1.3.4- Thiadiazoles spectra

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. 

When the N-3 atom is quaternized, as is the case of 4,5-diphenyl-3-trimethylsilylmethyl-l,2,3-thiadiazol-3-ium triflate, there is a large upfield shift for the N-3 atom of 160ppm, and a smaller shift is also observed for the N-2 atom of 25 ppm in the 15N NMR spectrum <1999J(P1)1415>. 

Simple 1,2,3-thiadiazoles show three absorption bands in the ultraviolet (UV) 211-217 (emax 4380-5300), 249-253 (1460-2100), 290-294 (195-245) nm <1996CHEC-II(4)289>. The ESR spectrum for the radical anion generated by the electrochemical reduction of the 1,2,3-thiadiazolium ion 8 has been reported. A number of 5-substituted derivatives were also examined and the splitting constants in the ESR spectrum were analyzed <1998MRC8>. 

A comparison between the positive and negative ion mass spectra of 3-amino-5-methylthio-l,2,4-thiadiazole and a study of the positive ion mass spectrum of 3-amino-5-methylthio-l,2,4-thiadiazole using 1SN isotopes appeared in Cl I EC-11(1996) <1996CHEC-II(4)307>. Since the publication of CHEC-II(1996), no new studies focusing on the mass spectra of 1,2,4-thiadiazoles have appeared. 

The thermal decomposition of some 3,5-disubstituted-l,2,4-thiadiazoles has been studied and some nonisothermal kinetic parameters have been reported <1986MI239>. Polarographic measurements of a series of methylated 5-amino-l,2,4-thiadiazoles show that thiadiazoles are not reducible in methanolic lithium chloride solution, while thiadiazolines are uniformily reduced at 0.5 = — 1.6 0.02 V. This technique has been used to assign structures to compounds which may exist theoretically as either thiadiazoles or thiadiazolines <1984CHEC(6)463>. The photoelectron spectrum for 1,2,4-thiadiazole has been published <1996CHEC-II(4)307>. 

Amino and 5-amino-l,2,4-thiadiazoles both exist predominantly in the amino forms. The IR spectrum of 5-mercapto-l,2,4-thiadiazole does not show a clear SH absorption as would be expected for structure 6 and therefore the thione tautomers 7 and 8 have been suggested (Scheme 2). Similarly, IR evidence suggests that perthiocyanic acid exists as the dithione 9 as opposed to stmcture 10 <1984CHEC(6)463>. 

Alkylation of 3,5-diaryl-l,2,4-thiadiazoles 22 with trimethylsilylmethyl triflate, in contrast to methyl iodide, occurs at N-2 to afford the salt 23 (Equation 5) and the quaternization at N-2 was confirmed by analysis of the 1SN NMR spectrum <1999J(P1)1709>. 

The positive ion mass spectrum of 3-amino-5-methylthio-l,2,4-thiadiazole (3) has also been studied using N isotopes. When a N label was incorporated into the 2-position or the exocyclic nitrogen a 13-16% incorporation of the N label was found in the mercaptothiazirinium ion (6) (Equation (1)). This incorporation is explained by a series of Dimroth rearrangements (Scheme 4) <86MI 408-01 >. 

Mercapto-l,2,4-thiadiazoles are distinctly acidic. The pK of 5-thio-3-methyl-l,2,4-thiadiazole at 25°C is 5.18 <65AHC(5)119>. The position of equilibrium in the tautomers of 5-thio-l,2,4-thiadiazoles (10) (R = H) appears to be on the thione side (11) or (12). The solid state IR spectrum of (10) (R = Ph) shows no sign of SH absorption <92PS(66)32i>. However, treatment of (10) (R = Ph, / -Tol) with diazomethane does not produce any A-methylated products, but only the 5-methyl derivatives (137) (R = Ph, /)-Tol). Methylation of (10) (R = Ph) with methyl sulfate and with methyl iodide in sodium hydroxide gives only the S-methyl derivatives (137) (Scheme 31) <92PS(66)321>. In 1989 Yousef et al. reported that (10) (R = Ph) reacted with aromatic sulfenyl chlorides and with formaldehyde to give the A-substituted products (26) and (27) (Scheme 31). At the same time, alkylation... 

In the search for structural diversity, and novel therapeutic agents, unique ring structures like the 1,2,5-thiadiazole have always captured the imagination of chemists. Often, as in the case of timolol (4), the interest is rewarded. In the early 1990s, a simple thiadiazole was appended to a penem in the development of the structure-activity relationships for a series of ) -lactamase inhibitors. The result was enhanced penetration of the bacterial membrane and a broader spectrum of activity versus clavulanic acid <9lJAN33l>. 

Pappalardo and co-workers studied the mass spectral characteristics of alkyl and aryl substituted 2,5-dithio-1,3,4-thiadiazoles. Selected ions in the mass spectra of SH, S-CH3, and S-aryl thiadiazoles were tabulated. The S-aryl thiadiazoles form stable cyclic ions yielding additional fragments. The fragmentation pattern is dependent on the structural characteristics of the substituents. If both tautomers—thiol and thione—are present, the molecular ion will also lose CS2. Besides the base peak, intense peaks observed in the MS spectrum are due to extensive fission of the thiadiazole ring. Some of the fragments formed are shown in Scheme 4 <820MS(17)335). 

A. 1,2,4-Thiadiazole and Homoloqs The parent compound, first obtained in 1955, is a volatile liquid, soluble in polar solvents, less so in non-polar ones. Its physical properties are summarized in Table II. Its I.R. spectrum has been recorded.8... 

In connection with a study of the electron impact-induced fragmentations of 1,2,3-thiadiazoles, the mass spectrum of 5-phenylthiatriazole has been scrutinized.13 Jensen et al.1 have undertaken a detailed investigation including 5-aryl-, 5-amino-, and 5-alkylthiothiatriazoles. The electron impact-induced decompositions resemble the pyrolytic loss of N2S (Section III, A). In all cases the M—N2S ion together with its fragmentation is responsible for the major part of the total ion current. A detailed discussion of the spectra is outside the scope of this review. 

Flufenacet (Cadou , Drago ), the 5-trifluoromethyl-1,3,4-thiadiazol-2-yloxy acetanilide herbicide developed by Bayer CropScience, belongs to the oxyacet-amide class of herbicides. Flufenacet is effective in controlling a broad spectrum of annual grass, hedges, and small broadleaf weeds [74]. 

The UV and MCD <72MI 705-01) spectra for the [l,2,5]thiadiazolo[3,4-c][l,2,5]-thiadiazole-5-S(IV) (6) have been recorded in ethanol. The observed MCD spectrum showed positive and negative extrema at 29900 cm-1 and 33700 cm-1, respectively. The inflection point appears to coincide with the absorption maximum of the UV spectrum (32200 cm- ). Since the molecule (6) has C2v symmetry, the MCD spectrum is due only to the Faraday B term, and thus the MCD experiment reveals two components of absorption in the lowest-wavenumber absorption band of compound (6). The electronic transition associated with this absorption, judged from the intensity of absorption and... 

In the 15N NMR spectrum of the systems (29 X = O or S) the chemical shifts of the nitrogens at position 1 correspond reasonably well with the nitrogen signals in benzo[c]-l,2,5-oxadiazole ( —35.6 ppm) and benzo[c]-l,2,5-thiadiazole (49.1 ppm). The nitrogens at position 3 appear to be deshielded by the effect of nitrogen at position 4. In the thiadiazine rings the pyridine-like nitrogens at... 

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. 

In their mass spectra 1,2,3-thiadiazoles commonly fragment initially by expulsion of nitrogen, and the fragmentation then proceeds to form thiirene ion radical (8 Scheme 1). These studies have been reviewed (73SST(2)717) and additional studies have shown, depending on substituents, that thioketene radical (9) can be formed in the mass spectrum (72T1353). 

The course of the thermal as well as photochemical reactions of 1,2,3-thiadiazole is believed to proceed, as in the case of the mass spectrum, with the expulsion of nitrogen forming a diradical intermediate which can react to form products or generate additional intermediates (B-79MI42400). The latter have been pursued with great interest. 

The position of equilibrium in the tautomers of l,2,4-thiadiazole-5-thiol (178) appears to be on the thione side (178b) or (178c). The solid state IR spectrum of (178) shows no signs of SH absorption. On treatment with potassium hydroxide, (178) is converted into a stable potassium salt (179) which reacts with methyl iodide yielding the 5-methyl ether (180 Scheme 67) (73CJC2353). 

The IR spectrum in Nujol of l,2,4-thiadiazolidine-3,5-dithione indicates that the dithione structure (18a) predominates. However, the dithione can be readily dialkylated on sulfur. Thus, treatment with 2,3-dichloropropene in aqueous sodium hydroxide forms (208 Scheme 73) (65AHC(5)119). The disulfenamide (209) condenses with aldehydes and ketones to give the corresponding imines (210) and (211 Scheme 74) (74ZOB2553). 5-Mercapto-3-methyl-thio-l,2,4-thiadiazole (212) reacts with di- -butyltin chloride in THF to give di-n-butyltin derivative (213 Scheme 75) (72USP3634442). 

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