1.2.5- Thiadiazoles structural data

The charge transfer salt (BDNT)2[Ni(mnt)2] (BDNT = 4,9-bis(l,3-benzodithiol-2-ylidene)-4,9-dihydronaphtho[2,3-c]l,2,5-thiadiazole) also shows ferromagnetic interaction with /=3.4K, which was concluded to arise from the [Ni(mnt)2]- component on the basis of EPR evidence. In the absence of structural data, however, further understanding of this behavior could not be obtained. The anion was shown to be monoanionic, hence the valence of BDNT is +0.5.1051... 

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). 

Of recent interest have been structural data on a novel class of MMP-binding inhibitors, represented by PNU-107859 (13) and PNU-142372 (14), which contain a thiadiazole moiety that coordinates the catalytic zinc atom through its exocyclic sulfur atom (130). 

Table 15.10 Enzymatic inhibitor indices logllso, structural data, and MTD and MVD values for a series of twelve 2-substituted-l, 3, 4-thiadiazole-5-sulfonamide derivatives...

The precise geometrical data obtained by microwave spectroscopy allow conclusions regarding bond delocalization and hence aromaticity. For example, the microwave spectrum of thiazole has shown that the structure is very close to the average of the structures of thiophene and 1,3,4-thiadiazole, which indicates a similar trend in aromaticity. However, different methods have frequently given inconsistent results. 

Carbon-13 NMR is often a more useful tool than H NMR for the elucidation of heterocyclic structures in which there are few or no ring protons. For symmetrically substituted 1,2,3-thiadiazoles, the carbon adjacent to the nitrogen atom is expected to have a lower field chemical shift than the carbon atom adjacent to the sulfur atom, as exemplified in CHEC-II(1996) <1996CHEC-II(4)289>. Several examples that follow this rule are illustrated in Table 5. There is now a more extensive body of data available and it is possible to more accurately predict the chemical shift of ring carbons. In the case of monosubstituted 1,2,3-thiadiazoles, the substituted carbon usually has a lower field chemical shift than the unsubstituted carbon. 

The use of infrared (IR) as a technique for structure determination is not very common in recent times. The reviews by Kurzer <1965AHC(5)119, 1982AHC285> contain a table of IR spectral absorptions of 1,2,4-thiadiazoles which covers spectra published before 1982. Additional spectral data was published in CHEC(1984) <1984CHEC(6)463>. 

While 1,2,5-thiadiazole 1,1-dioxide has not yet been prepared, extrapolation of data on the known 3,4-dimethyl-l,2,5-thiadiazole 1,1-dioxide 23 <1998JP091> indicated that the nonaromatic or antiaromatic 1,2,5-thiadiazole 1,1-dioxide has a more delocalized structure than its isomeric thiadiazole 1,1-dioxide anologues <1997JMT119, 2001JMT285>. 

However, there are some cases when an unpaired electron is localized not on the n, but on the o orbital of an anion-radical. Of course, in such a case, a simple molecular orbital consideration that is based on the n approach does not coincide with experimental data. Chlorobenzothiadiazole may serve as a representative example (Gul maliev et al. 1975). Although the thiadiazole ring is a weaker acceptor than the nitro group, the elimination of the chloride ion from the 5-chlorobenzothiadiazole anion-radical does not take place (Solodovnikov and Todres 1968). At the same time, the anion-radical of 7-chloroquinoline readily loses the chlorine anion (Fujinaga et al. 1968). Notably, 7-chloroquinoline is very close to 5-chlorobenzothiadiazole in the sense of structure and electrophilicity of the heterocycle. To explain the mentioned difference, calculations are needed to clearly take into account the o electron framework of the molecules compared. It would also be interesting to exploit the concept of an increased valency in the consideration of anion-radical electronic structures, especially of those anion-radicals that contain atoms (fragments) with available d orbitals. This concept is traditionally derived from valence-shell expansion through the use of d orbital, but it is also understandable in terms of simple (and cheaper for calculations) MO theory, without t(-orbital participation. For a comparative analysis refer the paper by ElSolhy et al. (2005). Solvation of intermediary states on the way to a final product should be involved in the calculations as well (Parker 1981). 

The x-ray structure of 1,2,3-benzothiadiazole complexed with AsFj (9) shows that the arsenic binds at N3 <86CJC849>. When Fe2(CO)9 reacted with (10) one of the products was (11), for which x-ray diffraction revealed the unusual feature of the nitrogen and sulfur joined by an iron atom (Equation (2)) <890M296l>. The mesoionic structure (13) is formed by methylation of 1,2,3-thiadiazole (12). It can best be described as a resonance hybrid of structures (13a) and (13b) and this was corroborated by the x-ray data (Scheme 1) <91jhC477>. 

While it may be intellectually unsatisfying, the electronic structure of 1,2,5-thiadiazole cannot be depicted in a single drawing. The physical and chemical data as they relate to the position and nature of the double bonds can best be represented by a series of canonical forms (Scheme 1) <84CHEC-I(6)513>. 

Proton NMR data are reported for substituted mesoionic l,2,3,4-thiatriazolium-5-olates and 5-thiolates. Although the spectra are of little diagnostic value they are consistent with the mesoionic structures <79JCS(P1)732>. Representative C shifts for C(5) of 5-substituted thiadiazoles are 5-Ph, 178.46 ppm 5-PhNH, 173.8 ppm 5-BzS, 179.8 ppm 5-PhCOS, 171.5 ppm and for the thiatriazolium salt (9) 186.42 ppm <84CHEC-I(6)579>. 

Information concerning the infrared absorption spectra of 1,2,4-thiadiazoles is rather sparse, and existing data are listed in Table IX. Recent investigations have materially contributed to the elucidation of the structures of perthiocyanic and isoperthiocyanic adds and related compounds154, 155 (see Section III, J, 1) and of those of isothiocyanate oxides and sulfides164 (see Section II, D, 3). 

Little data has been reported on x-ray structural methods. In a study of benzo[l,2-c 3,4-c ]bis-thiadiazole and a monoselenium analogue, S—N bond distances of the order of 1.62 A were found and attributed to the heterocyclic rings being quasi aromatic, but with severe distortion of the aromatic character of the carbocyclic ring <84ZN(B)485>. 

An X-ray diffraction study, when possible, is the ultimate structure proof. Bond lengths are known for certainty to 0.001 A and bond angles to 0. T. Although the literature abounds with X-ray data for heterocycles there are no X-ray spectra for a 4,5-dialkyl substituted, nonionic 1,2,3-thiadiazole. However, an X-ray structure has been reported for a 1,2,3-benzothiadiazole (5), and the bond lengths and bond angles are listed in Table 1 (79AX(B)3114>. 

Analysis of the data indicates the bond lengths are in the normal range for this essentially planar molecule and the benzene portion exhibits considerable tr-conjugation. The best resonance structure for the thiadiazole is a partial double bond for S—C(7a) and S—N(2), and a nearly complete double bond for N(2)—N(3) and C(7a)—C(3a). One might expect the bond angles and lengths for thiadiazole to vary if it were not fused to the benzene ring. 

C NMR data can be quite diagnostic for heterocyclic structures. With reasonable certainty one can usually expect the carbon atom adjacent to the nitrogen atom in a 1,2,3-thiadiazole to have a lower field chemical shift than the carbon atom adjacent to the sulfur. Several examples are illustrated in Table 6. 

Acetylation of benzaldehyde thiosemicarbazone (165) yields the thiadiazoline (166) and not the diacyl derivative (167) as previously suggested (Scheme 18). Structural proof rests on spectroscopic data and on oxidation to the thiadiazole (168) followed by deacetylation with hydrazine to (169). Mild acid or base hydrolysis of (166) furnishes the starting (165) while methylation gives (170), a product identical to that obtained from the acetylation of (171) (80JOC1473). 

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