A theoretical study on the structure of 2-amino-1,3,4-thiadiazole and its 5-substituted derivatives in the gas phase, water, THF and DMSO solutions

doi:10.1016/j.molliq.2015.01.002

Journal of Molecular Liquids

Volume 203, March 2015, Pages 137-142

https://doi.org/10.1016/j.molliq.2015.01.002 Get rights and content

Highlights

•
Investigation of the structure of 2-amino-1,3,4-thiadiazole and its 5-substituted derivatives
•
Investigation of the thermodynamic parameters in the gas phase and solutions
•
Investigation of the effect of different solvents on geometry and stability

Abstract

The results of a detailed DFT (B3LYP) and ab initio (HF and MP2) investigation on one of the amino–imino tautomers and its derivatives are presented here. The energy, geometrical parameters and vibrational frequencies of 2-amino-1,3,4-thiadiazole tautomerization in the gas phase, water, THF and DMSO solutions were calculated using 6-311++G(d,p), 6-311G(d) and 6-31+G(d,p) basis sets. The solvent effect was explored using the PCM method and the related conformers have been fully optimized at the B3LYP/6-311++G** level of theory. For the investigated molecule, proton-transfer from N to N and from N to C occurred, which leads to three tautomers: 2-amino-1,3,4-thiadiazole (A), 2(3H)-imino-1,3,4-thiadiazole (B) and 2(5H)-imino-1,3,4-thiadiazole (C). For B and C, geometrical isomerism (E and Z) was also considered. This leads to five isomers: A, B₁, B₂, C₁ and C₂ for each derivative. However, all calculations evidently show that isomer A strongly or solely dominates and dictates the structure of 2-amino-1,3,4-thiadiazoles. Substituents and solvents have no effect on the tautomeric preferences.

Introduction

The 1,3,4-thiadiazole derivatives were synthesized with the aim of new antituberculosis drug's development. The family of heterocyclic compounds, containing both nitrogen and sulfur atoms is considered as an important class of compounds in medicinal chemistry because of their interesting and diversified biological applications. The 1,3,4-thiadiazole and amino-thiazole groups are associated with various biological activities, probably due to the presence of a toxophoric ( single bond N = CS) group [1], [2], [3], [4]. The importance of the sulfur atom in drugs as sulfide or disulfide linkages provides great stability for the three-dimensional structure within the molecule [5]. 2-Amino-1,3,4-thiadiazole and certain structurally related compounds have been known for 50 years to have antitumor activity [6]. Compounds of this class are uricogenic agents in man [7]. Both the antitumor and the uricogenic activities can be prevented or reversed by nicotinamide [8], [9]. Due to the structural properties of 2-amino-1,3,4-thiadiazoles, they can also participate in several chemical reactions, and they are found to have significant use as intermediate for the synthesis of nitrogen atom containing heterocyclic compounds. To elucidate the reaction mechanisms and reactivity correctly, it is important to obtain information about the tautomeric structures of these compounds [10]. The tautomerism in the title compound is a type of prototropic tautomerism. This phenomenon exists in structures having more than one position to which the mobile proton can be bound. Due to this property one molecule may have more than one structure. It is noteworthy that solvents and substituents have a considerable effect on prototropy.

In this work, the three levels of calculations; HF, MP2 and B3LYP, will be applied to study various tautomerizations of 2-amino-1,3,4-thiadiazole with the specific aim to:

(1)
Study the conformational preference of different 2-amino-1,3,4-thiadiazole tautomers.
(2)
Investigate the energetics of their tautomers and their relative stabilities in the gas phase and solutions.
(3)
Compare the different tautomers with respect to their structure and tautomerization ability.
(4)
Explore the effect of substituent type on the structure of 2-amino-1,3,4-thiadiazole tautomers.
(5)
Investigate the Cartesian coordinates obtained from the optimized geometry.

Section snippets

Computational methods

The outcomes of the geometry optimizations are presented in Section 3. The total energies are given in hartrees; the relative energies and stabilization energies are given in kcal mol^− 1; using the conversion factor: 1 hartree = 627.5095 kcal mol^− 1.

The ab initio (HF [11] and MP2 [12]) and DFT [13] calculations using 6-311++G(d,p), 6-311G(d) and 6-31 + G(d,p) basis sets, full geometry optimizations and harmonic vibrational frequency calculations were performed using the Gaussian 03 program [14]. Density

Geometries

Tables of the optimized structural parameters of the studied molecules are given in Table 1, in accordance with the atom-numbering scheme given in Fig. 1.

Calculated geometrical parameters in the gas phase, water, THF and DMSO solutions for all species were very similar. In tautomer A, going from the gas phase to polar solvents, the C₂ single bond N₇ bond length decreases and the C₂N₃ bond length increases, and in tautomer B, the C₂N₃ bond length decreases and the C₂N₇ bond length increases. These changes

Conclusion

In this work, the tautomerization of 2-amino-1,3,4-thiadiazole in the gas phase and solution were investigated by means of HF, MP2 and DFT methods with 6-311++G(d,p), 6-311G(d) and 6-31 + G(d,p) basis sets. The amino form of 2-amino-1,3,4-thiadiazole is the most stable tautomer. The total energy of all tautomers decreases from the gas phase to the polar solvents. The effect of substitution on the tautomerism of 2-amino-1,3,4-thiadiazole has also been studied. Furthermore, we can conclude that in

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A theoretical study on the structure of 2-amino-1,3,4-thiadiazole and its 5-substituted derivatives in the gas phase, water, THF and DMSO solutions

Highlights

Abstract

Introduction

Section snippets

Computational methods

Geometries

Conclusion

II Farm.

Proteins

Biochem. Pharmacol.

Tetrahedron Lett.

Comput. Theor. Chem.

Comput. Theor. Chem.

Oral absorption of cephalosporin antibiotics 2. Expanded structure-activity relationships of 7-arylacetamido-3-substituted cephalosporins

J. Med. Chem.

Synthesis and biological evaluation of some 5-aryl-2-amino-1,3,4-oxa(thia)diazoles

Farm. Sci.

Synthesis and structure-activity relationships of 7β-[(z)-2-(2-aminothiazol-4-yl)-3-(substituted)-2-propenoyl-amino]-3-cephems with c-3 substitutions

J. Antibiot.

The carcinostatic activity of some 2-amino-1, 3, 4-thiadiazoles

J. Am. Chem. Soc.

Effects of nicotinamide and related compounds on the antileukemic activity of 2-amino-1, 3, 4-thiadiazole

Cancer Res.

Quantitative biochemical differences between tumor and host as a basis for cancer chemotherapy IV. Niacin and 2-ethylamino-1, 3, 4-thiadiazole

Cancer Res.

The Tautomerism of Heterocycles

Density-functional Theory of Atoms and Molecules