Thioamides Research Articles

Synthesis and Biological evalution of heterocyclic oxazine-2-carbonothioyl)quinazolin-4(3H)-one and oxazine-2(3H)-carbothioamide derivatives

An efficient route for the preparation of novel heterocyclic oxazine-carbonothioyl-quinazolin-(3H)-one and oxazine-(3H)-carbothioamide derivatives is through synthesis of 2-phenyl-4H-benzo[d][1,3] oxazin-4-one(anthranilic acid and benzoyl chlordide) which further reacts with thiourea and thiosemicarbazide to give substituted amines, which formed oxo-2-phenylquinazoline-3(4H)-carbothioa mide and oxo-2-phenylquinazolin-3(4H)-yl)thiourea (β-naphthol,substituted aromatic formedehyde). The structures of all the prepared derivatives were elucidated by using UV-Vis IR, 1HNMR and Mass spectral studies and antimicrobial activity in vitro was studied by serial dilution method. The newly prepared derivatives showed noticeable antimicrobial properties.

Synthesis, Characterization and In vitro Antibacterial Activity of Novel Ligand and its Metal Complexes

1H-benzimidazole reacting with chloroacetone yielded 1-(1H-Benzo[d]imidazol-1-yl) propan-2-one.1-(1H-Benzo[d]imidazol-1-yl) propan-2-one further reacts with thiosemicarbazone to form novel ligand,2-(1-(1H- benzo[d] imidazol-1-yl) propan-2-ylidene) hydrazine carbo thioamide (BITS). Cu+2, Co+2, Ni+2, Mn+2 and Zn+2 metal complexes of BITS were synthesised from ligand BITS. Elemental analysis, IR-NMR spectral analysis, metal: ligand ratio and magnetic properties of all the ligand BITS and all metal complexes were characterized. The ligand BITS and all metal complexes also were screened for antibacterial Activity.

The Synthesis and Chemistry of 2-Imino-2H-Chromene-3-Carbo(Thio) Amides

2-Imino-2H-chromene-3-carbo(thio)amides are considered versatile compounds because of their significance as building blocks in synthetic chemistry. In this review, we display all the available synthetic methods for 2-imino-2H-chromene-3-carbo(thio)amides as well as their reactions towards the different reagents. The presence of the imino and amide groups in these compounds makes C-4 the only reactive site of the pyran ring with a unique reactivity that could react with different reagents. The appropriate applications for the synthesis of condensed chromene derivatives and their relevancy are reported. The reactions of 2-imino-2H-chromene-3- carbo(thio)amides were divided into several categories depending on the used reagents in the reactions.

Conventional and Microwave-Assisted Synthesis of Novel 1,2,4-Triazole Derivatives Containing Tryptamine Skeleton and Evaluation of Antimicrobial Activity

1,2,4-Triazole-3-one (3) obtained from tryptamine was transformed to the corresponding carbox( thio)amides via several steps (6a-d). Their reaction with sodium hydroxide performed the 1,2,4- triazole derivatives (7a-d). Compounds 7a-d treatment by 2-bromo-1-(4-chlorophenyl)ethanoneain an ambiance with sodium ethoxide afforded the compounds (8a-d). The reduction reaction of 8a-d afforded 1,2,4-triazoles (9a-d). The synthesis of (10a-d), (11a-d) and (12a-d) was afforded treatment of products 9a-d with 4-chlorobenzyl chloride (for 10a-d) or 2,6-dichlorobenzyl chloride (for 11a-d) or 2,4-dichlorobenzyl chloride (for 12a-d). Besides the improved of entirely novel agents having various chemical features than those of the existing ones, another aim is to combined two or more groups into a single hybrid compound. For this reason, a single compound containing more than one group, each with various modes of effect, could be helpful for the cure of bacterial infections. Microwave-assisted and conventional techniques were utilized for the syntheses. The structures of recently obtained molecules were elucidated on the foundation of 1H NMR, <sup>13</sup>C NMR, FT IR, EI MS methods and elemental analysis. All novel synthesized molecules were investigated for their antimicrobial activity using MIC (minimum inhibitory concentration) method. The aminoalkylation of triazoles (7a-d) formed products 8a-d which have excellent activity against testing bacteria with values between 0.24 and 125 μg/mL. Especially compounds 8a and 8d exhibited much better activity against E. coli than ampicillin used as standard drug. The microwave process ensured a more efficient road to the creation of desired molecules. The antibacterial examination demonstrated that after the carbonyl group is increased the antibacterial activity of the compounds is greatly increased. That's why molecules formed as a result of the alkylation reactions of triazoles has high activity.

Catalytic Cyclothiomethylation of Diamides and Dihydrazides of (Thio)carbonic Acid Using Bis(dimethylamino)methane, H2S, and Na2S·9H2O

An efficient method for the synthesis of N,S-heterocycles with (thio)amide fragments by the catalytic cyclothiomethylation of diamides and dihydrazides of (thio)carbonic acid with H2S, sodium sulfide crystallohydrate, or bis(dimethylamino)methane has been developed.

The synthesis and antiviral activity of 1-(4-сhlorophenyl)-4-(para-tolyl)-5,6,7,8-tetrahydro-2а,4a-diazacyclopenta[cd]-azulene-2-carboxylic acid derivatives

Aim. To synthesize, prove the structural framework and study the antiviral activity of 1-(4-chlorophenyl)-4-(para-tolyl)-5,6,7,8-tetrahydro-2a,4a-diazacyclopenta[cd]azulene-2-carboxylic acid derivatives.Results and discussion. The antiviral activity of 1-(4-chlorophenyl)-4-(para-tolyl)-5,6,7,8-tetrahydro-2a,4adiazacyclopenta[cd]azulene-2-carboxylic acid (4-methoxyphenyl)amide was determined in the Southern Research Institute (SRI, Birmingham, Alabama). The efficacy of this compound was expressed by EC50, IC50 and SI values determined in vitro within a range of concentrations of 0.1 – 100 μg/mL. The antiviral drug Ribavirin (Sigma) and the active substance of Amizon – 4-(N-benzyl)aminocarbonyl-1-methylpyridinium iodide were used as the reference drugs.Experimental part. Condensation of 2-methoxy-3,4,5,6-tetrahydro-7H-azepine with α-amino-4-methylacetophenone hydrochloride led to 3-(4-methylphenyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepine. By boiling the latter with α-bromo-4-chloroacetophenone in ethyl acetate 1-[2-(4-chlorophenyl)-2-oxoethyl]-3-(para-tolyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-1-ium bromide was isolated, which in aqueous alkali solution was converted into 1-(4-chlorophenyl)-4-(para-tolyl)-5,6,7,8-tetrahydro-2а,4a-diazacyclopenta[cd]azulene. The latter while reacting with the corresponding aryliso(thio)cyanates in a dry benzene gave 1-(4-chlorophenyl)-4-(para-tolyl)-5,6,7,8-tetrahydro-2a,4a-diazacyclopenta[cd]azulene-2-carboxylic acid (thio)amides. 1H NMR-spectra for the compounds synthesized were recorded on a Bruker VXR-300 spectrometer (Germany) with the operating frequency of 299.945 MHz, and also on a Bruker DRX300 (Germany) spectrometer with the operating frequency of 500.13 MHz, in DMSO-d6 using tetramethylsilane (TMS) as an internal standard. The melting points were measured using a RNMK 05 apparatus (VEB Analytik, Dresden).Conclusions. The series of new 1-(4-chlorophenyl)-4-(para-tolyl)-5,6,7,8-tetrahydro-2a,4a-diazacyclopenta[cd]azulene-2-carboxylic acid (thio)amides has been synthesized. The antiviral activity of 1-(4-chlorophenyl)-4-(para-tolyl)-5,6,7,8-tetrahydro-2a,4a-diazacyclopenta[cd]azulene-2-carboxylic acid (4-methoxyphenyl)amide has been studied in the Southern American Research Institute (SRI, Birmingham, Alabama), and the high level of the antiviral activity has been found against Flu A H1N1 California/07/2009 virus.

Crystal structure of N-(2-methylphenyl)(propan-2-yloxy)carbothioamide, C11H15NOS

Abstract C11H15NOS, monoclinic, P21/n (no. 14), a = 7.3979(4) Å, b = 8.5384(4) Å, c = 18.2771(10) Å, β = 90.999(3)°, V = 1154.32(10) Å3, Z = 4, R gt(F) = 0.0409, wR ref(F 2) = 0.1093, T = 100(2) K.

Highly chemoselective difluoromethylative homologation of iso(thio)cyanates: expeditious access to unprecedented α,α-difluoro(thio)amides.

The new motif - α,α-difluoromethyl thioamide - has been assembled starting from isothiocyanate (as thioamide precursor) and a formal difluoromethyl-carbanion generated from commercially available TMSCHF2. Upon proper activation of this reagent with potassium tert-amylate, the high-yielding transfer of the difluorinated nucleophile takes place under high chemocontrol. Various sensitive functionalities (e.g. ester, nitrile, nitro, azido groups) can be accommodated across the isothiocyanate core, thus allowing a wide scope. The methodology is highly flexible and adaptable to prepare analogous α,α-difluoromethyl oxoamides by conveniently using isocyanates as the electrophilic building-blocks.

Determination of Au(III) and Pd(II) ions by flame atomic absorption spectrometry in some environmental samples after solid phase extraction

ABSTRACTA simple and sensitive solid phase extraction method was developed for simultaneous separation and preconcentration of gold and palladium ions with N-(4-methylphenyl)-2-{[(4-phenyl-5-pyridine-4-yl-4H-1,2,4-triazol-3-yl)thio]acetyl}hydrazine carbo thioamide complex on Amberlite XAD-1180 resin before their determination by flame atomic absorption spectrometry. Some analytical parameters such as HNO3 concentration of the sample solution, amount of complexing agent, sample volume, eluent type and volume, effects of foreign ions and adsorption capacity of the resin were investigated for quantitative recovery of gold and palladium ions. The effects of some anions and cations were also examined. Under optimum conditions, the detection limits for gold and palladium ions were found to be 0.29 and 0.19 μg L−1, respectively. The preconcentration factor for gold and palladium was 250. After being validated by standard addition and analysis of standard reference material, the procedure was successfully applied to the analysis of sea and stream water, anodic slime, gold ore, soil and electronic waste.

Synthesis of some optically active terpenoid-derived thioamides

GRAPHICAL ABSTRACT

A Modified Polymer from Polyacrylonitrile

Polyacrylonitrile has been modified by introducing thioamide groups (-CSNH/sub 2/) in place of nitride groups (-CN) in the chain by passing dry H/sub 2/ S gas through a 5% solution of the polymer in N-N dimethylformamide. The modified polymer is soluble in acetone. X-ray study revealed the complete loss of crystallinity in the modified polymer. Infra-red spectrum of the polymer film shows strong absorption bands at 3390 cm/sup 1/, 2273 cm/sup 1/ and 1667 cm/sup 1/ indicating the presence of both thioamide and nitride groups in the polymer chain.

ChemInform Abstract: Stereoselective or Exclusive Synthesis of Ethyl (Z)‐2‐(2‐Substituted‐thiazol‐4‐yl)pent‐2‐enoates from Ethyl (E/Z)‐2‐(2‐Bromoacetyl)pent‐2‐enoate.

AbstractThe investigation of the reaction of ketoester (I) with thioureas or thioamides suggests that these reactions generate Z‐isomers (III) only.

ChemInform Abstract: Ruthenium‐Catalyzed Synthesis of Enaminones.

AbstractGrubbs I catalyst efficiently promotes the condensation of various thioamides with α‐diazodicarbonyl compounds.

Chronic Effects of Propylthiouracil on Metabolism and Secretion of Adrenocorticotropin and Corticosterone in Male Rats

Background: Propylthiouracil (PTU) is a thioamide drug for treating hyperthyroidism. We have already found that chronic administration of PTU decreases the level of plasma corticosterone and attenuates both the activities of 11β- hydroxylase and the generation of cyclic adenosine monophosphate (cyclic AMP) in rat zona fasciculata-reticularis (ZFR) cells. The present study aimed to investigate the chronic effects of PTU on metabolism, adrenocorticotropic hormone (ACTH) and corticosterone secretion. Methods: Male rats were randomly divided into four groups and injected subcutaneously with saline, PTU, thyroxine (T4) or PTU plus T4 once daily for 2 weeks. For metabolism studies, the body weight, food intake, water intake, urine volume, and feces weight of every rat were recorded daily. The rats were sacrificed after treatment, and the plasma thyroid stimulating hormone (TSH), ACTH, and corticosterone were measured. ZFR cells were separated from adrenal glands and then stimulated by forskolin (an activator of adenylyl cyclase, 10^(-5) M), 8-bromo-cAMP (8-Br-cAMP, a permeable analogue of cAMP, 10^(-5) M), ACTH (a stimulator to increase corticosterone secretion, 10^(-9) M), and deoxycorticosterone (DOC, a steroidogenic precursor of corticosterone, 10^(-5) M) in order to investigate the alternation of corticosterone secretion and enzyme activity. Results: Chronic administration of PTU decreased food intake and feces weight but increased urine volume. The concentration of plasma TSH increased after chronic PTU treatment. PTU also suppressed release of ACTH and decreased production of corticosterone. After the isolation of ZFR cells from PTU and PTU plus T4-treated rats, both basal and evoked levels of corticosterone release were enhanced. Conclusion: Chronic administration of PTU inhibited pituitary gland from releasing ACTH, and this reaction led to decrease in corticosterone production in vivo. PTU treatment might upregulate downstream messengers of ACTH signal pathway in ZFR cells, thus enhancing release of corticosterone in vitro.

Synthesis and Spectroscopic Characterization of New Ligand and Its Pd(II), Cu(II) Metal Complexes

A novel Schiff base ligand containing nitrogen and sulfur donor atoms was synthesized by condensing thioamide (TA) with imidothioic acid (IT) to form 1, 4 dithiane-2, 3-diamine (TAIT). Metal complexes of this ligand were prepared using Cu (II) chloride dihydrates and Pd (III) chloride. These complexes have been characterized using various physico-chemical and spectroscopic techniques. Based on physico-chemical and spectroscopic analyses, the structure of Cu (II) complex is expected to be octahedral, while Pd (II) complex is proposed to be square planner geometry. Schiff base and its metal complexes were expected to show strong bioactivity against microbes and cancer cells.

An expedient approach to ferrocenyl thioamides via Fischer carbenes

Oxidative demetalation of Fischer ferrocenyl ethoxy carbene complexes ( 1a– c, M = Cr, Mo, W) and new Fischer ferrocenyl R-amino carbene complexes [ 2– 5 ( a– c), 11– 15 ( a– c), and 21– 22 ( a– c); M = Cr, Mo, W; R = H, CH 3, C 2H 5, C 3H 7, (CH 2) 2OH, (CH 2) 3OH, (CH 2) 2(OMe) 2, (CH 2) 3N(Me) 2, CH 2CH CH 2, (CH 2) 2OSi(CH 3) 3, (CH 2) 3OSi(CH 3) 3] with elemental sulfur–NaBH 4 were carried out under mild conditions, obtaining O-ethyl ferrocenecarbothioate ( 6) and novel ferrocenyl thioamides ( 7– 10 and 16– 20) in excellent yields.

Competitive bulk liquid membrane transport of some metal ions using RC(S)NHP(S)(OiPr)2 as ionophores. Unusual supramolecular “honeycomb” aggregate of the polynuclear copper(I) complex of H2NC(S)NHP(S)(OiPr)2

Competitive transport experiments involving metal ions from an aqueous source phase through a chloroform membrane into an aqueous receiving phase have been carried out using a series of N-(thio)phosphorylated (thio)amide and thiourea ligands as ionophores in the organic phase. The source phase contained equimolar concentrations of Co(II), Ni(II), Cu(II), Zn(II), Ag(I), Cd(II) and Pb(II) with the source and receiving phases being buffered at different pH. Good transport properties were observed for Ag(I) in the case of (13). The best extraction properties have been shown by (3)L(1), (3)L(8), (2)L(7), (3)L(9) and (3)L(11) which contain an unsubstituted nitrogen atom at the C[double bond, length as m-dash]S groups ((3)L(1) and (3)L(9)), or a third nitrogen atom, capable of participating in additional coordination ((3)L(8), (2)L(7) and (3)L(11)). Reaction of Cu(NO(3))(2).6H(2)O with the potassium salt of the N-thiophosphorylated thiourea NH(2)C(S)NHP(S)(OiPr)(2) formed a new supramolecular Cu(I) complex, [{Cu(6)((2)L(1))(6)}{Cu(3)((2)L(1))(3)}.4Me(2)CO] that contains both trinuclear and hexanuclear forms in its solid state structure, and in solution.

Synthesis and Characterization of Some Novel Complexes of Rh(I), Pd(0) and Pt(0) with N-Carboethoxy-4-chlorobenzene and N-Carboethoxy-4-bromobenzene Thioamide Ligands

Reactions of ligands N-Carboethoxy-4-chlorobenzene thio amide (Hcct) and N-Carboethoxy-4-bromobenzene thioamide (Hcbt) with [Rh1Cl-(PPh3)3]. [Pd0(PPh3)4], [Pt0(PPh3)4] yields [Rh1Cl(HL)2(PPhf3)], [Pd0(HL)2(PPh3)2], [Pt0(HL)2(PPh3)2], respectively. The coordination modes of the ligands have been established on the basis of analytical, IR, electronic, spectral and magnetic measurements.

Phosphorylacetic Acid Thioamides As Key Substances for Phosphorylated Heterocycles

Diethoxyphosphorylthioacetamide in a reaction with 2,3-dichloroquinoxaline acted as a thionating reagent, giving diethoxyphosphorylacetonitrile and 2-chloro-3-[(3-chloro-2-quinoxalinyl)-thio]quinoxaline. Base-catalyzed reactions of phosphorythioacetamides with N-methylquinoxalinium iodide proceeded stereoselectively to yield cis-3-phosphoryl-1,3,3a,4,9,9a-hexahydro-2H-pynola[2,3-b]quinoxaline-2-thiones.

Reactions of alpha,beta-unsaturated Thioamides with Diazo compounds

Several reactions of the a,b-unsaturated thioamide 8 with diazo compounds 1a–1d were investigated. The reactions with CH2N2 (1a), diazocyclohexane (1b), and phenyldiazomethane (1c) proceeded via a 1,3-dipolar cycloaddition of the diazo dipole at the C=C bond to give the corresponding 4,5-dihydro-1H-pyrazole-3-carbothioamides 12a–12c, i.e., the regioisomer which arose from the bond formation between the N-terminus of the diazo compound and the C(alpha)-atom of 8. In the reaction of 1a with 8, the initially formed cycloadduct, the 4,5-dihydro-3H-pyrazole-3-carbothioamide 11a, was obtained after a short reaction time. In the case of 1c, two tautomers 12c and 12c’ were formed, which, by derivatization with 2-chlorobenzoyl chloride 14, led to the crystalline products 15 and 15’. Their structures were established by X-ray crystallography. From the reaction of 8 and ethyl diazoacetate (1d), the opposite regioisomer 13 was formed. The monosubstituted thioamide 16 reacted with 1a to give the unstable 4,5-dihydro-1H-pyrazole-3-carbothioamide 17.