Preparation of α-aminothioamides from aldehydes

Abstract

MARTINO PAVENTI and JOHN T. EDWARD. Can. J. Chem. 65, 282 (1987). The conversion of aldehydes into a-aminonitriles and thence into imidazolidin-4-thiones has been studied. Hydrolysis of the appropriate imidazolidin-4-thiones gave thioamides of nine naturally occurring a-amino acids. The possible pre-biotic significance of these compounds is discussed.MARTINO PAVENTI et JOHN T. EDWARD. Can. J. Chem. 65,282 (1987). On a CtudiC la transformation des aldChydes en a-amino-nitriles et Cventuellement en imidazolidinethiones-4. L'hydrolyse des imidazolidinethiones-4 appropriCes conduit aux thioamides de neuf acides a-aminCs naturels. On discute de I'implication prC-biotique possible de ces composts.[Traduit par la revue]In 1953, Miller (1) showed that sparking a mixture of methane, ammonia, hydrogen, and water vapour furnished traces of glycine, alanine, and other common a-amino acids. This historic experiment awakened the interest of many organic chemists in possible pre-biotic routes to proteins, nucleic acids, and polysaccharides on the primitive earth.It seems likely that under the conditions of Miller's experiment aldehydes and hydrogen cyanide are formed (2). These can react with ammonia to give a-aminonitriles 1, which are hydrolysed to a-amino acids-(2). However, the polymerization .of a-amino acids to polypeptides and proteins requires an activation process. Various possible modes of activation that might operate under pre-biotic conditions (heat, cyanamide, adsorption on clays, etc.) have been suggested (2, 3) but are not very plausible.This activation step might have been avoided on the primitive earth if a-aminonitriles had been converted into reactive a-amino acid derivatives rather than into unreactive a-amino acid zwitterions. One such derivative might have been the thioamide. The reactivity of these compounds was demonstrated more than 70 years ago by Johnson and Burnham (4), in the course of their attempts to obtain the thioamide 2 (R' = R~ = H) by treatment of the nitrile 1 (R' = R2 = H) amounts of the cyclic product 4 (R' = R2 = H), all presumably arising from further reaction of the sought-for thioamide 2 (R1 = R 2 = H) (Scheme 1). Later attempts by Gatewood and Johnson (5,6) to obtain other a-aminothioamides by this route gave either no product (6), or products from further reaction of initially formed a-aminothioamides (5, 6). However, Cook et al. (7) obtained 2 (R' = Ph, R2 = H) in 12% yield by treating 1 (R' = Ph, R2 = H) with H2S for 24 h in ether containing a little pyridine.This work indicates a possibility of producing thiopolypeptides and thence polypeptides by the general route of Scheme 1.Consequently, we have prepared a-aminothioamides 2 corresponding to several common a-amino acids a s a preliminary t o searching for conditions to convert them into linear thiopolypeptides.We first required a convenient and general preparation of a-aminonitriles 1. These compounds have long been obtained by the Strecker reaction: ience, NH4Cl and NaCN (= NaCl + NH4CN = NaCl + NH3 + HCN) were used instead...

2-Amino-2-alkyl(aryl)propanenitriles as key building blocks for the synthesis of five-membered heterocycles

“…[53][54][55][56][57] This reaction course was explained by cyclo-condensation of the corresponding ketone released from α-aminonitrile together with the formed α-aminothioamide (Scheme 9).…”

“…[53][54][55][56][57] A particular case of hydrolysis of 2,2,5,5-tetramethylimidazoline-4-thione gave 2-amino-2-methylthiopropanamide (Scheme 11). …”

Assisted hydrolysis of the nitrile group of 2-aminoadamantane-2-carbonitrile

“…This would be expected to yield the imidazolidine-4-thione 10 by the mechanism shown in Scheme 2 (15). In fact, this compound was obtained, but in small yield, along with the compounds 11 and 13 (15).…”

“…This would be expected to yield the imidazolidine-4-thione 10 by the mechanism shown in Scheme 2 (15). In fact, this compound was obtained, but in small yield, along with the compounds 11 and 13 (15). Evidently steric hindrance at the cyclization step leading to 10 is sufficient to allow the competing hydrolysis of the intermediate to yield 11, and steric hindrance at an earlier stage causes 2 to react so slowly that the competing breakdown of 2 to adamantanone, NH3, and HCN (13) can result in the formation of significant amounts of 12 and thence of 13.…”

Selective prebiotic synthesis of phosphoroaminonitriles and aminothioamides in neutral water

“…The implication of HCN in both amino acid and nucleotide synthesis strongly suggests the importance of cyanide chemistry at the origins of life 2 . However, Strecker synthesis is highly pH dependant and is reversible under sufficiently acidic or alkaline conditions 3 . Moreover, if a successful synthesis of aminonitrile 2 (or amino acid 3) can be achieved under prebiotic constraints, subsequent activation is required for peptide synthesis.…”