Synthesis and Antimicrobial Activity of N-[(3-Aryl-2-thiocyanatopropionylamino)-methyl]acrylamides and N,N-Methylene-bis(2- thiocyanato-3-arylpropionamides)

Abstract

Previously [1, 2], we have used anionarylation reactions to synthesize a series of thiocyanates, among which some compounds exhibited pronounced antimicrobial properties. Recently [3], it was demonstrated that N-allyl-3-arene-2thiocyanatopropionamides also show a high antibacterial activity with respect to staphylococci, bacilli, and pseudomonads. In this context, it was of interest to synthesize and characterize some other acrylamide derivatives, in particular, N-[(3-aryl-2-thiocyanatopropionylamino)methyl]acrylamides and N,N-methylene-bis(2-thiocyanato-3-arylpropionamides). We have obtained a series of such compounds by means of the anionarylation process [4, 5]. The interaction of aryldiazonium tetrafluoroborates with N,N-methylene-bisacrylamide in the presence of an external nucleophile (rhodane group) yielded compounds I – X by the scheme. The interaction of aryldiazonium tetrafluoroborates with 4-N,N-methylene-bisacrylamide proceeds in a water – DMF (1 : 3) or water – DMSO (1 : 4) mixture at temperatures in the interval from 10 to 15°C in the presence of a catalytic amount of copper salts. The character of the thiocyanatoarylation products depends on the ratio of the aromatic diazo salt, N,N-methylene-bisacrylamide, and potassium (ammonium) thiocyanate. For a reagent ratio of 1.1 : 1.0 : 1.1, the reaction yields monoadducts – N-[(3-aryl2-thiocyanatopropionylamino)methyl]acrylamides (I – III), while a twofold increase in the relative content of diazonium salt and rhodanide leads to the formation of biadducts – N,N-methylene-bis(2-thiocyanato-3-arylpropionamides) (IV – X). The proposed structures of mono- and biadducts were confirmed by converting the monoadducts into biadducts by means of thiocyanatoarylation. The experimental data indicate that thiocyanatoarylation of N,N-methylene-bisacrylamide proceeds via an intermediate stage of monoadduct formation. The yields, physicochemical constants, data of elemental analyses, and the parameters of 1 H NMR spectra of monoadducts I – III and biadducts IV – X are presented in Table 1. The IR spectra of the products display the characteristic absorption bands due to amide, thiocyanate, and NH groups in the regions of 1720 – 1728, 2152 – 2160, and 3412 – 3420 cm –1 , respectively.