The preparation and some reactions of 3,6‐dimethyl‐2‐pyraziny llithium

Abstract

The widespread use of the halogen-metal interconversion reaction in the preparation of organolithium compounds, in which the metal is directly attached to a variety of heterocyclic ring systems i s well documented (2). A survey of the literature reveals however, that no organometallic derivative of pyrazine, in which the metal i s directly attached to the pyrazine nucleus has been prepared, although a number of attempts utilizing chloro and bromopyrazines have been reported (3,4,5). It has now been found that a pyrazinyllithium derivative can be readily obtained by halogenmetal interconversion using a more reactive iodopyrazine derivative (6).Addition of an ether solution of n-butyllithium to a solution of 2-iodo-3,6-dimethylpyrazine (I) in ether resulted in the formation of a reddish mixture.Carbonation of this mixture allowed the isolation of a solid which proved to be 3,6-dimethyl-a-pyrazinoic acid monohydrate (II), a compound previously prepared by Sbehr (7) by the selective oxidation of 2-ethyl-3,6-dimethylpyrazine (III).A comparison sample of the acid was prepared by the hydrolysis of 2-cyano-3,6-dimethylpyrazine (N), a new compound readily synthesized by treating 2-iodo-3,6-dimethylpyrazine (I) with cuprous cyanide in refluxing 3-picoline (8). Alkaline hydrolysis of the nitrile (N) led to the isolation of an acid which proved to be identical with the acid isolated from the carbonation procedure a s shown by mixture melting point and infrared examination of the two materials.This evidence constituted unequivocal proof that the carbonation product was 3,6-dimethyl-2-pyrazinoic acid monohydrate (II) and that nuclear metalation had indeed occurred. These inter-relationships are summarized in the following chart.Treatment of the dimethylpyrazinyllithium reagent

Quinazolines and 1,4-benzodiazepines. 82. 5-Pyrimidyl- and 5-pyrazinylbenzodiazepines

“…(D) 2-Pyrimidyl. Carbon-carbon bond formation in this series involved the reaction of the carbanion generated from o-chlorophenylacetonitrile (4) and sodium hydride with 2-chloropyrimidine (13). The benzyl cyanide 22 thus obtained (28%) underwent air oxidation in the presence of sodium hydride to give the ketone 23 in 60% yield.…”