Biguanide, l-

An effective, but not very practical, flame retardant for cotton based on 2,4-diamino-6-(3,3,3-tribromopropyl)-l,3,5-tria2ine [62160-38-7] (DABT) was prepared from ethyl y-tribromobutyrate and biguanide [56-03-1] ... 

Ghlorhexidine Gluconate. Chlorhexidine gluconate [18472-51 -0] (l,l -hexamethylene bis[5-(p-chlorophenyl) biguanide] di-D-gluconate) is used as an antimicrobial against both aerobic and anaerobic bacteria ia the oral cavity. It is used as a therapeutic supplement ia the treatment of gingivitis, periodontal disease, and dental caries. A mouth riase form is available as a 0.12 wt% aqueous solution (288). 

To a solution of l-(4-methoxyphenyl)-biguanide (2.07 g, 10 mmol) and l-(4-methoxyphenyl)-biguanide hydrochloride (0.2 g, 1 mmol) in EtOH (50 mL) was added 1-benzoylacetone (1.62 g, 10 mmol) and the solution was heated under reflux for 10 h. After the solution was concentrated, the oily residue was poured into H20 and repeatedly washed with H20. The resulting solidified mass was collected by filtration and dissolved in EtOH by heating. After standing overnight at rt, a mixture of needles and prisms was isolated yield 1.5 g (45%). The mixture was dissolved in a suitable amount of EtOH by heating and, after 2 h at rt, the deposited, needles were collected by filtration mp 166 C. The needles were dissolved in a suitable amount of EtOH and the solution was left to stand at rt for a couple of days. The deposited prisms were collected by filtration mp 166°C. 

C20H22CINO2 118108-64-8) see Propiverine 7-chloro-5-phenyl-3ff-l -benzodiazepin-2-amine (C15H12CIN3 7564-07-0) see Estazolam l-(4-chl rophenyl)biguanide hydrochloride (CjHjjCliNs 4022-81-5) see Chlorazanil... 

A recent X-ray-crystallographic investigation [86) has provided the first accurate structural picture of a biguanide derivative, namely that of the antimalarial Paludrine (l-p-chlorophenyl-5-isopropyibiguanide hydrochloride) (Fig. 1). The biguanide part of the cation consists of two... 

It is noteworthy that cyanoguanidine and p-aminosalicylic acid react in acidified boiling water with simultaneous decarboxylation [608), giving m-hydroxyphenylbiguanide instead of the expected l-(3-hydroxy-4-carboxyphenyl)biguanide. The decarboxylation under such mild conditions appears to be anomalous, since p-aminobenzoic acid [100) and its esters [97) do give the expected biguanides. 

Acylaminobiguanides are cyclised by alkalis without difficulty, with loss of water, to 5-guanidino-l,2,4-triazoles. Their interaction with formic acid affords the expected guanamines in the majority of examples 391, 392) (see also Section VII, I). Contrary to a previous claim 91), isonicotinic acid hydrazide dihydrochloride and cyanoguanidine do not give the biguanide under neutral conditions, but form merely a molecular adduct of the reactants 416). 

The interaction (575) of O-methylisourea and N-methylglycine occurs normally at low temperatures to yield the expected creatine (XXXII) (21%). At 40—50° the production of 1-methyl-l-biguanide acetic acid (XXXIII) in low yield has been reported, but the mechanism of its formation ist not clear. 

The interaction of p-methoxybenzylideneaminoguanidine (XXXVII R = p-MeO CeH4 ) and dimethylcyanamide (580) gave 17% 5delds of alleged l-dimethyl-3-(p-methoxybenzylideneamino) biguanide (XXXVIII). The possible condensation at the free amidino-grouping (of XXXVII) was not considered by the author. 

Aminomagnesium halides (XLIX) may also serve as a source of the same substituted biguanides (XLVIII) by reaction with substituted cyanoguanidines (L), but 3delds are again low and variable. The possible mechanism of this group of reactions has been discussed [59), but the studies are as yet incomplete. 

An unexpected formation of a biguanide occurred 754) in the reaction of trans-l-amino-2-hydroxycyclohexane (LI) with cyanogen bromide in the presence of sodium acetate. In addition to the expected trans-2-amino-3a,4,5,6,7,7a-hexahydro-benzoxazole (LII), traces of its trimer having the biguanide structure (LIII) were obtained. 

Attempts to gain further insight into the more detailed structure of biguanides in general, and of Paludrine in particular, were made by studies of their ultraviolet spectra, including those of simpler molecules, which may be regarded as the component parts of l-aryl-5-alkyl-biguanides (227), but the succes of this approach was at first limited (227). 

A further comprehensive study, but limited to l-(p-phenethyl)-biguanide has been undertaken by Shapiro et al. 602). On the basis of their experimental findings (Table 4) they summarised [602) the behaviour of this compound at various hydrogen ion concentrations by equations (i) - (vii) (B = PhCH2CH2-NH-C( NH)NH-C( NH)NH2). 

Infrared data are available for biguanide 688) and l,l-anhydrobis(P-hydroxyethyl)biguanide hydrochloride 432). 

The interaction of l-(p-arsonophenyl)biguanide and ethyl acetoacetate failed to give the expected 2-(p-arsonophenylguanidino)-4-hydroxy-6-methylpyrimidine under a variety of conditions (408), as did the corresponding reaction with diethyl malonate. Condensation did occur, however, with acetylacetone (see Section VII J5) (see also ref. 590). 

The condensation of 2-naphthylamine hydrochloride, cyanoguanidine and acetone yields, in addition to the expected dihydro-s-triazine, l-(2-naphthyl)biguanide and 3-guanidino-l-methylbenzo[f]quinazoline (554). 

In the general reaction, 1,1-disubstituted biguanides (95) (e.g. 1-p-chlorophenyl-l-methylbiguanide) afford the same product (CXXXIII) under both acidic and basic conditions. The phenyl analogue gave similar results (95). Independent studies by Modest et al. (443) confirmed the assigned structure (CXXXIII). 

The interaction of 1,2-disubstituted biguanides and acetone has provided particularly significant results (95). l-p-Chlorophenyl-2-methylbiguanide and acetone reacted in the expected manner, under acidic or basic conditions respectively, to yield the isomers (CXXXIV) or (CXXXV). 

Studies have recently become available concerning the kinetics and mechanism of the isomerisation, in dilute aqueous solution, of dihydrotriazines of this type (e.g. 4,6-diamino-l-(3,5-dichlorophenyl)-l,2-dihydro-2,2-dimethyl-l,3,5-triazine), and of their degradation to substituted biguanides 683). 

The resulting l-(p-chlorophenylazo)-5-isopropylbiguarude is cleaved by hydrochloric acid to p-chlorophenol and 1-isopropylbiguanide. Similar observations concerning the reaction of diazonium salts with biguanides have appeared in the patent literature 403). 

A procedure for estimating hexamethylene l,6-bis[l-(5-p-chloro-phenyl)biguanide] ( chlorohexidine") in the presence of anesthesine in tablets has been described (617). Nt,NiAnhydro[bis(p-hydroxyethyl)]-biguanide (616) and other biguanides (137) have been determined by spectrophotometric (137, 616) (including infra-red (563)) techniques. Chromatographic procedures have also been described (26, 449, 467). 

---