2-Hydroxypyrazine with phosphoryl chloride

The reaction of simple hydroxypyrazines with phosphoryl chloride has been used extensively for the preparation of chloropyrazines. 2-Hydroxypyrazine with phosphoryl chloride alone (818) gave 2-chloropyrazine (819-821), and 2-chloro-[l- N]pyrazine (822) and 2-chloro(2- C)pyrazine (823) have been prepared by the method described by Karmas and Spoerri (362). 

Dichloropyrazines have also been prepared from the corresponding hydroxy compounds as follows 2,3-dihydroxypyrazine with phosphoryl chloride containing pyridine (481, 757) [see Schneller and May (828) re the use of phenylphosphonic dichloride at 150-170°] 2,3-dihydroxypyrazine and its methyl, dimethyl, phenyl, diphenyl, and 5-methy 1-6-phenyl derivatives with phosphoryl chloride (483, 829) [N.B. error in work of Minovici and Bente (830)] 2-chloro-5-hydroxypyrazine with phosphoryl chloride (831) 2-chloro-6-hydroxypyrazine with phosphoryl chloride at reflux for 6hours (832) and 2,5-dihydroxy-3-phenylpyrazine and3,5-dihydroxy-2-phenylpyrazine with phosphoryl chloride at 180-200° (829). 

Amino chloropyrazines may be prepared from amino hydroxypyrazines with phosphoryl chloride. 2-Amino-3-hydroxypyrazine with phosphoryl chloride gave... 

The classical route to chloropyrazines is by treatment of a hydroxy-pyrazine with phosphoryl chloride bromopyrazines are similarly prepared by using phosphoryl bromide, phosphorus tribromide, or a mixture of both. Thus, treatment of hydroxypyrazine with phosphoryl chloride gives chloropyrazine in 92% yield,147 and treatment of the hydroxy compound with a mixture of phosphoryl bromide and phosphorus tribromide gives bromopyrazine in 58% yield.266 The use of phosphorus pentahalides frequently leads to substitution products (Scheme 22) for example, when hydroxypyrazine is treated with a mixture of phosphoryl bromide and phosphorus pentabromide both monobromo- and 2,6-dibromopyrazines are formed.267,268 Bromina-tion of hydroxypyrazine with bromine in the presence of small... 

Palamidessi and Bernardi have obtained 2-chloropyrazine 1-oxide by mild treatment of pyrazine 1,4-dioxide with phosphoryl chloride. The structure of the 1-oxide was confirmed by hydrolysis to 2-hydroxy-pyrazine 1-oxide, which was also prepared by direct synthesis from glyoxal and glycine hydroxamic acid.398 This synthesis is illustrative of a general method for preparing 2-hydroxypyrazine 1-oxides by condensation of a,/3-dicarbonyl compounds with a-aminohydroxamic acids. An analogous synthesis of 2-aminopyrazine 1-oxides has already... 

Amino-2-carbamoyl-5-hydroxypyrazine in dimethylformamide with phosphoryl chloride gave 3-amino-5-chloro-2-cyanopyrazine (538). 

Many derivatives of carboxy chloropyrazines have been prepared by the action of phosphoryl chloride on the corresponding hydroxypyrazine. In this way were prepared 2-chloro-3-methoxycarbonylpyrazine (371, 423, 836), 2-chloro-3-methoxycarbonyl-5,6-diphenylpyrazine (but the corresponding hydroxy compound did not react with phosphorus tribromide) (837), and 3-chloro-2-methoxycarbonyl-... 

Many chloropyrazines have been prepared from hydroxypyrazines by reaction with mixed phosphorus pentachloride-phosphoryl chloride as follows 2-hydroxy-pyrazine to 2-chloropyrazine (818), 2-hydroxy-3-phenylpyrazine to 2-chloro-3-phenylpyrazine (535), 2-hydroxy-6-methyl- and 5-hydroxy-23-[Pg.102]

The reactions of phosphoryl chloride and some hydroxypyrazine A-oxides with an unsubstituted position adjacent to the A-oxide function to give chlorohydroxy-pyrazines have been described in Section V.IG. In this way 3-hydroxy-2,5-diisobutylpyrazine 1-oxide was converted to 2-chloro-5-hydroxy-3,6-diisobutyl-pyrazine (101) and 2-hydroxy-3,5-diphenylpyrazine 1-oxide gave 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873). 

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