Synthesis of New Functionally Substituted 1-R-tetrazoles and Their 5-Amino Derivatives

Abstract

Keywords: 1-R-5-aminotetrazoles, N-arylcyanamides, 1-R-tetrazoles.C-and N-tetrazolyl groups enter into the composition of a series of biologically active compounds, many of which are used in medicinal practice [1,2]. This is linked primarily with the unique structure of the tetrazole ring which, depending on the location of substituents, may be a bioisostere of a carboxyl or an amide grouping, possessing several advantages over them [2,3]. One of the most preferred routes for making a 1-monosubstituted tetrazole ring is the heterocyclization of primary amines with triethyl orthoformate and sodium azide [3]. This process is used for the synthesis of tetrazoles, starting from primary amines of various nature, including aliphatic, aromatic, and heterocyclic [4][5][6][7][8][9]. It was shown that the reaction proceeds smoothly with the participation of only the simplest alkyl and aryl amines. It was discovered that 2,4-dinitroaniline does not react [7], and in the case of ortho-phenylenediamine the process stops at the stage of forming benzimidazole, the condensation product of triethyl orthoformate with the initial amine [6]. Under analogous conditions thiosemicarbazide forms a 2-aminothiadiazole [7]. Conversion products of several other compounds with a primary amino group, including hydrazine, phenylhydrazine, melamine, and aminoguanidine, failed to be identified [7]. The behavior of other functionally substituted primary amines has not been studied up to the present time, in spite of the obvious effect of the nature of the substituent on the course of the heterocyclization reaction.In the development of these investigations and with the aim of broadening the preparative possibilities of this reaction, the heterocyclization of some alkyl-, aryl-, and hetarylamines has been studied in this work. These include substances of a series of widely known pharmaceutical preparations possessing antibacterial and antiviral action, comprising sulfanilamide, sulfaethidole, sulfadimidine, rimantadine, etc. It was discovered that primary amines 1 react with sodium azide and triethyl orthoformate in acetic acid at a molar ratio of reactants of 1:1.1:3, forming the corresponding 1-monosubstituted tetrazoles 2.

Application of the Fe3O4@1,10‐phenanthroline‐5,6‐diol@Mn nano‐catalyst for the green synthesis of tetrazoles and its biological performance

“…In addition, a byproduct of this reaction is trimethylsilane (Me 3 SiH), which is a toxic and flammable substance and may cause flash fire and target organ damage. [26] 3…”

Synthesis, single crystal analysis, biological and docking evaluation of tetrazole derivatives

“…The best known method for the synthesis of Tetrazoles is by treating sodium azide and triethyl orthoformate with aromatic amines in glacial acetic acid as shown in Fig. 1 [19] . Using this synthetic methodology, three different tetrazole derivatives (2, 4, 6) were successfully synthesized in higher yields.…”

Alkylation of N-arylcyanamides and electron-deficient phenols with (chloromethyl)thiirane

“…All reagents and solvents were commercially available and were used as supplied without additional purification. The starting N-arylcyanamides 1a-k were synthesized according to literature methods (1a [11], 1b [26], 1c,f,g [17], 1d [23], 1e [12], 1h [27], 1i [28], 1j,k [20]). Method).…”

“…More recently, an efficient method for the synthesis of 1-aryltetrazoles has been proposed [21]. The latter compounds produce N-arylcyanamides when treated with KOH in DMSO [22,23].…”