Thiosemicarbazide, in synthesis

Thionyl fluoride, as by-product in sulfur tetrafluoride reactions, 41, 105 toxidty of, 41,105 Thiophene-2-OL, 43, 55 2(5H)-Thiophenone, 43, 55 Thiosemicarbazide, in synthesis of 1,2,4 triazole, 40, 99 reaction with formic acid to yield l-formyl-3-thiosemicarbazide, 40,99... 

Sugar thiosemicarbazones have been the subject of further interest because of their capability to act as water-soluble tetradentated ligands for divalent transition-metal cations. Horton and co-workers341 reported the synthesis of 3-deoxyaidos-2-ulose bis(thiosemicarbazones) by the reaction of reducing aldoses with thiosemicarbazide in the presence of p-toluidine (Scheme 59), The authors observed in vivo antitumoral activity in the... 

Thiosemicarbazides in the synthesis of five- and six-membered heterocyclic compounds 12UK494. 

One of the classic methods used in qualitative organic analysis to characterize carbonyl compounds depends on the ready formation of crystalline thiosemicarbazones by the action of a thiosemicarbazide on the carbonyl compounds. Not surprisingly, therefore, several recent papers deal with this particular reaction, reporting on investigations of the reaction as such as well as on new examples of its use in synthesis. Carroll and his coworkers found that the course of the reaction of 2-hydroxy-l,4-naphtho-... 

Synthesis of 2-heterocyclic thiosemicarbazones can be summarized in three reaction sequences following the lead of Klayman et al. [5]. Condensation of equimolar quantities of a thiosemicarbazide and a 2-heterocyclic aldehyde or ketone in an alcoholic solvent is represented by Eq. (1). The product s superscripts refer to positions of substitution in the thiosemicarbazone moiety in accord with lUPAC. 

The literature describes a general method for the synthesis of l,4-dioxo-3,4-dihydrophthalazine-2(l/7)-carbothio-amide 655 based on heating an equimolar mixture of phthalic anhydride and thiosemicarbazide at 160 °C for 30 min in the presence of PPA. However, it has been reported that this treatment provides 654 instead (Scheme 107) <2003JHC1011>. 

Several 3-mercapto-l,2,4-trizines have been synthesized through the condensation of thiosemicarbazide with diketones under microwave irradiation in a solventless system <06PS87>. The synthesis and cyclocondensation reactions of 3-substituted-5-(2-aminobenzyl)-l//-[l,2,4]triazin-6-ones have been reported <06JHC613>. 

The synthesis of 6-oxo-2,3,4,6-tetrahydro[l,2,4]triazino[5,6-c]isoquino-line-3-thione 178 was achieved by the reaction of the keto acid 174 with thiosemicarbazide to give azauracil 175. Its esterification gave 176, which was converted to the amide 177 and cyclized (84PHA186 92CCC123) in presence of acetic acid to give 178. 

This ring system has been covered in several reviews <1984CHEC(5)305, 1984CHEC(5)607, 1987AHC(41)319, 1996CHEC-II(8)345, B-2002SOS(12)613>. The methods used for synthesis are quite diverse, and include the reactions of thiosemicarbazide with 1,3,5-tricarbonyl compounds and unsaturated dicarbonyl compounds, or their equivalents. 

Jain and Handa reported [82IJC(B)732] that the mode of ring closure may depend critically on the 5-substituent of the triazole. 3-Mercapto-5-(4 -pyridyl)[l,2,4]triazole 143 was reacted with phenacyl bromides to give 144, which on treatment with PPA resulted in the formation of thiazolo[2,3-c][l,3,4]triazoles 145. The structure of 145 [R = (4-Cl)C6H4] was proved by an independent synthesis starting with isonicotinyl thiosemicarbazide. 

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-... 

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). 

In a similar way, reactions of phenanthroquinone, chrysenoquinone, ninhydrin, acenaph-thoquinone or phenalene-l,2,3-trione with amidrazones (453), semicarbazide (459a), thiosemicarbazide (459b) or aminoguanidine (460a) have been used for the synthesis of phenanthro[9,10-e][l,2,4]triazines (503), chryseno[5,6-e][l,2,4]triazines (504), indeno[l,2-e][l,2,4]triazines (505), acenaphtho[l,2-e][l,2,4]triazines (506) and phenaleno[l,2-e][l,2,4]triazines (507), respectively (78HC(33)189, pp. 740-748). 

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. 

The synthesis of 1,3,4-thiadiazoIes is discussed in terms of the number of bonds being formed and by ring transformation. Thiadiazole synthesis by one-bond formation is exemplified by the cyclization of an acylated thiosemicarbazide as shown in Scheme 16. The most common two bond formation takes place via 1,3-dipolar cycloadditions presented in Scheme 23. 

Mahler and co-workers [140] reported a tandem procedure for the synthesis of 2-hydrazolyl-4-thiazolidinones 103 from a three-component reaction of an aldehyde, a thiosemicarbazide and maleic anhydride, efficiently assisted by microwave irradiation in a solvent mixture of toluene/DMF (1 1). Short reaction times and high product yields were obtained as compared to conventional heating. This process could be generally applied for aromatic as well as for aliphatic aldehydes, although for aliphatic aldehydes a slightly lower temperature of 100°C should be used (Scheme 80). 

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