1,3,4-Thiadiazole 2-nitro-5-amino

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... 

SYNS 2-AMINO-5-(5-NITRO-2-FURYL)-l,3,4-THIADIAZOLE 5-AMINO-2-(5-NITRO-2-FURYL)-l,3,4-THIADIAZOLE FURIDIAZINE 5-(5-NITRO-2-FURANYL)-l,3,4-THIADIAZOL-2-AMINE 5-(5-NITRO-2-FURYL)-2-AMINO-l, 3,4-THIADIAZOLE... 

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)...

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. 

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. 

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. 

A patent describes the preparation of 2-amino-5-nitro-l,3,4-thiadiazole (142) by nitration of 2-amino-1,3,4-thiadiazole (4, R = H) with fuming nitric acid at 40°. However, the product has the same melting point as the 2-nitramino-1,3,4-thiadiazole (46, R = H) described by Kanaoka, which was obtained under very similar conditions. Since the structure of 46 (R = H) was demonstrated by reduction to 2-hydrazino-l,3,4-thiadiazole, the structure 142 may be viewed with some skepticism. 

The antibacterial action of several new nitrofurans in vitro against a number of organisms has been reported by Skagius . These data indicate that 5-(5-nitro-2-furyl)-2-amino-l,3,4-thiadiazole (NF-475, ASA-140, Ph/ 778, LXXI) and its formyl derivative LXXII) have been recommended for further study in the treatment of intestinal infections of various aetiology. 

The activity in vivo of a nitrofuran, 2-amino-5-[2-(5-nitro-2-furyI)-vinyl]-l,3,4-thiadiazole LX) was tested against Strep. pyogenes-mLccttA mice . The in vivo effectiveness against streptococcal infection of this compound is superior to that of sulphamethizole LXXIII) which is widely used in urinary tract infections. The same compound was synthesized independently by workers of Boehringer Soehne C.m.b.H. and its clinical effectiveness on urinary tract infections was studied. 

Amino-5-(5-nitro-2-luryl)-l,3,4-thiadiazole has been used in gastroenteritis (25 mg/kg per day) with 85 per cent efficacy , and also as a topical agent for the symptomatic relief of chronic inflammatory disorders of the anorectal area (haemorrhoidal, anal fissures and proctitis) > . 

From Thiosemicarbazides. Cyclization of acylthiosemicarbazides. The dehydrative cyclization of acylthiosemicarbazides, one of the oldest syntheses in this field, has now provided compounds of stereochemical interest, viz. trans- and c/j-5-[2-(5-nitro-2-furyl)-l-(2-furyl)vinyl]-2-amino-1,3,4-thiadiazoles (59) and (60). Analogues of type (61) were similarly obtained. ... 

Existing syntheses of 2-amino-5-(l-methyl-5-nitro-2-imidazoIyl)-l,3,4-thiadiazole (140), an outstandingly powerful antimicrobial and antiprotozoal agent, have been supplemented by a route in which the imidazole ring is built upon a preformed thiadiazole nucleus. 

Although nucleophilic substitution of 3-halo-1,2,5-thiadiazoles is known, the symmetry of the heterocyclic nucleus prevents the detection of the aryne 567 by cine-substitution in the absence of isotopic labeling. An attempt to trap this species with anthracene (147) from the aprotic diazotization " of the amino acid 568 gave, instead of the heterotriptycene 569, a mixture of 9-nitro- (341) and 9-thiocyanoanthracene (570). The former compound is also observed in a similar reaction in the thiophene series (Section III.3.A.d) and could arise by direct nitration of anthracene with nitrous acid " present in the alkyl nitrite. 

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