Thiosemicarbazides thiazoles

Li and co-workers introduced a rapid and efficient microwave-assisted method to prepare new disubstituted 1,3,4-thiazoles from 1,4-disubtituted thiosemicarbazides with the objective to obtain biologically active molecules. The intermediate l-aryloxyacetyl-4-(4-methoxybenzoyl)thiosemicarbazide was irradiated in an excess of glacial acetic acid in a domestic microwave oven and led to the formation of 2-(methoxybenzoyl-5-aryloxymethyl)-l,3,4-dithiazoles in good yields [30] (Scheme 20). 

Dichlorophthalazine on condensation with thiosemicarbazide in DMF afforded l,4-bis(thiosemicarbazi-do)phthalazine 444, that undergoes cyclization with carbon disulfide in the presence of potassium hydroxide to give l,4-bis(3, 5 -dithioxy-[l,2,4]triazol-l-yl)phthalazine 445. Compound 445 reacts with monochloric acid in the presence of NaOH to give l,4-bis-(l -thioxy-6 -oxo-[l,2,4]triazolo[3,4-A]-l,3-thiazol-2 -yl]phthalazine 446 (Scheme 51) <2001IJC(B)500>. 

Acyloin 213 with thioamides, thiosemicarbazides, and methyl dithio-carbazate in trifluoroacetic acid give photochromic thiazole-, thiadiazine-, and pyrazole-bridged dihetarylethenes 254,255, and 256-258, respectively (Scheme 72) (OlIZVllS, 06ZOR882). 

II. Thiazoles from a-Halocarbonyl Compounds and Derivatives 249 D. Thiosemicarbazides and Thiosemicarbazones... 

Eine Arbeitsvorschrift zur Herstellung von 2-Hydrazino-4-phenyl-l,3-thiazol aus m-Brom-ace-tophenon und Thiosemicarbazid findet sich in Bd. E16a, S. 781383a. Zur Arbeitsvorschrift zur Herstellung von 2-(2-Acetyl-hydrazino)-4-phenyl-1,3-thiazol aus w-Chlor-acetophenon und 4-Acetyl-thiosemicarbazid s. Bd. X/2, S. 323402. 

A generalized reaction scheme has been developed for the reactions of thiosemicarbazides with a-halocarbonyl compounds. Depending on whether condensation occurs at the N1, N2, or N4 atom, three different sulfur-containing heterocyclic rings may be expected after ring closure 1,3,4-thiadiazines, 2-alkyl(aryl)imino-2,3-dihydrothiazol-3-amines, and 3-alkyl(aryl)-2-hydra-zono-2,3-dihydrothiazoles as well as, with R3 = H, thiazole-2-hydrazines (see p 494). 

A noteworthy difference is observed in the condensation of thiosemicarbazide with aromatic a-halocarbonyl compounds in comparison to aliphatic a-halocarbonyl compounds. It has been found26 that the reaction of phenacyl bromide with thiosemicarbazide furnishes 5-phenyl-1,3,4-thiadiazin-2-amine together with a small amount of 5-phenylthiazolc-2-hydrazine, Similarly, the reactions of thiosemicarbazide with 2-bromo-l,2-diphenylethan-l-one,7 8,41 2-bro-mo-l-phenylpropan-l-one,10,41 and 2-bromo-l-phenylbutan-l-one 10,41 in ethanolic solution give 1,3,4-thiadizines. However, the main products are the thiazole-2-hydrazine derivatives (cf. Houben-Weyl, Vol. E8b, p 72ff). The addition of an equimolar amount of 48% hydro-bromic acid results in the exclusive formation of the 1,3,4-thiadiazines 2 a, c, and d. When the condensations of thiosemicarbazide with 2-bromo-l,2-diphenylethan-l-one, 2-bromo-1-phenylpropan-l-one or 2-bromo-l-phenylbutan-l-one are performed in ethanol at room temperature, the S-(oxoalkyl)-isothiosemicarbazide hydrobromides are formed as open-chain intermediates and also undergo cyclization in ethanol upon addition of an equimolar amount of 48% hydrobromic acid to furnish 2 a, c, and d. 

The ester 5 reacts with thiosemicarbazide to yield the thiazole 6, the thiadiazine 8, or the corresponding carboxylic acids, depending on the acidity of the medium, but no triazine is obtained. The covalent hydrate 7 is an intermediate in the formation of 8. Acetylation of the thiazole 6 leads to unidentified thiadiazines or pyrazoles <96KGS1266 97CA(126)89345>. 

Thiadiadiazines are prepared best by condensation of thiohydrazides with a-halocarbonyl compounds. As thiohydrazide components, most substituted thiosemicarbazides, aryl and alkyl thiocarbonylhydrazides, or 0-alkyl dithiocarbazates can be used. The cyclocondensation with thiosemicarbazides and a-halocarbonyl compounds can provide three isomeric compounds, 2-amino-l,3,4-thiadiazines A, 2-hydrazino-l,3-thiazoles or 2-hydrazono-2,3-dihy-dro-l,3-thiazoles B, and 2-alkyl(aryl)imino-3-amino-2,3-dihydro-l,3-thiazoles C (Scheme 31). The course of the cyclization of thiosemicarbazides with a-halocarbonyl compounds depends on the acidity of the reaction medium and the substituents R, R, and R. The reaction of aromatic a-halo ketones with thiosemicarbazides leads under neutral... 

The Hantzsch reaction has also been incorporated in a multi-component reaction described by Rao et al. to produce 2-pyrazol 4-yl-substituted diiazole system in one step. The reaction involves a one-pot cyclization to form thiazole, pyrazolone and cyclopropane rings via the reaction of aryl bromomethylketonewith, thiosemicarbazide, and a-acetyl-y-butyro lactone in phosphorus oxychloride. 

The construction of two heterocyclic rings in one S)mthetic step has been developed for the preparation of coumarin derivatives. In this process, the thiazole ring (31 - 40) is accomplished by Flantzsch reaction monitored by fabrication of pyrazole by reacting a 3-(2-bromoacetyl) coumarin with thiosemicarbazide and acetylacetone at room temperature [87]. 

Beyer H, Passing W, Ruhlig G. Uber Thiazole, XV. Mitteil. Uber die Kondensation von Chloraceton mit Thiosemicarbazid und einige Umlagemngen in der Thiazol-reihe, Chem. Ber. 1953. p. 764 - 769. DOI 10.1002/cber.l9530860621... 

The Hantzsch reaction, discovered in 1889, remains one of the most reliable routes to thiazoles. The reaction involves a [3 + 2] atom cyclization between thioamide 1, and an a-halo carbonyl compound 2 and is one of the most direct routes to thiazoles. The reaction can also be carried out with thioureas, thiosemicarbazides and other compounds containing the —N-0=S structural unit. " ... 

Gomha and Khalil (2012) developed a successful application of ultrasound irradiation for the rapid synthesis of a novel series of 3-[l-(4-substituted-5-(aryldiazenyl) thiazol-2-yl)hydrazono)ethyl]-2//-chromen-2-ones (48) in good yields (72%-76%), via reactions of 2-(l-(2-oxo-2//-chromen-3-yl)ethylidene)thiosemicarbazide (47) and hydrazonoyl halides (39) in dioxane in the presence of a catalytic amount of... 

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