Thiadiazole crystal structures

Thiadiazole-2-suifonamide, 5-acetamido-carbonic anhydrase inhibitor, 6, 576 crystal structure, 6, 548... 

The first single-crystal structure was reported for 6-methyl-3-phenyl-.r-triazolo[3,4-3]-l,3,4-thiadiazole in which the nucleus of the triazolothiadiazole system was planar confirming the aromatic character of the lOn-electron system <1974CSC7>. This is generally the case for the entire series of 5,5-fused heterocycles. 

Four x-ray structures have been reported which confirm the spectroscopic conclusions made about 1,2,5-thiadiazole. The planar, symmetric, and aromatic nature of the 1,2,5-thiadiazole ring can be seen in the crystal structure of s-timolol hemihydrate (4) <90AX(C)243l>. These structural elements are virtually unaffected by the nature of the 3,4-substituents (5) <90AX(C)1749>. 

Disubstituted and unsubstituted l,2,5-thiadiazolo[3,4- ]quinoxaline-4,9-diones (110) have been prepared in good yield by condensation of 5,6-diaminobenzo[c][l,2,5]thiadiazole with a-dicarbonyl reagents (Equation (62)) <92H(33)337>. These quinones were then converted into 1,2,5-thiadiazolo-, pyrazino-fused TCNQ analogues by condensation with malononitrile in the presence of TiCl4 in dry pyridine. The x-ray crystal structure determination of the product derived from compound (110 R1 = R2 = H) has been accomplished. 

Thiadiazole AT-oxides isomerize, when irradiated, from one AT-oxide isomer to the other. An X-ray crystal structure of (21) established the AT-oxide is at the 3 position. The authors (78ZN(B)316) then concluded that the product from photolysis of (21) must be the Af-oxide (22 equation 10). 

The crystal structure of acetazolamide (5-acetamido-l,3,4-thiadiazole-2-sulfonamide), a potent inhibitor of carbonic anhydrase, is known. Bond distances are shown in (17) <74JCS(P2)532). 

The crystal structure of a highly insoluble thiadiazole derivative is shown in (18). There is an intramolecular hydrogen bond between the hydroxyl and the carbonyl groups, and there is one intermolecular hydrogen bond between N(6) in the open chain and N(3) in the thiadiazole ring (80JOC4860) (see also Section 4.27.3.9.4). 

Aminothiadiazoles also react with halo aldehydes and halo ketones in a bidentate fashion to give imidazo[2,1-b ][1,3,4]thiadiazoles (145). The NMR properties, aromatic character, basicity and crystal structure data are available (80JCS(P2)42l). Aminothiadiazoles also react with trichloromethanesulfenyl chloride to give the sulfenamide (146) which in the presence of an aromatic amine cyclizes to 3//- [1,3,4]thiadiazolo[2,3-c ][1,2,4]thiadiazole (147) (75JOC2600). 

The CYP450 3A4 model based on the ketoconazole crystal structure was used within MetaSite3 to predict SOM for compound 4 (Figure 11.5a). Built-in corrections for reactivity of the cytochrome and the ligand were applied. Both for compounds 3 and 4, the predicted primary SOM is the benzylic alpha position to the thiadiazole ring (Figure 11.5b). The SOM predicted by MetaSite next in hierarchy, the hydroxylation of the benzylic position of the cyclohexyl moiety, was not observed experimentally, nor was the aromatic oxidation of the benzothiazole sulfur. Instead, in vitro metabolism studies are in agreement with the primary SOM and confirmed a labile cyclopentyl-ethyl moiety, but a stable thiadiazol scaffold and a stable... 

Physical Properties. - The X-ray crystal structure for 5-acylimino-1,2,3 thiadiazole has been reported. The thiadiazole ring is planar and almost coplanar with the remaining non-H atoms. 

The molecular structure of both 1,2,5-thiadiazole 1 and 2,1,3-benzothiadiazole 2 were described in CHEC(1984) <1984CHEC(6)513>. Since the publication of CHEC-II(1996) <1996CHEC-II(4)355>, a large number of single crystal X-ray structures have been published for various monocyclic, fused, and related thiadiazoles. 

In the search for new organic conducting materials, x-ray structure determinations of fused 1,2,5-selenadiazoles and 1,2,5-thiadiazoles have been carried out. Compounds (25a) and (25b) are planar molecules possessing a two-fold axis and mirror plane. Short C=N S and C N Se contacts connect each molecule in the crystal with four neighbors, forming a virtually planar sheet network (Figure 7), The sheets stack to form infinite layers with face-to-face overlapping between... 

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