- AMINE-BORANES AS BIFUNCTIONAL REAGENTS FOR DIRECT AMIDATION OF CARBOXYLIC ACIDS
-
The present invention generally relates to a process for selective and direct activation and subsequent amidation of aliphatic and aromatic carboxylic acids to afford an amide R3CONR1R2. That the process is capable of delivering gaseous or low-boiling point amines provides a major advantage over existing methodologies, which involves an intermediate of triacyloxyborane-amine complex [(R3CO2)3—B—NHR1R2]. This procedure readily produces primary, secondary, and tertiary amides, and is compatible with the chirality of the acid and amine involved. The preparation of known pharmaceutical molecules and intermediates has also been demonstrated.
- -
-
Paragraph 0008-0009; 0063-0064
(2022/03/04)
-
- 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)
-
- Efficient and accessible silane-mediated direct amide coupling of carboxylic acids and amines
-
A straightforward method for the direct synthesis of amides from amines and carboxylic acids without exclusion of air or moisture using diphenylsilane with N-methylpyrrolidine has been developed. Various amides are made efficiently, and broad functional group compatibility is shown through a Glorius robustness study. A gram-scale synthesis demonstrates the scalability of this method. This journal is
- D'Amaral, Melissa C.,Jamkhou, Nick,Adler, Marc J.
-
supporting information
p. 288 - 295
(2021/01/28)
-
- Near-Ambient-Temperature Dehydrogenative Synthesis of the Amide Bond: Mechanistic Insight and Applications
-
The current existing methods for the amide bond synthesis via acceptorless dehydrogenative coupling of amines and alcohols all require high reaction temperatures for effective catalysis, typically involving reflux in toluene, limiting their potential practical applications. Herein, we report a system for this reaction that proceeds under mild conditions (reflux in diethyl ether, boiling point 34.6 °C) using ruthenium PNNH complexes. The low-temperature activity stems from the ability of Ru-PNNH complexes to activate alcohol and hemiaminals at near-ambient temperatures through the assistance of the terminal N-H proton. Mechanistic studies reveal the presence of an unexpected aldehyde-bound ruthenium species during the reaction, which is also the catalytic resting state. We further utilize the low-temperature activity to synthesize several simple amide bond-containing commercially available pharmaceutical drugs from the corresponding amines and alcohols via the dehydrogenative coupling method.
- Kar, Sayan,Xie, Yinjun,Zhou, Quan Quan,Diskin-Posner, Yael,Ben-David, Yehoshoa,Milstein, David
-
p. 7383 - 7393
(2021/06/30)
-
- Dehydrogenative amide synthesis from alcohols and amines utilizing N-heterocyclic carbene-based ruthenium complexes as efficient catalysts: The influence of catalyst loadings, ancillary and added ligands
-
The metal-catalyzed dehydrogenative coupling of alcohols and amines to access amides has been recognized as an atom-economic and environmental-friendly process. Apart from the formation of the amide products, three other kinds of compounds (esters, imines and amines) may also be produced. Therefore, it is of vital importance to investigate product distribution in this transformation. Herein, N-heterocyclic carbene-based Ru (NHC/Ru) complexes [Ru-1]-[Ru-5] with different ancillary ligands were prepared and characterized. Based on these complexes, we selected condition A (without an added NHC precursor) and condition B (with an added NHC precursor) to comprehensively explore the selectivity and yield of the desired amides. After careful evaluation of various parameters, the Ru loadings, added NHC precursors and the electronic/steric properties of ancillary NHC ligands were found to have considerable influence on this catalytic process.
- Wang, Wan-Qiang,Wang, Zhi-Qin,Sang, Wei,Zhang, Rui,Cheng, Hua,Chen, Cheng,Peng, Da-Yong
-
-
- Direct amidation of non-activated carboxylic acid and amine derivatives catalyzed by TiCp2Cl2
-
This paper described a mild and efficient direct amidation of non-activated carboxylic acid and amine derivatives catalyzed by TiCp2Cl2. Arylacetic acid derivatives reacted with different amines to afford the corresponding amides in good to excellent yield except of aniline. Aryl formic acids failed to react with aniline but smoothly reacted with aliphatic amines and benzylamine in moderate to good yield, fatty acids reacting with benzyl and aliphatic amines give amides in good to excellent yield. Chiral amino acids derivatives were transformed into amides without racemization in moderate yield. The possible mechanism of direct amidation catalyzed by TiCp2Cl2 was discussed. This catalytic method is very suitable for the amidation of low sterically hindered arylacetic acid, fatty acids with different low sterically hindered amines except aniline, as well as the amidation of aryl formic acid with benzyl and aliphatic amines.
- Wang, Hui,Dong, Wei,Hou, Zhipeng,Cheng, Lidan,Li, Xiufen,Huang, Longjiang
-
-
- Environmentally benign decarboxylative: N-, O-, and S-Acetylations and acylations
-
An operationally simple and general method for acetylation and acylation of a wide variety of substrates (amines, alcohols, phenols, thiols, and hydrazones) has been reported. Meldrum's acid and its derivatives have been used as an air-stable, non-volatile, cost-effective, and easy to handle acetylating/acylating agent. Easily separable byproducts (CO2 and acetone) allowed the isolation of analytically pure acetylated products without the requirement of work-up and any chromatography. This journal is
- Ghosh, Santanu,Purkait, Anisha,Jana, Chandan K.
-
supporting information
p. 8721 - 8727
(2020/12/30)
-
- Amine-boranes as Dual-Purpose Reagents for Direct Amidation of Carboxylic Acids
-
Amine-boranes serve as dual-purpose reagents for direct amidation, activating aliphatic and aromatic carboxylic acids and, subsequently, delivering amines to provide the corresponding amides in up to 99% yields. Delivery of gaseous or low-boiling amines as their borane complexes provides a major advantage over existing methodologies. Utilizing amine-boranes containing borane incompatible functionalities allows for the preparation of functionalized amides. An intermolecular mechanism proceeding through a triacyloxyborane-amine complex is proposed.
- Choudhary, Shivani,Hamann, Henry J.,Ramachandran, P. Veeraraghavan
-
-
- N-Hydroxybenzimidazole as a structurally modifiable platform forN-oxyl radicals for direct C-H functionalization reactions
-
Methods for direct functionalization of C-H bonds mediated byN-oxyl radicals constitute a powerful tool in modern organic synthesis. While severalN-oxyl radicals have been developed to date, the lack of structural diversity for these species has hampered further progress in this field. Here we designed a novel class ofN-oxyl radicals based onN-hydroxybenzimidazole, and applied them to the direct C-H functionalization reactions. The flexibly modifiable features of these structures enabled facile tuning of their catalytic performance. Moreover, with these organoradicals, we have developed a metal-free approach for the synthesis of acyl fluoridesviadirect C-H fluorination of aldehydes under mild conditions.
- Hatanaka, Miho,Jiang, Julong,Maruoka, Keiji,Matsumoto, Akira,Sakamoto, Ryu,Sakurai, Shunya,Tsuzuki, Saori,Yoshii, Tomomi
-
p. 5772 - 5778
(2020/06/22)
-
- Well-defined N-heterocyclic carbene/ruthenium complexes for the alcohol amidation with amines: The dual role of cesium carbonate and improved activities applying an added ligand
-
Dehydrogenative amide bond formation from alcohols and amines has been regarded as an atom-economic and sustainable process. Among various catalytic systems, N-heterocyclic carbene (NHC)-based Ru catalytic systems have attracted growing interest due to the outstanding properties of NHCs as ligands. Herein, an NHC/Ru complex (1) was prepared and its structure was further confirmed with X-ray crystallography. In the presence of Cs2CO3, two NHC/Ru-based catalytic systems were disclosed to be active for this amide synthesis. System A, which did not contain any added ligand, required a catalyst loading of 1.00 mol%. Interestingly, improved catalytic performance was realized by the addition of an NHC precursor (L). Optimization of the amounts of L and other conditions gave rise to system B, a much more potent system with the Ru loading as low as 0.25 mol%. Moreover, an NHC-Ru-carbonate complex 6 was identified from the refluxing toluene of 1 and Cs2CO3, and further investigations revealed that 6 was an important intermediate for this catalytic reaction. Based on the above results, we claimed that the role of Cs2CO3 was to facilitate the formation of key intermediate 6. On the other hand, it provided the optimized basicity for the selective amide formation.
- Wang, Wan-Qiang,Yuan, Ye,Miao, Yang,Yu, Bao-Yi,Wang, Hua-Jing,Wang, Zhi-Qin,Sang, Wei,Chen, Cheng,Verpoort, Francis
-
-
- Chemoselective Synthesis of Aryl Ketones from Amides and Grignard Reagents via C(O)-N Bond Cleavage under Catalyst-Free Conditions
-
Conversion of a wide range of N-Boc amides to aryl ketones was achieved with Grignard reagents via chemoselective C(O)-N bond cleavage. The reactions proceeded under catalyst-free conditions with different aryl, alkyl, and alkynyl Grignard reagents. α-Ketoamide was successfully converted to aryl diketones, while α,β-unsaturated amide underwent 1,4-addition followed by C(O)-N bond cleavage to provide diaryl propiophenones. N-Boc amides displayed higher reactivity than Weinreb amides with Grignard reagents. A broad substrate scope, excellent yields, and quick conversion are important features of this methodology.
- Sureshbabu, Popuri,Azeez, Sadaf,Muniyappan, Nalluchamy,Sabiah, Shahulhameed,Kandasamy, Jeyakumar
-
p. 11823 - 11838
(2019/10/02)
-
- Diboron-Catalyzed Dehydrative Amidation of Aromatic Carboxylic Acids with Amines
-
Tetrakis(dimethylamido)diboron and tetrahydroxydiboron are herein reported as new catalysts for the synthesis of aryl amides by catalytic condensation of aromatic carboxylic acids with amines. The developed protocol is both simple and highly efficient over a broad range of substrates. This method thus represents an attractive approach for the use of diboron catalysts in the synthesis of amides without having to resort to stoichiometric or additional dehydrating agents.
- Sawant, Dinesh N.,Bagal, Dattatraya B.,Ogawa, Saeko,Selvam, Kaliyamoorthy,Saito, Susumu
-
supporting information
p. 4397 - 4400
(2018/08/09)
-
- Triphenyl borate catalyzed synthesis of amides from carboxylic acids and amines
-
Herein we report triphenyl borate as a new catalyst for synthesis of amides by catalytic condensation of carboxylic acids and amines. Our protocol is applicable for synthesis of wide range of amides furnishing excellent yields up to 92%. In addition developed method requires low catalyst loading, short time, less amount of solvent, works under air atmosphere and notably no need of azeotropic reflux using special Dean Stark apparatus or molecular sieves.
- Ghorpade, Seema A.,Sawant, Dinesh N.,Sekar, Nagaiyan
-
p. 6954 - 6958
(2018/10/24)
-
- Amide Synthesis via Aminolysis of Ester or Acid with an Intracellular Lipase
-
A unique lipase (SpL) from Sphingomonas sp. HXN-200 was discovered as the first intracellular enzyme for the aminolysis of ester or acid to produce amide. Reactions of a series of esters and amines with SpL gave the corresponding amides 3a-g in high yield with high activity. SpL also showed high enantioselectivity and high activity for enantioselective ester aminolysis, producing amides (R)-3h-j in high ee from the corresponding racemic ester or amine. Moreover, SpL was found to be highly active for the aminolysis of carboxylic acid, which was generally considered infeasible with the known aminolysis enzymes. The aminolysis of several carboxylic acids afforded the corresponding amides 3a, 3d, 3k, 3l, and 3n in good yield. The intracellular SpL was expressed in Escherichia coli cells to give an efficient whole-cell biocatalyst for amide synthesis. Remarkably, high catalytic activity was observed in the presence of water at 2-4% (v/v) for free enzyme and 16% (v/v) for whole cells, respectively. Accordingly, E. coli (SpL) wet cells were used as easily available and practical catalysts for the aminolysis of ester or acid, producing a group of useful and valuable amides in high concentration (up to 103 mM) and high yield. The newly discovered intracellular SpL with unique properties is a promising catalyst for green and efficient synthesis of amides.
- Zeng, Shichao,Liu, Ji,Anankanbil, Sampson,Chen, Ming,Guo, Zheng,Adams, Joseph P.,Snajdrova, Radka,Li, Zhi
-
p. 8856 - 8865
(2018/09/06)
-
- 1,1-Diacyloxy-1-phenylmethanes as versatile N-acylating agents for amines
-
1,1-Diacyloxy-1-phenylmethanes and 1-pivaloxy-1-acyloxy-1-phenylmethanes have been used as bench stable N-acylating reagents for primary and secondary amines and anilines under solvent-free conditions to afford their corresponding amides in good yield.
- Chapman, Robert. S.L.,Tibbetts, Joshua. D.,Bull, Steven. D.
-
p. 5330 - 5339
(2018/06/15)
-
- Efficient N-Heterocyclic Carbene/Ruthenium Catalytic Systems for the Alcohol Amidation with Amines: Involvement of Poly-Carbene Complexes?
-
The atom-economic direct amidation of alcohols with amines has been recently highlighted as an attractive and promising transformation. Among the versatile reported catalytic systems, in situ generated N-heterocyclic carbene (NHC)/ruthenium (Ru) catalytic systems have demonstrated their advantages such as easy operation and use of commercial Ru compounds. However, the existing catalyst loadings are relatively high, and additional insights for the in situ catalyst generation are still not well-documented. In this work, a variety of benzimidazole-based NHC precursors were initially synthesized. Through the screening of various NHC precursors and other reaction conditions, active in situ catalytic systems were discovered for the efficient amide synthesis. Notably, the catalyst loading is as low as 0.5 mol %. Furthermore, additional experiments were performed to validate the rationale for the superiority of the current catalytic systems over our previous system. It was observed that the ligand structure is one of the reasons for the higher activity. In addition, the higher ratio of the NHC precursor/[Ru] is another important factor for the improvement. Further HR-MS analysis identified the formation of two mono-NHC-Ru species as major species and two Ru species bearing multiple NHC ligands as minor species. Hopefully, the efficient and readily-accessible catalytic systems reported herein could demonstrate great potential for further practical applications.
- Cheng, Hua,Xiong, Mao-Qian,Zhang, Ni,Wang, Hua-Jing,Miao, Yang,Su, Wei,Yuan, Ye,Chen, Cheng,Verpoort, Francis
-
p. 4338 - 4345
(2018/09/06)
-
- In situ Generated Ruthenium Catalyst Systems Bearing Diverse N-Heterocyclic Carbene Precursors for Atom-Economic Amide Synthesis from Alcohols and Amines
-
The transition-metal-catalyzed direct synthesis of amides from alcohols and amines is herein demonstrated as a highly environmentally benign and atom-economic process. Among various catalyst systems, in situ generated N-heterocyclic carbene (NHC)-based ruthenium (Ru) halide catalyst systems have been proven to be active for this transformation. However, these existing catalyst systems usually require an additional ligand to achieve satisfactory results. In this work, through extensive screening of a diverse variety of NHC precursors, we discovered an active in situ catalyst system for efficient amide synthesis without any additional ligand. Notably, this catalyst system was found to be insensitive to the electronic effects of the substrates, and various electron-deficient substrates, which were not highly reactive with our previous catalyst systems, could be employed to afford the corresponding amides efficiently. Furthermore, mechanistic investigations were performed to provide a rationale for the high activity of the optimized catalyst system. NMR-scale reactions indicated that the rapid formation of a Ru hydride intermediate (signal at δ=?7.8 ppm in the 1H NMR spectrum) after the addition of the alcohol substrate should be pivotal in establishing the high catalyst activity. Besides, HRMS analysis provided possible structures of the in situ generated catalyst system.
- Cheng, Hua,Xiong, Mao-Qian,Cheng, Chuan-Xiang,Wang, Hua-Jing,Lu, Qiang,Liu, Hong-Fu,Yao, Fu-Bin,Chen, Cheng,Verpoort, Francis
-
p. 440 - 448
(2018/02/06)
-
- Ruthenium-based catalytic systems incorporating a labile cyclooctadiene ligand with N-heterocyclic carbene precursors for the atom-economic alcohol amidation using amines
-
Transition-metal-catalyzed amide-bond formation from alcohols and amines is an atom-economic and eco-friendly route. Herein, we identified a highly active in situ N-heterocyclic carbene (NHC)/ruthenium (Ru) catalytic system for this amide synthesis. Various substrates, including sterically hindered ones, could be directly transformed into the corresponding amides with the catalyst loading as low as 0.25 mol.%. In this system, we replaced the p-cymene ligand of the Ru source with a relatively labile cyclooctadiene (cod) ligand so as to more efficiently obtain the corresponding poly-carbene Ru species. Expectedly, the weaker cod ligand could be more easily substituted with multiple mono-NHC ligands. Further high-resolution mass spectrometry (HRMS) analyses revealed that two tetra-carbene complexes were probably generated from the in situ catalytic system.
- Chen, Cheng,Miao, Yang,De Winter, Kimmy,Wang, Hua-Jing,Demeyere, Patrick,Yuan, Ye,Verpoort, Francis
-
-
- SNS-Ligands for Ru-Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions
-
A detailed study of literature-known and novel S-containing pincer-type ligands for ruthenium-catalyzed homogeneous hydrogenation and dehydrogenation reactions was carried out. The scope and limitations of these catalysts were carefully investigated, and it was shown that simple bench-stable SNS-Ru complexes can be used to facilitate the hydrogenation of a variety of different substrates at a maximum H2 pressure of 20 bar under operationally simple, easy to scale up, glovebox-free conditions by using starting materials and reagents that do not require any special purification prior to use. It was also shown that such complexes can be used to catalyze the dehydrogenative coupling of alcohols and amines to get amides as well as for the dehydrogenative dimerization of alcohols to esters.
- Sch?rgenhumer, Johannes,Zimmermann, Axel,Waser, Mario
-
supporting information
p. 862 - 870
(2018/06/18)
-
- Direct Synthesis of Amides by Dehydrogenative Coupling of Amines with either Alcohols or Esters: Manganese Pincer Complex as Catalyst
-
The first example of base-metal-catalysed synthesis of amides from the coupling of primary amines with either alcohols or esters is reported. The reactions are catalysed by a new manganese pincer complex and generate hydrogen gas as the sole byproduct, thus making the overall process atom-economical and sustainable.
- Kumar, Amit,Espinosa-Jalapa, Noel Angel,Leitus, Gregory,Diskin-Posner, Yael,Avram, Liat,Milstein, David
-
supporting information
p. 14992 - 14996
(2017/10/25)
-
- MANGANESE BASED COMPLEXES AND USES THEREOF FOR HOMOGENEOUS CATALYSIS
-
The present invention relates to novel manganese complexes and their use, inter alia, for homogeneous catalysis in (1) the preparation of imine by dehydrogenative coupling of an alcohol and amine; (2) C-C coupling in Michael addition reaction using nitriles as Michael donors; (3) dehydrogenative coupling of alcohols to give esters and hydrogen gas (4) hydrogenation of esters to form alcohols (including hydrogenation of cyclic esters (lactones) or cyclic di-esters (di- lactones), or polyesters); (5) hydrogenation of amides (including cyclic dipeptides, lactams, diamide, polypeptides and polyamides) to alcohols and amines (or diamine); (6) hydrogenation of organic carbonates (including polycarbonates) to alcohols or hydrogenation of carbamates (including polycarbamates) or urea derivatives to alcohols and amines; (7) dehydrogenation of secondary alcohols to ketones; (8) amidation of esters (i.e., synthesis of amides from esters and amines); (9) acylation of alcohols using esters; (10) coupling of alcohols with water and a base to form carboxylic acids; and (11) preparation of amino acids or their salts by coupling of amino alcohols with water and a base. (12) preparation of amides (including formamides, cyclic dipeptides, diamide, lactams, polypeptides and polyamides) by dehydrogenative coupling of alcohols and amines; (13) preparation of imides from diols.
- -
-
-
- N-Acyl-N-(4-chlorophenyl)-4-nitrobenzenesulfonamides: Highly selective and efficient reagents for acylation of amines in water
-
A variety of N-acyl-N-(4-chlorophenyl)-4-nitrobenzenesulfonamides (1a-e) were synthesized in one pot from 4-chloroaniline under solvent-free conditions and have been developed as chemoselective N-acylation reagents. Selective protection of primary amines in the presence of secondary amines, acylation of aliphatic amines in the presence of aryl amines, and monofunctionalization of primary-secondary diamines as well as selective N-acylation of amino alcohols using these reagents are described. All of the acylation reactions were carried out in water as a green solvent. High stability and easy preparation of these acylating reagents are other advantages of this method.
- Ebrahimi, Sara,Saiadi, Safoura,Dakhilpour, Simin,Mirsattari, Seyed Nezamoddin,Massah, Ahmad Reza
-
-
- Design and synthesis of ruthenium(II) OCO pincer type NHC complexes and their catalytic role towards the synthesis of amides
-
The present contribution describes the synthesis and characterization of a family of robust ruthenium complexes, supported by a tridentate pincer ligand of the type bis-phenolate-N-heterocyclic carbene [ tBu(OCO) 2-] (NHC). Ruthenium(II) complexes (1-3) bearing bis-phenolate-N-heterocyclic carbene ligand were synthesized in good yields by the reaction of imidazolinium proligand (HL) with metal precursors [RuHCl(CO)(EPh3)2(B)] (E = P or As; B = PPh3, AsPh3 or Py) by transmetalation from the corresponding silver carbene complex. All the Ru(II)-NHC complexes have been characterized by elemental analyses, spectroscopic methods as well as ESI mass spectrometry. Based on the spectral results, an octahedral geometry was assigned for all the complexes. The tridentate nature of the tBu(OCO) 2- ligand as well as some level of steric protection provided by the t Bu groups may rationalize the excellent stability of the Ru-Ccarbene bond in the present systems. Moreover, for the explorations of catalytic potential of the synthesized compounds, all the three [Ru-NHC] complexes (1-3) were tested as catalysts for amidation of alcohols with amines. Notably, the complex 1 was found to be very efficient and versatile catalyst towards amidation of a wide range of alcohols with amines. [Figure not available: see fulltext.].
- Nirmala, Muthukumaran,Viswanathamurthi, Periasamy
-
-
- Ruthenium(II) carbonyl complexes containing bidentate 2-oxo-1,2-dihydroquinoline-3-carbaldehyde hydrazone ligands as efficient catalysts for catalytic amidation reaction
-
The coordination behavior of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde hydrazone ligands in ruthenium(II) and the catalytic activity of newly synthesized complexes have been studied. The complexes [RuCl(CO)(PPh3)2(L1)] (1), [RuCl(CO)(AsPh3)2(L1)] (2), [RuCl(CO)(PPh3)2(L2)] (3) and [RuCl(CO)(AsPh3)2(L2)] (4) were synthesized by reactions of [RuHCl(CO)(EPh3)3] (E = P or As) precursors with hydrazone ligands and characterized by analytical and spectroscopic methods. The molecular structure of complex 2 was identified by means of single-crystal X-ray diffraction analysis. The structural analysis revealed that all the complexes possess a distorted octahedral geometry with the ligand coordinating in a uni-negative bidentate NO fashion. Further, the catalytic efficiency of the complexes have been investigated in the case of direct amidation of alcohols with amines. The influence of base, reaction temperature and catalyst loading in the amidation reaction was also evaluated. Notably, complex 3 was found to be very efficient catalyst towards amidation of alcohols with amine. A variety of aromatic (hetero) amines and alcohols with various functional groups have also been successfully used for amidations.
- Selvamurugan, Sellappan,Ramachandran, Rangasamy,Prakash, Govindan,Viswanathamurthi, Periasamy,Malecki, Jan Grzegorz,Endo, Akira
-
supporting information
p. 119 - 127
(2015/12/30)
-
- A One-Pot, fast, and efficient amidation of carboxylic acids, α-amino acids and sulfonic acids using pph3/n-chlorobenzotriazole system
-
Triphenylphosphine (PPh3)/N-chlorobenzotriazole (NCBT), and amine (primary and secondary aliphatic amines and also substituted anilines) in CH2Cl2 efficiently converted carboxylic acids, α-amino acids, and sulfonic acids to the corresponding amides and sulfonamides at room temperature. Good to excellent yields, inexpensive, and fast reaction conditions are the important features of this procedure.
- Rouhi-Saadabad, Hamed,Akhlaghinia, Batool
-
p. 1703 - 1714
(2015/09/15)
-
- Synergistic cascade catalysis by metal nanoparticles and Lewis acids in hydrogen autotransfer
-
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
-
p. 1719 - 1727
(2015/08/12)
-
- C-N Coupling of Amides with Alcohols Catalyzed by N-Heterocyclic Carbene-Phosphine Iridium Complexes
-
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.
-
p. 11529 - 11537
(2015/12/04)
-
- Comprehensive Study of the Organic-Solvent-Free CDI-Mediated Acylation of Various Nucleophiles by Mechanochemistry
-
Acylation reactions are ubiquitous in the synthesis of natural products and biologically active compounds. Unfortunately, these reactions often require the use of large quantities of volatile and/or toxic solvents, either for the reaction, purification or isolation of the products. Herein we describe and discuss the possibility of completely eliminating the use of organic solvents for the synthesis, purification and isolation of products resulting from the acylation of amines and other nucleophiles. Thus, utilisation of N,N′-carbonyldiimidazole (CDI) allows efficient coupling between carboxylic acids and various nucleophiles under solvent-free mechanical agitation, and water-assisted grinding enables both the purification and isolation of pure products. Critical parameters such as the physical state and water solubility of the products, milling material, type of agitation (vibratory or planetary) as well as contamination from wear are analysed and discussed. In addition, original organic-solvent-free conditions are proposed to overcome the limitations of this approach. The calculations of various green metrics are included, highlighting the particularly low environmental impact of this strategy.
- Mtro, Thomas-Xavier,Bonnamour, Julien,Reidon, Thomas,Duprez, Anthony,Sarpoulet, Jordi,Martinez, Jean,Lamaty, Frdric
-
supporting information
p. 12787 - 12796
(2015/09/01)
-
- Ce(III) immobilised on aminated epichlorohydrin-activated agarose matrix - "green" and efficient catalyst for transamidation of carboxamides
-
The present study reports the preparation and characterisation of Ce(III) immobilised on an aminated epichlorohydrin-activated agarose matrix (CAEA) as a "green" catalyst. The catalyst was synthesised by the reaction of the epichlorohydrin-activated agarose matrix with ammonia solution, which was then treated with Ce(NO3)3 · 6H2O. The catalyst (CAEA) was characterised by FT-IR, far IR, CHN, XRD, TGA, and ICP techniques. CAEA is shown to be an effective and reusable heterogeneous catalyst for the transamidation of carboxamides with amines under solventfree conditions. The catalyst was successfully applied to the synthesis of a wide range of aromatic and aliphatic amides. High efficiency, mild reaction conditions, easy work-up, simple separation and also reusability are important advantages of this catalyst.
- Zarei, Zeinab,Akhlaghinia, Batool
-
p. 1421 - 1437
(2015/09/15)
-
- Polymer-anchored Ru(II) complex as an efficient catalyst for the synthesis of primary amides from nitriles and of secondary amides from alcohols and amines
-
A polymer-anchored ruthenium(II) catalyst was synthesized and characterized. Its catalytic activity was evaluated for the preparation of primary amides from aqueous hydration of nitriles in neutral condition. A range of nitriles were successfully converted to their corresponding amides in good to excellent yields. The catalyst was also effective in the preparation of secondary amides from the coupling of alcohols and amines. The catalyst can be facilely recovered and reused six times without a significant decrease in its activity.
- Islam, Sk Manirul,Ghosh, Kajari,Roy, Anupam Singha,Molla, Rostam Ali
-
p. 900 - 907
(2015/02/19)
-
- Ruthenium-catalysed oxidation of alcohols to amides using a hydrogen acceptor
-
A wider investigation into the synthesis of secondary amides from primary alcohols using a hydrogen acceptor using commercially available [Ru(p-cymene)Cl2]2 with bis(diphenylphosphino)butane (dppb) as the catalyst. The report looks at over 50 examples with varying functionality and steric bulk, whilst also covering the first reported results using microwave heating to effect the transformation.
- Watson, Andrew J.A.,Wakeham, Russell J.,Maxwell, Aoife C.,Williams, Jonathan M.J.
-
supporting information
p. 3683 - 3690
(2014/05/20)
-
- Amide synthesis from alcohols and amines catalyzed by a RuII-N-heterocyclic carbene (NHC)-carbonyl complex
-
Treatment of [Ru2(CO)4(CH3CN)6](BF4)2 with 3-methyl-1-(pyridin-2-yl)-imidazolium bromide in the presence of tetrabutylammonium bromide at room temperature in dichloromethane affords a RuII-N-heterocyclic carbene-carbonyl complex [Ru(py-NHC)(CO)2Br2] (1). Catalyst 1 displays diverse substrate scope for phosphine-free acceptorless coupling between alcohols and amines to amides at low catalyst loading. A RuII-dihydride/Ru0 sequence is proposed in the catalytic cycle.
- Saha, Biswajit,Sengupta, Gargi,Sarbajna, Abir,Dutta, Indranil,Bera, Jitendra K.
-
p. 124 - 130
(2014/12/11)
-
- Amide formation in one pot from carboxylic acids and amines via carboxyl and sulfinyl mixed anhydrides
-
An efficient method has been developed for the preparation of yet unknown acyclic mixed anhydrides of carboxylic and sulfinic acids. Sterically hindered 2-methylbut-3-ene-2-sulfinyl carboxylates add primary and secondary amines preferentially onto the carbonyl moieties realizing a new method for the one-pot preparation of carboxamides. It uses 1:1 mixtures of carboxylic acids and amines without a base, requires no excess of reagents, and liberates only volatile coproducts. Protected di- and tripeptides have been prepared in solution without epimerization by application of this method.
- Zambron, Bartosz K.,Dubbaka, Srinivas R.,Markovic, Dean,Moreno-Clavijo, Elena,Vogel, Pierre
-
supporting information
p. 2550 - 2553
(2013/07/05)
-
- Sulfated tungstate: A highly efficient catalyst for transamidation of carboxamides with amines
-
An environmentally benign protocol for the transamidation of carboxamides with amines using sulfated tungstate, as a heterogeneous catalyst, has been developed. The method has been successfully applied to the synthesis of a wide range of aromatic and aliphatic amides and phthalimides. Efficient transformation, mild reaction conditions, easy product isolation and the potential reusability of the catalyst are attractive features.
- Pathare, Sagar P.,Jain, Ashish Kumar H.,Akamanchi, Krishnacharya G.
-
p. 7697 - 7703
(2013/06/27)
-
- BORONIC ACID CATALYSTS AND METHODS OF USE THEREOF FOR ACTIVATION AND TRANSFORMATION OF CARBOXYLIC ACIDS
-
The present application provides methods and catalysts for activation of carboxylic acids for organic reactions. In particular, methods are disclosed for direct nucleophilic addition reactions, such as, amidation reactions with amines, cycloadditions, and conjugate additions, using boronic acid catalysts of formula I, II or III: Also included are novel boronic acid catalysts of formula IV, V and III:
- -
-
Page/Page column 56
(2012/09/10)
-
- Recyclable hypervalent iodine(III) reagent iodosodilactone as an efficient coupling reagent for direct esterification, amidation, and peptide coupling
-
A hypervalent iodine(III) reagent plays a novel role as an efficient coupling reagent to promote the direct condensation between carboxylic acids and alcohols or amines to provide esters, macrocyclic lactones, amides, as well as peptides without racemization. The regeneration of iodosodilactone (1) can also be readily achieved. The intermediate acyloxyphosphonium ion C from the activation of a carboxylic acid is thought to be involved in the present esterification reaction.
- Tian, Jun,Gao, Wen-Chao,Zhou, Dong-Mei,Zhang, Chi
-
supporting information; experimental part
p. 3020 - 3023
(2012/08/07)
-
- Dehydrogenative amide synthesis: Azide as a nitrogen source
-
A new atom-economical strategy to amide linkage from an azide and alcohol liberating hydrogen and nitrogen was developed with an in situ generated ruthenium catalytic system. The reaction has broad substrate generality including diols for the synthesis of cyclic imides.
- Fu, Zhenqian,Lee, Jeongbin,Kang, Byungjoon,Hong, Soon Hyeok
-
supporting information
p. 6028 - 6031
(2013/02/22)
-
- Mechanosynthesis of amides in the total absence of organic solvent from reaction to product recovery
-
The synthesis of various amides has been realised avoiding the use of any organic solvent from activation of carboxylic acids with CDI to isolation of the amides. Mechanochemistry was the key point of the process allowing rapid formation of the amide bond and efficient water-based purification of the final products.
- Metro, Thomas-Xavier,Bonnamour, Julien,Reidon, Thomas,Sarpoulet, Jordi,Martinez, Jean,Lamaty, Frederic
-
supporting information
p. 11781 - 11783
(2013/01/15)
-
- Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: Catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect
-
The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.
- Gernigon, Nicolas,Al-Zoubi, Raed M.,Hall, Dennis G.
-
p. 8386 - 8400,15
(2012/12/11)
-
- Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: Catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect
-
The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.
- Gernigon, Nicolas,Al-Zoubi, Raed M.,Hall, Dennis G.
-
p. 8386 - 8400
(2013/01/15)
-
- PNS-type ruthenium pincer complexes
-
The PNS pincer-type ligand 1 and the novel Ru(PNS) complexes 2-8 were synthesized and characterized. The (PNS)RuH(Cl)CO complex 2 was prepared by reaction of ligand 1 with RuH(Cl)CO(PPh3)3. 2 reacted with KHMDS (potassium bis(trimethylsilyl)amide) to form the symmetrical dimeric complex 4 via the intermediacy of the dearomatized complex (PNS*)Ru(H)CO 3, in which deprotonation of the benzylic-S arm took place. Reaction of 2 with excess NaH gave the dimeric 4, by a formal intermolecular attack of the benzylic arm on a second ruthenium center. Complex 4 underwent spontaneous transformation in solution to the dinuclear complex 5 via C-S bond cleavage, resulting in the loss of a S-bound tBu group. Treatment of 2 with KHMDS in the presence of PEt3 resulted in the trapping of intermediate 3 in the form of the dearomatized complex 8. Reaction of 2 with LiHBEt3 gave the trans-dihydride complex 6, which reacted with CO2 to give the formato complex 7, in which the formato ligand is located trans to the hydride. Complexes 2, 4, and 5 were also investigated as catalysts for the dehydrogenative coupling of alcohols with amines.
- Gargir, Moti,Ben-David, Yehoshua,Leitus, Gregory,Diskin-Posner, Yael,Shimon, Linda J. W.,Milstein, David
-
p. 6207 - 6214
(2012/10/29)
-
- Transamidation of amides with amines under solvent-free conditions using a CeO2 catalyst
-
Among various metal oxides, cerium oxide (CeO2) shows the highest catalytic activity for transamidation of picolinamide with n-octylamine. CeO2 acts as a reusable and effective heterogeneous catalyst for transamidation under solvent-free conditions. Transamidation of a variety of amides and amines produced the corresponding N-alkyl amides in high yields. This method provides the first example of a heterogeneous catalyst for transamidation using aliphatic amines as substrates. Characterization of acid-base properties and kinetic studies suggest that the cooperation of the weak Lewis acid sites and adjacent strong base sites play important roles in the transamidation reaction. The Royal Society of Chemistry 2012.
- Tamura, Masazumi,Tonomura, Takuya,Shimizu, Ken-Ichi,Satsuma, Atsushi
-
experimental part
p. 717 - 724
(2012/05/07)
-
- PROCESS OF FORMING AN AMIDE
-
A process is provided for the synthesis of an amide. A primary or secondary amine and a primary alcohol, with the amine and the alcohol being either moieties of different reactants or moieties of the same molecule, are contacted in the presence of a Ruthenium (II) catalyst. The Ruthenium (II) catalyst is free of a phosphine ligand. The process is also carried out in the absence of a phosphine. Providing the Ruthenium (II) catalyst includes providing an N-heterocyclic carbene.
- -
-
Page/Page column 20-23
(2011/04/19)
-
- METHOD FOR PREPARATION OF AMIDES FROM ALCOHOLS AND AMINES BY EXTRUSION OF HYDROGEN
-
The present invention relates to a method for preparation of carboxamides using alcohols and amines as starting materials in a dehydrogenative coupling reaction catalyzed by a ruthenium N-heterocyciic carbene (NHC) complex, which may be prepared in situ.
- -
-
Page/Page column 9
(2012/01/13)
-
- Amide synthesis from alcohols and amines catalyzed by ruthenium N-Heterocyclic carbene complexes
-
The direct synthesis of amides from alcohols and amines is described with the simultaneous liberation of dihydrogen. The reaction does not require any stoichiometric additives or hydrogen acceptors and is catalyzed by ruthenium N-heterocyclic carbene complexes. Three different catalyst systems are presented that all employ 1,3-diisopropylimidazol-2-ylidene (IiPr) as the carbene ligand. In addition, potassium iert-butoxide and a tricycloalkylphosphine are required for the amidation to proceed. In the first system, the active catalyst is generated in situ from [RuCl2(cod)] (cod = 1,5-cyclooctadiene), 1,3-diisopropylimidazolium chloride, tricyclopentylphosphonium tetrafluoroborate, and base. The second system uses the complex [RuCl 2(IiPr)(p-cymene)] together with tricyclohexylphosphine and base, whereas the third system employs the Hoveyda-Grubbs lst-generation metathesis catalyst together with 1,3-diisopropylimidazolium chloride and base. A range of different primary alcohols and amines have been coupled in the presence of the three catalyst systems to afford the corresponding amides in moderate to excellent yields. The best results are obtained with sterically unhindered alcohols and amines. The three catalyst systems do not show any significant differences in reactivity, which indicates that the same catalytically active species is operating. The reaction is believed to proceed by initial dehydrogenation of the primary alcohol to the aldehyde that stays coordinated to ruthenium and is not released into the reaction mixture. Addition of the amine forms the hemiaminal that undergoes dehydrogenation to the amide. A catalytic cycle is proposed with the {(I(Pr)RuII} species as the catalytically active components.
- Dam, Johan Hygum,Osztrovszky, Gyorgyi,Nordstrom, Lars Ulrik,Madsen, Robert
-
supporting information; experimental part
p. 6820 - 6827
(2010/08/07)
-
- Direct amide synthesis from either alcohols or aldehydes with amines: Activity of Ru(II) hydride and Ru(0) complexes
-
An in situ generated catalyst from readily available RuH 2(PPh3)4, an N-heterocyclic carbene (NHC) precursor, NaH, and acetonitrile was developed. The catalyst showed high activity for the amide synthesis directly from either alcohols or aldehydes with amines. When a mixture of an alcohol and an aldehyde was reacted with an amine, both of the corresponding amides were obtained with good yields. Homogeneous Ru(0) complexes such as (4-1,5-cyclooctadiene)(6-1,3,5- cyclooctatriene)ruthenium [Ru(cod)(cot)] and Ru3(CO)12 were also active in the amidation of an alcohol or an aldehyde with the help of an in situ generated NHC ligand.
- Muthaiah, Senthilkumar,Ghosh, Subhash Chandra,Jee, Joo-Eun,Chen, Cheng,Zhang, Jian,Hong, Soon Hyeok
-
experimental part
p. 3002 - 3006
(2010/07/05)
-
- Simple RuCl3-catalyzed amide synthesis from alcohols and amines
-
A catalyst for the direct synthesis of amides from amines and alcohols, generated in situ from the economically attractive and readily available RuCl3, an N-heterocyclic carbene (NHC), and pyridine, was developed. Of the screened NHC precursors, a less bulky one gave better yields for modestly sterically hindered substrates. In a search for the true catalytic intermediates, Grubbs catalysts were found to be active for the amidation of alcohols under basic conditions, suggesting that an Ru complex supported by an NHC ligand can catalyze the reaction.
- Ghosh, Subhash Chandra,Hong, Soon Hyeok
-
experimental part
p. 4266 - 4270
(2010/09/20)
-
- Direct synthesis of imines from alcohols and amines with liberation of H2
-
"Chemical equation presented" A clean sweep: Aryl and aliphatic mines can be synthesized directly and efficiently from alcohols and amines under mild, neutral conditions with the liberation of only molecular hydrogen and water (see scheme; R=isopropyl, tert-butyl). This general, environmentally benign reaction is catalyzed by a de-aromatized ruthenium PNP pincer complex (0.2 mol%), and can proceed in toluene under an inert atmosphere or under air.
- Gnanaprakasam, Boopathy,Zhang, Jing,Milstein, David
-
supporting information; experimental part
p. 1468 - 1471
(2010/05/02)
-
- Direct amide synthesis from alcohols and amines by phosphine-free ruthenium catalyst systems
-
Amides are synthesized directly from alcohols and amines in high yields using an in situ generated catalyst from easily available ruthenium complexes such as the (p-cymene)ruthenium dichloride dimer, [Ru(p-cymeme)Cl 2]2, or the (benz
- Ghosh, Subhash Chandra,Muthaiah, Senthilkumar,Zhang, Yao,Xu, Xiangya,Hong, Soon Hyeok
-
experimental part
p. 2643 - 2649
(2009/12/28)
-
- PROCESS FOR PREPARING AMIDES FROM ALCOHOLS AND AMINES
-
The present invention provides a process for preparing amides, by reacting a primary amine and a primary alcohol in the presence of a Ruthenium catalyst, to generate the amide and molecular hydrogen. According to the process of the invention, primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only byproduct) in high yields and high turnover numbers. This reaction is catalyzed by a Ruthenium complex, which is preferably based on a dearomatized PNN-type ligand of formula A1 or precursors thereof of formulae A2 or A3. Use of diamines in the reaction leads to bis-amides, whereas with a mixed primary/secondary amine substrate, chemoselective acylation of the primary amine group occurs.
- -
-
Page/Page column 7; 11
(2009/05/28)
-