ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 8, pp. 1258–1267. © Pleiades Publishing, Ltd., 2017. Original Russian Text © F. Hamoud, S.М. Ramsh, V.S. Fundamenskii, V.V. Gurzhii, V.I. Zakharov, V.А. Kuznetsov, D.V. Krivorotov, Е.S. Khrabrova, 2017, published in Zhurnal Organicheskoi Khimii, 2017, Vol. 53, No. 8, pp. 1242–1250. 1258 Guanidine Hydrochloride Aminomethylation with Formaldehyde and Simplest Amino Acids F. Hamoud a , S. М. Ramsh a ,* V. S. Fundamenskii a , V. V. Gurzhii b , V. I. Zakharov c , V. А. Kuznetsov c , D. V. Krivorotov c , and Е. S. Khrabrova a a St. Petersburg State Technological Institute (Technical University), Moskovskii pr. 26, St. Petersburg, 190013 Russia *e-mail: sramsh@technolog.edu.ru b St. Petersburg State University, St. Petersburg, Russia c Research Institute of Hygiene, Occupational Pathology, and Human Ecology, Federal Medical Biological Agency of Russia, Kuz’molovskii, Leningrad oblast, Russia Received March 3, 2017 Abstract—Aminomethylation of guanidine hydrochloride with aqueous formaldehyde and simplest amino acids depending on the reagents ratio results in bicyclic hydrochlorides (1 : 4 : 2) or tricyclic iminium chlorides (1 : 6 : 3) that in their turn may be converted into internal salts: zwitter-ions or betaines respectively. Aminomethylation of unsubstituted guanidine with formaldehyde and primary amines is poorly studied [1–3]. It was assumed that in the reaction with monoamines 5-alkyl-1,3,5-triazinan-2-imines were generated, in reaction with diamines, 5,5'-alkylenebis- (1,3,5-triazinan-2-imines), but there was no definite proof of structures of obtained compounds, particularly, NMR spectra were not registered. Our attempts to perform the aminomethylation of guanidine with aqueous formaldehyde and aminoacids C 2 –C 4 with terminal amino groups (glycine, β-alanine, γ- aminobutyric acid) following the reported procedures were unsuccessful: Only the initial guanidine salt was isolated from the reaction mixtures. Aiming to find out the reason of this failure we “modeled” the investigated reaction by the amino- methylation of S-methylisothiourea hydrobromide 1 with aqueous formaldehyde and β-alanine. As a result the expected cyclic isothiuronium salt 2 was obtained present in an equilibrium with the corresponding zwitter-ion 3 (Scheme 1). Previously there were no reports on the aminomethylation of S-alkylisothiourea hydrohalides. As a result, basing on known methods of the aminomethylation of urea and thiourea [4–10] and our own results on aminomethylation of S-methyl- isothiourea hydrobromide 1 mentioned above, we successfully performed the aminomethylation of guanidine hydrochloride 4 with 37% aqueous solution of formaldehyde and primary amino acids, and also with amino pelargonic acid (Scheme 2). The amino- methylation products were isolated in considerable yields, yet the products were not monocyclic (5- (carboxyalkyl)-1,3,5-triazinan-2-imines but depending on the reagents ratio bicyclic hydrochlorides 5 or tricyclic iminium chlorides 6. For instance, the DOI: 10.1134/S1070428017080176 Scheme 1. Br NH 2 HN S HBr 1 2 3 + HBr HN N NH S (CH 2 ) 2 COOH HN N NH S (CH 2 ) 2 COO CH 2 O, NH 2 (CH 2 ) 2 COOH i-PrOH _ H 2 O