Thiazoles, and Thiadiazoles

II and 13C NMR shifts (DMSO, ppm) and spin-spin coupling constants (Hz) of isothiazole 4-derivatives, including 4-nitroisothiazole, have been examined [527, 529]  

The NMR data have been compared with the calculated total charge densities for isothiazoles. 

The structure of anew alkylating agent, 2-(l-methyl-l-nitroethyl)-5-nitrothiazole and its C-alkylation product of the reaction with 2-nitropropane anion by SRN1 mechanism has been assigned by proton and carbon NMR spectroscopy (Table 3.20) [541, 542], 

The 13C (C-5) chemical shifts in these nitrothiazoles are significantly displaced toward lower frequency field in comparison with other azoles. 

The structure of 2-substituted 4-(2-furyl)-5-nitrothiazoles [543], 5-nitrothiazolyl-2-semicarbazides (homolog of strong antitrichomonade agent) [539] was proved by II NMR spectroscopy. The NMR spectra were used for the identification of 5-nitrothiazole 2-amino derivatives [532, 544, 545], The polymorphic azodyes containing 2-amino-5-nitrothiazole have been investigated by multinuclear NMR spectroscopy in solution and in solid-state (13C CP/MAS) [544, 545], 

---

Heteroaromatic sulfur compounds do form sulfoxides and sulfones, but these derivatives have their own special reactivity. Francesca Clerici (Milan, Italy) has now provided an up-to-date survey of the preparation and properties of the S-oxides of thiazoles and thiadiazoles, collecting literature scattered in many publications. 

A reliable calculation of polarizabilities requires an adequate description of the outer part of the electron density. For this reason Kassimi and Lin [98JPC(A)9906] used augmented basis sets of triple- quality to study polarizabilities and dipole moments of thiazoles and thiadiazoles. They expect their results to be reliable within 5%. In addition, the authors provide MP2/6-31G geometries for most of their structures. Hyperpolarizabilities for substituted thiazoles obtained from calculations at lower levels are also provided [99MI2]. 

The bicyclic system of isoquinoline and quinazoline has been replaced by several monocyclic rings (Van Muijlwijk-Koezen et al. 2001). Some thiazole and thiadiazole derivatives revealed to be the most promising candidates for the identification of new A3 AR ligands. 

Binding affinity data of thiazoles and thiadiazoles at the hA3 AR have been subjected to QSAR analysis (Bhattacharya et al. 2005). This study disclosed the importance of molecular electrostatic potential surface (Wang-Ford charges) in correspondence of atoms C2, C5, C7, X8 and S9 (Fig. 7.6), the last two playing the most important roles. Furthermore, the A3 binding affinity increases with decrease of lipophilicity of the compounds and in the presence of short alkyl chains (Me or Et) at the R position. 

Bhattacharya P, Leonard JT, Roy K (2005) Exploring QSAR of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists using FA and GFA techniques. Bioorg Med Chem 13 1159-1165... 

Microwave spectroscopy is a powerful tool for the determination of molecular structure. Thiazoles and thiadiazoles have been studied by this technique, but it was not until 1976 that a paper on the microwave spectrum of 1,2,3-thiadiazole appeared. Bond distances and angles for 1,2,3-thiadiazole (7) are listed in Table 4 (76MI42400). The success of this project is owed in part to the development of double resonance modulated (DRM) microwave spectroscopy which allows for quick analysis of an individual spectrum. 

Fig. 9 General structure of thiazole and thiadiazole class of adenosine Ai and A3 receptor antagonists and their quinazoline, isoquinoline seed structures...

Table 7 Thiazole and thiadiazole analogues in modeling the adenosine A3 receptor antagonistic activity (Fig. 9) [103-105]...

---