- Contribution of Solvents to Geometrical Preference in the Z/ E Equilibrium of N-Phenylthioacetamide
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We studied the Z/E preference of N-phenylthioacetamide (thioacetanilide) derivatives in various solvents by means of 1H NMR spectroscopy, as well as molecular dynamics (MD) and other computational analyses. Our experimental results indicate that the Z/E isomer preference of secondary (NH)thioamides of N-phenylthioacetamides shows substantial solvent dependency, whereas the corresponding amides do not show solvent dependency of the Z/E isomer ratios. Detailed study of the solvent effects based on molecular dynamics simulations revealed that there are two main modes of hydrogen (H)-bond formation between solvent and (NH)thioacetamide, which influence the Z/E isomer preference of (NH)thioamides. DFT calculations of NH-thioamide in the presence of one or two explicit solvent molecules in the continuum solvent model can effectively mimic the solvation by multiple solvent molecules surrounding the thioamide in MD simulations and shed light on the precise nature of the interactions between thioamide and solvent. Orbital interaction analysis showed that, counterintuitively, the Z/E preference of NH-thioacetamides is mainly determined by steric repulsion, while that of sterically congested N-methylthioacetamides is mainly determined by thioamide conjugation.
- Chan, Erika S.,Hyodo, Tadashi,Ikeda, Hirotaka,Inagaki, Satoshi,Ohwada, Tomohiko,Otani, Yuko,Song, Shuyi,Tang, Yulan,Vu, Kim Anh L.,Yamaguchi, Kentaro
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- Rational design and synthesis of 2-anilinopyridinyl-benzothiazole Schiff bases as antimitotic agents
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Based on our previous results and literature precedence, a series of 2-anilinopyridinyl-benzothiazole Schiff bases were rationally designed by performing molecular modeling experiments on some selected molecules. The binding energies of the docked molecules were better than the E7010, and the Schiff base with trimethoxy group on benzothiazole moiety, 4y was the best. This was followed by the synthesis of a series of the designed molecules by a convenient synthetic route and evaluation of their anticancer potential. Most of the compounds have shown significant growth inhibition against the tested cell lines and the compound 4y exhibited good antiproliferative activity with a GI50 value of 3.8?μM specifically against the cell line DU145. In agreement with the docking results, 4y exerted cytotoxicity by the disruption of the microtubule dynamics by inhibiting tubulin polymerization via effective binding into colchicine domain, comparable to E7010. Detailed binding modes of 4y with colchicine binding site of tubulin were studied by molecular docking. Furthermore, 4y induced apoptosis as evidenced by biological studies like mitochondrial membrane potential, caspase-3, and Annexin V-FITC assays.
- Shaik, Thokhir B.,Hussaini, S.M. Ali,Nayak, V. Lakshma,Sucharitha, M. Lakshmi,Malik, M. Shaheer,Kamal, Ahmed
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supporting information
p. 2549 - 2558
(2017/05/09)
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- Evaluation of dipole moment and electrophilicity on the nature of click-type coupling reaction between thioamide and sulfonyl azide
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A cooperated experimental and computational investigation on sulfonyl amidine formation from thioamides and sulfonyl azides is described. The data support a non-concerted two-step pathway for the coupling reaction and also indicate that dipole moment of t
- Aswad, Muhammad,Chiba, Junya,Tomohiro, Takenori,Hatanaka, Yasumaru
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supporting information
p. 1313 - 1316
(2018/03/26)
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- Transamidation of thioacetamide catalyzed by SbCl3
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A transamidation reaction of thioacetamide with primary and secondary amines is described. The use of catalytic amounts of SbCl3 notably increases the yields and diminishes the reaction times. Typically, the amines should be aliphatic, but aromatic amines can be used as well, though with lower yields. This is one of the few examples where antimony has been used as a catalyst in organic reactions.
- Ojeda-Porras, Andrea,Gamba-Sánchez, Diego
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supporting information
p. 4308 - 4311
(2015/06/22)
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- Enaminones via ruthenium-catalyzed coupling of thioamides and α-diazocarbonyl compounds
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Enaminones can be prepared via the Rh2(OAc)4- catalyzed coupling of α-diazocarbonyl compounds with thioamides. However, rhodium is the most expensive and least abundant among the dominant precious metals used for catalysis. Furthermore, a very limited substrate scope is known for the intermolecular rhodium catalyzed coupling reaction. Therefore, there is a need to find a more economical catalyst substitute with a broad substrate scope. In this paper, we describe the use of Ru(II) catalysts for the synthesis of enaminones. The reaction can be performed efficiently with the Grubbs first-generation catalyst or [(Ph)3P]3RuCl2 in a sealed tube. Both catalysts are much less expensive than Rh 2(OAc)4. Secondary and tertiary thioamides, when reacted with α-diazodiesters, α-diazoketoesters, α-diazodiketones, and α-diazomonoketones give enaminones. Primary thioamides give thiazole derivatives when reacted with α-diazomonoketones. However, with other diazo compounds, primary thioamides also give enaminones. All enaminones are obtained in good yields and with good diastereoselectivity. Accordingly, the method described in this paper is an efficient and economical alternative to the Rh2(OAc)4-catalyzed coupling process.
- Koduri, Naga D.,Wang, Zhiguo,Cannell, Garrett,Cooley, Kate,Lemma, Tsebaot Mesfin,Miao, Kun,Nguyen, Michael,Frohock, Bram,Castaneda, Maria,Scott, Halee,Albinescu, Dragos,Hussaini, Syed R.
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p. 7405 - 7414
(2014/09/17)
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- O,O-Diethyl dithiophosphoric acid mediated direct synthesis of thioamides from aldehydes and ketones
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A general and convenient method for a one-pot conversion of aldehydes and ketones into thioamides has been developed. The protocol involves oximation of aldehydes and ketones followed by deoxygenative thioamidation of oximes with O,O-diethyl dithiophosphoric acid which acts as an acid as well a source of sulfur. The method is operationally simple, high yielding, and also applicable to the conversion of amides and nitriles into the corresponding thioamides.
- Yadav, Arvind K.,Srivastava, Vishnu P.,Yadav, Lal Dhar S.
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p. 7113 - 7116
(2013/01/15)
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- Facile and odorless one-pot process for the synthesis of N-substituted thioamides via TsCl-mediated Beckmann rearrangement of ketoximes
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A facile and odorless one-pot thionation process for the synthesis of N-substituted thioamides using chemically stable and inexpensive thiourea reagent via the Beckmann rearrangement of ketoximes, has been described. Georg Thieme Verlag Stuttgart · New York.
- Liu, Li-Feng,An, Na,Pi, Hong-Jun,Ying, Jun,Du, Wenting,Deng, Wei-Ping
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supporting information; experimental part
p. 979 - 981
(2011/06/11)
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- Searching for new cures for tuberculosis: Design, synthesis, and biological evaluation of 2-methylbenzothiazoles
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The actual development and clinical use of new therapeutics for tuberculosis (TB) have remained stagnant for years because of the complexity of the disease process, the treatment of which at present requires the administration of drug combinations over a 6month period. There is thus an urgent need for the discovery and development of novel, more active, and less toxic anti-TB agents. In this study, we report on the chemistry and biology of a series of potent 5-(2-methylbenzothiazol-5-yloxymethyl) isoxazole-3-carboxamide derivatives, which proved to be active against replicating Mycobacterium tuberculosis (Mtb) H37Rv. The most potent compounds 7j and 7s were found to inhibit Mtb growth at micromolar concentrations, with MICvalues of 1.4 and 1.9 μM, respectively. Impressively, all active compounds were nontoxic toward Vero cells (IC50 > 128 μM). Moreover, the best of these compounds were also tested against protozoan parasites, and some of these compounds were found to show activity, especially against Plasmodium falciparum. These studies thus suggest that certain 2-methylbenzothiazole based compounds may serve as promising lead scaffolds for further elaboration as anti-TB drugs and as possible antimalaria drugs. 2009 American Chemical Society.
- Huang, Qingqing,Mao, Jialin,Wan, Baojie,Wang, Yuehong,Brun, Reto,Franzblau, Scott G.,Kozikowski, Alan P.
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supporting information; experimental part
p. 6757 - 6767
(2010/04/24)
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- Ketoximes to N-substituted thioamides via PSCl3 mediated Beckmann rearrangement
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N-Substituted thioamides were accessed from ketoximes by utilising PSCl3 as a uniquely capable reagent to induce Beckmann rearrangement as well as to capture the intermediate nitrilium ion. The Royal Society of Chemistry 2009.
- Pathak, Uma,Pandey, Lokesh Kumar,Mathur, Sweta,Suryanarayana
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scheme or table
p. 5409 - 5411
(2009/12/08)
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- Microwave-assisted synthesis of substituted 1,2,4-triazoles
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An efficient synthesis of substituted 1,2,4-triazoles has been extended, utilising a wide range of N-substituted amides and hydrazides.
- Wu, Dong-Qing,He, Jian- Li,Wang, Jun-Ke,Wang, Xi-Cun,Zong, Ying-Xiao
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p. 293 - 294
(2007/10/03)
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- Lawesson's reagent for direct thionation of hydroxamic acids: Substituent effects on LR reactivity
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To explore the generality and scope of direct thionation of hydroxamic acids (HAs), the reaction of various structurally diverse HAs with Lawesson's reagent was investigated. The yield of thiohydroxamic acid (THAs) is poor when HAs possess bulky acyl and/or N-substituents, acidic α-hydrogen atoms, or an N-phenyl ring. THAs yields were correlated with Brown sigma parameter. The relative rates of two subsequent processes kT2 and kR2 were also measured. Correlation was also found for methine proton chemical shifts of N-isopropyl benzothiohydroxamic acids.
- Przychodzen, Witold
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p. 676 - 684
(2007/10/03)
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- Kinetics and Mechanism of the Aminolysis of Phenyl Dithioacetates in Acetonitrile
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The aminolysis reactions of phenyl dithioacetates with anilines (AN), N,N-dimethylanilines (DMA), and benzylamines (BA) in acetonitrile are investigated. The mechanism is relatively simple, involving a zwitterionic tetrahedral intermediate, T±, and is uncomplicated by the fast proton transfer step which may become rate limiting in the aminolysis of thiono and dithio esters and carbonates with poor leaving groups in water. The mechanism changes from rate-limiting expulsion of the leaving group with βX = 0.80-0.86 and βZ = -0.71 to -0.84 for ANs and DMAs to rate-limiting attack by the nucleophile with much smaller magnitudes of βX and βZ for BAs. The relatively large βXZ values for the former series and a smaller βXZ for the latter series support the proposed mechanistic change.
- Oh, Hyuck Keun,Woo, So Young,Shin, Chul Ho,Park, Young Sook,Lee, Ikchoon
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p. 5780 - 5784
(2007/10/03)
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- A convenient synthesis of β-lactams from alkylthioimidates
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Stereoselective syntheses of trans-3,4,4-substituted-azetidin-2-ones from alkylthioimidates are described. Reduction of these compounds gave stereoselectively cis-4-alkyl-azetidin-2-ones which could be useful intermediates for preparation of biologically
- Grochowski, Edward,Pupek, Krzysztof
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p. 6759 - 6768
(2007/10/02)
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- STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XLVII PREPARATION OF THIATED SYNTHONS OF AMIDES, LACTAMS AND IMIDES BY USE OF SOME NEW P,S-CONTAINING REAGENTS
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The thionation properties of 2,4-bismethylthio-1,3,2,4-dithiadiphosphetane 2,4-disulfide, 1, 2,4-bis(4-phenoxyphenyl)-1,3,2,4-dithiaphosphetane 2,4-disulfide, 2, 2,4-bis(4-phenylthiophenyl)-1,3,2,4-dithiaphosphetane 2,4-disulfide, 3, and 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiaphosphetane 2,4-disulfide (LR), 4, have been investigated on a series of amides, lactams and imides.The most remarkable feature is that 2, 3 and 4 thionate most amides and lactams in THF at room temperature (reaction time 5 min) to give the corresponding thionated compounds.Imides are easily thionated by 2, 3 and 4 in DME at 60 oC.The reactions of 1 with amides, imides and most lactams are run at 60 oC to give good yields of the corresponding thionated compounds.
- Yde, B.,Yousif, N. M.,Pedersen, U.,Thomsen, I.,Lawesson, S. -O.
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p. 2047 - 2052
(2007/10/02)
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