Nitro-1,3,4-thiadiazoles

Ohta et aiy subjected 2-phenyl-l,3,4-thiadiazole to a mixture of concentrated nitric and sulfuric acids at 0° and obtained a mixture of the three isomeric 2-nitrophenyl-l,3,4-thiadiazoles in the ratio p m o = 2 3 l, but no 2-phenyl-5-nitro-1,3,4-thiadiazole. The products were identified by oxidation to the corresponding nitro-benzoic acids. 

Fig. 1. HeterocycHc amines usedia azo dyes, (a) 2-Amino-6-nitrohenzothiazo1e [6285-57-0], (b) 3-amiao-5-nitro-2,l-benzisothiazole [14346-19-1], (c) 3-amiQo-4JT-l,2,4-triazole [65312-61 -0], (d) 5-amiQo-l,2,4-thiadiazole [7552-07-0, (e) 4,4 -diamiQo-2,2 -biphenylsulfone [6259-19-4], (f)...

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). 

Sulfamethizole Sulfamethizole, AfL(5 niethyl-l,3,4-thiadiazole-2-yl)sulfanilamide (33.1.15), is synthesized in two ways. According to the first, 5-amino-2-methyl-l,3,4-thiadiazole is reacted with 4-nitrobenzenesulfonyl chloride to make a nitro derivative (33.1.14), which is then reduced using iron filings in acetic acid to give the desired sulfamethizole. 

The electrophilic substitution of the 3-aryl compounds (265, R = Ar, R = H) exemplified by the formation of 5-bromo- (265, R = Ar, R = Br) and 5-nitro derivatives (265, R = Ar, R = NOj) has been put forward as evidence against the meso-ionic formulation 265. lliis approach is unacceptable since ground state charge distribution cannot be deduced from reaction products. The aluminum-amalgam reduction of meso-ionic l,2,3-thiadiazol-4-ones (265) yields either N-mercaptoacetyl-A-arylhydrazines or Ar-acyl-A-arylbydrazines. Triethyl-oxonium tetrafluoroborate and meso-ionic l,2,3-thiadiazol-4-ones (265) yield 1,2,3-thiadiazolium tetrafluoroborates (267). The effect of solvent on the ultraviolet spectra of meso-ionic l,2,3-thiadiazol-4-ones (265) has been reported. ... 

Amino-l-methyl-527-pyrido[4,3-6]indole (see Trp-P-2) 2-Amino-5-(5-nitro-2-furyl)-l,3,4-thiadiazole 2-Amino-4-nitrophenol 2-Amino-5-nitrophenol... 

Although 3-amino-l,2,4-thiadiazoles (e.g. the 5-phenyl homolog) fail to yield nitrosamines under the usual conditions,126 5-nitrosamines are well known.81, 5,190,191 Thus, 3-alkoxy-,8 3-alkylthio-,85 3-dialkyl-amino-,87 and 3-alkylsulfonyl-5-amino-86 (243) as well as 3-aryl-5-arylamino-l,2,4-thiadiazoles,74 on treatment with the calculated quantity of sodium nitrite in dilute mineral acid, or concentrated formic acid, yield crystalline nitrosamines (244). Their unusual stability has permitted a close study of their formation and properties. 170 Their positive Liebermann reaction85,87,170 and the results of their methylation (outlined in the reaction scheme) show that nitro-sation occurs in the side-chain and not in the nucleus.170... 

In addition, the following have been described as diazo components 2,5-dichloro-4-nitroaniline (red) [49], 2-chloro-5-trifluoromethylaniline (yellow) [50], 4-nitro-2-trifluoromethylaniline (red) [51], 2-amino-5-trifluoromethyl-l,3,4-thia-diazole (red) [52], 3-methylmercapto-5-amino-l,2,4-thiadiazole (red) [53], 3-methyl-4-nitro-5-aminoisothiazole (blue-violet) [54], 2-amino-6-chlorobenzothia-zole (red) [55], and 3-amino-5-nitro-7-bromobenzisothiazole (blue with a red cast) [56],... 

The reaction of 5-amino-l,2,4-thiadiazoles (16) with aldehydes produces a-amino alcohols (145), azomethines (146) or bis-amines (147) depending on the reactants and reaction conditions, as illustrated in Scheme 58. The nitration of 5-amino-3-methyl-l,2,4-thiadiazole (25) in a mixture of 98% sulfuric acid and 95% nitric acid at 0°C is reported to produce (148) in good yield (65AHC(5)119), but a similar reaction with 3-amino-l,2,4-thiadiazoles has not been described. Products of type (149) can be obtained, however, by the ring closure of Af-nitro-AT-thiocarbamylguanidines with alkaline hydrogen peroxide. 

As a rule, oxadiazoles and thiadiazoles are not nitrated. Reports on the production of 2-nitro-5-amino-l,3,4-thiadiazole during the nitration of 2-amino-l,3,4-thiadiaz-ole [274] proved erroneous [275], The compound obtained in this case was 2-nit-ramino-l,3,4-thiadiazole [275], There is only a single paper on the nitration of derivatives of 1,3,4-oxa- and 1,3,4-thiadiazoles [276], 2-Dimethylamino-l,3,4-oxa-and 2-dimethylamino-l,3,4-thiadiazoles react with the nitrating mixture with the formation of 2-dimethylamino-5-nitro derivatives. Aryl-substituted oxadiazoles and thiadiazoles are nitrated in the phenyl ring [277, 278],... 

The data of the NMR spectra of l- [(5-nitro-l,3,4-thiadiazol-2-yl)methylen]-amino -2-imidazolidinone [540], 2-[(2-methyl-5-nitrothiazol-4-yl)methylene]-malonate and its imidazole analogs [547, 548] have been reported. 

The route of polarographic reduction of 4-nitro-l,2,3-thiadiazole is presented in Scheme 3.39 [990],... 

Benzothiadiazole is oxidized by ozone, potassium permanganate,and chromic acid which all lead to the dicarboxylic acid (8). In the ozonolysis the intermediate crystalline ozonide is decomposed to l,2,5-thiadiazole-3,4-dicarboxaldehyde (isolated as the semicarbazone) as well as 8. Permanganate oxidation has been applied to a number of derivatives of 7, among them being the 5-methyl, 4-nitro, and 4,7-dichloro derivatives. In some cases, particularly in the permanganate oxidation of 4-nitro-2,l,3-benzo-thiadiazole, the yield of 8 is much higher than in the oxidation of the unsuhstituted compound (7). 

Nitro-l,3,4-thiadiazole seems to be the only known representative of this class. It was formed in a Sandmeyer reaction between 1,3,4-thiadiazole diazonium chloride and sodium cobaltinitrite in the presence of copper sulfite. An alleged 2-amino-5-nitro-l,3,4-thiadiazole is discussed in Section IV,B. 

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