Aminopyrazines extranuclear

This section covers primary, secondary, tertiary, and quaternary aminopyrazines (both nuclear and extranuclear) but not (functionally substituted amino)pyrazines such as hydrazino-, hydroxyamino-, or azidopyrazines. General discussions have appeared on the spectra of 2-pyrazinamine,255 257 991 the proton-sponge properties of 2,3,5,6-tetra(pyridin-2-yl)pyrazine in relation to its fine structure,925 the fluorescene properties of 3,6-diamino-2,5-pyrazinedicarboxylic acid derivatives in relation to their fine structures,1646,1659 the basic properties of aminopyrazines and other such azines in relation to their electronic structures,412,928 and the fine structures of 3-amino-2-pyrazinecarboxylic acid1340 and l,4-diacetyl-2,3-diphenylpiperazine.559... 

Note Such deacylation may be done by hydrolysis or treatment with hydrazine to afford primary or secondary nuclear or extranuclear aminopyrazines. 

Note Hydrolysis removes the alkylidene group as an aldehyde or ketone to afford a nuclear or extranuclear primary aminopyrazine reduction could afford a secondary aminopyrazine of either type, but there appear to be no recent examples. 

Note For the production of extranuclear primary or secondary aminopyrazines. 

Note For making nuclear or extranuclear primary aminopyrazines these substrates are easily made from azidopyrazines (see Section 7.5). 

Note For the preparation of extranuclear primary aminopyrazines only. 

Note For the formation of extranuclear primary, secondary, or tetrtiary aminopyrazines the only available examples gave a primary amine. 

Note Could be used for the preparation of nuclear or extranuclear primary aminopyrazines. 

Note The reduction of azido- to aminopyrazines appears to be somewhat unpredictable but a reasonably good yield can usually be obtained with one or other of the reducing agents mentioned in these examples. For nuclear or extranuclear primary aminopyrazines only. 

Extranuclear acetoxyalkylpyrazines have been prepared from hydroxyalkyl-pyrazines by acetylation with acetic anhydride and dry pyridine as follows 2-methyl-6-(D-flraho-tetraacetoxybutyl)pyrazine (182), 2,5-bis(D-araho-tetraacetoxybutyl)-pyrazine (182), and 2-acetoxymethyl-3-aminopyrazine (1075) and 2-methyI-5-(D-3-(D- 0 pyrazine with benzoyl chloride and dry pyridine (182). 

Preparations of pyrazine A -oxides containing extranuclear hydroxyl groups are also described in Qiapter III as follows Section III.l, 2-aminopyrazine 1-oxides from a-amino nitriles and a-hydroxyimino carbonyl compounds (540, 541) Section III.2, 3-substituted pyrazine 1-oxides from 2-amino-2-deoxy-D-glucose(or mannose) oxime with glyoxal (543, 544) and Section III.5, ring closure of the C-C-N-C-C-N-0 system (553). 

The preparation of extranuclear aminopyrazines by the Mannich reaction has been described in Section IV.2C(6) (657, 715, 716). 

Some preparations of extranuclear aminopyrazines from extranuclear halogenopyrazines and amines have been described in Section V.6B (542, 679, 932,1029-1031). 2-Chloromethylpyrazine also reacted with sodium azide and gave 2-azidomethylpyrazine, which was hydrogenated in 95% ethanol over Adams catalyst to 2-aminomethylpyrazine (690). 

One only known extranuclear aminopyrazine has been prepared by the Hofmann reaction 2-(2 -carbamoylethyl)pyrazine with sodium hypochlorite gave 2-(2 -aminoethyl)pyrazine (405). 

Aminopyrazine is a yellowish crystalline solid with m.p. 118-120 (420). It is a weak base with reported pAj, values of 3.14 (123) and 2.96 (821) (others are recorded in Chapter X). The similarity in the ultraviolet spectra (in water) of the neutral molecules of 2-amino-, 2-methylamino-, and 2-dimethylaminopyrazines, and of their monocations, and their similar basic strengths (2.96,3.42,3.27) (821) supports the conclusion that in aqueous solution 2-aminopyrazine exists mainly in the amino form (20) (821). The ultraviolet spectrum of 2-aminopyrazine cation differs from that of the neutral molecule of pyrazine, thus indicating that protonation does not take place at the extranuclear nitrogen atom (821) 2-aminopyrazine in fact protonates at Ni (see below). 

Aminopyrazine is a stronger base than pyrazine moreover, 2-amino-, 2-methylamino-, and 2-dimethylaminopyrazine have closely similar basic strengths, which supports the conclusion that, in aqueous solution, 2-aminopyrazine exists mainly in the amino form (1) (821). Ultraviolet spectral evidence (see Section VIII. 1C) indicates that the protonation does not take place at the extranuclear amino group (821). This and other evidence (p.m.r.) (1136) are consistent with monoprotonation of 2-aminopyrazine at Ni, and the second protonation at N4. 2,3-Diaminopyrazine (pAg 4.88) is a much stronger base than 2-aminopyrazine, but... 

---