2-Chloropyrazine amide/ammonia

When treated with potassium amide in liquid ammonia, chloropyrazines undergo ring contraction to imidazoles. The reaction has synthetic importance and resembles similar reactions of pyridines and pyrimidines (Section 4.08.2.3.1). As before, labelling experiments have been utilized to establish the origins of the nitrogen atoms in the products, and complex... 

There are considerable data available on imidazole formation by ring contractions of pyrimidines, pyrazincs and triazines [15, 43, 59-61]. Few of the reactions, however, have synthetic potential except perhaps for the thermolytic conversions of azidopyrimidines and azidopyrazines into 1-cyano-substituled imidazoles, and the reactions of chloropyrimidines and chloropyrazines with potassium amide in liquid ammonia to give 4- and 2-cyanoimidazoles, respectively. Ring contractions of quinoxaline 1-oxides may also have some applications. 

Chloropyrazines undergo ring contraction when treated with potassium amide in liquid ammonia. The reactions resemble those of pyridines and pyrimidines, and may be useful for making 2-cyanoimidazoles despite the formation of product mixtures and low yields. For example, 2-chloropyrazine is converted into a mixture of 2-aminopyrazine (15%), imidazole (14-15%) and 2-cyanoimidazole (30-36%) [82]. In a similar experiment, 2-cyano-4-phenylimidazole (19%) can be obtained 83J. 

The reaction of 2potassium amide in liquid ammonia to give 2-cyanoimidazole, imidazole, and 2-aminopyridine has been investigated (911). It has been found that 2-chloropyrazine containing an excess of in position 1, on treatment with potassium amide in liquid ammonia at — 65° yields 2-aminopyrazine in which the exocyclic nitrogen contains all the excess and an addition-nucleophilic-ring opening-ring closure (ANRORC) mechanism was proposed (822). The mechanism of the conversions into imidazole (823) and... 

Normal nucleophilic substitution occurred on treatment of 2-carbamoyl-3-chloropyrazine with alcoholic methylamine at 130° (423, 836) 2-chloro-3-(4 -morpholinocarbonyOpyrazine with morpholine at reflux in benzene (867) 2dimethyl sulfoxide at 65° (857) and cyclohexylamine in benzene at reflux (946) 3-chloro-2-methoxycarbonyl-5-phenylpyrazine with alcoholic methylamine at 140° (375) 2-carboxy-3-chloropyrazine with anhydrous ammonia at 100° for 5 hours (947) 2-carbamoyl-6-chloropyrazine with aqueous methylamine at reflux (940) 2-chloro-6-(4 -morpholinocarbonyl)pyrazine (and other amides) and 2-chloro-6-methoxycarbonylpyrazine with morpholine (and other amines) (870, 948, 949) and 2-chloro-6-methoxycarbonylpyrazine with liquid ammonia at 80° (870). 2-Chloro-3-methoxycarbonylpyrazine fused with guanidine carbonate gave 2-amino4-hydroxypteridine and its 7-methyl-, 7-phenyl, and 6,7-diphenyl analogues were prepared similarly (371,375). 

The ring contraction of chloropyrazines to 2-cyanoimidazoles when treated with potassium amide in liquid ammonia has synthetic importance. Labeling experiments have proved the origins of the nitrogen... 

---