Pteridine studies. Part XL. The synthesis of 4-unsubstituted pteridines from 3-aminopyrazine-2-carbaldehyde

Abstract

3-Aminopyrazine-2-carbaldehyde (Ia) could be prepared by oxidizing 2-amino-3-hydroxymethylpyrazine (Ib) but not by reducing 3-aminopyrazine-2-carbonitrile (Ic), N-(3-aminopyrazine-2-carbonyl)piperidine (Id), or S-methyl 3-aminopyrazine-2-thiocarboxylate (Ie)(the latter was made by hydrolysing methyl 3-aminopyrazine-2-thiocarboximidate). The aldehyde (Ia) was converted into 2-amino-3-dimethoxymethylpyrazine (IIIa), which was acylated to give the N-acetyl, ethoxycarbonyl, formyl, ethoxalyl, and trifluoroacetyl derivatives. These acetals were hydrolysed to 3-acetamido-, 3-ethoxycarbonylamino-, 3-formamido-, and 3-ethoxalylamino-pyrazine-2-carbaldehyde. These aldehydes were cyclized with ammonia to 2-methylpteridine (IVc), pteridin-2-one, pteridine, and ethyl pteridine-2-carboxylate. Pteridine was shown to form a double-bond adduct with ammonia. The analogous methylamine adduct (Vb)(5,6,7,8-tetrahydro-6,7-bismethylaminopteridine) was isolated and characterized. The electronic patterns influencing these reactions are discussed.

Both mild acetylation of 2-amino-3-hydroxymethylpyrazine (Ib) and acid hydrolysis of 2-acetamido-3-acetoxymethylpyrazine gave 2-acetoxymethyl-3-aminopyrazine.

Ionization constants and u.v., i.r., and n.m.r. spectra are recorded and discussed.