Biguanides 3- guanidine

Oximes, biguanides, guanidines, N-coordinated ureas and amides 849... 

Reaction with ammonium salts gives biguanide salts which react further with the ammonium salt forming guanidine salts. Guanidine nitrate [506-93 ] is manufactured by this route (46). 

Uses. Dicyandiamide is used as a raw material for the manufacture of several chemicals, such as guanamines, biguanide and guanidine salts, and various resias. Siace 1975, it has also been used ia the manufacture of potassium or sodium dicyanamide which are used as iasecticides and ia chemotherapy. Melamine has extensive appHcations ia the resia and plastic iadustry guanamines are used as copolymers (qv) ia many resia compositions. Guanidine phosphate [1763-07-1] is employed as a fire retardant ia appHcations where water solubiHty is not a drawback. 

Benzoguanamine has been prepared by the reaction of dicyandiamide with benzonitrile in a sealed tube at 220-230°,2 with an excess of benzonitrile in the presence of piperidine and potassium carbonate,3 with benzonitrile in a solvent in the presence of a basic catalyst,4 and with benzamidine hydrochloride at elevated temperatures.5 It has also been prepared from the reaction of biguanide acetate with benzamidine hydrochloride,5 or of bigua-nide sulfate with benzoyl chloride in an alkaline medium,7 and by the distillation of guanidine benzoate.5... 

A recent new synthesis of biguanide, affording 50—60% yields of product, utilises the reaction between 0-adkylisoureas and equimolar proportions of guanidine and its hydrochloride in ethanol (612). Small amounts of melamine and cycuioguanidine are formed as by-products. 

Later workers (489) have postulated the existence of intermediate biguanide in the interaction of cyanoguanidine and ammonium nitrate in liquid ammonia (at relatively high temperatures). The reaction is thus thought to adopt the same reaction path as that of the analogous fusion, but positive evidence for this view is difficult to obtain, because of the rapidity with which all postulated intermediates are onverted into guanidine salts. 

The reaction may be carried out successfully by the conventional fusion-technique. In the course of the s5mthesis of numerous aryl- and alkyl-biguanides by this procedure, the substituted guanidine rather than the biguanide was occasionally formed in a side reaction. In such cases the biguanide first formed may be cleaved partially by way of an intramolecular hydrogen-bonded form (602) (cf. section VI, B3). 

Under the influence of desulphurising agents, guanidines and thioureas combine to form biguanides (XIX), albeit in low yields (722, 575). In their re-examination of this reaction. Curd, Rose et al. (24, 57, 754) synthesised 1,5-disubstituted biguanides however, the yields did not... 

The preparation and subsequent pyrolysis of a monoalkylcyanamide salt of a guanidine has been suggested (50) as a route to biguanides. 

With N,N -disubstituted guanidines the problem arises whether 1,2,5- (XXXV) or 1,3,5-trisubstituted biguanides (XXXVI) are produced, or a mixture of both. Relevant experiments (5) show that the former (XXXV) are in fact obtained to the exclusion of the latter. 

An ingenious use of monoalkyl- or alkoxyalkylcyanamides in the synth is of biguanides utilises (201) their rapid dimerisation at elevated temperatures to cyanoguanidines (XXXIX), which are subsequently treated with hydroxyalkylamines any unchanged cyanamide would yield a guanidine ... 

The formation of a biguanide as a by-product in a condensation of a cyanamide and amine (225) (which would normally be expected to yield a guanidine) and as main product in the reaction of glucosamine and cyanamide (437) has been noted. In the former example, the small amount of biguanide probably arose by further reaction of the primary guanidine (which formed the main product) with C5 namide. In the second example the biguanide may be the result of the interaction of the amine and intermediate cyanoguanidine. 

Disnbstituted biguanides and more highly substituted analogues may be s3uithesised by the addition of carbodiimides to guanidines (122). 

Elution curves for biguanide in the presence of related compounds (e.g. cyanamide, cyanoguanidine, guanidine, urea, thiourea) have been established (690). Various ion-exchange resins are suitable (108,686,689). 

The acid hydrolysis of biguanides under a variety of conditions 5uelds chiefly amidinoureas the subject has been reviewed by Ray (531). The reaction proceeds slowly under very mild conditions at room temperature thus, Paludrine, when stored in 2N hydrochloric add slowly deposits N-p-chlorophenyl-N -isopropylamidinourea hydrochloride (140). That this product was not the isomeric N-isopropyl-N -p-chlorophenyl-amidinourea was verified by its rmequivocal s3uithesis from isopropyl-guanidine and p-chlorophenyl isocyanate (140) ... 

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). 

The preparation of alkylguanidines by fusing amine salts with dicyandiamide at 180° for three hours has been advocated [104], however it has been shown that, depending on the conditions, a guanidine or a biguanide can result [105, 106]. 

Certain aromatic guanidines (and biguanides) are known to cause a reflex fall of blood pressure and heart rate by an action on receptors in the heart [288]. However, there have been no reports of arylguanidines exhibiting activity at sympathetic nerve endings. o-Bromophenylguanidine (LXXIV) does not affect cat nictitating membranes [239]. 

A carbodiimide-grafted polystyrene resin was reacted with tetramethyl-guanidine to give an interesting biguanide structure (Scheme 13). This was assayed as a catalyst for a transesterification reaction.33 Incidentally, resin-bound guanidines are useful bases for processes involving resin capture.34... 

The filtrate contains guanidine nitrate along with a small amount of ammonium nitrate and very small amounts of dicyano-diamide and biguanide nitrate (Note 6). The solution is concentrated to about 1 1. and the guanidine nitrate which crystallizes on cooling is filtered off. A second crop is obtained by... 

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