Cyanic acid, sodium salt

CYANHYDRINE d ACETONE (FRENCH) see MLC750 CYANIC ACID, POTASSIUM SALT see PLC250 CYANIC ACID, SODIUM SALT see COI250 CYANIC ACID, TRIMETHYLSTANNYL ESTER see TMIlOO... 

In 1937 Hunter and Hlynka were able to reduce a methanolic solution of 4(5)-nitroimidazole (27 R = H) with sodium amalgam and trap the 4(5)-aminoimidazole (25 R = H) with cyanic acid giving the urea derivative (31) (37BJ488). Other reducing agents gave inferior results. Subsequently, 4(5)-aminoimidazole (25 R = H) was obtained as either its dihydrochloride (30%) or dipicrate salt but the isolation procedures were lengthy and difficult (41 Mil). 

The earliest method of this type was the old Marckwald synthesis (1] in which a suitable a-aminocarbonyl compound is cyclized with cyanate, thiocyanate or isothiocyanatc. More recent modifications have employed the acetals of the a-amino aldehyde or ketone or an a-amino acid ester. The two-carbon fragment can also be provided by cyanamide, a thioxamate, a carbodiimidc or an imidic ester. When cyanates, thiocyanates or isothiocyanates are used, the imidazolin-2-ones or -2-thiones (1) are formed initially, but they can be converted into 2-unsubstituted imidazoles quite readily by oxidative or dehydrogenative means (Scheme 4.1.1). The chief limitations of the method arc the difficulty of making some a-aminocarbonyls and the very limited range of 2 substituents which are possible in the eventual imidazole products. The method is nonetheless valuable and widely used, and typically condenses the hydrochloride of an a-amino aldehyde or ketone (or the acetals or ketals), or an a-amino-)6-ketoester with the salt of a cyanic or thiocyanic acid. Usually the aminocarbonyl hydrochloride is warmed in aqueous solution with one equivalent of sodium or potassium cyanate or thiocyanate. An alkyl or aryl isocyanate or isothiocyanate will give an A-substituted imidazole product (2), as will a substituted aminocarbonyl compound (Scheme 4.1.1) [2-4]. 

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