Chloroformamidine hydrochloride

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

The 4-aminopyrazole-5-carboxamide (381) cyclizes to give compound (383) on heating with chloroformamidine hydrochloride in DMSO it is most likely that intermediate amidine (382) is first formed (Scheme 35) <78NJC357>. 

The reaction of carbodiimides with hydrogen chloride affords chloroformamidine hydrochlorides 699. ... 

Benzoylcyanamide in DMF reacts with anthranilic acid, its allyl ester or amide to form 4-quinazolinone in moderate-to-good yield, but an electron-withdrawing substituent in the amino acid prevented cyclization [2625]. Cyciization of anthranilic esters with an imino ether proceeds without external heating and can give high yields [2574]. An almost theoretical yield of a 2-amino-4-quinazolinone is reported in a reaction between an anthranilic ester and chloroformamidine hydrochloride [3772]. 

Annelated 2,4-diaminopyrimidines can also be obtained with chloro-formamidine [C1C(NH)NH2], which is easily prepared from cyanamide and hydrochloric acid.164 It was called cyanamide dihydrochloride until its true nature was determined.165 Substituted benzonitriles, heated with chloroformamidine hydrochloride for 30 min in 2-methoxyethyl ether (diglyme) at 150°C, gave good yields of 2,4-diaminoquinazolines in one... 

Successive treatment of 5-bromo-6-chloroisatoic anhydride with boiling methanol and then with chloroformamidine hydrochloride in boiling diglyme led to 2-amino-5-bromo-6-chloro-4(3H)-quinazolinone with a yield of 67% [81]... 

The elimination of hydrogen chloride from chloroformamidine hydrochlorides is another example illustrating the utility of imidoyl halides. Thermolysis of diarylchloroformamidine hydrochlorides PCIV), obtained from N,N -disubstituted thioureas and phosgene, is the best method of synthesis of unsymmetrical carbodiimides (XV) because the generated... 

Haloformamidines are derivatives of formic acid the name haloforma-midines is used by Chemical Abstracts, which numbers the center carbon atom 1, and lists the nitrogens as N and N. However, this class of compounds is more closely related to carbamic acid, as evidenced by its synthesis from urea (carbamic acid amide) and cyanamide (carbamic acid nitrile). In a recent article ( ) concerned with the synthesis and reactions of substituted chloroformamidine hydrochlorides, the term carbamido chlorides was used. Since chloroformamidine hydrochlorides I are the amido chlorides of carbamide, this generic name is not unreasonable. There is no evidence for the isomeric geminate chloride structure II, and the polar character of I is evidenced by the relatively high melting points of chloroformamidine hydrochlorides, and by their insolubility in nonpolar solvents ( ). 

The first substituted chloroformamidine hydrochloride was synthesized in 1895 by Lengfeld and Stieglitz C " ), who added hydrogen chloride to di-phenylcarbodiimide. Several years later, Steindorff ( ) synthesized the first free chloroformamidine by reacting 1,1,3-triphenylurea with phosphorus pentachloride. 

In general, chloroformamidine hydrochlorides are formed in the reaction of thiourea and urea derivatives with either carbonyl chloride or... 

The use of an excess of carbonyl chloride in the reaction with di-substituted thioureas has to be avoided, because the chloroformamidine hydrochlorides eliminate hydrogen chloride and the generated carbodi-imides add carbonyl chloride to afford chloroformamidine-N-carbonyl chlorides XI... 

The use of carbonyl chloride in the conversion of thioureas to chloro-formamidines offers the advantage of gaseous by-product. Phosphorus pentachloride can be used equally well, but complete separation from the liquid trichlorophosphorus sulfide is sometimes more difficult to accomplish. In one instance, chlorine has been used to convert a pseudothiourea derivative to the corresponding chloroformamidine hydrochloride. Thus, addition of chlorine to a solution of the pseudothiourea derivative XIII in carbon tetrachloride afforded a quantitative yield of trimethylchloro-formamidine hydrochloride (XIV) C ). 

However, the reaction of tri- and tetrasubstituted ureas with carbonyl chloride affords high yields of the chloroformamidine hydrochlorides ( ). 

The reaction of thionyl chloride with 1,3-disubstituted ureas affords either N-sulfinylamines and isocyanates (R = n-alkyl), or chloroformamidine hydrochlorides (R = sec-alkyl, t-alkyl) However, the reaction of oxalyl chloride with ureas does not produce chloroformamidines, parabanic acids being the sole reaction product (51.6 5,66 ... 

Upon reaction of chloroformamidine hydrochloride with nitric acid, the corresponding chloroformamidine nitrate, an explosive, was obtained... 

Chloroformamidine hydrochlorides were also obtained by addition of hydrogen chloride to dicyano imide ( ), and to mono- (39.48,7 disubstituted cyanamides. 

By addition of hydrogen chloride to diphenylcarbodiimide, Lengfeld and Stieglitz synthesized l-chloro-N,N -diphenylformamidine hydrochloride (XXII) in 1895. The reaction is not limited to diarylcarbodiimides, and from dialkylcarbodiimides the corresponding chloroformamidine hydrochlorides can be obtained in quantitative yield... 

In the reaction of the cyanamide derivative XXXVIII with hydrogen chloride, the chloroformamidine hydrochloride derivative XXI (see page 119) is obtained ( °). ... 

The chloroformamidines are basic compounds, but their base strength has not been reported. However, it is indicated that the alkylchloroformami-dines are considerably more basic than the aryl derivatives because moderate heating causes elimination of hydrogen chloride from disubstituted aryl-chloroformamidine hydrochlorides ( ). N-Arenesulfonyl-N -alkylchloro-formamidines are almost neutral compounds because no hydrochloride formation was observed... 

The reaction of chloroformamidines ( ) and chloroformamidine hydrochlorides (i ) with water yields the corresponding ureas. 

Symmetrically disubstituted chloroformamidine hydrochlorides eliminate hydrogen chloride to form the corresponding carbodiimides, which add water to yield the corresponding ureas. The addition of water to the carbodiimides is catalyzed by the generated hydrochloric acid. 

In contrast, pseudourea derivatives are obtained in the reaction of chloroformamidine hydrochlorides with alkoxide ion... 

In contrast, arenesulfonyldialkylchloroformamidines can be recrystallized from ethanol However, the geminate dichlorides LI (nonpolar form of a chloroformamidine hydrochloride), on reaction with methanol, yield the acetals LII ( ). 

The reaction of chloroformamidine hydrochlorides with sodium hydrogen sulfide produces thiourea derivatives (6.is.i6,69j... 

In the reaction of substituted chloroformamidine hydrochlorides with phenylhydrazine or with benzoic acid hydrazide the corresponding guanidines are obtained. Thus, from tetramethylchloroformamidinium chloride (LX) and phenylhydrazine, a guanidine LXI is obtained in good yield ( ). 

The reactions of symmetrically disubstituted chloroformamidine hydrochlorides with a great variety of nucleophiles often proceed via initial elimination of hydrogen chloride to afford carbodiimide, the latter being attacked by the nucleophile. 

At more elevated temperature, and in the absence of a diluent, symmetrically disubstituted chloroformamidine hydrochlorides are in equilibrium with the carbonimidoyl dichloride, as evidenced by the isolation of tri-n-butylbiuret hydrochloride (LXII) in the pyrolysis of 1-chloro-N-n-butyl-N -n-butylformamidine hydrochloride (LXIII) ( ). 

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