- Ammonia-borane as a Catalyst for the Direct Amidation of Carboxylic Acids
-
Ammonia-borane serves as an efficient substoichiometric (10%) precatalyst for the direct amidation of both aromatic and aliphatic carboxylic acids. In situ generation of amine-boranes precedes the amidation and, unlike the amidation with stoichiometric amine-boranes, this process is facile with 1 equiv of the acid. This methodology has high functional group tolerance and chromatography-free purification but is not amenable for esterification. The latter feature has been exploited to prepare hydroxyl- and thiol-containing amides.
- Ramachandran, P. Veeraraghavan,Hamann, Henry J.
-
supporting information
p. 2938 - 2942
(2021/05/04)
-
- Water-promoted dehydrative coupling of 2-aminopyridines in heptane: Via a borrowing hydrogen strategy
-
A synthetic method for dehydrative N-benzylation promoted by water molecules in heptane using a π-benzylpalladium system has been developed. The presence of water significantly accelerates carbon-nitrogen bond formation, which is accomplished in an atom-economical process to afford the corresponding N-monobenzylated products. A crossover experiment afforded H/D scrambled products, which is consistent with a borrowing hydrogen mechanism. Kinetic isotope effect measurements revealed that benzylic carbon-hydrogen bond cleavage was the rate-determining step.
- Azumaya, Isao,Hikawa, Hidemasa,Kikkawa, Shoko,Nakayama, Taku
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p. 23144 - 23150
(2021/07/21)
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- Reductive N-alkylation of primary amides using nickel-nanoparticles
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Here we report Ni-nanoparticles as reusable catalysts for reductive N-alkylation of amides. These Ni-nanoparticles based catalysts have been prepared by the template synthesis of tartaric acid and 2-methyl imidazole ligated Ni-complex on SiO2 and subsequent pyrolysis under argon. Applying optimal Ni-nanostructured catalyst, N-alkylation of aromatic and heterocyclic primary amides with different aldehydes in presence of molecular hydrogen was performed to access structurally diverse N-alkylated amides in good to excellent yields. In addition, the applicability of this N-alkylation protocol has been demonstrated for the selective functionalization of primary amide group in Levetiracetam drug.
- Alenad, Asma M.,Alshammari, Ahmad S.,Jagadeesh, Rajenahally V.,Murugesan, Kathiravan,Sohail, Manzar
-
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- Graphene oxide: A convenient metal-free carbocatalyst for facilitating amidation of esters with amines
-
Herein, we report a graphene oxide (GO) catalyzed condensation of non-activated esters and amines, that can enable diverse amides to be synthesized from abundant ethyl esters forming only volatile alcohol as a by-product. GO accelerates ester to amide conversion in the absence of any additives, unlike other catalysts. A wide range of ester and amine substrates are screened to yield the respective amides in good to excellent yields. The improved catalytic activity can be ascribed to the oxygenated functionalities present on the graphene oxide surface which forms H-bonding with the reactants accelerating the reaction. Improved yields and a wide range of functional group tolerance are some of the important features of the developed protocol.
- Patel, Khushbu P.,Gayakwad, Eknath M.,Shankarling, Ganapati S.
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p. 2661 - 2668
(2020/02/20)
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- Nickel-catalyzed reductive amidation of aryl-triazine ethers
-
The reaction of activated phenolic compounds, 2,4,6-triaryloxy-1,3,5-triazine (aryl-triazine ethers), with various isocyanates or carbodiimides in the presence of a nickel pre-catalyst resulted in the synthesis of aryl amides in good to excellent yields.
- Heravi, Majid M.,Panahi, Farhad,Iranpoor, Nasser
-
supporting information
p. 1992 - 1995
(2020/02/22)
-
- Water-Tolerant and Atom Economical Amide Bond Formation by Metal-Substituted Polyoxometalate Catalysts
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A simple, safe, and inexpensive amide bond formation directly from nonactivated carboxylic acids and free amines is presented in this work. Readily available Zr(IV)- and Hf(IV)-substituted polyoxometalates (POM) are shown to be catalysts for the amide bond formation reaction under mild conditions, low catalyst loading, and without the use of water scavengers, dry solvents, additives for facilitating the amine attack, or specialized experimental setups commonly employed to remove water. Detailed mechanistic investigations revealed the key role of POM scaffolds which act as inorganic ligands to protect Zr(IV) and Hf(IV) Lewis acidic metals against hydrolysis and preserve their catalytic activity in amide bond formation reactions. The catalysts are compatible with a range of functional groups and heterocycles useful for medicinal, agrochemical, and material chemists. The robustness of the Lewis acid-POM complexes is further supported by the catalyst reuse without loss of activity. This prolific combination of Zr(IV)/Hf(IV) and POMs inaugurates a powerful class of catalysts for the amide bond formation, which overcomes key limitations of previously established Zr(IV)/Hf(IV) salts and boron-based catalysts.
- De Azambuja, Francisco,Parac-Vogt, Tatjana N.
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p. 10245 - 10252
(2019/11/03)
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- All Non-Carbon B3NO2 Exotic Heterocycles: Synthesis, Dynamics, and Catalysis
-
The B3NO2 six-membered heterocycle (1,3-dioxa-5-aza-2,4,6-triborinane=DATB), comprising three different non-carbon period 2 elements, has been recently demonstrated to be a powerful catalyst for dehydrative condensation of carboxylic acids and amines. The tedious synthesis of DATB, however, has significantly diminished its utility as a catalyst, and thus the inherent chemical properties of the ring system have remained virtually unexplored. Here, a general and facile synthetic strategy that harnesses a pyrimidine-containing scaffold for the reliable installation of boron atoms is disclosed, giving rise to a series of Pym-DATBs from inexpensive materials in a modular fashion. The identification of a soluble Pym-DATB derivative allowed for the investigation of the dynamic nature of the B3NO2 ring system, revealing differential ring-closing and -opening behaviors depending on the medium. Readily accessible Pym-DATBs proved their utility as efficient catalysts for dehydrative amidation with broad substrate scope and functional-group tolerance, offering a general and practical catalytic alternative to reagent-driven amidation.
- Opie, Christopher R.,Noda, Hidetoshi,Shibasaki, Masakatsu,Kumagai, Naoya
-
supporting information
p. 4648 - 4653
(2019/03/17)
-
- Synthesis, biological evaluation and in silico studies of tetrazole-heterocycle hybrids
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The series of three different chemical entities of tetrazole-heterocycle hybrids such as thiophene, pyridine and quinoline tetrazoles were synthesized and characterized for the purpose to develop new lead molecules. Biological evaluations such as in vitro antimicrobial and anti-inflammatory activities were studied. Further, the in silico studies such as Molecular docking (with COX-1, COX-2 and 3TTZ), DFT calculations, the Molecular electrostatic potential (MEP) and ADME were investigated.
- Sribalan, Rajendran,Banuppriya, Govindharasu,Kirubavathi, Maruthan,Padmini, Vediappen
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p. 577 - 586
(2018/09/14)
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- Solvent-Free N-Alkylation of Amides with Alcohols Catalyzed by Nickel on Silica–Alumina
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The N-alkylation of phenylacetamide with benzyl alcohol has been studied using Ni/SiO2–Al2O3. In the optimized conditions, the desired product was isolated in an excellent 98 % yield. The reaction could advantageously be performed in neat conditions, with a slight excess of amide and a catalytic amount of base. These conditions were tested on a large range of amides and alcohols, affording 24 compounds in 13 to 99 % isolated yields.
- Charvieux, Aubin,Le Moigne, Louis,Borrego, Lorenzo G.,Duguet, Nicolas,Métay, Estelle
-
supporting information
p. 6842 - 6846
(2019/11/11)
-
- Repurposing n-butyl stannoic acid as highly efficient catalyst for direct amidation of carboxylic acids with amines
-
This is the first-time report on the repurposing n-butyl stannoic acid as a catalyst for direct amidation of carboxylic acids with amines. Notably, efficient amidation observed in comparison with all other catalytic methods reported up until now. The protocol has successfully applied to the synthesis of a variety of amides. Moderate reaction parameters, clean amidation with excellent yields of desired amides, ability to tolerate a variety of functional groups, easy product isolation; commercial availability and recyclability of the catalyst are key advantages of the current protocol.
- Potadar, Santoshkumar M.,Mali, Anil S.,Waghmode, Krishnakant T.,Chaturbhuj, Ganesh U.
-
supporting information
p. 4582 - 4586
(2018/11/27)
-
- Nickel-Catalyzed Phosphine Free Direct N-Alkylation of Amides with Alcohols
-
Herein, we developed an operational simple, practical, and selective Ni-catalyzed synthesis of secondary amides. Application of renewable alcohols, earth-abundant and nonprecious nickel catalyst facilitates the transformations, releasing water as byproduct. The catalytic system is tolerant to a variety of functional groups including nitrile, allylic ether, and alkene and could be extended to the synthesis of bis-amide, antiemetic drug Tigan, and dopamine D2 receptor antagonist Itopride. Preliminary mechanistic studies revealed the participation of a benzylic C-H bond in the rate-determining step.
- Das, Jagadish,Banerjee, Debasis
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p. 3378 - 3384
(2018/03/26)
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- Synthesis of acyl fluorides via photocatalytic fluorination of aldehydic C-H bonds
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Acyl fluorides are versatile acylating agents owing to their unique stability. Their synthesis, however, can present challenges and is typically accomplished through deoxyfluorination of carboxylic acids. Here, we demonstrate that acyl fluorides can be prepared directly from aldehydes via a C(sp2)-H fluorination reaction involving the inexpensive photocatalyst sodium decatungstate and electrophilic fluorinating agent N-fluorobenzenesulfonimide. This convenient fluorination strategy enables direct conversion of aliphatic and aromatic aldehydes into acylating agents.
- Meanwell, Michael,Lehmann, Johannes,Eichenberger, Marc,Martin, Rainer E.,Britton, Robert
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p. 9985 - 9988
(2018/09/11)
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- Method of preparing amides by catalyzed reaction of esters and amines
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The invention provides a method of preparing amides by catalyzed reaction of esters and amines. Raw materials in the method are simple and easily obtainable, the method is simple to perform, has no need for adding solvents and has high yield, and the applicable range of substrates is wide. The method comprises the steps of allowing an ester of formula (I) shown in the description and an amine of formula (II) shown in the description to react under the catalysis of the catalyst alkoxy rare-earth metal cluster containing the basic metal sodium to obtain a compound of formula (III) shown in the description; alternatively, allowing the ester of formula (I) and the amine of formula (II) to react under the catalysis of the catalyst alkoxy rare-earth metal cluster containing the basic metal sodium to obtain a compound of formula (V) shown in the description, wherein R1 is selected from alkyl, aryl or heteroaryl, R2, R3 and R4 are independently selected from alkyl alcohol, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, or R3 and R4 are independently selected from alkyl alcohol and alkyl while R3, R4 and atoms connected to them form a ring. The reaction formulas are shown in the description.
- -
-
Paragraph 0086; 0088; 0089
(2018/04/27)
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- Poly(methylhydrosiloxane) as a green reducing agent in organophosphorus-catalysed amide bond formation
-
Development of catalytic amide bond formation reactions has been the subject of the intensive investigations in the past decade. Herein we report an efficient organophosphorus-catalysed amidation reaction between unactivated carboxylic acids and amines. Poly(methylhydrosiloxane), a waste product of the silicon industry, is used as an inexpensive and green reducing agent for in situ reduction of phosphine oxide to phosphine. The reported method enables the synthesis of a wide range of secondary and tertiary amides in very good to excellent yields.
- Hamstra, Daan F. J.,Lenstra, Danny C.,Koenders, Tjeu J.,Rutjes, Floris P. J. T.,Mecinovi?, Jasmin
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supporting information
p. 6426 - 6432
(2017/08/10)
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- An Unconventional Reaction of 2,2-Diazido Acylacetates with Amines
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We have discovered that 2,2-diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2-Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2-diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.
- H?ring, Andreas P.,Biallas, Phillip,Kirsch, Stefan F.
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p. 1526 - 1539
(2017/04/01)
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- Green synthesis of primary, secondary, and tertiary amides through oxidative amidation of methyl groups with amine hydrochlorides over recyclable CoFe2O4 NPs
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A practical and efficient method is developed for efficient synthesis of a wide variety of 1°, 2°, and 3° amides through amidation of methylarenes with amine hydrochloride salts, over magnetic CoFe2O4 NPs as a recyclable nanocatalyst, and aqueous tert-butyl hydroperoxide as an oxidant. This economically sound amidation reaction is operationally straightforward and provides desired amides in good to excellent yields, under mild conditions.
- Eidi, Esmaiel,Kassaee, Mohammad Zaman
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p. 106873 - 106879
(2016/11/23)
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- N-Heterocyclic Carbene-Mediated Microfluidic Oxidative Electrosynthesis of Amides from Aldehydes
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A flow process for N-Heterocyclic Carbene (NHC)-mediated anodic oxidative amidation of aldehydes is described, employing an undivided microfluidic electrolysis cell to oxidize Breslow intermediates. After electrochemical oxidation, the reaction of the intermediate N-acylated thiazolium cation with primary amines is completed by passage through a heating cell to achieve high conversion in a single pass. The flow mixing regimen circumvented the issue of competing imine formation between the aldehyde and amine substrates, which otherwise prevented formation of the desired product. High yields (71-99%), productivities (up to 2.6 g h-1), and current efficiencies (65-91%) were realized for 19 amides.
- Green, Robert A.,Pletcher, Derek,Leach, Stuart G.,Brown, Richard C. D.
-
supporting information
p. 1198 - 1201
(2016/03/15)
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- Transamidation of carboxamides with amines over nanosized zeolite beta under solvent-free conditions
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A highly efficient approach to transamidation of carboxamides with amines over nanosized zeolite beta under solvent-free conditions has been successfully demonstrated. Transamidation of a variety of amides with amines produced the respective N-alkyl amides in moderate to excellent yields.
- Durgaiah, Chevella,Naresh, Mameda,Swamy, Peraka,Srujana, Kodumuri,Rammurthy, Banothu,Narender, Nama
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- AMIDATION METHOD AND ESTERIFICATION METHOD USING SULFONIC ACID HALIDE
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PROBLEM TO BE SOLVED: To provide a safe and economical method for rapidly synthesizing amides and esters in high yield. SOLUTION: There is provided a method for amidating an amine or a derivative thereof using a sulfonic acid halide, where a sulfonic acid halide is allowed to act as an activator on a carboxylic acid or a derivative thereof to synthesize an active ester, and the active ester is reacted with an amine or a derivative thereof as a nucleophile to amidate the amine or the derivative thereof to obtain a corresponding amide or a derivative thereof. In a similar manner, a sulfonic acid halide is allowed to act as an activator on a carboxylic acid or a derivative thereof to synthesize an active ester, and the active ester is reacted with an alcohol or a derivative thereof as a nucleophile to esterify the alcohol or the derivative thereof to obtain a corresponding ester or a derivative thereof. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0038
(2017/01/17)
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- Efficient conversion of acids and esters to amides and transamidation of primary amides using OSU-6
-
OSU-6, an MCM-41 type hexagonal mesoporous silica with strong Bronsted acid properties, has been used to promote the high-yield conversion of carboxylic acids and esters to carboxamides as well as transamidations of primary amides in a one-pot solventless approach. A metal-free heterogeneous catalyst that promotes all of these processes has not been previously reported. OSU-6 enables these transformations to proceed in shorter times and at lower temperatures for a broad range of substrates. An added benefit is that the catalyst can be recycled and reused multiple times without significant loss of activity.
- Nammalwar, Baskar,Muddala, Nagendra Prasad,Watts, Field M.,Bunce, Richard A.
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p. 9101 - 9111
(2015/11/09)
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- Significance of reagent addition sequence in the amidation of carboxylic acids mediated by PPh3 and I2
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The outcome of the amidation reaction mediated by PPh3-I2 was found to be highly dependent on the addition sequence of the reagents. When triethylamine was subjected to a mixture containing PPh3, I2, and a carboxylic acid, acid anhydride was generated almost instantly, before treatment with an amine, presumably via an attack of carboxylate ion onto the acyl function of an acyloxyphosphonium salt. Nevertheless, when a PPh3-I2 mixture was treated with an amine, then a carboxylic acid, prior to adding the base, amide was rapidly formed in high yield with high chemoselectivity, most likely through an intermediate O,N-pentacoordinate phosphorane species as confirmed by ESI-MS technique.
- Wangngae, Sirilak,Duangkamol, Chuthamat,Pattarawarapan, Mookda,Phakhodee, Wong
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p. 25789 - 25793
(2015/10/20)
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- C-N Coupling of Amides with Alcohols Catalyzed by N-Heterocyclic Carbene-Phosphine Iridium Complexes
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N-Heterocyclic carbene-phosphine iridium complexes (NHC-Ir) were developed/found to be a highly reactive catalyst for N-monoalkylation of amides with alcohols via hydrogen transfer. The reaction produced the desired product in high isolated yields using a wide range of substrates with low catalyst loading and short reaction times.
- Kerdphon, Sutthichat,Quan, Xu,Parihar, Vijay Singh,Andersson, Pher G.
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p. 11529 - 11537
(2015/12/04)
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- Synergistic cascade catalysis by metal nanoparticles and Lewis acids in hydrogen autotransfer
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Of the many types of catalysis involving two or more catalysts, synergistic catalysis is of great interest because novel reactions or reaction pathways may be discovered when there is synergy between the catalysts. Herein, we describe a synergistic cascade catalysis, in which immobilized Au/Pd bimetallic nanoparticles and Lewis acids work in tandem to achieve the N-alkylation of primary amides to secondary amides with alcohols via hydrogen autotransfer. When Au/Pd nanoparticles were used with metal triflates, a significant rate acceleration was observed, and the desired secondary amides were obtained in excellent yields. The metal triflate is thought to not only facilitate the addition of primary amides to aldehydes generated in situ, but also enhance the returning of hydrogen from nanoparticles to hydrogen-accepting intermediates. This resulted in a more rapid turnover of the nanoparticle catalyst, and ultimately translated into an increase in the overall rate of the reaction. The two catalysts in this co-catalytic system work in a synergistic and cascade fashion, resulting in an efficient hydrogen autotransfer process.
- Choo, Gerald C. Y.,Miyamura, Hiroyuki,Kobayashi, Shuˉ
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p. 1719 - 1727
(2015/08/12)
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- TEMPO-Catalyzed Oxidative Amidation of Alcohols via Hexafluoroisopropyl Esters
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Stepwise oxidative amidation of alcohols using trichloroisocyanuric acid, a catalytic amount of TEMPO in combination with pyridine and hexafluoroisopropyl (HFIP) alcohol followed by amines is described. This procedure used HFIP esters as activating esters which were found to be very efficient acylating agents for amide bond formation. This process is compatible with a number of functional groups and acid-sensitive protecting groups.
- Vatèle, Jean-Michel
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p. 2280 - 2284
(2015/09/28)
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- Catalytic amidation of unactivated ester derivatives mediated by trifluoroethanol
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A catalytic amidation method has been developed, employing 2,2,2-trifluoroethanol to facilitate condensation of unactivated esters and amines, enabling the synthesis of a range of amide products in good to excellent yields. Mechanistic studies indicate the reaction proceeds through a trifluoroethanol-derived active ester intermediate.
- Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
-
supporting information
p. 9495 - 9498
(2015/06/08)
-
- An attractive route to transamidation catalysis: Facile synthesis of new o-aryloxide-N-heterocyclic carbene ruthenium(II) complexes containing trans triphenylphosphine donors
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Well-defined robust ruthenium(II) complexes 3a-d bearing o-aryloxide-N-heterocyclic carbene ligands with different wingtip substituents (3a (R = Me), 3b (R = Ph), 3c (R = iPr) and 3d (R = Mes)) in the imidazole ring were synthesized in good yields by the reaction of imidazolium proligands with metal precursor [RuHCl(CO)(PPh3)3] by transmetallation from the corresponding silver carbene complexes. All the Ru(II)-NHC complexes have been characterized by elemental analyses, spectroscopic methods as well as ESI mass spectrometry. The molecular structure of the complex 3a was identified by means of single-crystal X-ray diffraction analysis, which revealed that the complexes possess a distorted octahedral geometry. In order to explore the catalytic potential of the synthesized complexes, all the four [Ru-NHC] complexes [3a-d] were tested as catalysts for transamidation of carboxamides with amines. Notably, the complex 3a was found to be very efficient and versatile catalyst toward transamidation of a wide range of amides with amines.
- Nirmala, Muthukumaran,Prakash, Govindan,Viswanathamurthi, Periasamy,Malecki, Jan Grzegorz
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- Semi-catalytic reduction of secondary amides to imines and aldehydes
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Secondary amides can be reduced by silane HSiMe2Ph into imines and aldehydes by a two-stage process involving prior conversion of amides into iminoyl chlorides followed by catalytic reduction mediated by the ruthenium complex [Cp(i-Pr3P)Ru(NCCH3)2]PF6 (1). Alkyl and aryl amides bearing halogen, ketone, and ester groups were converted with moderate to good yields under mild reaction conditions to the corresponding imines and aldehydes. This procedure does not work for substrates bearing the nitro-group and fails for heteroaromatic amides. In the case of cyano substituted amides, the cyano group is reduced to imine.
- Lee, Sun-Hwa,Nikonov, Georgii I.
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supporting information
p. 8888 - 8893
(2014/06/09)
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- METHOD FOR THE CATALYTIC REDUCTION OF ACID CHLORIDES AND IMIDOYL CHLORIDES
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The present application relates to methods for the catalytic reduction of acid chlorides and/or imidoyl chlorides. The methods comprise reacting the acid chloride or imidoyl chloride with a silane reducing agent in the presence of a catalyst such as [Cp(Pri3P)Ru(NCMe)2]+[PF6]?.
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-
Paragraph 0140
(2014/08/19)
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- Polymer supported Pd catalyzed carbonylation of aryl bromides for the synthesis of aryl esters and amides
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A polymer-anchored palladium(ii) catalyst was synthesized and characterized using various spectroscopic techniques. Its catalytic activity was evaluated for the alkoxycarbonylation and aminocarbonylation reactions. These carbonylation reactions were carried out for various substituted aryl bromides using alcohols and amines. Both the reactions were optimized by varying the bases, temperature and solvents. These experiments were carried out under high CO pressure. The catalyst was very stable and can be facilely recovered and reused six times without a significant decrease in its activity and selectivity. the Partner Organisations 2014.
- Islam, Sk Manirul,Ghosh, Kajari,Roy, Anupam Singha,Molla, Rostam Ali
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p. 38986 - 38999
(2014/11/07)
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- Benzoic acid-catalyzed transamidation reactions of carboxamides, phthalimide, ureas and thioamide with amines
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An efficient and simple method for the transamidation of carboxamides, phthalimide, ureas and thioamide with amines catalyzed by commercially available benzoic acid under metal-free conditions is described. Furthermore, to the best of our knowledge, this is the first report about the transamidation of an aromatic thioamide with amines.
- Wu, Ji-Wei,Wu, Ya-Dong,Dai, Jian-Jun,Xu, Hua-Jian
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supporting information
p. 2429 - 2436
(2014/09/30)
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- XtalFluor-E, an efficient coupling reagent for amidation of carboxylic acids
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Amides were produced from carboxylic acids and amines by using XtalFluor-E as an activator. Even poorly reactive carboxylic acids can be transformed to amides. In addition, optically active amines and/or carboxylic acids were not epimerized/racemized during the process.
- Orliac, Aurélie,Gomez Pardo, Domingo,Bombrun, Agnès,Cossy, Janine
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supporting information
p. 902 - 905
(2013/03/29)
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- On DABAL-Me3 promoted formation of amides
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The range and utility of DABAL-Me3 couplings of methyl esters and free carboxylic acids with primary and secondary amines under a variety of conditions (reflux, sealed tube, microwave) has been compared for a significant range of coupling partners of relevance to the preparation of amides of interest in pharmaceutical chemistry. Commercial microwave reactors promote the fastest couplings and allow the use of significantly sterically hindered amines (primary and secondary) and carboxylic acids derivatives. The influence of microwave energy on the reaction system was shown to be typically related to thermal effects (over-pressuring and superheating).
- Dubois, Nathalie,Glynn, Daniel,McInally, Thomas,Rhodes, Barrie,Woodward, Simon,Irvine, Derek J.,Dodds, Chris
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supporting information
p. 9890 - 9897
(2013/10/22)
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- Green and selective synthesis of N-substituted amides using water soluble porphyrazinato copper(II) catalyst
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N,N',N",N"'-Tetramethyl tetra-2,3-pyridinoporphyrazinato copper(II) methyl sulfate ([Cu(2,3-tmtppa)](MeSO4)4) efficiently catalyzed the direct conversion of nitriles to N-substituted amides. The one pot selective synthesis of the N-substituted amides from nitriles and primary amines was performed in refluxing H2O. The catalyst was recovered and reused at least four times,maintaining its efficiency.
- Ghodsinia, Sara S. E.,Akhlaghinia, Batool,Safaei, Elham,Eshghi, Hossein
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p. 895 - 903
(2013/08/23)
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- Hypervalent iodine catalyzed transamidation of carboxamides with amines
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This protocol describes the catalytic use of diacetoxyiodobenzene (DIB) for the efficient transamidation of carboxamides with amines under mild conditions.
- Vanjari, Rajeshwer,Kumar Allam, Bharat,Nand Singh, Krishna
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p. 1691 - 1694
(2013/03/28)
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- Transamidation of primary amides with amines catalyzed by zirconocene dichloride
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Zirconocene dichloride (Cp2ZrCl2) has been shown to be an effective catalyst for the transamidation of primary amides with amines in cyclohexane at 80°C in 5-24 hours. For favourable substrates, the reaction can be performed at temperatures as low as 30°C.
- Atkinson, Benjamin N.,Chhatwal, A. Rosie,Lomax, Helen V.,Walton, James W.,Williams, Jonathan M. J.
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supporting information
p. 11626 - 11628,3
(2012/12/12)
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- Transamidation of primary amides with amines catalyzed by zirconocene dichloride
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Zirconocene dichloride (Cp2ZrCl2) has been shown to be an effective catalyst for the transamidation of primary amides with amines in cyclohexane at 80°C in 5-24 hours. For favourable substrates, the reaction can be performed at temperatures as low as 30°C.
- Atkinson, Benjamin N.,Chhatwal, A. Rosie,Lomax, Helen V.,Walton, James W.,Williams, Jonathan M. J.
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supporting information
p. 11626 - 11628
(2013/01/15)
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- Organic ligand-free alkylation of amines, carboxamides, sulfonamides, and ketones by using alcohols catalyzed by heterogeneous Ag/Mo oxides
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Complicated and expensive organic ligands are normally essential in fine chemical synthesis at preparative or industrial levels. The synthesis of fine chemicals by using heterogeneous catalyst systems without additive organic ligand is highly desirable but severely limited due to their poor generality and rigorous reaction conditions. Here, we show the results of carbon-nitrogen or carbon-carbon bond formation catalyzed by an Ag/Mo hybrid material with specific Ag6Mo10O33 crystal structure. 48 nitrogen- or oxygen-containing compounds, that is, amines, carboxamides, sulfonamides, and ketones, were successfully synthesized through a borrowing-hydrogen mechanism. Up to 99% isolated yields were obtained under relatively mild conditions without additive organic ligand. The catalytic process shows promise for the efficient and economic synthesis of amine, carboxamide, sulfonamide, and ketone derivatives because of the simplicity of the system and ease of operation. Copyright
- Cui, Xinjiang,Zhang, Yan,Shi, Feng,Deng, Youquan
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supporting information; experimental part
p. 1021 - 1028
(2011/03/20)
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- Discovery and mechanistic studies of a general air-promoted metal-catalyzed aerobic n- alkylation reaction of amides and amines with alcohols
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The thermodynamically unfavorable anaerobic dehydrogenative alcohol activation to aldehydes and hydridometal species is found to be the bottleneck in metal-catalyzed N-alkylations due to a general and unnoticed catalyst deactivation by amines/amides. Thus, different from the anaerobic dehydrogenation process in borrowing hydrogen or hydrogen autotransfer reactions that require noble metal complexes or addition of capricious ligands for catalyst activation, the water-producing, exothermic, metal-catalyzed aerobic alcohol oxidation is thermodynamically more favorable and the most effective and advantageous aldehyde generation protocol. This leads to a general and advantageous air-promoted metal-catalyzed aerobic N-alkylation methodology that effectively uses many simpler, less expensive, more available, and ligand-free metal catalysts that were inactive under typical anaerobic borrowing hydrogen conditions, avoiding the use of preformed metal complexes and activating ligands and the exclusive requirement of inert atmosphere protection. This aerobic method is quite general in substrate scope and tolerates various amides, amines, and alcohols, revealing its potentially broad utilities and interests in academy and industry. In contrast to the commonly accepted borrowing hydrogen mechanism, based on a thorough mechanistic study and supported by the related literature background, a new mechanism analogous to the relay race game that has never been proposed in metal-catalyzed N-alkylation reactions is presented.
- Liu, Chuanzhi,Liao, Shiheng,Li, Qiang,Feng, Sunlin,Sun, Qing,Yu, Xiaochun,Xu, Qing
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supporting information; scheme or table
p. 5759 - 5773
(2011/09/16)
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- A method for the reductive scission of heterocyclic thioethers
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A mild, chemoselective, and generally high-yielding method for the reductive scission of heterocyclic thioethers is described. Suitable heterocycles have a thioether substituent at the 2-position relative to a ring heteroatom. The convenient and straightforward method is demonstrated with reactants which are not compatible with the standard Raney nickel conditions such as sulfides, sulfones, and thiophenes. In addition, benzyl esters, benzyl amides, and benzyl carbamates are tolerated by the reductive reaction conditions.
- Graham, Thomas H.,Liu, Wensheng,Shen, Dong-Ming
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supporting information; experimental part
p. 6232 - 6235
(2012/01/03)
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- Molybdenum-mediated carbonylation of aryl halides with nucleophiles using microwave irradiation
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Figure Presented. A new, efficient, and practical molybdenum-mediated carbonylation of aryl and heteroaryl halides with a variety of nucleophiles is described using microwave irradiation. A range of reactions illustrating the wide scope of this chemistry were carried out and proceeded in good to excellent yields.
- Roberts, Bryan,Liptrot, David,Alcaraz, Lilian,Luker, Tim,Stocks, Michael J.
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supporting information; experimental part
p. 4280 - 4283
(2010/11/04)
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- Formation of acrylanilides, acrylamides, and amides directly from carboxylic acids using thionyl chloride in dimethylacetamide in the absence of bases
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A general one-pot procedure is described that rapidly converts acrylic acid to anilides upon sequential treatment of the acid in dimethylacetamide (DMAC) with thionyl chloride and stoichiometric amounts of anilines in 88-98% yields, with DMAC offering rate and stability advantages over the use of DMF. The use of DMAC was extended to other organic acids in forming anilides. Benzylamine amides can also be formed using stoichiometric amounts of benzylamine and brought to completion by warming in the absence of additional base. In addition, it was shown that tert-butylamides can be easily formed with the addition of excess tert-butylamine at 20 °C.
- Cvetovich, Raymond J.,DiMichele, Lisa
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p. 944 - 946
(2012/12/23)
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- Aryl triflates and [11C]/(13C)carbon monoxide in the synthesis of 11C-/13C-amides
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Palladium(0)-mediated carbonylation reactions using aryl triflates, amines, and a low concentration of [11C]carbon monoxide were used in the syntheses of 13 11C-labeled amides. Lithium bromide was used as an additive to facilitate the reaction. The 11C-labeled products were obtained with decay-corrected radiochemical yields in the range of 2-63%. The radiochemical purity of the final products exceeded 98%. As an example, a reaction starting with 1.79 GBq [11C]carbon monoxide gave 0.38 GBq of LC-purified N-isopropyl-4-nitro-[11C]benzamide within 27 min from the start of the carbonylation reaction (54% decay-corrected radiochemical yield). The specific radioactivity of this compound was 191 GBq/μmol, 35 min after the end of a 10 μAh bombardment. N-Benzyliso-quinoline-1-(13C)carboxamide was prepared and analyzed by NMR for confirmation of the labeling position. The triflates 16, 20, 21, and 22 were synthesized from the corresponding alcohols and trifluoromethanesulfonic anhydride. The reference compounds 30a and 30b were prepared from the corresponding carboxylic acids and benzylamine. The other nine reference compounds 32a to 32i were synthesized from the respective acid chlorides and amines. The presented report shows that the sometimes more easily obtainable aryl triflates can be a useful alternative to the commonly used aryl halides in palladium(0)-mediated synthesis of 11C/13C-amides.
- Rahman, Obaidur,Kihlberg, Tor,Langstroem, Bengt
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p. 3558 - 3562
(2007/10/03)
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- Synthesis of 11C-labelled amides by palladium-mediated carboxamination using [11C]carbon monoxide, in situ activated amines and 1,2,2,6,6-pentamethylpiperidine
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Twenty-seven 11C-labelled amides were synthesised using [11C]carbon monoxide in low concentrations, palladium(0), organohalides and amines in a small micro-autoclave (200 μL). The focus of the study was to improve the radiochemical yields in this palladium-mediated amide synthesis when employing less-reactive amines, such as methylamine, [(2R)-1-ethylpyrrolidin-2-yl]methylamine (40) and 2-(pyridin-2-yl)ethanamine (41). The radiochemical yields were improved when utilizing 1,2,2,6,6-pentamethylpiperidine (pempidine) in combination with the amine substrates. The 11C-labelled amides were obtained mostly in high radiochemical yields (in the range 16-94%) and the specific radioactivity varied between 650 and 1250GBq/μmol. 1-(1,3-Benzodioxol-5-yl[13C]carbonyl)piperidine (6a) was synthesised to verify the labelling position (δ = 169.8 ppm) using 13C NMR spectroscopy. The radiochemical purity of the target compounds was determined by analytical HPLC and exceeded 95%. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Karimi, Farhad,Langstroem, Bengt
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p. 2132 - 2137
(2007/10/03)
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- Improved synthesis of N-substituted 2,3-pyridine-dicarboximides with microwave irradiation
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The microwave-induced synthesis of N-substituted 2,3- pyridinedicarboximides (1) by means of two different approaches is presented. One involves direct N-alkylation of quinolinimide (2) (Method A) and the other, dehydrative condensation of quinolinic anhydride (4) and amines (Method B). Reactions resulted highly accelerated, with improved yields in relation to those obtained by conventional heating. The scope and limitations of each method and its variants are discussed.
- Blanco, Maria M.,Levin, Gustavo J.,Schapira, Celia B.,Perillo, Isabel A.
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p. 1881 - 1890
(2007/10/03)
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- Enhancing Reductive Cleavage of Aromatic Carboxamides
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(matrix presented) A set of aromatic and especially heteroaromatic N-benzyl carboxamides, derived from naphthalene, pyridine, pyrazine, and quinoline, and the corresponding tert-butyl acylcarbamates have been synthesized and studied by cyclic voltammetry with respect to facilitated reduction. The latter undergo regiospecific cleavage of their C(O)-N bonds under very mild reductive conditions with formation of Boc-protected (benzyl)-amine in most cases in nearly quantitative yields. Examples of preparative cleavage by controlled potential electrolysis, activated aluminum, and NaBH4 are given.
- Ragnarsson, Ulf,Grehn, Leif,Maia, Hernani L. S.,Monteiro, Luis S.
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p. 2021 - 2022
(2007/10/03)
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- Versatile Acylation of N-Nucleophiles Using a New Polymer-Supported 1-Hydroxybenzotriazole Derivative
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The synthesis of a new polymer-supported coupling reagent derived from 1-hydroxybenzotriazole is described. An aminomethylated polystyrene was functionalized by reaction with 3-nitro-4- chlorobenzenesulfonyl chloride (2) followed by treatement with hydrazine hydrate, to give the polymeric N-benzyl-1-hydroxybenzotriazole-6-sulfonamide (4).The polymeric reagent 4 was shown to be highly efficient for the synthesis of amides. The efficiency of 4 could be attributed to its high acidity, conferred by the sulfonyl moiety. The procedure for amide synthesis involves the formation of an activated ester on the derivatized polymer followed, in a second step, by treatment with an amine to generate the amide in solution. Simple filtration allows the separation of the product from the polymeric reagent which in this case plays the role of leaving group. An optimization study of this two-step procedure was performed. As amides are obtained in solution free of reaction byproducts, this method can be used in an automated procedure to recover them directly into a 96 well plate, ready to be used in high throughput screening assays. Thus 4 was shown to be particularly suitable for the high throughput parallel synthesis of amides libraries.
- Pop, Iuliana E.,Déprez, Beno?t P.,Tartar, André L.
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p. 2594 - 2603
(2007/10/03)
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- Molecular Determinants of the Platelet Aggregation Inhibitory Activity of Carbamoylpiperidines
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A series of α,α'-bis-p-xylenes were synthesized and tested for their inhibitory activity on ADP-induced aggregation of human platelets.A parabolic curve was obtained when log 1/C (activity) was plotted against log P (octanol/water partition coefficient).Using this as a model, a new analogue, α,α'-bis-p-xylene (3g), was synthesized with a predicted IC50 of 25 μM.When this compound was subsequently evaluated, the IC50 was 22.1 +/- 5.5 μM, demonstrating the applicability of this model.The amide oxygen of the carbamoyl substituent appeared necessary for activity.Thus, for example, when the amide carbonyl group of 3a (IC50 = 44.5 μM) was reduced to CH2, the resulting compound 4 had a dramatically reduced activity, IC50 = 1565 μM.Compound 3a was resolved into (+) and (-) enantiomers and a meso (0) diastereomer using fractional crystallization, diastereomeric tartrate formation, and chiral HPLC.Compared to (-)-3a, the (+) isomer was 15 times more potent when ADP was the agonist and 19 times more active when collagen was used as the agonist.Molecullar modeling of R,R and S,S-3a using the SYBYL program was used to examine their interactions with phosphatidylinositol (PI).There was a better fit between PI and the R,R-3a with the energy of interaction being 17.6 kcal/mol less than that of S,S-3a/PI complex.Although the absolute stereochemistry of individual enantiomers is not known, this study shows that R,R-3a interacts more favorably with PI than does S,S-3a and that (+)-3a is a more potent inhibitor of human platelet aggregation than (-)-3a.It is postulated that because of their lipophilicity, these compounds penetrate the platelet membrane and are then protonated at the pH of the cytosol.The protonated N then neutralizes the anionic charge on the membrane phosphoinositides, thereby rendering them less susceptible to hydrolysis by phospholipase C.Thus, the determinant parameters for optimum antiplatelet activity in 3-carbamoylpiperidines are (1) the amide carbonyl, (2) appropriate stereochemistry of the 3-substituent and (3) a log P value of about 4.5.
- Feng, Zixia,Gollamudi, Ramachander,Dillingham, Elwood O.,Bond, Stephen E.,Lyman, Beverly A.,et, al.
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p. 2952 - 2958
(2007/10/02)
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- The Use of a Nicotinoyl Group as a Protective Group for Hydroxyl and Amino Functions
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The effective use of a nicotinoyl group as an easily introducible and cleavable protective group for hydroxyl and amino groups is described.Deprotection by alkaline hydrolysis is performed after activation by quarternization of pyridine moiety with methyl iodide.
- Ushida, Satoshi
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