HCN Tetramers

Fig. 4.5 The adenine synthesis can be varied to give other purine derivatives. Structures I-IX are those of I aminomalonitrile, II HCN tetramer, III aminoimidazole-carbonitrile, IV 4-aminoimidazole-5-carboxamide, V adenine, VI diaminopurine, VII xanthine, VIII guanine and IX hypo xanthine (Sanchez et al., 1966a)... 

Photochemical reactions of HCN tetramers in such eutectic solutions to give 4-amino-3-cyanoimidazole (Orgel, 2004)... 

A charge-transfer complex [ZnLQ] (H2L = 28 Q = p-chloranil) has been characterized, and a weak n-n interaction between the ZnL and Q moieties demonstrated.338 A related complex, [ZnL] (H2L = 29), is formed from the template condensation of HCN tetramer, H2N(NC)C=C(CN)NH2 with salicylaldehyde in the presence of ZnCl2.339 In the absence of the zinc salt, unsymmetrical mono-Schiff bases are obtained. 

All the carbon atoms of the purine ring were supposedly provided by HCN molecules through a complex step-by-step condensation process. In particular, oligomers of HCN, such as the HCN-trimer aminomaleonitrile (AMN) and the HCN-tetramer diaminomaleonitrile (DAMN), were found to be intermediates in this transformation (Scheme 1) [43,44]. In accordance with the present-day biosynthesis of purines in the cell, two 4,5-di-substituted imidazole derivatives, 4-aminoimidazole-5-carbonitrile (AICN) and 4-aminoimidazole-5-carboxamide (AICA) were successively formed from AMN and DAMN by chemical or, most probably, photochemical reactions [45-47]. Finally, a ring-closure process of AICA and HCN yielded adenine 1. 

The application of HCN to fine-chemical synthesis has been considered, particularly in the steroid field, and very elaborate and valuable chemicals are also prepared from HCN derivatives. In this prospect, oligomers of HCN. such as triaxine (an HCN t rimer), diaminomaleonitrUe (an HCN tetramer) and adenine (an HCN pentamer), are interesting e.xamples of derivatives for pharmaceutical synthesis. 

The synthesis of 1,2,5-thiadiazoles from a-diamines was studied as early as 1897 when Michaelis attempted the preparation of the parent compound by reaction of ethylenediamine with sulfur dioxide. The product, however, was bissulfimic acid (28) which readily lost sulfur dioxide to form the betaine (28a). Later Shew reported that 3,4-dicyano-l,2,5-thiadiazole (30) results from the reaction of cis-diaminomaleonitrile (29, HCN tetramer) with thionyl chloride, a reaction which is analogous to 2,1,3-benzothiadiazole formation from o-phenylenediamines. The synthesis of the parent 1,2,5-thiadiazole and some alkyl analogs (32) was accomplished by reaction of salts of... 

An alternative route to purines is via the self-condensation of dilute solution (>0.01 M) of HCN at pH 9 to a tetramer of HCN. Photolysis of the HCN tetramer yields 4-aminoimidazole-5-carbonitrile (9,10), This aminoimidazole reacts with HCN to generate adenine. Other purine bases are also formed by the reaction of the aminoimidazole carbonitrile with other one or two carbon compounds (5). 

In line with my earlier suggestion on the role of cyanamide, several investigators, particularly G. D. Steinman, R. M. Lemmon and M. Calvin, have shown that this compound and dicyandiamide will condense amino acids under mild aqueous conditions into normal peptides. The HCN tetramer, diaminomaleodinitrile, formed in the HCN-NH4OH mixtures has also been found to condense amino acids into simple biological peptides as shown by Chang and co-workers. Recent experiments indicate that oligopeptides can also be formed on the surface of minerals or clays by heating, after evaporation, at temperatures below 100°C. 

A proposed step in the prebiotic polymerization of hydrogen cyanide, the dimerization of iminoacetonitrile (22) to the HCN tetramer, diaminomaleo-nitrile (23), has been achieved with the A-t-butyl derivative of (22). Di-iminosuccinonitrile (24), an oxidized form of the tetramer, has been pre-... 

The steady state concentrations of HCN would have depended on the pH and temperature of the early oceans and the input rate of HCN from atmospheric synthesis. Assuming favorable production rates, Miyakawa et al (30) estimated steady state concentrations of HCN of 2 x 10 M at pH 8 and 0°C in the primitive oceans. At 100° C and pH 8 the steady state concentration was estimated as 7 x 10 M. HCN hydrolyzes to formamide which then hydrolyzes to formic acid and ammonia. It has been estimated that oligomerization and hydrolysis compete at approximately 10 M concentrations of HCN at pH 9 (31), although it has been shown that adenine is still produced from solutions as dilute as 10 M (32). If the concentration of HCN were as low as estimated, it is possible that HCN tetramer formation may have occurred on the primitive Earth in eutectic solutions of HCN-H2O, which may have existed in the polar regions of an Earth of the present average temperature. High yields of the HCN tetramer have been reported by cooling dilute cyanide solutions to temperatures between -10° C and -30° C for a few months (31). Production of adenine by HCN polymerization is accelerated by the presence of formaldehyde and other aldehydes, which could have also been available in the prebiotic environment (29). 

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