- 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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p. 2549 - 2558
(2017/05/09)
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- Iodoalkyne-Based Catalyst-Mediated Activation of Thioamides through Halogen Bonding
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Halogen bonding catalysis has recently gained increasing attention as a powerful tool to activate organic molecules. However, the variety of the catalyst structure has been quite limited so far. Herein, we report the first example of the use of an iodoalkyne as a halogen bond donor catalyst. By using an iodoalkyne bearing a pentafluorophenyl group as a catalyst, thioamides were efficiently activated and reacted with 2-aminophenol to generate benzoxazoles in good yield. Mechanistic studies, including 13C NMR spectroscopic analysis and several control experiments, provided concrete evidence that this catalytic activation is based on halogen bonding. Thus, the results obtained in this study demonstrate that iodoalkynes can serve as a new scaffold for future development of halogen bonding catalysis.
- Matsuzawa, Akinobu,Takeuchi, Shiho,Sugita, Kazuyuki
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supporting information
p. 2863 - 2866
(2016/10/25)
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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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- Organocatalytic, difluorocarbene-based S-difluoromethylation of thiocarbonyl compounds
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Upon treatment with trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate (TFDA) and a catalytic amount of N,N,N′,N′-tetramethyl-1,8-diaminonaphthalene, secondary thioamides and thiocarbamates undergo selective difluoromethylation on the sulfur atom to give S-difluoromethyl thioimidates and thioiminocarbonates in good yields, respectively. This is the first report on the synthesis of acyclic difluoromethyl thioimidates and thioiminocarbonates. The key for S-difluoromethylation is the organocatalytic generation of difluorocarbene (:CF2) under mild conditions, which prevents decomposition of the substrates. This process provides an efficient approach to pharmaceuticals and agrochemicals bearing a difluoromethylsulfanyl group, starting from widely available thiocarbonyl compounds.
- Fuchibe, Kohei,Bando, Masaki,Takayama, Ryo,Ichikawa, Junji
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p. 133 - 138
(2015/03/04)
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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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- A new application of rhodanine as a green sulfur transferring agent for a clean functional group interconversion of amide to thioamide using reusable MCM-41 mesoporous silica
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A novel thionation protocol for amide compounds, with the system rhodanine/secondary amine has been discovered. Clean and efficient synthesis of a variety of thioamides can be achieved through this simple and convenient method using MCM-41 mesoporous silica as an acid catalyst. For this purpose we have synthesized MCM-41 silica and characterized by using an array of sophisticated analytical techniques like BET, HR TEM, EDX, XRD, 29Si MAS NMR and FTIR. This reaction is therefore a very neat example of a functional group interconversion.
- Ray, Suman,Bhaumik, Asim,Dutta, Arghya,Butcher, Ray J.,Mukhopadhyay, Chhanda
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p. 2164 - 2170
(2013/05/08)
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- Desulfurization and H-migration of secondary thioamides catalyzed by an iron complex to yield imines and their reaction mechanism
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Secondary thioamides were converted into imines as the major products using hydrosilane in the presence of an iron catalyst. An iron carbene complex with a silyl thiolato ligand was isolated as one of the intermediates of the catalytic cycle and was characterized by X-ray analysis.
- Fukumoto, Kozo,Sakai, Akane,Hayasaka, Kazumasa,Nakazawa, Hiroshi
-
supporting information
p. 2889 - 2892
(2013/06/27)
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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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- Highly selective mono-N-benzylation and amidation of amines with alcohols or carboxylic acids using the Ph2PCl/I2/imidazole reagent system
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Chlorodiphenylphosphine, imidazole, and molecular iodine in refluxing dichloromethane are used for the efficient preparation of amides under mild reaction conditions. This reagent system also shows excellent selectivity for mono-N-alkylation of amines with alcohols. In this system, the resulting phosphorus byproduct (diphenylphosphinic acid) is easily removed by extraction using an aqueous basic solution in the workup processes, which avoids the tedious and time-consuming chromatographic methods.
- Nowrouzi, Najmeh,Jonaghani, Mohammad Zareh
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experimental part
p. 498 - 509
(2012/07/30)
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- Facile synthesis of thioamides via P2S5-mediated beckmann rearrangement of oximes
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A facile and efficient approach to the synthesis of secondary thioamides from ketoximes via Beckmann rearrangement has been established, using phosphorus pentasulfide as a dehydrating and thiating agent. It is also efficient for the preparation of primary thiobenzamide from benzaldoxime. This approach features simple-operation, easy-control and good to excellent yields.
- Li, Jiangsheng,Cheng, Chao,Zhang, Xinrui,Li, Zhiwei,Cai, Feifei,Xue, Yuan,Liu, Weidong
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p. 1687 - 1689
(2012/10/29)
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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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- New heteroaromatic azo compounds based on pyridine, isoxazole, and benzothiazole for efficient and highly selective amidation and mono-N-benzylation of amines under Mitsunobu conditions
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4,4′-Azopyridine (2c) is used in conjunction with triphenylphosphine for the efficient conversion of carboxylic acids into amides via Mitsunobu reaction with primary and secondary aliphatic and aromatic amines. The highly selective amidation of only primary aromatic amines with new heterogeneous azo compounds based on benzothiazole 2d and isoxazole 2e is also described. These azo compounds 2c-2e can also be applied for selective mono-N-benzylation of primary aromatic amines. The solid side product heteroaromatic hydrazines obtained under the developed Mitsunobu conditions are easily separated by simple filtration and can be reoxidized to azo compounds for further use.
- Iranpoor, Nasser,Firouzabadi, Habib,Khalili, Dariush
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experimental part
p. 923 - 934
(2010/10/01)
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- A convenient one-pot preparation of N-substituted thioamides
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A convenient one-pot preparation of N-substituted thioamides from acyl halides, amines and H2O/PSCl3/Et3N in good to excellent yield has been reported through a solvent-free, microwave assisted method.
- Pandey, Lokesh Kumar,Pathak, Uma,Mazumder, Avik,Mathura, Sweta
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experimental part
p. 1225 - 1228
(2010/12/20)
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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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- Expeditious microwave-assisted thionation with the system PSCl 3/H2O/Et3N under solvent-free condition
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(Chemical Equation Presented) A novel thionation protocol for carbonyl compounds, with the system PSCl3/H2O/Et3N has been discovered. Clean, rapid, and efficient synthesis of a variety of thiocarbonyl compounds such as thioamides, thiolactams, thioketones, thioxanthones, and thioacridone can be achieved through this simple and convenient method under solventless condition with microwave irradiation.
- Pathak, Uma,Pandey, Lokesh Kumar,Tank, Rekha
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p. 2890 - 2893
(2008/09/19)
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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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- Thionation using fluorous Lawesson's reagent
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Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).
- Kaleta, Zoltan,Makowski, Brian T.,Soos, Tibor,Dembinski, Roman
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p. 1625 - 1628
(2007/10/03)
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- Synthesis and application of a fluorous Lawesson's reagent: Convenient chromatography-free product purification
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A fluorous analogue of Lawesson's reagent for thionation of carbonyl compounds has been developed and its use demonstrated on a series of amides, esters, and ketones. The separation of the Lawesson's reagent-derived byproducts can be achieved by a simple fluorous solid-phase extraction.
- Kaleta, Zoltan,Tarkanyi, Gabor,Goemoery, Agnes,Kalman, Ferenc,Nagy, Tamas,Soos, Tibor
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p. 1093 - 1095
(2007/10/03)
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- Alumina encapsulated phosphorus pentasulfide (P4S10/Al2O3) mediated efficient thionation of long chain amides
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Alumina encapsulated phosphorus pentasulfide (P4S10/Al2O3) was found to be an efficient solid supported reagent for the thionation of long chain amides. This method is advantageous in terms of use of inexpensive reagent, simple reaction processing, and clean product in good to excellent yield.
- Polshettiwar, Vivek,Kaushik
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p. 2315 - 2317
(2007/10/03)
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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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- Synthesis of S-thioacyl dithiophosphates, efficient and chemoselective thioacylating agents
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Easily available acyl dithiophosphates are not stable and isomerise reversibly to O-thioacyl monothiophosphates, especially when subjected to heating. Much slower but probably irreversible isomerisation to S-thioacyl monothiophosphates occurs. Since equilibrium states are established and S-thioacyl (mono)thiophosphates form slowly, reaction mixtures contain generally both thioacylating and acylating agents, and consequently cannot be used for efficient thioacylation. On the other hand, treatment of a mixture of isomeric anhydrides with an excess of a dithiophosphoric acid leads to exclusive formation of S-thioacyl dithiophosphates. They appear to be excellent thioacylating agents: relatively stable, inert towards water and oxygen and therefore easy to handle. Reactions with nitrogen or sulfur nucleophiles proceed very rapidly under ambient conditions, yielding respective thioacyl derivatives. Isolation of the products is very simple. Due to the low reactivity of S-thioacyl dithiophosphates towards oxygen nucleophiles they can be used for direct thioacylation of multifunctional nucleophiles with unprotected hydroxy groups. Respective thioacyl derivatives cannot readily be obtained using other methods.
- Doszczak, Leszek,Rachon, Janusz
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p. 1271 - 1279
(2007/10/03)
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- Thionation with the reagent combination of phosphorus pentasulfide and hexamethyldisiloxane
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The combination of P4S10 and hexamethyldisiloxane efficiently converts esters, lactones, amides, lactams, and ketones to their corresponding thiono derivatives. In the presence of elemental sulfur, 3-oxoesters are converted to dithiolethiones by this reagent. Yields are comparable to or superior to those obtained with Lawesson's reagent. The method has the advantage that reagent-derived byproducts may be removed by a simple hydrolytic workup or by filtration through silica gel, rather than by chromatography, as required for Lawesson's reagent.
- Curphey, Thomas J.
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p. 6461 - 6473
(2007/10/03)
-
- Facile preparation of amides from thioamides by ceric ammonium nitrate
-
Ceric ammonium nitrate (CAN) is found to be a good oxidizing agent which converts thioamides into their oxygen analogues in aqueous acetic acid under very mild conditions.
- Movassagh, Barahman,Meibodi, Forhatosadat,Sobhani, Shahin
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p. 1296 - 1298
(2007/10/03)
-
- A polymer-supported thionating reagent
-
A new polymer-supported reagent for the conversion of carbonyls to thiocarbonyls has been developed and its use demonstrated on a range of amides. Secondary or tertiary amides are converted cleanly and efficiently through to the corresponding thioamides and primary amides are converted to the corresponding nitriles. The reactions can be facilitated by conventional heating. However, if microwave heating is used, in the presence of an ionic liquid, enhanced reaction rates are achieved.
- Ley, Steven V.,Leach, Andrew G.,Storer, R.Ian
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p. 358 - 361
(2007/10/03)
-
- New, efficient and chemoselective method of thioacylation, starting from carboxylic acids
-
S-Acylation of dithiophosphoric acids yields mixed anhydrides 3; they readily isomerize to O-thioacyl 4 and S-thioacyl monothiophosphates 5, which treated with the excess of dithiophosphoric acid 2 can be easily converted into thioacyl dithiophosphates 6, excellent thioacylating reagents.
- Doszczak,Rachon
-
p. 2093 - 2094
(2007/10/03)
-
- Microwave-accelerated solvent-free synthesis of thioketones, thiolactones, thioamides, thionoesters, and thioflavonoids
-
Formula presented An expeditious, solvent-free, and high yield conversion of ketones, flavones, isoflavones, lactones, amides, and esters to the corresponding thio analogues is described utilizing Lawesson's reagent in a process that circumvents the use of dry solvents and excess of the reagent.
- Varma, Rajender S.,Kumar, Dalip
-
p. 697 - 700
(2008/02/11)
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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
-
p. 5780 - 5784
(2007/10/03)
-
- Reactions of thioamides with metal carboxylates in organic media
-
Reactions of thioamides with metal carboxylates in organic solvents are described. These processes enable the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material. Mechanistic hypotheses supported by experimental evidences, including the unequivocal synthesis of bis(thioacetanilide)mercury(II) as a key reaction intermediate, are also proposed.
- Avalos, Martin,Babiano, Reyes,Cintas, Pedro,Duran, Carlos J.,Higes, Francisco J.,Jimenez, Jose L.,Lopez, Ignacio,Palacios, Juan C.
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p. 14463 - 14480
(2007/10/03)
-
- New direct synthesis of thioamides from carboxylic acids
-
The synthesis of a series of thiomides by a novel one-pot reaction between carboxylic acids and amines in the presence of O,O-diethyl dithiophosphoric acid (DDTPA) is described.
- Borthakur, Naleen
-
p. 6745 - 6746
(2007/10/02)
-
- STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XLVII PREPARATION OF THIATED SYNTHONS OF AMIDES, LACTAMS AND IMIDES BY USE OF SOME NEW P,S-CONTAINING REAGENTS
-
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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- Acid-catalysed Rearrangement of Bis-5,6-Dihydro-4H-1,3-thiazin-2-yl and Other Disulphides and Related Reactions
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Some dithiocarbamates, thiocarbamates, and thiourea derivatives have been oxidised to the disulphides 1X(R2N=)C>2S2 with iodine.In the presence of trifluoroacetic acid, these lost sulphur giving the thiocarbonyl derivatives R1X(R2N=)C-N(R2)CSR1 (R1, R2, X =3, S; 2, S; Me, Me, S; Et, PhCH2, O; 5α-cholestan-3β-yl, Et, O; and Me, Ph, NMe).These rearrangements were most plausibly intramolecular, but proceeded by varying extents of intermolecular scrambling.
- Barrett, Anthony G. M.,Barton, Derek H. R.,Colle, Roberto
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p. 665 - 671
(2007/10/02)
-
- A convenient method for the selective reduction of amides to amines
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A variety of amides have been selectively reduced to the corresponding amines via conversion to their thioamides and treatment with triethyloxonium tetrafluoroborate followed by sodium borohydride. This procedure is compatible with isolated and conjugated double bonds, esters, intro groups, and sulfonamides.
- Raucher, Stanley,Klein, Peter
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p. 4061 - 4064
(2007/10/02)
-