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
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 (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 C2N7 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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