- Direct Amidation of Esters by Ball Milling**
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The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
- Barreteau, Fabien,Battilocchio, Claudio,Browne, Duncan L.,Godineau, Edouard,Leitch, Jamie A.,Nicholson, William I.,Payne, Riley,Priestley, Ian
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supporting information
p. 21868 - 21874
(2021/09/02)
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- Manganese Catalyzed Direct Amidation of Esters with Amines
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The transition metal catalyzed amide bond forming reaction of esters with amines has been developed as an advanced approach for overcoming the shortcomings of traditional methods. The broad scope of substrates in transition metal catalyzed amidations remains a challenge. Here, a manganese(I)-catalyzed method for the direct synthesis of amides from a various number of esters and amines is reported with unprecedented substrate scope using a low catalyst loading. A wide range of aromatic, aliphatic, and heterocyclic esters, even in fatty acid esters, reacted with a diverse range of primary aryl amines, primary alkyl amines, and secondary alkyl amines to form amides. It is noteworthy that this approach provides the first example of the transition metal catalyzed amide bond forming reaction from fatty acid esters and amines. The acid-base mechanism for the manganese(I)-catalyzed direct amidation of esters with amines was elucidated by DFT calculations.
- Fu, Zhengqiang,Wang, Xinghua,Tao, Sheng,Bu, Qingqing,Wei, Donghui,Liu, Ning
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p. 2339 - 2358
(2021/02/03)
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- Nickel-Catalyzed Amide Bond Formation from Methyl Esters
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Despite being one of the most important and frequently run chemical reactions, the synthesis of amide bonds is accomplished primarily by wasteful methods that proceed by stoichiometric activation of one of the starting materials. We report a nickel-catalyzed procedure that can enable diverse amides to be synthesized from abundant methyl ester starting materials, producing only volatile alcohol as a stoichiometric waste product. In contrast to acid- and base-mediated amidations, the reaction is proposed to proceed by a neutral cross coupling-type mechanism, opening up new opportunities for direct, efficient, chemoselective synthesis.
- Ben Halima, Taoufik,Masson-Makdissi, Jeanne,Newman, Stephen G.
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supporting information
p. 12925 - 12929
(2018/09/14)
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- Base-Controlled Completely Selective Linear or Branched Rhodium(I)-Catalyzed C?H ortho-Alkylation of Azines without Preactivation
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A [RhI]/bisphosphine/base catalytic system for the ortho-selective C?H alkylation of azines by acrylates and acrylamides is reported. This catalytic system features an unprecedented complete linear or branched selectivity that is solely dependent on the catalytic base that is used. Complete branched selectivity is even achieved for ethyl methacrylate, which enables the introduction of a quaternary carbon center. Excellent functional group compatibility is demonstrated for both linear and branched alkylations. The operational simplicity and broad scope of this transformation allow for rapid access to functionalized azines of direct pharmaceutical and agrochemical relevance.
- Tran, Ga?l,Hesp, Kevin D.,Mascitti, Vincent,Ellman, Jonathan A.
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supporting information
p. 5899 - 5903
(2017/05/12)
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- Copper-Catalyzed Aerobic Oxidative Amidation of Benzyl Alcohols
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A Cu-catalyzed synthesis of amides from alcohols and secondary amines using the oxygen in air as the terminal oxidant has been developed. The methodology is operationally simple requiring no high pressure equipment or handling of pure oxygen. The commercially available, nonprecious metal catalyst, Cu(phen)Cl2, in conjunction with di-tert-butyl hydrazine dicarboxylate and an inorganic base provides a variety of benzamides in moderate to excellent yields. The pKa of amine conjugate acid and electronics of alcohol were shown to impact the selection of base for optimal reactivity. A mechanism consistent with the observed reactivity trends, KIE, and Hammett study is proposed.
- Krabbe, Scott W.,Chan, Vincent S.,Franczyk, Thaddeus S.,Shekhar, Shashank,Napolitano, José G.,Presto, Carmina A.,Simanis, Justin A.
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p. 10688 - 10697
(2016/11/29)
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- Chloroform as a Carbon Monoxide Precursor: In or Ex Situ Generation of CO for Pd-Catalyzed Aminocarbonylations
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Conditions for the rapid hydrolysis of chloroform to carbon monoxide (CO) using heterogeneous CsOH·H2O are described. CO and 13CO can be generated cleanly and rapidly under mild conditions and can be captured either in or ex situ in palladium-catalyzed aminocarbonylation reactions. Utilizing only 1-3 equiv of CO allows for the aminocarbonylation of aryl, vinyl, and benzyl halides with a wide variety of primary and secondary amines giving amide products in good to excellent yields. (Chemical Equation Presented).
- Gockel, Samuel N.,Hull, Kami L.
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supporting information
p. 3236 - 3239
(2015/07/15)
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- Novel methanone derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating blindness related diseases containing the same as an active ingredient
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The present invention relates to novel methanone derivatives, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for preventing or treating retinal diseases. Since the novel methanone derivatives according to the present invention, optical isomers thereof or pharmaceutically acceptable salts thereof have an excellent effect of inhibiting receptor-interacting serine/threonine-protein kinase 1 (RIPK1), the composition comprising the same as an active ingredient can be advantageously used as a pharmaceutical composition for preventing or treating retinal diseases such as retinitis pigmentosa (RP), Leberandprime;s congenital amaurosis (LCA), Stargardts disease, Usher syndrome, choroideremia, rod-cone or cone-rod dystrophy, ciliopathies, a mitochondrial disorder, progressive retinal atrophy, a degenerative retinal disease, age-related macular degeneration (AMD), wet AMD, dry AMD, geographic atrophy, hereditary or acquired maculopathy, a retinal photoreceptor disease, a retinal pigment epithelial disease, diabetic retinopathy, cystic macular edema, uveitis, retinal detachment, traumatic retinal damage, iatrogenic retinal damage, a macular hole, macular capillary ectasia, a ganglion cell disease, an optic nerve disease, glaucoma, optic neuropathy, ischemic retinal disease , retinopathy of prematurity (ROP), retinal vascular occlusion, hereditary macroaneurysm, a retinal vascular disease , an ophthalmovascular disease, degeneration of retinal neuronal cells caused by glaucoma, or ischemic optic neuropathy.COPYRIGHT KIPO 2015
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Paragraph 0130-0132
(2016/10/10)
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- Photoinduced Aminocarbonylation of Aryl Iodides
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Transition metal-catalyzed aminocarbonylation of aryl halides with CO and amines, pioneered by Heck and co-workers in the 1970s, is among the most commonly employed reactions to make aromatic amides. A catalyst-free aminocarbonylation of aryl iodides with CO and amines, which simply uses photoirradiation conditions by Xe-lamp, has now been developed. This methodology shows broad functional-group tolerance, including that of heteroaromatic amides. A hybrid radical/ionic chain mechanism, involving electron transfer from zwitterionic radical intermediates generated by nucleophilic attack of amines to aroyl radicals, is proposed.
- Kawamoto, Takuji,Sato, Aoi,Ryu, Ilhyong
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supporting information
p. 14764 - 14767
(2015/10/19)
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- Co2(CO)8 as a convenient in situ CO source for the direct synthesis of benzamides from aryl halides (Br/I) via aminocarbonylation
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A fast, mild, and functional group tolerant method for the direct synthesis of benzamides from aryl halides (Br, I) via aminocarbonylation, using solid Co2(CO)8 as a convenient CO source, has been demonstrated. The developed method is applicable to a wide variety of 1 and cyclic and acyclic 2 amines. Nitro substituted (o, m and p) aryl halides have easily been converted to the corresponding benzamides, without the reduction of the nitro group, in high yields using this in situ carbonylation methodology under microwave irradiation.
- Baburajan, Poongavanam,Elango, Kuppanagounder P.
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supporting information
p. 1006 - 1010
(2014/02/14)
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- Co2(CO)8 as a convenient in situ CO source for the direct synthesis of benzamides from aryl halides (Br/I) via aminocarbonylation
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A fast, mild, and functional group tolerant method for the direct synthesis of benzamides from aryl halides (Br, I) via aminocarbonylation, using solid Co2(CO)8 as a convenient CO source, has been demonstrated. The developed method is applicable to a wide variety of 1° and cyclic and acyclic 2°amines. Nitro substituted (o, m and p) aryl halides have easily been converted to the corresponding benzamides, without the reduction of the nitro group, in high yields using this in situ carbonylation methodology under microwave irradiation.
- Baburajan, Poongavanam,Elango, Kuppanagounder P.
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supporting information
p. 1006 - 1010
(2015/02/19)
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- Mesoporous poly-melamine-formaldehyde stabilized palladium nanoparticle (Pd@mPMF) catalyzed mono and double carbonylation of aryl halides with amines
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A new mesoporous poly-melamine-formaldehyde material supported Pd nano catalyst (mPMF-Pd0) has been synthesized and characterized by thermogravimetric analysis (TGA), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), high-resolution transmission electron microscopy (HRTEM), UV-vis diffuse reflection spectroscopy (DRS), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and a N2 adsorption study. The mPMF-Pd0 material showed very good catalytic activity in the field of mono and double amino carbonylation of aryl bromides/iodides. Moreover, the catalyst is easily recoverable and can be reused six times without appreciable loss of catalytic activity in the above reactions. So, the highly dispersed and strongly bound palladium(0) sites in the mPMF-Pd0 could be responsible for the observed high activities. Due to strong binding with the functional groups of the polymer, no evidence of leached Pd from the catalyst during the course of reaction occurred, suggesting true heterogeneity in the catalytic process. This journal is
- Molla, Rostam Ali,Iqubal, Md. Asif,Ghosh, Kajari,Roy, Anupam Singha,Kamaluddin,Islam, Sk. Manirul
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p. 48177 - 48190
(2014/12/10)
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- Multistep synthesis of amides from alcohols and amines in continuous flow microreactor systems using oxygen and urea hydrogen peroxide as oxidants
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By integrating a heterogeneous oxidation step, gas-liquid separation, and an oxidative amidation reaction to form a continuous system, a multistep synthetic protocol has been demonstrated to produce amides under mild conditions using alcohols and amines as the starting materials. The use of inexpensive oxygen and urea hydrogen peroxide as the only oxidants affords an economical and adaptable synthetic route for amides.
- Liu, Xiaoying,Jensen, Klavs F.
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p. 1538 - 1541
(2013/09/24)
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- Highly efficient aminocarbonylation of iodoarenes at atmospheric pressure catalyzed by a robust acenaphthoimidazolyidene allylic palladium complex
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A robust allylic palladium-NHC complex was developed and exhibited extremely high catalytic activity toward aminocarbonylation of various (hetero)aryl iodides under atmospheric carbon monoxide pressure, in which a broad range of secondary and primary amines were well tolerated. In addition, the concise synthesis of an anticancer drug tamibarotene was accomplished even in a gram scale, further highlighting the practical applicability of the protocol.
- Fang, Weiwei,Deng, Qinyue,Xu, Mizhi,Tu, Tao
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supporting information
p. 3678 - 3681
(2013/08/23)
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- Palladium nanoparticles supported on ZIF-8 as an efficient heterogeneous catalyst for aminocarbonylation
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Pd nanoparticles supported on ZIF-8 (PdNPs/ZIF-8) are described as an efficient heterogeneous catalyst for the aminocarbonylation of bromoarenes in the presence of phosphines and iodoarenes under phosphine-free conditions. The catalyst can be readily prepared and is air-stable. The palladium loading can be as low as 1 wt %, and the catalyst was recycled four times with negligible change in catalytic performance. A variety of pharmaceutically important amides was readily synthesized. A TON of 2540 was easily achieved in a batch reaction by scaling up to a gram scale. The catalyst reported can also be applied to the synthesis of cyclic and primary amides as well as an alkoxycarbonylation reaction to form an ester.
- Dang, Tuan T.,Zhu, Yinghuai,Ngiam, Joyce S. Y.,Ghosh, Subhash C.,Chen, Anqi,Seayad, Abdul M.
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p. 1406 - 1410
(2013/07/26)
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- Dehydrogenative amide synthesis from alcohol and amine catalyzed by hydrotalcite-supported gold nanoparticles
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Hydrotalcite-supported nano-gold (Au/HT) was found to be a highly efficient heterogeneous catalyst for the dehydrogenative synthesis of amide from alcohol and amine. Amines and alcohols with different structures could be converted into the amides under mild reaction conditions with up to 98% isolated yields. Mechanism exploration suggested that ester might be the reaction intermediate.
- Zhu, Jiangling,Zhang, Yan,Shi, Feng,Deng, Youquan
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supporting information; experimental part
p. 3178 - 3180
(2012/07/31)
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- Mild conversion of esters lacking acidic α-hydrogens into amides via samarium(III) tris[hexamethyldisilazide] and amines
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Samarium(III) tris[hexamethyldisilazide] (Sm[(Me3Si) 2N]3 = Sm[HMDS]3) promotes the direct conversion of an ester admixed with an amine into the corresponding carboxamide under exceptionally mild conditions (≤0°) and in high yields. Only a slight excess of amine and the lanthanide complex are required to effect complete conversion of the ester into the amide. Esters with acidic α-hydrogens undergo a competing Claisen-like condensation along with the desired conversion into amides. Georg Thieme Verlag Stuttgart New York.
- Campbell, James B.,Sparks, Richard B.,Dedinas, Robert F.
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experimental part
p. 357 - 360
(2011/03/22)
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- Silica gel-mediated amide bond formation: An environmentally benign method for liquid-phase synthesis and cytotoxic activities of amides
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An efficient, functional group tolerable, and environmentally benign process for the synthesis of amides was developed. No activation reagents or scavengers are required in this process. Purification of desired compounds is easy, rapid, and cost-effective. This protocol provides an alternative for the combinatorial liquid-phase synthesis of amide libraries for drug discovery. By this method, a number of amides were prepared and evaluated in vitro against a panel of human tumor cell lines. Cinnamic amide IV-4 was found to be the most potent compound synthesized against four human tumor cell lines.
- Yang, Xiao-Dong,Zeng, Xiang-Hui,Zhao, Yuan-Hong,Wang, Xue-Quan,Pan, Zhi-Qiang,Li, Liang,Zhang, Hong-Bin
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scheme or table
p. 307 - 310
(2010/11/18)
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- Homogeneous catalytic aminocarbonylation of nitrogen-containing iodo-heteroaromatics. Synthesis of N-substituted nicotinamide related compounds
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Various primary and secondary amines, including amino acid methyl esters, were used as nucleophiles in palladium-catalysed aminocarbonylation of 2-iodopyridine, 3-iodopyridine and iodopyrazine. N-Substituted nicotinamides and 3-pyridyl-glyoxylamides (2-oxo-carboxamide type derivatives) of potential biological importance can be obtained from 3-iodopyridine as a result of simple and double carbon monoxide insertions, respectively. The latter examples can be obtained in synthetically acceptable yields by using elevated carbon monoxide pressure. On the contrary, N-alkyl/aryl-carboxamides were obtained exclusively in the whole pressure range by using 2-iodopyridine and iodopyrazine.
- Takács, Attila,Jakab, Balázs,Petz, Andrea,Kollár, László
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p. 10372 - 10378
(2008/02/13)
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- Abnormal Nucleophilic Substitution in 3-Trichloromethylpyridine, its N-Oxide and 3,5-Bis(trichloromethyl)pyridine
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The scope of abnormal reactions of nucleophiles with β-trichloromethylazines is further explored: reactions of 3-trichloromethylpyridine with nucleophiles other than methoxide, and reactions of 3-trichloromethylpyridine N-oxide and 3,5-bis(trichloromethyl)pyridine with methoxide.Attack at a ring carbon, followed by hydrogen migration to the side-chain, occured in most cases, though attack at the trichloromethyl carbon was also sometimes observed.
- Cartwright, David,Ferguson, John R.,Giannopoulos, Thomas,Varvounis, George,Wakefield, Basil J.
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p. 12791 - 12796
(2007/10/02)
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