next potential synthetic transformation. The reduction of the nitro group, relatively easy in benzene derivatives, has proven challenging in azole systems due to metastability of the resulting amines [3,4]. To this end the reduction and further protection of the nitro functionality appears to be an important synthetic problem.…”

1,4-Dinitro-1H-imidazoles

“…The only exception was the reaction with 4-aminopyridine mentioned earlier (Section 4.2). 44 Instead, primary amines with 1,4-dinitro-1H-imidazoles formed the respective 1-alkyl-(13) or 1-aryl-4-nitro-1H-imidazoles (14). A new original approach to the synthesis of 4-nitro-1-phenyl-1H-imidazole and its substituted derivatives 34 in the reaction of dinitroimidazoles 1-3 with primary anilines 33 was patented and published.…”

“…2-Amino-and 3-aminopyridines reacted with compounds 1 and 2 in the same manner as anilines to afford 1-(2 or 3-pyridyl)-4-nitro-1H-imidazoles in moderate to high yields. 44 An ANRORC mechanism for the reaction was proposed, although no details and no proof supporting the mechanism were given then. Effects of solvents on the reaction of dinitroimidazole 2 with ptoluidine, was studied in details.…”

“…63 In a search for a new efficient method for synthesis of chiral imidazole derivatives as purine precursors, the reactions of dinitroimidazoles 1 and 2 with chiral esters of α-aminoacids or chiral 3-amino-1,2-propandiols were successfully performed. 64 …”