With cyanamide

Condensation of 2-phenyl-4-amino-5-benzoylthiazole with cyanamide yields the pyrimidothiazole (Scheme 88) (133) (49) 2-imino-3-aryl-4-amino-5-carbethoxy-4-thiazolines condense similarly with alkyl isothiocyanates (276). 

In 1880, R. Andreasch (52) confirmed the new formula (37) by preparing thiohydantoine through condensation of thioglycolic acid with cyanamide (the reverse reaction of the basic hydrolysis of thiohydantoin). 

Another method used less often for these syntheses consists in condensing ketones with cyanamid and sulfur (527) (Method D). 

Aminolhtazoles were synthetized from thiourea by three methods Method A, from a-haloketones or aldehydes designated as (Cl) or (Br) Method B, from ketones and iodine (fj) or bromine (Btj) Method C, from iodomercuriketones. Method D consists in condensing ketones with cyanamid and sulfur. 

Several 4-amino-2,5-disubstituted thiazoles (257) have been obtained recently (702, 756, 776, 814, 820) by a ring cyclization reaction of halogeno compounds with cyanamide derivatives (263) according to the general Scheme 135. 

Reaction of 1,3-oxathiolium salts (264) with cyanamide in the presence of sodium ethoxide produces also substituted 4-aniinothiazolcs (265) (Scheme 136) (777). 

Alkylation with a vatiety of common alkyl halides oi sulfates gives stable dialkylcyanamides. However, the intermediate monoalkylated compounds usually cannot be isolated and cychc trimers or cotrimers with cyanamide ate obtained (13). The reaction can be carried out efficientiy in water or alcohol. Allyl chloride is an especially useful reagent, producing diallylcyanamide [538-08-9J (4). 

Cyanamide-50 is considered to be slightly toxic by ingestion in single dose and moderately toxic by single-skin appHcations. The degree of irritation to rabbit skin and eye produced by this product is only slightly less than that observed with Cyanamide-100. 

Treatment of 3-amino-4-oxoquinazolines (9) with cyanamide gave the 2-amino-l,2,4-triazolo [l,5-c]quinazolines 11 as a result of cyclodehydration of the intermediate 3-guanidino-4-oxoquinazolines 10 (68CB2106) (Scheme 9). Similarly, reaction of the 3-amino-4-thioxoquinazoline 12 with alkyl or aryl isothiocyanates yielded the mesoionic l,2,4-triazolo[l,5-cjquinazolines 14 (84S881) (Scheme 10). 

It was found that 1,2,4-triazine 4-oxides 55 are active enough to react with cyanamide under basic conditions according to the deoxygenative mechanism to form 5-cyanamino-l,2,4-triazines 73 (00TZV1128). This reaction seems to be facilitated by the easy aromatization of cr -adducts by the Elcb elimination of water. 

The reaction of 2-nitroanilines with cyanamide gives 3-amino-1,2,4-benzotiia-zine 1-oides 133 (88MI1, 94GEP4244009). 

Benzaldehyde and hydroxylamine may be reacted, the product chlorinated and then reacted with cyanamid to give 5-amino-3-phenyl-1,2,4-oxadiazole. 

A synthesis of variously substituted imidazo[l,2- ]imidazol-2-ones 448 was described. These compounds were prepared by cyclocondensation of ct-amino acid derivatives 447 with cyanamide (Equation 210) <1995JHC141>. 

An efficient synthesis of 2-amino derivatives 256 is depicted in Scheme 70 2-halopyridines are first Ar-alkylated with various halides under microwave activation and next reacted with cyanamide under basic conditions <1999T2317>. A rapid parallel synthesis of derivatives bearing a benzoyl substituent at C-3 based on this reaction has been described <2002SL1544>. 

If thymidylic acid is heated with cyanamide at pH 3, oligomers, for the most part cyclic, are formed, presumably via activated phosphate intermediates such as (68).107 On addition of acid salts, the same reactions can be realized at neutral pH.108... 

The synthesis of the oligomers involved the known reaction of isocyanates and cyanamide (Nl CN). For example, N-cyano-N -phenyl urea has been synthesized from phenyl isocyanate and an aqueous alkaline solution of cyanamide in high yield.(3) Recently, similar reactions were used to prepare various di-N-cyanourea compounds from diisocyanates. ( 1) These monomers were also synthesized directly by reacting diisocyanates with cyanamide at melt temperatures. 

The condensation of biguanide and cyanamide (which, in its diimino-form, may be regarded as the parent compound of carbodiimides (373)) has apparently not been studied. The patent literature (85,109) describes the manufacture of melamine by heating mixtures of biguanide or guanidine or their salts with cyanamide or dicyandiamide to 140—240°. but since each of these compounds alone yields melamine under these conditions, the course of these reactions is not clear. The only valid example appears to be the condensation of p-chlorophenylcyanamide and p-chlorophenylbiguanide to 2.4-di(p-chlorophenyl)melamine (304). 

Based on this mechanism, one can expect that in reactions of both phenylpyrimidinium salts with cyanamide, the 2-amino compound would also be obtained. This has indeed been found (76RTC209). Reaction of both 4-phenyl- and 5-phenylpyrimidinium iodides with cyanamide gave the corresponding 2-amino compounds (60 and 35%,respectively). With guanidine no reaction occurs no explanation was offered. 

Very dilute acetic acid [102] and ethyl acetate [103] have also been used as solvents. The fusion of amine salts with cyanamide or a substituted cyanamide is often more satisfactory than using a solvent [107—109, 228], particularly for sterically hindered guanidines such as t-butyiguanidine [228]. 

Pyrimidinamine derivatives 446 were produced by Ti -mediated reaction of imidoyl chlorides 444 with cyanamides 445 (equation 189). 

Imidates such as (115) react with cyanamide to give A -cyanoamidines (116), while the hydrochloride (117) is transformed to (118). Both (116) and (118) give 3-amino-1,2,4-oxadiazoles on treatment with hydroxylamine (Scheme 50) <81JHC37, 86JMC1540,92JMC369l>. However, other alkyl-idene cyanamides form either mixtures of 3- and 5-amino-1,2,4-oxadiazoles <87JHC275> or exclusively the 5-amino compounds (Equations (25), (26)) <94BCJ307>. 

Reaction with cyanamide in the presence of basic catalyst yields thiourea ... 

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