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Cyclization of thiosemicarbazide derivative: As a source of novel synthesis of some azoles and azines

Cyclization of thiosemicarbazide derivative: As a source of novel synthesis of some azoles and azines

Abstract

In our study, we aimed to synthesize novel, some biologically active compounds, Azoles and Azines derivatives, that to be nitrogen‐containing heterocycles, and have their diverse therapeutic values. Thiosemicarbazide, 2 , was obtained from the attack of nitrogen of hydrazine to the carbon of heteroallene function of compound 1. Triazolotriazole derivative, 4 , was obtained from the reaction of 2 with diethyl malonate. Cyclization of thiourea unit of compound 2 with heteroallene, 1 , gave trazine, 6 . Benzolyation of 2 using benzoyl chloride formed triazole derivative, 8 . Reaction of 2 and maleic anhydride gave furothiadazine, 10. Cyclohexanopyrimidinthione, 12 , was obtained from cyclocondensation of cyclohexanone with 2. Triazole, 14 , was obtained from 2 and ammonium isothiocynate under thermal condition. Reaction of 2 with ethyl bromoacetate gave thiazole derivative, 16. [2+3] Cyclocondensation of acetyl acetone with 2 provided pyrazole, 18 . Triazolotriazole, 20 , was obtained from formalin and 2. Compound 2 suffers intramolecular base mediated cyclization affording pyrazole, 21. Keeping 2 and propinaldehyde under reflux provided triazolotriazole, 24. Acylation of 2 by succinic acid formed pyridazine derivative, 27.

Synthesis and antioxidant activity study of carbothioamide and their corresponding thiazole derivatives

Synthesis and antioxidant activity study of carbothioamide and their corresponding thiazole derivatives

Abstract

A novel series of 5‐(p‐(prop‐2‐ynyloxy)phenyl)‐3‐aryl‐4,5‐dihydropyrazole‐1‐carbothioamides 2a‐f and functionalized 2‐(3‐(aryl)‐5‐(4‐(prop‐2‐ynyloxy)phenyl)‐4,5‐dihydropyrazol‐1‐yl)‐4‐(3‐arylsydnone‐4‐yl)thiazoles 4a‐l were synthesized. The newly synthesized compounds were elucidated by analytical and spectral analysis. From the single‐crystal X‐ray diffraction method, it was observed that 2d crystallizes in a monoclinic crystal system with P21/n space group. The compounds 2d crystallized with cell parameters a = 15.0614 (19) Å, b = 6.0805 (7) Å, c = 20.903 (7) Å, α = 114.136 (6)o, β = 110.709 (14) o, γ = 96.553 (5) o, V = 1790.6 (4) Å3, Z = 4. From the Hirshfeld surface computational method, the major intercontacts present in these molecules are H…H (31.6%), C…H (18.2%) and S…H (12.2%), respectively. The newly synthesized compounds were tested for their ability to bleach 2,2’‐diphenyl‐1‐picrylhydrazyl (DPPH) radical using DPPH scavenging assay. Among the synthesized compounds carbothioamide compounds 2c (90.7%) and 2b (89.8%) exhibited good DPPH scavenging activity compared to the rest of the compounds. Most of the synthesized carbothioamide molecules (2a‐f ) found to be potent compared to the thiazole derivatives (4a‐l ).

Synthesis and biological evaluation of some heterocyclic scaffolds based on the multifunctional N‐(4‐acetylphenyl)‐2‐chloroacetamide

Synthesis and biological evaluation of some heterocyclic scaffolds based on the multifunctional N‐(4‐acetylphenyl)‐2‐chloroacetamide

Abstract

The chloroacetamide derivative, 1 , was used as a versatile precursor for the synthesis of various types of N ‐aryl‐2‐(benzothiazol‐2‐ylthio)acetamide derivatives. The reaction of 1 with 2‐mercaptobenzothiazole followed by condensation reaction of the produced sulfide with phenylhydrazine, 2‐cyanoacetohydrazide, and/or thiosemicarbazide furnished the conforming condensation products, 4 , 7 , and 10 , respectively. Treatment of the phenylhydrazone product, 4 , with Vilsmeier formylation reagent (POCl3/DMF) yielded the corresponding 4‐formylpyrazole derivative, 5 . The thiosemicarbazone product, 10 , was reacted with ethyl bromoacetate to furnish the thiazolin‐4‐one derivative, 11 . The substitution reactions of chloroacetamide derivative, 1 , with 2‐mercapto‐4,6‐dimethylnicotinonitrile and 6‐amino‐2‐mercaptopyrimidin‐4‐ol, were explored to identify the sulfide products, 14 and 17 . Cyclization of 14 into its corresponding thieno[2,3‐b ]pyridine compound, 15 , was performed using sodium ethoxide. The thiosemicarbazone, 10 , and sulfide derivative, 14 , were found to be the most potent antibacterial compounds against Escherichia coli and Staphylococcus aureus , exhibiting growth inhibitory activities of 80.8% and 91.7%, respectively. Moreover, the thiosemicarbazone, 10 , displayed the most significant antioxidant activity with inhibitory activity of 82.6%, which comes close to the antioxidant activity of L‐ascorbic acid.

2H‐Indazolo[2,1‐b]phthalazine‐trione derivatives: Inhibition on some metabolic enzymes and molecular docking studies

2H‐Indazolo[2,1‐b]phthalazine‐trione derivatives: Inhibition on some metabolic enzymes and molecular docking studies

Abstract

In this study, substituted 2H‐indazolo[2,1‐b ]phthalazine‐1,6,11‐trione compounds (4a–d ) obtained via one‐pot three‐component condensation reaction of aromatic aldehydes, cyclic 1,3‐dione, and phthalhydrazide in ethanol catalyzed by Y(OTf)3 showed satisfactory inhibitory effects against some important enzymes. Also, these molecules had Ki values in the row of 185.92 ± 36.03‐294.82 ± 50.76 nM vs carbonic anhydrase I (CA I), 204.93 ± 46.90‐374.10 ± 83.63 nM against human CA II, 937.16 ± 205.82‐1021.83 ± 193.66 nM against α‐glycosidase (α‐Gly), respectively. For cholinesterase enzymes, the Ki values were found in the range of 47.26 ± 9.62‐72.05 ± 19.47 nM against acetylcholinesterase (AChE) and 65.03 ± 9.88‐102.83 ± 25.04 nM against butyrylcholinesterase (BChE), respectively. The inhibition effects of these compounds against enzymes whose name are AChE, BChE, α‐Gly, hCA I, and hCA II, were compared with control molecules like tacrine, acarbose, and acetazolamide.

Exo/endo stereocontrolled synthesis of spiroindoloindolizidines by using classical and microwave conditions via the 1,3‐dipolar cycloaddition reaction

Exo/endo stereocontrolled synthesis of spiroindoloindolizidines by using classical and microwave conditions via the 1,3‐dipolar cycloaddition reaction

Abstract

Using both classical reflux and microwave‐mediated conditions, a series of new spiroindoloindolizidines was synthesized by multicomponent 1,3‐dipolar cycloaddition of azomethine ylides in unprecedented exo /endo stereocontrolled. Both conditions easily afforded two identical and separable exo /endo diastereomeric ratios of cycloadducts. However, the ratio of two diastereomeric products obtained from conventional conditions was reversed in all examined cases when the reactions were explored under microwave‐mediated conditions. As expected, utilizing the microwave‐assisted conditions produced higher yields and reaction rates compared to classical conditions. The structure and exact stereochemistry of synthesized cycloadducts were determined by applying various 2D‐NMR spectroscopic techniques and single‐crystal X‐ray diffraction. Finally, the mechanism of the reaction has been briefly investigated by using density functional theory (DFT) calculations.

A robotic platform for flow synthesis of organic compounds informed by AI planning

[new paper by Timothy F. Jamison and Klavs F. Jensen]

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  • C.W. Coley, D.A. Thomas, J.A.M. Lummiss, J.N. Jaworski, C.P. Breen, V. Schultz, T. Hart, J.S. Fishman, L. Rogers, H. Gao, R.W. Hicklin, P.P. Plehiers, J. Byington, J.S. Piotti, W.H. Green, A.J. Hart, T.F. Jamison, and K.F. Jensen, "A robotic platform for flow synthesis of organic compounds informed by AI planning", Science, vol. 365, pp. eaax1566, 2019. http://dx.doi.org/10.1126/science.aax1566