4-substituted Thiosemicarbazides Research Articles

Some Features of Phosphorylation of 4-Substituted Thiosemicarbazides with Chloroethynylphosphonates

The reactions of chloroethynylphosphonates with 4-substituted thiosemicarbazides leads to the predominant formation of dialkyl esters of 5-substituted (1,3,4-thiadiazol-2-yl)methylphosphonic acids with an admixture (up to 31%) of dialkyl [3-amino-2-(alkylimino)-2,3-dihydro-1,3-thiazol-4-yl)phosphonates as a minor product.

Synthesis and In Vitro Anti-Toxoplasma gondii Activity of Novel Thiazolidin-4-one Derivatives.

Recent findings on the biological activity of thiazolidin-4-ones and taking into account the lack of effective drugs used in the treatment of toxoplasmosis, their numerous side effects, as well as the problem of drug resistance of parasites prompted us to look for new agents. We designed and synthesized a series of new thiazolidin-4-one derivatives through a two-step reaction between 4-substituted thiosemicarbazides with hydroxybenzaldehydes followed by the treatment with ethyl bromoacetate; maleic anhydride and dimethyl acetylenedicarboxylate afforded target compounds. The thiazolidin-4-one derivatives were used to assess the inhibition of Toxoplasma gondii growth in vitro. All active thiazolidine-4-one derivatives (12 compounds) inhibited T. gondii proliferation in vitro much better than used references drugs both sulfadiazine as well as the synergistic effect of sulfadiazine + trimethoprim (weight ratio 5:1). Most active among them derivatives 94 and 95 showed inhibition of proliferation at about 392-fold better than sulfadiazine and 18-fold better than sulfadiazine with trimethoprim. All active compounds (82–88 and 91–95) against T. gondii represent values from 1.75 to 15.86 (CC30/IC50) lower than no cytotoxic value (CC30).

Investigation of Reactions Between Binucleophilic Reagents with 2-(2-Oxindolin-3-ylidene)malononitrile Derivatives

Nucleophilic addition of hydrazines and thiosemicarbazide to the 2-(2-oxoindolin-3-ylidene) malononitrile derivatives 1, followed by elimination of malononitrile, lead to 3-(2-arylhydrazono)indolin-2-ones and 1-(2-oxoindolin-3- ylidene)thiosemicarbzides respectively. Also the reaction of compounds 1 with 4-substituted thiosemicarbazides, followed by elimination and cyclization, afforded spiro(indolone-3,2´-[1,3,4]thiadiazol)-2-ones. So all of these nucleophilic reactions with isatin and substituted isatins released the same products. Keywords: Hydrazones, 2-(2-oxindolin-3-ylidene)malononitriles, 4-substituted thiosemicarbazides.

A simple and efficient synthesis of 3-amino-5-benzyl-6-phenylpyridazine-4-carbonitrile

3-Amino-5-benzyl-6-pyridazine-4-carbonitrile has been synthesized by the reaction of 4-substituted thiosemicarbazides with (2,3-diphenylcyclopropen-1-ylidene)propanedinitrile. The structure of the pyridazine derivative has been confirmed unambiguously by single crystal X-ray crystallography.

Synthesis and antiaggregant activity of 2-cycloalkylamino-5-thienyl- and -5-furyl-6H-1,3,4-thiadiazines

A series of new 5-(thienyl-2)-, 5-(furyl-2)-, and 5-(thienyl-3)-1,3,4-thiadiazine derivatives have been synthesized using methods based on the cyclocondensation of -bromoacetylthiophenes or -bromo-2-acetylfurans with 4-substituted thiosemicarbazides. The effects of the synthesized compounds on human platelet aggregation in vitro and on rabbit platelet aggregation ex vivo have been studied. The most active 5-(thienyl-2)-1,3,4-thiadiazines inhibit human platelet aggregation induced by ADP and arachidonic acid in a broad concentration range. These compounds have good potential as emergency drugs for the treatment and prophylaxis of infarction and stroke.

Synthesis of Spiro(indenepyrazole) and Indenotriazinone Derivatives from 4-substituted Thiosemicarbazides and (1,3-dioxo-2,3-dihydro-1H-Inden-2-Ylidene)Propanedinitrile

In a multistep reaction, N-substituted-5′-amino-4′-cyano-1,3-dioxo-1,3-dihydro-spiro[indene-2,3′-pyrazole]-2′(1 H) carbothioamides (63–71 %) and 4-substituted-3-thioxo-3 H-indeno[1,2- e][1,2,4] triazin-9(4 H)-ones (17–26 %) have been formed, from a series of 4-substituted thiosemicarbazides 1a–f with (1,3-dioxo-2,3-dihydro-1 H-inden-2-ylidene)propanedinitrile 3 in aerated ethyl acetate. Rationales of these conversions involving the nucleophilic reactions and condensation are presented.

ChemInform Abstract: Synthesis of 1,3,4-Thiadiazole Derivatives (III), (IV), (VI) by Reaction of 1- and 4-Substituted Thiosemicarbazides (I), (V) with 1- Bromo-2-acylacetylenes (II).

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Spectroscopic, thermal and electrochemical characterization of synthesized divalent transition metal complexes with cysteine and 4-substituted thiosemicarbazides

Mixed ligand complexes of CoII, NiII and CuII with cysteine and 4-substituted thiosemicarbazides (l1–l3) have been synthesized. The elemental analyses, molar conductance, spectra [electronic, i.r., 1H-n.m.r., mass] and thermal studies were used to characterize the isolated complexes. Cyclic voltammetry was used to study the electrochemical behaviour of the NiII complexes. The i.r. and 1H-n.m.r. showed that cysteine is deprotonated in the complex and acts as a binegative ligand coordinating through thiol sulphur and COOH groups. Also, thiosemicarbazides act as a bidentate ligand, coordination via NH2 and (C=S) groups. Square-planar geometry has been proposed for CoII, NiII and CuII ternary complexes.

Novel Pd(II) complexes of 1- N-substituted 3-phenyl-2-pyrazoline derivatives and evaluation of antiamoebic activity

Cyclization of Mannich base with N 4-substituted thiosemicarbazides by different aliphatic, aromatic and cyclic amines afforded a series of new 1- N-substituted cyclised pyrazoline analogues of thiosemicarbazones (PYZ-TSC) 1– 10. Reaction of [Pd(DMSO) 2Cl 2] with pyrazoline derivatives led to new palladium(II) complexes [Pd(PYZ-TSC)Cl 2] 1a– 10a. The structures of all the compounds were characterized by spectroscopic methods. It was concluded that the pyrazoline thiosemicarbazone derivatives have two chelating arms, one attached at the 2-position of the pyrazole ring (that is, N donor) and other (S donor) linked to the thiosemicarbazone branch. The determination of antiamoebic activity of all the compounds was done using HM1:IMSS strain of Entamoeba histolytica, among all the complexes, 8a showed the most promising IC 50 = 0.37 μM vs. IC 50 = 1.81 μM of metronidazole, the reference drug. MTT assay showed that the compounds are non-toxic to human kidney epithelial cell line.

Indazole, oxathiadiazole, and thiadiazine derivatives from thiosemicarbazides

4-Substituted thiosemicarbazides 1a–c reacted with 2,3-dicyano-5,6-dichloro-1,4-benzoquinone (DDQ, 2), 2,3,5,6-tetrachloro-1,4-benzoquinone (CHL-p, 6) and 2,3-dichloro-1,4-naphthoquinone (DCHNQ, 7) in ethyl acetate with admission of air and form the derivatives of 1,5,2,3-oxathiadiazole 8a–c, indazole 9a–c, 1,3,4-thiadiazine-6-one 10a–c, 1,3,4-thiadiazaphenanthren-9-one 11a–c, naphtho[1,2-e:4,3-è]bis134thiadiazine 12 and dibenzo[b,i]thianthrene-5,7,12,14-tetraone 13. A rationale for the conversions observed is presented.

Reaction of 4‐substituted thiosemicarbazides with (2,4,7‐trinitro‐9H‐fluoren‐9‐ylidene)propanedinitrile

Abstractmagnified image4‐Substituted thiosemicarbazides 4a‐c reacted with (2,4,7‐trinitro‐9H‐fluoren‐9‐ylidene)‐propanedinitrile (2) in pyridine with admission of air to form spiro[fluorene‐9,3′‐(1,2,4‐triazole)]derivatives 5a‐c and (4‐substituted thiosemicarbazono)propanedinitriles 6a‐c in modest yields. 2,4,7‐Trinitro‐9‐fluorenone (8) as well as one reduction product thereof and of 2, namely compounds 9 and 10, respectively are also found. A rationale for the conversions observed is presented.

Synthesis of 2‐Aminoaryl‐5‐substituted‐1,3,4‐thiadiazoles in a Thermal 1,3‐Dipolar Cycloaddition Reaction.

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Synthesis of 2-Aminoaryl-5-Substituted-1,3,4- Thiadiazoles in a Thermal 1,3-Dipolar Cycloaddition Reaction

The preparation of a series of new 2-aminoaryl-1,3,4-thiadiazoles substituted with methylsulfanyl, methansulfinyl, or amine in the 5-position is described in this article. The compounds were obtained from N-hydroxyimidoyl chlorides and methyl dithiocarbazinate or 4-substituted thiosemicarbazides in a thermal 1,3-dipolar cycloaddition reaction. The new derivatives were tested for their activity against Mycobacterium tuberculosis.

Ambident Properties of 4-Substituted Thiosemicarbazides in Condensations with Fluoroacetic Acids

4-Substituted thiosemicarbazides react with di- and trifluoroacetic acids to give the corresponding 3-fluoroalkyl-4,5-dihydro-1,2,4-triazole-5(1H)-thiones. Condensation of 4,4-disubstituted thiosemicarbazides with trifluoroacetic acid leads to formation of 2-amino-5-trifluoromethyl-1,3,4-thiadiazoles.

Copper(II) complexes with substituted thiosemicarbazones of thiophene-2-carboxaldehyde: synthesis, characterization and antiamoebic activity against E. histolytica

In an effort to develop potent antiamoebic agents, a series of thiosemicarbazone (TSC) ligands 1– 5 derived from thiophene-2-carboxaldehyde and N 4-substituted thiosemicarbazides has been prepared and characterized using various spectroscopic techniques. Treatment of the ligands with cupric chloride produced the copper(II) complexes [Cu(TSC) 2Cl 2] 1a– 5a where ligand bind through thionic sulfur and the azomethine nitrogen. The possible geometries of the complexes were assigned on the basis of magnetic moment, electronic and thermal patterns as well as infrared spectral studies. The thiosemicarbazones and their copper complexes were tested for their in vitro antiamoebic activity against HK-9 strain of Entamoeba histolytica and showed significant growth inhibition. The results revealed that these complexes are effective chemicals in inhibiting amoebal growth, with compound 5 (having –N(CH 3)(C 6H 5) substituent at N 4) and complexes 1a– 5a being more effective than the commercial antiamoebic drug, metronidazole, based on IC 50 values. These data also indicated that the compounds 3a and 5a are most effective among the complexes studied (IC 50 = 0.26 μM of 3a and IC 50 = 0.21 μM of 5a versus IC 50 = 1.81 μM of metronidazole).

Synthesis and structures of acetylferrocene thiosemicarbazones and their dimethylthallium(III) complexes, which have four- or five-membered chelate rings

Five thiosemicarbazones HL n =Fc(Me)C(2)N(3)N(2)(H)C(1)(S)N(1)R 1R 2 (Fc=ferrocenyl) were prepared by condensing acetylferrocene with thiosemicarbazide or 4-substituted thiosemicarbazides: acetylferrocene thiosemicarbazone (HL 1), acetylferrocene 1 N-methylthiosemicarbazone (HL 2), acetylferrocene 1 N-phenylthiosemicarbazone (HL 3), acetylferrocene 1 N-ethylthiosemicarbazone (HL 4) and acetylferrocene 1 N-dimethylthiosemicarbazone (HL 5). All were characterized by IR and 1H and 13C NMR spectroscopy, and the structures of HL 3, HL 4 and HL 5 were elucidated by X-ray crystallography. Reaction of dimethylthallium hydroxide with HL 1HL 5 afforded complexes [TlMe 2(L n )]. X-ray studies of [TlMe 2(L 2)], [TlMe 2(L 3)(dmso)]·dmso, [TlMe 2(L 4)] and [TlMe 2(L 5)] showed them to vary considerably as regards the coordination mode of the ligand. (L 2) − and (L 4) − form four-membered chelate rings via N(2) and S, and in the (L 2) − complex an additional weak Tl⋯S interaction increases the coordination number of the metal to five and links the molecules in chains. [TlMe 2(L 4)] is the first thiosemicarbazone complex of TlMe 2 + to have a coordination number of only four. In [TlMe 2(L 3)(dmso)]·dmso the more usual N(3),S-chelating mode gives rise to a five-membered chelate ring and there is an additional weak bond with a dmso oxygen. (L 5) − is also N(3),S-chelating, but in this case dimers are formed by sulfur bridges. The differences in coordination are reflected in the TlL n distances.

Synthesis of derivatives of 1,2,4-triazin-3-thione and 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts from 1,2-dicarbonyl compounds and 4-substituted thiosemicarbazides

The reactions of methyl- and phenylglyoxal with 2,4-disubstituted thiosemicarbazides and of diacetyl with 4-monosubstituted thiosemicarbazides gave monothiosemicarbazones which were converted in trifluoroacetic acid into previously unknown 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts. Diacetyl monosemithiocarbazones are cyclized to 5-methylene-1,2,4-triazin-3-thiones which are also obtained in the reaction ofdiacetyl with 2,4-disubstituted thiosemicarbazides. In particular cases the monothiosemicarbazones are converted into the corresponding 5-alkoxy-1,2,4-triazin-3-thiones in the presence of alcohols. The 3-thio-1,2,4-triazinium cations are formed from the 5-methylene- and 5-alkoxy derivatives in trifluoroacetic acid.

Chemistry of molybdenum with hard-soft donor ligands—III. Oxomolybdenum(VI) and cis-dioxomolybdenum(VI) mixed ligand complexes

The syntheses and characterization of a number of oxomolybdenum(VI) and cis-dioxomolybdenum(VI) complexes with 4-substituted thiosemicarbazides in the form of 4-phenyl, 4-( p-methylphenyl) and 4-( p-chlorophenyl)thiosemicarbazide (represented as LH) as the NS donor metal binding substrates are described. The oxomolybdenum(VI) complexes are of the type MoO(NS) 2X 2 and MoO(NS) 2(OO) (where X = Br or SCN and OO = oxalate or malonate) with a pentagonal bipyramidal geometry. The cis-dioxomolybdenum(VI) complexes are mixed chelate complexes, MoO 2(NS)L′, where L′H is either a monoprotic NO donor like oxine, 2-methyloxine or a NS donor such as 2-aminobenzenethiol, 2-aminocyclopent-1-ene-1-dithiocarboxylic acid and its methyl ester. The electrochemical behaviour of these complexes along with cis-MoO 2(NS) 2 and MoO(NS) 2Cl 2 complexes are discussed.

Synthesis of 3-thio-1,2,4-triazines from diacetyl and 4-substituted thiosemicarbazides

Synthesis of 3-thio-1,2,4-triazines from diacetyl and 4-substituted thiosemicarbazides

Organotin(IV) complexes with tridentate ligandsI. Dimethyltin(IV) complexes with N-salicylidene derivatives of Aroylhydrazines, S-methylhydrazinecarbodithioate and 4-substituted thiosemicarbazides

Abstract Dimethyltin(IV) complexes with N-salicylidene derivatives of aroylhydrazines, S-methylhydrazinecarbodithioate and 4-substituted thiosemicarbazides have been prepared and their IR, NMR ( 1 H, 13 C) and mass spectra have been studied. A slightly distorted five coordinate trigonal bipyramidal structure is proposed for these complexes. The two methyl carbons and the azomethine nitrogen occupy the trigonal plane, while the highly polar OSnO and OSnS are axial. The chemical shifts (δ) of the SnCH 3 carbon and the corresponding 1 J SnC values show a dependence on the nature of the donor atoms in the axial position.