6954-85-4

Upstream product

• 1147550-11-5 ammonium thiocyanate 
• 3024-72-4 3,4-dichlorobenzoyl chloride 
• 51-44-5 3,4-dichlorbenzoic acid 
• 333-20-0 potassium thioacyanate 

Downstream Products

• 1047953-91-2 2-chloro-N-(4-(5-(3,4-dichlorophenyl)-3-(2-methoxyethoxy)-1H-1,2,4-triazol-1-yl)phenyl)acetamide 

Relevant academic research and scientific papers

Evaluation of Novel N -(Dibenzylcarbamothioyl)benzamide Derivatives as Antibacterial Agents by Using DFT and Drug-Likeness Assessment

Isomers of monothioureas, 2a-2d, derived from the reaction of disubstituted benzoyl isothiocyanate and dibenzylamine were synthesised and characterised by using elementary analysis CHNS and IR, 1H NMR, and 13C NMR spectroscopies. The compounds were screened for their in vitro antibacterial activity by using selected Gram-positive bacteria, and moderate inhibition activity was displayed for compound 2b with the value of inhibition zone 11 ± 0.8 mm at a concentration of 50 mg/ml. The outcomes of Lipinski's rule of five assessment appeared to be in agreement with all compounds as they adhered to most of the rules, in which they can be preliminarily classified as active drug-like. The frontier molecular orbitals (HOMO and LUMO) for halogen-substituted 3,4-dichloro (2a) and 3,4-difluoro (2b) were also determined by applying the computational method of density functional theory (DFT) to determine their relationship as a molecular descriptor in antibacterial activities. The value of LUMO energy for compound 2b (1.8229 eV) is lower than that of compound 2a (1.8492 eV) which indicates higher antibacterial activities.

Electrochemical studies of novel 3,4-dichloro-n-((5-chloropyridin-2- yl)carbamothioyl)benzamide based on its complexes with copper(ii), cobalt(ii), nickel(ii) and zinc(ii) ions

The synthesis of novel N,N'-disubstituted benzoyl thiourea ligand [3,4-dichloro-N-((5-chloropyridin-2-yl)carbamothioyl) benzamide] (L) is achieved in two steps. First step by refluxing KSCN with 3,4-dichloro benzoyl chloride in CH3CN solvent and the other step by the reaction of the resulting filtrate from the first step with 2-amino-5-chloropyridine. The copper(II), Cobalt(II), Nickel(II) and Zinc(II) chloride and acetate salts were coordinated with L ligand in the 1:1 and 1:2 mole ratios (M:L) in the solvent mixture of DMF/H2O or CHCl3/methanol to form the complexes with structural formulas {[LMCl2] and [L2M](CH3COO)2, M= Copper(II), Cobalt(II), Nickel(II) and Zinc(II) ions}. Two mole ratios of the starting materials, 1:1 and 1:2 (M:L) were experimented to form chloride complexes, the product was with structural formula [LMCl2] while acetate complexes with [L2M](CH3COO)2 formula are resulted with the same conditions. Ligand L and its complexes [LCuCl2], [LCoCl2], [LNiCl2], [LZnCl2], [L2Cu](CH3COO)2, [L2Co](CH3COO)2, [L2Ni](CH3COO)2 and [(L)2Zn](CH3COO)2 have been characterized by mass spectrometry, elemental analysis, magnetic moments, conductivity measurements, solubility test, UVvisible, FTIR, 1H and 13C NMR spectroscopies. Electrochemical studies were probed by using cyclic voltammetry technique(CV). The data reflect the quasi-reversible reductive nature for the Copper(II) complexes with one electron transfer process while Nickel(II) and Cobalt(II) complexes exhibited two consecutive irreversible reductive nature. The observed UVvisible, elemental analysis, molar conductivity, magnetic moment measurements and solubility test revealed that the metal ion in the all prepared complexes adopted four coordinated square planar structures and [LCuCl2], [LCoCl2], [LNiCl2], [LZnCl2], are formed as neutral complexes while [L2Cu](CH3COO)2, [L2Co](CH3COO)2, [L2Ni](CH3COO)2 and [(L)2Zn](CH3COO)2 adopted anion complexes. The observed magnetic moments show diamagnetic properties of Zinc(II) and Nickel(II) complexes while Copper(II) and Cobalt(II) appeared as paramagnetic species. FT-IR analysis confirmed the coordination sites between the central metal ion with ligand L through two sites, the nitrogen atom in pyridyl ring and the sulphur atom in C=S group.

The Coordination chemistry and cyclic voltammetry exploration of Cu(II), Co(II), Ni(II) and Zn(II) complexes of novel (E)-3,4-dichloro-N-(2-(1-(pyridin-2-yl)ethylidene)hydrazine-1-carbonothioyl) benzamide ligand

A novel thiosemicarbazone derivative ligand (DEHC-H), (E)-3,4-dichloro-N-(2-(1-(pyridin-2-yl)ethylidene) hydrazine-1-carbonothioyl) benzamide ligand was synthesized after three steps. Firstly, the reaction between acetyl pyridine with hydrazine hydrate at room temperature to obtain (E)-2-(1-hydrazonoethyl)pyridine. Secondly, 3,4-dichlorobenzoyl chloride was refluxed with potassium thiocyanate in acetonitrile solvent forming 3,4-dichlorobenzoyl isothiocyanate. The last step of the reaction is summarized by the refluxing the mixture of (E)-2-(1-hydrazonoethyl) pyridine and 3,4-dichlorobenzoyl isothiocyanate in acetonitrile solvent. A series of eight new metal complexes, Copper(II), Cobalt(II), Nickel(II) and Zinc(II) chloride and acetate complexes of the thiosemicarbazone derivative ligand (DEHC-H) were accomplished in DMF/H2O or CHCl3/CH3OH mixture solvents. The {[(DEHC)CuCl], [(DEHC)CoCl], [(DEHC)NiCl], [(DEHC-H)ZnCl2], [(DEHC-H)2Cu](CH3COO)2, [(DEHC-H)2Co](CH3COO)2, [(DEHC-H)2Ni](CH3COO)2 and [(DEHC-H)2Zn](CH3COO)2} were prepared by the reaction of the free ligand with chloride and acetate metal salts, CuCl2.2H2O, CoCl2.6H2O, NiCl2.6H2O, ZnCl2, Cu(CH3COO)2.H2O, Co(CH3COO)2.4H2O, Ni(CH3COO)2.4H2O and Zn(CH3COO)2.2H2O. The preparation of the metal complexes was achieved in 1:1 and 1:2 mole ratios of (Metal salt: free Ligand). The identities of the thiosemicarbazone derivative ligand (DEHC-H) and its metal chloride and acetate complexes were characterized and confirmed by 1HNMR, 13CNMR, UV-visible, Infrared, mass spectroscopy, elemental analysis, solubility test, magnetic moments and conductivity measurements. The spectroscopic techniques and measurements indicate that the metal chloride complexes were formed with the neutral structural formula [(DEHC)MCl], where M= Copper(II), Cobalt(II) and Nickel(II) and with the neutral structural formula [(DEHC-H)ZnCl2] for Zinc(II) complexes in spite of two mole ratios were examined 1:1 and 1:2 (Metal: Ligand). In the other side, the acetate complexes were formed as the anionic formula [(DEHC-H)2M](CH3COO)2. The employed techniques indicate that thiosemicarbazone chloride complexes with formula [(DEHC)MCl], one tridentate [(DEHC) ligand coordinating in the thiole form with the metal ion and the fourth site was the chloride anion to form square planar geometry. While Zinc(II) complex [(DEHC-H)ZnCl2] show coordinating of the one tridentate [(DEHC-H) ligand as thione where the fourth and the fifth sites coordinating with the Zinc(II) ion to adopt a square pyramidal geometry. The characterization of the all acetate complexes [(DEHC-H)2M](CH3COO)2 pointed to two moles of tridentate [(DEHC-H) ligands in thione form coordinating with the metal ions to fill six sites forming octahedral geometry as well as to two moles of acetate ions as counter ions. It is worth noting that tridentate thiosemicarbazone [(DEHC-H) ligand coordinates through the nitrogen pyridyl, thionic sulfur and the azomethine nitrogen atoms. The observed magnetic moments data exhibit diamagnetic properties of Zinc(II) chloride and acetate complexes and Nickel(II) square planar chloride complexes. While Cu(II) and Co(II) square planar chloride compounds and Copper(II), Cobalt(II) and Nickel(II) octahedral acetate complexes appeared as paramagnetic species. The electrochemical behavior of a set Copper(II), Cobalt(II) and Nickel(II) chloride and acetate complexes of (E)-3,4-dichloro-N-(2-(1-(pyridin-2-yl)ethylidene) hydrazine-1-carbonothioyl) benzamide ligand were recorded using cyclic voltammetry technique. The voltammetric analysis of Copper(II) chloride and acetate complexes displays a quasi-reversible one electron reduction in the range –1.0728 to –1.1439 volt versus Fc/Fc+ ascribable to the Copper(II)/Copper(I) redox couple. The Co(II) and Ni(II) chloride and acetate compounds display one and two irreversible oxidation processes respectively in the range +0.419 to +0.479 in Co(II) compounds and +0.449 to +0.491 as well as to +0.656 to +0.721 volt versus Fc/Fc+ in Ni(II) compounds.

Pharmacomodulations of the benzoyl-thiosemicarbazide scaffold reveal antimicrobial agents targeting D-alanyl-D-alanine ligase in bacterio

D-Alanyl-D-alanine ligase (Ddl) is a validated and attractive target among the bacterial enzymes involved in peptidoglycan biosynthesis. In the present work, we investigated the pharmacomodulations of the benzoylthiosemicarbazide scaffold to identify new Ddl inhibitors with antibacterial potency. Five novel series of thiosemicarbazide analogues, 1,2,4-thiotriazole-3-thiones, 1,3,4-thiadiazoles, phenylthiosemicarbazones, diacylthiosemicarbazides and thioureas were synthesized via straightforward procedures, then tested against Ddl and on susceptible or resistant bacterial strains. Among these, the thiosemicarbazone and thiotriazole were identified as the most promising scaffolds with Ddl inhibition potency in the micromolar range. Antimicrobial evaluation of salicylaldehyde-4(N)-(3,4-dichlorophenyl) thiosemicarbazone 33, one of the best compounds in our study, revealed interesting antimicrobial activities with values of 3.12–6.25 μM (1.06–2.12 μg/mL) against VRE strains and 12.5–25.0 μM (4.25–8.50 μg/mL) towards MRSA and VRSA strains. A detailed mechanistic study was conducted on the Ddl inhibitors 4-(3,4-dichlorophenyl)-5-(2-hydroxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 20 and compound 33, and revealed a bactericidal effect at 5 × MIC concentration after 7 h and 24 h, respectively, and a bacteriostatic effect at 1 × MIC or 2 × MIC without any sign of bacterial membrane disruption at these lower concentrations. Finally, 20 and 33 were proved to target Ddl in bacterio via intracellular LC-MS dosage of D-Ala, L-Ala and D-Ala-D-Ala. Although, at this stage, our results indicate that other mechanisms might be involved to explain the antimicrobial potency of our compounds, their ability to inhibit the growth of strains resistant to usual antibiotics, as well as strains that express alternative ligases, sets the stage for the development of new antimicrobial agents potentially less sensitive to resistance mechanisms.

Synthesis and antituberculosis activity of new acylthiosemicarbazides designed by structural modification

Acylthiosemicarbazides 8a–n were designed by structural modification of lead Compound 7. The syntheses of 8a–n involve a five-step procedure starting from carboxylic acids. Compounds 8a–n were tested against three Mycobacterium tuberculosis strains to measure their inhibitory antituberculosis activities. These activities could be explained according to the presence or absence of the chlorine substituent in the aromatic ring of the amide joined to the thiosemicarbazide core. Thiosemicarbazide derivative 8n is a candidate for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.

Synthesis and structure–activity relationship studies of MI-2 analogues as MALT1 inhibitors

Recent studies revealed that MALT1 is a promising therapeutic target for the treatment of ABC-DLBCL. Among several reported MALT1 inhibitors, MI-2 as an irreversible inhibitor represents a new class of ABC-DLBCL therapeutics. Due to its inherent potential cross-reactivity, further structure–activity relationship (SAR) study is imperative. In this work, five focused compound libraries based on the chemical structure of MI-2 are designed and synthesized. The systematic SARs revealed that the side chain of 2-methoxyethoxy has little impact on the activity and can be replaced by other functionalized groups, providing new MI-2 analogues with retained or enhanced potency. Compounds 81–83 with terminal hydroxyl group as side chain displayed enhanced activities against MALT1. Replacement of triazole core with pyrazole is also tolerant, while structural modifications on other sites are detrimental. These findings will facilitate further development of small-molecule MALT1 inhibitors.

MI-2 key intermediate and preparation method thereof

The invention belongs to the technical field of organic synthesis, and particularly discloses an MI-2 key intermediate and a preparation method thereof. The method includes the steps: taking 3, 4-dichlorobenzoic acid as a starting raw material; performing 7-step reaction to obtain the MI-2 key intermediate. Related reaction is simple to operate, mild in condition and easy to process, and used reagents and used instruments are commonly used in a laboratory and easily acquired and have high operability. According to the method, a lot of MALT1 inhibitors MI-2 can be rapidly obtained, analogs of the inhibitors MI-2 which are obtained after an ethylene glycol monomethyl ether branched chain is modified can also be rapidly obtained, and the inhibitors and the analogs of the inhibitors are used for medicine research and development.

Direct and facile synthesis of acyl isothiocyanates from carboxylic acids using trichloroisocyanuric acid/triphenylphosphine system

A mild, efficient, and practical method for one-step synthesis of alkanoyl and aroyl isothiocyanates from carboxylic acids using a safe and inexpensive mixed reagent, trichloroisocyanuric acid/triphenyl-phosphine is described at room temperature. Availability of the reagents and easy workup of the reaction make this method attractive for organic chemists.

Flexible 1-[(2-aminoethoxy)alkyl]-3-ar(o)yl(thio)ureas as novel acetylcholinesterase inhibitors. Synthesis and biochemical evaluation

A series of flexible 1-(2-aminoethoxy)-3-ar(o)yl(thio)ureas was synthesized and assessed for antiacetylcholinesterase activity. This series was designed in order to optimize the spacer length linking the two pharmacophoric moieties, i.e., the basic nitrog