Chloroformamidines chlorides

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

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... 

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 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],... 

Another useful method to convert thioureas into carbodiimides involves their reaction with reactive chlorine compounds, such as SOCI2, SO2CI2, SCI2 or S2CI2, The use of the sulfur chlorides involves chloroformamidines as intermediates (see Section 2.2.6). The reaction of thioureas 11 with methanesulfonyl chloride in methylene chloride in the presence of triethylamine/DMAP (4-dimethylaminopyridine) at room temperature produces carbodiimides 12 in 85-100% yield... 

The use of an excess of carbonyl chloride has to be avoided because the intermediate chloroformamidines react with carbonyl chloride to give chloroformamidine-N-carbonyl chlorides. 

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

Diisopropylcarbodiimide reacts with a-halo carboxyhc acid chlorides to give the same chloroformamidines, which on hydrolysis cyclize to form 5-oxazolidinones. ... 

Carbonyl dichloride (phosgene) phosphoryl chloride/ phosphorus trichloride thiophosgene, thionyl chloride/ sulfur dichloride and cyanuric chloride react with carbodiimides to give the expected chloroformamidine derivatives. In the reaction of carbodiimides with two equivalents of carbonyl chloride N,N -disubstituted chloroformamidine N-carbonyl chlorides 703 are obtained. 

Better results are obtained using carbonyl chloride or phosphorous pentachloride in the reaction with the sulfonylthioureas. Intermediates in this reaction are chloroformamidines 1, which, on heating, eliminate hydrogen chloride to give N-sulfonyl-N -alkylcarbodiimides 2. 

Biuret trichlorides .7 Dimethylcyananvide (1) reacts with the reagent in methylene chloride to give almost quantitative yields of N,N,N, N -tetramethyl-l,3-dichloro-2-azatrimethinecyanine (2), a biuret trichloride. This is hydrolyzed under mild conditions to N1,N1-dimethyl-N2-(dimethylcarbamoyl)chloroformamidine (3), hydrolyzable under stronger conditions to the biuret derivative (4). 

The loss of two molecules of HCl (often at room temperature) from the chloroformamidinium salts results in the formation of carbodiimides, RN=C=NR [2087,2087a]. The use of an excess of COClj should therefore be avoided, since carbodiimides themselves can react with phosgene to give chloroformamidine-iV-carbonyl chlorides, see Section 10.2.8. Indeed, in early work [2189a], diarylthioureas were found to react with an excess of COClj to form cyclic compounds ... 

The hydrolysis of hydroxamoyl chlorides, observed by Souchay et a/.( ), also occurs via an elimination sequence, with formation of the corresponding nitrile oxide intermediate. Likewise, solvolysis of N,N -disubstituted chloroformamidines may involve the carbodiimide as the reactive intermediate. 

This reaction is similar to the conversion of chloroformamidines (XII) with phosgene to the corresponding N-carbonyl chlorides (XIII) ( ). 

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... 

Upon reaction of LII with two equivalents of dimethylamine the corresponding chloroformamidine (LIV) can be obtained, which upon high-temperature chlorination yields the chloroimidoylcarbonimidoyl di-chloride derivative LV ( ). 

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 reaction of substituted thioureas with carbonyl chloride is perhaps the most useful synthetic method for chloroformamidines. Thus, alkyl... 

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 ). 

Chloroformamidines are not produced in the reaction of thioureas with oxalyl chloride, because ring closure occurs and 2-imino-l,3-thiazolidin-4,5-diones (XV) are obtained in high yield ( ). The heterocyclic derivatives XV isomerize readily to form thioparabanic acids XVI... 

The reaction of substituted ureas with carbonyl chloride provides another useful method of synthesis of chloroformamidines However, oxygen is not as nucleophilic as sulfur and consequently attack on nitrogen often occurs. In the case of 1,3-dialkylureas good yields of... 

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

Instead of carbonyl chloride, phosphorus pentachloride can be used to prepare chloroformamidines (8>2o,s5j hydrochlorides (6o.63.66j... 

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 ... 

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... 

The reaction of dialkylcyanamides with carboxylic acid chlorides at 150 C affords 1 1 adducts, which are formulated as chloroformamidines XXIII because they react with ammonia to give the corresponding guanidines (XXIV)... 

Carboxylic acid chlorides add in a like manner to carbodiimides to form the corresponding 1 1 adducts, which have a chloroformamidine structure. For example, acetyl chloride was added to carbodiimides, and the structure of the labile 1 1 adducts (XXVII) was established by subsequent reactions with anthranilamide, leading to 4-quinazolones XXVIII... 

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

The reaction of the uretone imine XXXIX (R = ethyl) with carbonyl chloride proceeds via ring opening with formation of the chloroformamidine XL(i ). 

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... 

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. 

Similarly, reaction of chloroformamidines with phenols, in the presence of triethylamine as hydrogen chloride scavenger, affords pseudourea derivatives ( ). 

In the reaction of chloroformamidine-N-carbonyl chlorides LVI with arylamines a mixture of carbodiimides and isocyanates is obtained ( ). 

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. 

The cyclic analogs of chloroformamidines are virtually unknown. Suzuki mentioned the synthesis of 2-chloroimidazolidine but reported no physical constants. The cyclic chloroformamidinium chloride XXV can be obtained from l,3-dimethylimidazolidine-2-one (XXVI) and carbonyl chloride, but this reaction is considerably slower than the phosgenation of the tetrasubstituted linear urea C ). 

The reaction of N-acylthioureas XXX with carbonyl chloride yields the chloroformamidines XXXI, which are readily dehydrochlorinated to N-acylcarbodiimides XXXII... 

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