Azines and Azoles: CXXII. New Regioselective Synthesis of 1-Substituted 6-Alkyluracils

Abstract

Readily available 5-acyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-diones with primary alkyland arylamines in mild conditions (boiling in propan-2-ol) to give Schiff bases. In more rigid conditions (boiling in DMF), the reaction is accompanied by COS liberation and provides 1-substituted 6-alkyluracils. This previously unknown reaction possesses a considerable synthetic potential and can be considered as a new, general, and regioselective synthetic approach to 1-substituted 6-alkyluracils.Over the past years 1,3-thiazines and their hydroxy derivatives have attracted increasing attention, which, in particular, is due to the fact that they can be converted into derivatives of malonic acid, azines, and azoles under the action of nucleophiles [234]. 2,4,6-Trioxo-1,3-thiazines have so far been hardly accessible, and, therefore, little has been known on their reactions with N-, O-, and S-nucleophiles, except for those involving the initial member of this series of compounds [5]. Recently we developed a facile and convenient synthesis of 5-acyl-4-hydroxy-1,3-thiazine-2,6-diones from malonic acid, potassium thiocyanate, and carboxylic acid anhydrides in a corresponding acid medium [6,7]. Here we present data on reaction of these compounds with certain N-nucleophiles.It was found that the reactions of thiazine Ia with primary alkyl-or arylamines in propan-2-ol results in exclusive formation, even in the presence of a considerable excess of the amine and under prolonged boiling, of Schiff bases IIa3IIs (Table 1). The products are stable, well-crystallized substances readily soluble in dioxane and acetone.Thus, the reactions of 5-acylthiazines Ia3Ic with primary amines under these conditions involve no thiazine ring cleavage and give rise to ketimines IIa3IIs.Under more rigid conditions, quite unexpected events occur: Boiling of thiazine Ia in excess aniline gives 6-methyl-1-phenyluracil (IIIe) in high yield. The same product was obtained by boiling of an equimolar mixture of thiazine Ia with aniline in DMF.We decided to find out if this previously unknown ÄÄÄÄÄÄÄÄÄÄÄÄ 1 For communication CXXI, see [1]. Scheme 1. 8 A = ?9 = l r j O O H R 1 O O S NH 7776 R 2 3NH 2 8 A = ?9 = l r j N O R 1

Structural variety of Cu (II), Ni (II), and Co (II) complexes of a hydrazone based on 5‐acetyl‐4‐hydroxy‐2H‐1,3‐thiazine‐2,6(3H)‐dione: Synthesis, spectroscopic, density functional theory, antitumor, and docking studies

“…All employed chemicals were of reagent grade and used as received. Salicylaldehyde hydrazone [ 40 ] and 5‐acetyl‐4‐hydroxy‐2H‐1,3‐thiazine‐2,6(3H)‐dione [ 41 ] were prepared as described in the literature. Copper (II) salts including Cu (OAc) 2 .H 2 O, Cu (NO 3 ) 2 .3H 2 O, CuSO 4 .5H 2 O, Cu (ClO 4 ) 2 .6H 2 O, CuCl 2 .2H 2 O, CuBr 2 , Ni (NO 3 ) 2 and Co (NO 3 ) 2 .6H 2 O were used.…”

One‐pot two‐step synthesis of fused thiazinofuranone linked geminal bis 1,2,3‐triazole hybrids and their in vitro cytotoxic screening

“…Our initial studies focused on the synthesis of desired molecules, for this at first we considered the preparation of the required 5-acetyl-4-hydroxy1,3-thiazine-2,6-dione (1) according to the method established by Yuskovets et al [44]. On successful preparation of 5-acetyl-4-hydroxy1,3-thiazine molecule (1), we next focused to transform it to 2,2-diazido furanone fused 1,3-thiazine-2,6-dione (2) using NaN 3 , I 2 , and NaHCO 3 in water [45].…”

“…A mixture [44] of acetic acid (10 ml) and malonic acid (2.1 g) stirred for 15 min at RT. Then acetic anhydride (4.5 ml) was added.…”

DFT Calculations, Spectroscopic Studies, Biological Activity and Non Linear Optical Properties (NLO) of Novel Ternary Cu(II)‐Chelates Derived from 5‐Acetyl‐4‐hydroxy‐2H‐1,3‐thiazinedione

“…The structure of HL ligand (Scheme ) was described elsewhere . The tautomeric forms of the studied ligand, where the electron repealing affinity of the NH and OH group (in tautomer I) increase the electron density on the oxygen atom of the carbonyl group and thus this oxygen coordinates preferentially with the metal ion (tautomer II in the coordination), therefore the structure of the ligand in the metal complexes exist as thiazine‐2,4‐dione (Scheme ).…”