2-Amino-3-cyano-5-chloromethylpyrazine 1-oxide

Aluminum bromide, 10,42,140 Aluminum chloride, 10-15,140,357 Aluminum cyclohexoxide, 15 Aluminum hydride, 357 AluminumOII) iodide, 106 Aluminum isopropoxide, 15-16 Amberlite-15, 266 Amberiite IR 120, 267 Amide acetals, 527-528 Amides, 424,456 Amidines, bicyclic, 16-18 Amine oxides, 270 p-Aminoacetophenone, 18 Amino adds, 252, 273, 368 Aminoalkenylation, 95 4-Aminobenzoic add, 45 2-Amino-3-cyano-5-chloromethylpyrazine 1-oxide, 459... 

AP (protected by acetylation at N-10, (650)) was prepared in an unequivocal fashion by a different strategy starting with 2-amino-3-cyano-6-formylpyra-zine (647), which was itself prepared by two independent procedures Scheme 3.141) [261], In the first, 2-amino-3-cyano-6-chloromethylpyrazine (645) was converted to (647) via (646) by the KrOhnke procedure in excellent overall yield. In the second, the 1-oxide (644) was treated with w-propylamine,... 

Deoxygenation of 2-amino-3-cyano-6-chloromethylpyrazine 1-oxide with phosphorus trichloride in tetrahydrofuran has been shown to give 3-amino-2-cyano-5-chloromethylpyrazine (534). 

Certain a-chloromethylpyrazine A -oxides have been deoxygenated with phosphorus trichloride. Treatment of 2-amino-5-chloromethyl-3-cyanopyrazine 1-oxide (and 2-amino-3-cyano-5-methoxymethylpyrazine 1-oxide) with phosphorus trichloride at room temperature in tetrahydrofuran resulted in smooth deoxygenation to 2-amino-5-chloromethyl-3-cyanopyrazine (and 2-amino-3-cyano-5-methoxy-methylpyrazine) (529), whereas 2-amino-6-chloromethyl-3-cyanopyrazine 1-oxide was best deoxygenated to 3-amino-5-chloromethyl-2-cyanopyrazine by phosphorus trichloride in refluxing tetrahydrofuran (534). The more vigorous conditions necessary for the last reaction may be a reflection of increased steric hindrance at the fV-oxide grouping (529). Use of solvents like chloroform or dioxane led to slow reactions which were accompanied by the formation of numerous unidentified by-products (534). 

Amino-5-chloromethyl-3-cyanopyrazine 1-oxide with triphenylphosphine in dimethylformamide at 80-90° gave 2-amino-3-cyano-5-(triphenylphosphonio)-methylpyrazine 1-oxide chloride (97) (520) and the 5-bromomethyl analogue reacted similarly with triphenylphosphine in propan-2-ol (542). Compound (97) on hydrolysis with 30% aqueous ethanol containing a small amount of triethylamine gave 2-amino-3-cyano-5-methylpyrazine 1-oxide and thus enabled removal of the chloro substituent from the chloromethylpyrazine (529) compound (97) with triethylamine and acetaldehyde (and other aldehydes) in chloroform at room temperature gave 2-amino-3-cyano-5-(prop-l -enyl)pyrazine 1-oxide (and other alkenyl analogues) (529). 

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