Thiosemicarbazides 2-amino

When thiourea or thiosemicarbazide are used for substitution of a chlorine atom with a mercapto group, thiouronium salts are formed first, and they are hydrolysed by aqueous base. Other groups, such as alkoxy, alkyl, amino and cyano, if present, are usually not... 

By reaction of thiosemicarbazide or its 4-alkyl derivatives with nitrous acid Freund and co-workers in 1896 prepared compounds which were formulated as amino or alkylamino derivatives of the ring system 1,2,3,4-thiatriazole (1). Oliveri-Mandala, however, argued that these compounds are actually thioazides (2), and this view seems to have been generally accepted (e.g. in Beilstein s Handbuch) until... 

A somewhat different scheme is used to gain entry to the alternate symmetrical 1,3,4-thiadiazole ring system. Reaction of thiosemicarbazide with isovaleric acid affords the ring system (217) in one step. The reaction may be rationalized by positing acylation to intermediate 216 as the first step. Sulfonylation of the amino group of 217 with p-methoxybenzenesulfonyl chloride affords the oral... 

Alkyl- and 5-aryl-2-amino-1,3,4-oxadiazoles were prepared by tosyl chloride/pyridine-mediated cyclization of thiosemicarbazides in good yields (79-99%). Interestingly, thiosemicarbazides exhibited a higher rate of cyclization than the corresponding semicarbazides. For example, 171 (X-S) was converted to oxadiazole 172 within 5 h <06JOC9548>. 

Amino-l,3,4-thiadiazol-2-yl)-l,2,5-oxadiazole-3-amine 175 was formed with a yield of more than 75% in a condensation of 3-amino 4-cyano-l,2,5-oxadiazole 174 with thiosemicarbazide in trifluoroacetic acid (Equation 30)... 

The reaction of the trichloromethylarenes 146 with thiosemicarbazide 138 in a boiling methanol-pyridine mixture afforded the 2-amino-5-aryl-l,3,4-thiadiazoles, while under similar conditions trichloromethylarenes 146 were converted to the diaryl-1,3,4-thiadiazoles with thiobenzhydrazide 147 (Equation 52, Table 7) <1996RCB1185>. 

The synthesis of numerous thiadiazoles substituted in the 5-position with carbamoyl or heteroaryl moieties and hydroxyl or amino groups in the 2-position (Scheme 20), was achieved by reacting dithioesters with semicarbazide or thiosemicarbazide and cyclizing the resulting acylated sem-... 

A-Substituted 5-amino-1,2,3,4-thiatriazoles (13) were obtained by Freund and Hempel in 1895 by treating thiosemicarbazides with nitrous acid (Equation (15)) <1895CB74>. This method has been used by others to prepare a number of different A-substituted 5-aminothiatriazoles (13) in good yields ( 80%) <81JIC1087>. 

The basic amino group of the 1-position in semicarbazide or thiosemi-carbazide may be used to react by a substitution reaction with activated halides [52], ethers [51], hydroxy [53], phenoxy [54], and amino groups [55] to yield substituted 1-semicarbazides or thiosemicarbazides. In addition, the amino group of the 1-position may add to electron-deficient double bonds [56]. Formaldehyde and other aldehydes may add to all the available free NH groups to give methylol, alkylol, or polymeric products under basic conditions [57]. Aldehydes or ketenes usually give semicarbazone derivatives, and these in turn are used analytically to identify the purity or structure of a known aldehyde [3]. 

Various extensions are possible (see CHEC 2.19 for full details). Use of aminoguanidines, semicarbazide and thiosemicarbazide gives respectively the 3-amino-1,2,4-triazine, and the 3-one and 3-thione derivatives. Use of a-keto esters and a-keto cyanides gives 5-ones and 5-amino derivatives, respectively. a-Hydroxy ketones afford dihydro-1,2,4-triazines. Intermediates (479) and (480) can sometimes be isolated. 

Amino-5-alkyl- or 5-phenyI-l,3,4-thiadiazoles are prepared most conveniently from thiosemicarbazide. For example, benzalthiosemicarbazone by oxidation with iron(III) chloride gives the 5-phenyl derivative. Thiosemicarbazide is also used in the synthesis of 2-amino-5-mercapto-l,3,4-thiadiazole by reaction with carbon disulfide. The product may be alkylated to yield the 5-alkylthio derivatives using a variety of alkylating agents (58MI11201). 

Reaction of acylcyanides (485) with amidrazones (453), semicarbazide (459a), thiosemicarbazide (459b) or aminoguanidine (460a) is used for the synthesis of 5-amino-... 

The reaction of a-amino ketones (508d) with thiosemicarbazides (761) affords 3-amino-4,5-dihydro-l,2,4-triazines (762) and the dihydrotriazine-3-thiones (763) (57MI21900). 2,2-Dimethyl-3-dimethylamino-2i/-azirine (764) reacts with benzohydrazides (765 R = Ar) via the open-chain intermediates (766) to give 3-aryl-6-dimethyIamino-2,5-dihydro-l,2,4-triazines (767 R = Ar). With ethyl carbazidate (765 R = OEt) the corresponding triazin-3-one (768) is formed (78HCA2419,78C332). 

The reaction of dicyandiamide with thiosemicarbazides provides an efficient route to the l-amino-l,3,5-triazines (119) (76AJC1051). 

N 54.87% ndls (from eth), columns (from methanol plus eth) mp, deton at 128—-30°. Sol in aniline, warm ethanol, acetic acid, and acetic anhydr sparingly sol in chlf and carbon disulfide insol in benz. Prepn is by reacting a cold Na nitrite soln with an aq soln of thiosemicarbazide hydrochloride. The hydrochloride of the thiotriazole is also an expl 5-Amino-1,2,3t4-Thiotriazole Hydrochloride, CH2N4S+HC1 mw 138.59 N 40.43% cryst mp, deton at 96°. V sol in w Ref Beil 27,781... 

Amino-substituted 1,2,3,4-thiatriazoles 87 were first prepared by a similar reaction starting from the readily available thiosemicarbazides <1895CB74>. In subsequent work this method has been widely used to prepare a variety of derivatives <1981JIC1087>. A modification of this method is to use the aza transfer reaction between aryl diazonium salts and 4-substituted thiosemicarbazide 139 (Equation 10) <19780PP59>. 

Carbonylation occurs by the oxidation of some amino acid side chains into ketone or aldehyde derivatives by reactions with compounds of lipid oxidation or by glycoxidation with reducing sugars. These protein-carbonyl compounds are markers of protein oxidation, and recently, several carbonylated proteins and protein oxidation sites in milk (96), meat (97), and fishes (98) have been identified using a classical bottom-up proteomics approach based on 2-DE and MS/MS. Specific labeling of protein carbonyls using fluorescein-5-thiosemicarbazide has been developed and combined with 2-DE and... 

A solution of 91 g. (1 mol) of thiosemicarbazide4 in 350 ml. of 3 N HC1 (1 mol) is prepared. A clear solution is obtained at 30°. The solution is placed in a 1-1., threenecked flask equipped with a mechanical stirrer, thermometer, and dropping funnel and cooled in an ice-salt bath to 10°. A portion of the dissolved thiosemicarbazide precipitates at this stage. A solution of sodium nitrite, 69 g. (1 mol) in 150 ml. of water, is placed in the dropping funnel. The total volume of the solution is 180 ml. The sodium nitrite solution is added dropwise to the stirred mixture, while the temperature is maintained at 10°. When about 130 ml. of the solution has been added (45 minutes), the addition is stopped and the fine white crystalline precipitate filtered off. The filtrate, which is pale blue in color, is put back into the reaction flask and the addition of the sodium nitrite solution continued. The temperature of the reaction mixture should be maintained at 10 to 15° throughout the addition of the sodium nitrite. When about 40 ml. more of the sodium nitrite solution has been added (15 minutes), the reaction mixture tends to assume a very pale yellow color. Addition of the sodium nitrite is stopped at this stage and the rest of the precipitate filtered off. The addition of even a few drops of the sodium nitrite solution to the filtrate causes an intense yellow color. The filtrate is discarded at this stage. The combined precipitates of 5-amino-l,2,3,4-thiatriazole is washed three times with small amounts of ice-cold distilled water and dried under vacuum over sulfuric acid. The yield is 81.5 g. or 80% of theory, f... 

The procedure is essentially similar to that described for the preparation of 5-amino-l,2,3,4-thiatriazole. Freund and Hempel6,7 have reported observing that the initial diazotization products of 4-aryl-substituted thiosemicarba-zides lead to the formation of tetrazoles, while the corresponding 4-alkyl-substituted thiosemicarbazides were considered by Freund and Schwarz8 to be thiatriazoles. However, Oliveri-Mandala,9 on the basis of his study of the reaction of alkyl and aryl isothiocyanates with hydrazoic acid, concluded that the initial diazotization product of either 4-aryl or 4-alkyl thiosemicarbazides were open-chain thiocarbamyl azides, RNHC( S)N3. Lieber, Pillai, and Hites10 have recently clarified this situation and have shown... 

The analogous condensation of methyl acetylenedicarboxylate with substituted thiosemicarbazides leads to 2-imino-3-amino-6-carbomethoxyl-l,3-thiazin-4-ones (67CJC953). 

PHA827). 3-Amino-6-phenylthieno[2,3-<7]pyrimidin-4-one-2(l H)-thione (17) was obtained similarly from isothiocyanate 15 (R1 = C02Et, R2 = H, R3 = Ph) via the thiosemicarbazide 16 (94PHA64). Isothiocyanate 15 [R1 = COPh, R2, R3 = (CH2)4] was reacted with hydrazine hydrate and various primary amines to give directly the 3-substituted 4-phenyl-2-thioxothieno[2,3-c/ pyrimidines 82b (90JHC269). 

Cyclization in phosphorus oxychloride of semicarbazides (79 X = NHR) yields aminooxadiazoles (81) whereas thermolysis leads to loss of ammonia (when X = NH2) and formation of an oxadiazolinone (80). Cyclization to aminooxadiazoles (81) occurs when thiosemicarbazides (82) are heated with an oxidizing agent such as lead oxide. This reaction has been widely applied to the synthesis of aminooxadiazoles, sometimes in low yields, and has been used to prepare 2-amino-l,3,4-oxadiazole (81 R1 =R2 = H). 5-Methyl ethers of thiosemicarbazides (82) cyclize, with loss of methanethiol, to aminooxadiazoles (81) on heating, but in PPA cyclization to 2-methylthio-l,3,4-oxadiazoles occurs. 

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