Chloroformamidines

Hydrogen chloride gives a dihydrochloride. Chloroformamidine hydrochloride [29671-92-9] is a convenient anhydrous form of cyanamide that is easily handled and stored (16). 

A single report 315) claims a synthesis of biguanides which utilises the replacement of a chlorine atom by an amino-group in suitable guanyl-chloroformamidines [e.g. R2N-C( NH) N=CC1-NR2] 313). The difficulty of preparing the starting materials 314) would appear to exclude the widespread use of this synthesis. 

Guanidines have been prepared by the reaction between an amine, or an amine salt, and a host of other reagents, such as a thiourea in the presence of lead or mercuric oxide [83, 157, 158], carbodi-imides [140, 174, 175],calcium cyanamide [176, 177], isonitrile dichlorides [178—180], chloroformamidines [181], dialkyl imidocarbonates [182], orthocarbonate esters [183], trichloro-methanesulphenyl chloride [184], and nitro- or nitroso-guanidines [185-188]. Substituted ureas can furnish guanidines, either by treatment with amines and phosphorus oxychloride [189], or by reaction with phenylisocyanate [190] or phosgene [191]. 

Aminophenylazobenzene, 3487 Azobenzene (Diphenyldiazene), 3483 2,2 -Azobis(2-amidiniopropane) chloride, 3089 2,2 -Azobis(2-amidiniopropane) peroxodisulfate, 3091 2,2 -Azobis(2,4-dimethylvaleronitrile), 3668 Azo-A-chloroformamidine, 0792 2,2 -Azo-3,5-dinitropyridine, 3238 Azoformaldoxime, 0815 Azoformamide, 0816 Azoisobutyronitrile, 3011 2,2 -Azoisovaleronitrile, 3345 Azomethane, 0910 Azo-A-methylformamide, 1601 Azo-A-nitroformamidine, 0825 3,3 -Azo-(l-nitro-l,2,4-triazole), 1401... 

An alternative synthesis of amidinothioureas involves the reaction of a-chloroformamidines (237)... 

Corresponding 4-diethylamino-substituted derivatives are formed by the reaction of 5,Af-diethyl-(iV -chlorosulfonyl) chloroformamidine (35) with hydrazines <85M1321> (Equation (9)). 

Another standard method of producing a fused pyrimidine ring is reaction with formamidine, which always provides for no substituent at position 2. However 391 reacts with chloroformamidine, obtained by reaction of cyanamide and HCI, to produce a variety of benzyl derivatives 392 (Equation 147) <2004JHC941> that mimic guanine analogs. 

Thermal cyclization of the /3-benzo[6]thienylvinyl isocyanate (30) produces the tricyclic compound (31) in 12% yield (70JHC1191). To the same category belongs the generation of the thieno[2,3-cf]pyrimidines (34) by reaction of N- (2-thienyl)chloroformamidines (32) with NCX- (X = O, S or Se) presumably (33) is the intermediate in this cyclization (80LA699). 

Calcium cyanamide treated with a halogen acid, such as HC1 or HBr, and then by HN03 or HCl04 results in explosive compds, such as Bromoformamidine Nitrate, Bromoformamidine Perchlorate, Chloroformamidine Nitrate, and Chloroformamidine Perchlorate (Ref 23)... 

Reportedly, simple alkyl isocyanates do not dimerize upon standing. They trimerize to isocyanurates under comparable reaction conditions (57). Aliphatic isocyanate dimers can, however, be synthesized via the phosgenation of A/,IV-disubstituted ureas to yield IV-(chlorocarbonyl)chloroformamidine intermediates which are subsequendy converted by partial hydrolysis and base catalyzed cyclization. This is also the method of choice for the synthesis of l-alkyl-3-aryl-l,3-diazetidiones (mixed dimers of aromatic and aliphatic isocyanates) (58). 

The in situ generated disubstituted ureas (26) also react with phosgene to yield thermally unstable allophanoyl chlorides (27) and chloroformamides (28) (75). As shown in Figure 5, the allophanoyl chlorides eliminate hydrogen chloride to form the isocyanate. The chloroformamides, however, yield chloroformamidine-A/-carbonyl chloride (29), which decomposes to yield both carbodiimides (30) and isocyanide dichlorides (31). The carbodiimides simply contribute to yield loss. The isocyanide dichlorides, although present in small amounts, are a contributor to chlorine-containing impurities which detrimentally affect product performance. 

A group at Parke-Davis reported the preparation of 5-deazaAP (80a) in 1974 [74,75], This was the first synthesis of a member of this class of DHFR inhibitor. As shown in Scheme 3.16, the key intermediate, 2,4-diamino-5-deazapteridine-6-carbonitrile (79), was constructed in a straightforward manner in five steps from malononitrile. The use of chloroformamidine for the conversion of (78) to (79) proved to be less satisfactory than the (traditional) use of guanidine. 

Azobis(2-amidiniopropane) peroxodisulfate, 3085 Azoformaldoxime, 0811 Azoformamide, 0812 Azoisobutyronitrile, 3006 2,2 -Azoisovaleronitrile, 3339 Azomethane, 0906 Azo-A-chloroformamidine, 0788 Azo-A-methylform amide, 1596 Azo-Amitroformamidine, 0821... 

A new synthesis of purines is illustrated by the reaction of l,3-dimethyl-6-aminouracil with MiV-dimethyldichloromethyleneiminium chloride (phosgeneiminium chloride), trimethylsilyl azide and arylamines in dry chloroform, followed by treatment with 20% aqueous potassium hydrogen carbonate. The reaction probably proceeds via a 4-amino-5-(chloroformamidin-l -yl)uracil (Scheme 10) [94JHC1185],... 

Chloroformamidine Nitrate. See under Formami-dine and Derivatives... 

Bromoformomidine Nitrate, Bromoformomidine Perchlorate, Chloroformamidine Nitrate, and Chloroformomidine Perchlorate (Ref 23)... 

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