Synthesis and crystal structure of β-N-(5-methyl-4-oxo-5,6-dihydro-4H-1,3-thiazin-2-yl)isonicotinohydrazide

Abstract

Keywords: methacryloylthiosemicarbazide of isonicotinic acid, intramolecular heterocyclization, X-ray crystallography.Previously the synthesis was reported of β-N-(methacryloylcarbamothioyl)isonicotinohydrazide (1) which, on boiling in 2-propanol for 10-16 h, underwent intramolecular cyclization to give β-N-(5-methyl-4-oxo-5,6-dihydro-4H-1,3-thiazin-2-yl)isonicotinohydrazide (2) [1]. The objective of the present work includes the study of the reaction of thiosemicarbazide 1 with a series of amines with the aim of obtaining the corresponding products of nucleophilic addition at the activated C=C bond.However mixing compound 1 with equimolar quantities of cyclic secondary amines (morpholine, piperidine) or alkaloids (anabasine, cytosine) in ethanol or 2-propanol solutions at about 30°C gave not the expected addition products 3 but the product of heterocyclization of compound 1 -the substituted 5,6-dihydro-1,3-thiazin-4-one 2 in 82% yield. Under these conditions cyclization of compound 1 occurred considerably faster (~1 h) than the same reaction in boiling 2-propanol reported previously [1]. The yield of product 2 did not depend on either the structure or the basicity of the amine and alkaloid starting materials.It is probable that the presence of base in the reaction medium facilitates the formation of the thiol form of compound 1 which is necessary for its cyclization. The 1 H NMR and IR spectra of samples of compound 2 obtained by using various amines or on boiling in 2-propanol [1] were identical.

Synthesis, Structure, and Antiradical Activity of New Methano[1,3]Thiazolo[2,3-d][1,3,5]Benzoxa-Diazocine Derivatives

“…Similarly to our previously obtained related structure [24], the thiazolidine ring in each molecule was nearly planar with sulfur atom deviating from the plane of other atoms by 0.09 Å, while the О(2) and О(6) atoms of carbonyl groups were in that plane. The pyrimidine ring assumed a nearly ideal "sofa" conformation (ΔC s 13 = 1.14 Å and ΔC s 31 = 4.37 Å) with the bridging С(13) and С(31) atoms in molecules 5с 1 and 5с 2 deviating by 0.70 and 0.74 Å, respectively.…”

“…With this goal we performed an X-ray structural study of compound 5с, the structure of which is presented in Figure 2. The crystal structure of compound 5с, similarly to the previously studied 5-(2,4-dimethoxyphenyl)-7-methyl-3-oxo-3,5-dihydro-2H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid [24], contained two geometrically independent molecules 5с 1 and 5с 2 (two enantiomers (5R,11R,13S) and (5S,11S,13R), respectively) packed in one independent unit cell. The bond lengths and valence angles in the structure were close to standard values [26].…”

“…We previously demonstrated a convenient method for the cyclization of 4-aryl-3,4-dihydropyrimidine-2-thiones into 3,5-dihydro-2H-thiazolo[3,2-a]pyrimidines [24] and explored some details of intramolecular cyclization [25]. While continuing these investigations, we attempted to perform analogous heterocyclization with derivatives of [1, 3,5] It was also shown that using α-chloroacetamide in this reaction instead of methyl chloroacetate led to not only higher yields and better purity of target products, but also easier isolation of products from the reaction mixture.…”

“…Of particular interest was the structural study of products from the reactions of [1,3,5]benzoxadiazocines 4a-d with chloroacetic acid derivatives and the differences of these compounds from the previously described thiazolopyrimidines [24], because the participation of 3-NH or 5-NH protons in the thione-thiol tautomerism may lead to the formation of methano[1,3]thiazolo [3,2- 3,5]benzoxadiazocine, respectively. With this goal we performed an X-ray structural study of compound 5с, the structure of which is presented in Figure 2.…”

Synthesis of bicyclic pyrimido[2,1-b][1, 3]thiazines based on 3,4-dihydropyrimidine-(1H)-2-thiones

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Keywords: 3,4-dihydropyrimidine(1H)-2-thiones, pyrimidino[2,1-b][1,3]thiazines, 3-bromopropionyl chloride, intramolecular heterocyclization, X-ray crystallographic analysis.

Today an enormous number of derivatives of 3,4-dihydropyrimidin-2-ones(2-thiones) with various aromatic and heterocyclic functional substituents have been synthesized by the Biginelli reaction, numerous methods including microwave and solvent-free methods have been developed for their production, and highly effective catalysts leading to a significant increase in the yields and reduction of the time for the condensation have been found [1][2][3][4][5][6][7]. [8-10], making further searches in the 3,4-dihydro-pyrimidin-2-one-(2-thione) series extremely promising.In [11] we proposed a convenient method for the synthesis of new derivatives of bicyclic 3,5-dihydro-2H-thiazolo[3,2-a]pyrimidines from 3,4-dihydropyrimidine-2-thiones, established their stereochemical structure, and studied the conditions for cyclization with various haloacetyl reagents [12]. [8-10], making further searches in the 3,4-dihydro-pyrimidin-2-one-(2-thione) series extremely promising.

In [11] we proposed a convenient method for the synthesis of new derivatives of bicyclic 3,5-dihydro-2H-thiazolo[3,2-a]pyrimidines from 3,4-dihydropyrimidine-2-thiones, established their stereochemical structure, and studied the conditions for cyclization with various haloacetyl reagents [12].

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