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A reinvestigation of the reaction of 2,5-dmethylpyrazine in carbon tetrachloride solution with chlorine under ultraviolet light revealed that the product was Z-chloro-3,6-dimethylpyrazine (11) and that recourse to ultraviolet treatment was unnecessary. Treatment of 2-methylpyrazine with chlorine afforded a mixture of Zchloro-&methyl-(VII) and 5-chloro-5-methylpyrazine (VIII). In allon~ing 2,6-dimethylpyrazine to react, with chlorine, it was found that ultraviolet radiation was essential and that the product was an unstable side chain halogenated compound, 2,6-bis( a-chloromethy1)pyrazine (XV). Alcoholysis converted XV to the bis ether XVI. Treating 2-methyl-and 2,5-dimethylpyrazine with one equivalent of K-chlorosuccinimide and a small quantity of benzoyl peroxide afforded unstable or-chloromethyl derivatives V and X I which were converted to the corresponding side chain ethers VI and XII.

filter cake was extracted with boiling benzene and acetone (1 to 1 mixture). Concentration and cooling of the extracts gave 25.0 g. of crude 2 '-amino-2-bromo-4'-dimethylsulfonamidodiphenvl ether (IXd). This compound was heated at 100°with 63 g. of 88% formic acid until the excess formic acid had evaporated.The residue (Xd) was taken up in 30 ml. of xylene, and the xylene was removed by distillation at atmospheric pressure to remove traces of formic acid. The residual gum was stirred at reflux for 18 hr. with 8.6 g. of potassium carbonate, 1 g. of copper carbonate and 40 ml. of xylene. Excess water and benzene were added to the cooled mixture and the organic layer was evaporated to leave a gum. Crystallization from benzene-hexane (1 to 3) gave 8.2 g. of 2-dimethylsulfonamidophenoxazine (Id) (19% overall yield); m.p. 184-185°.

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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