Haloformamidines

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 parent haloformamidines are not known however, their hydrohalides were isolated as early as 1875, when Drechsel ( ) treated cyanamide with hydrogen halides. However, its true structure was not recognized until recently ( ). 

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 

When two of the substituents R in II are hydrogen, two moles of hydrogen halide can be eliminated, and the resulting product is the corresponding carbodiimide (IV). The reversal of this reaction, i.e., the addition of hydrogen halide to carbodiimides, is a useful method of synthesis of haloformamidine hydrohalides. 

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Carbonimidoyl dihalides Imidoyl halides Haloformamidines Haloformimidates Halothioformimidates Hydroxamoyl halides Hydrazidoyl halides... 

The dehydrohalogenation to the corresponding haloformamidine, carbodiimide, or cyanamide is prevented in tetraalkylhaloformamidinium halides (I, R = alkyl), which in this respect resemble quaternary ammonium halides. 

Depending upon the basicity of the nitrogens, either haloformamidines or their hydrohalides are formed in the general synthetic procedures. The haloformamidines are in this, and in many other respects, quite closely related to the imidoyl halides (see Chapter 3). While the chloro and bromo compounds have a tendency to form the corresponding hydrohalides, the fluoro compounds, as usual, are nonpolar in character. 

A different group of haloformamidines can be obtained by adding acid halides, such as carbonyl chloride, oxalyl chloride, thiocarbonyl chloride, phosphorus oxychloride, phosphorus trichloride, sulfur chlorides, and acetyl chloride to carbodiimides. 

In view of their facile reaction with nucleophiles, haloformamidines are exceedingly useful in organic synthesis, and a wide variety of carbonic acid derivatives have been synthesized from haloformamidines, especially in recent years. 

The hitherto-synthesized haloformamidines and their hydrohalides are listed in Tables I-V. 

The free haloformamidines are either low-melting solids, or colorless liquids, which can be distilled under vacuum without decomposition. The halo group is readily displaced by a variety of nucleophiles, as shown in Section IV. 

The hydrohalides of chloroformamidine and alkylchloroformamidines are hydroscopic solids. The infrared spectra of haloformamidines show the characteristic C=N absorption at approximately 1546-1725 cm (see Table VI). 

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