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Synthesis of amides

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Aminocarbonylation


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Recent Literature


5-methoxy-2-iodophenylboronic acid (MIBA) is kinetically very active in a catalytic, direct amidation employing free carboxylic acids and amines providing high yields of amide products in short reaction times under mild conditions at ambient temperature in the presence of molecular sieves. A possible catalytic cycle is based on the presumed formation of an acylborate intermediate.
N. Gernigon, R. M. Al-Zoubi, D. G. Hall, J. Org. Chem., 2012, 77, 8386-8400.


Amides were produced from carboxylic acids and amines in the presence of XtalFluor-E as an activator. Optically active amines and/or carboxylic acids were not epimerized/racemized during the process and even poorly reactive carboxylic acids can be transformed to amides.
A. Orliac, D. G. Pardo, A. Bombrun, J. Cossy, Org. Lett., 2013, 15, 902-905.


An effective protocol for a waste-minimized, environmentally benign thermal condensation of carboxylic acids with amines has been identified. Fourteen examples demonstrate the applicability of this procedure to aliphatic, aromatic and heteroaromatic carboxylic acids and primary and secondary aliphatic as well as aromatic amines. The approach leads to the corresponding amides in good yields.
L. J. Gooßen, D. M. Ohlmann, P. P. Lange, Synthesis, 2009, 160-164.


Nanosized sulfated titania was prepared by a sol-gel hydrothermal process. The nanoparticles showed high catalytic activity in a direct amidation of fatty acids as well as benzoic acids with various amines under solvent-free conditions.
M. Hosseini-Sarvari, E. Sodagar, M. M. Doroodmand, J. Org. Chem., 2011, 76, 2853-2859.


The mild combination of T3P (n-propanephosphonic acid anhydride) and pyridine enables a low-epimerization amide bond formation. This robust and practical method is general for the coupling of various racemization-prone acid substrates and amines, including relatively non-nucleophilic anilines, and provides amides in high yields with very low epimerization.
J. R. Dunetz, Y. Xiang, A. Baldwin, J. Ringling, Org. Lett., 2011, 13, 5048-5051.


In the presence of the Oxyma derivative 2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyano-2-(hydroxyimino)acetate, short peptides to oligopeptides could be synthesized by using EDCI and NaHCO3 in water without measurable racemization. Significantly, a simple basic and acidic aqueous workup procedure can remove all reagents utilized in the reactions to afford only coupling products in consistently excellent yields.
Q. Wang, Y. Wang, M. Kurosu, Org. Lett., 2012, 14, 3372-3375.


Borane-tetrahydrofuran complex or borane-methyl sulfide complex is used to generate triacyloxyboranes, which can be effectively reacted with various nucleophiles (alkylamines, arylamines, hydrazides, alcohols, phenols) at reflux in toluene to provide the corresponding amides and esters in excellent yield.
Z. Huang, J. R. Reilly, R. N. Buckle, Synlett, 2007, 1026-1030.


Carboxylic acids are converted into amides in moderate to high yields in the presence of a stoichiometric amount of trimethylaluminium and amines in toluene at 90˚C after 1 hour.
S. Chung, D. P. Uccello, H. Choi, J. I. Montgomery, J. Chen, Synlett, 2011, 2072-2074.


A method for the preparation of N-acylpyrroles involves condensation of carboxylic acids with 2,4,4-trimethoxybutan-1-amine, followed by acid-mediated cyclization to form the pyrrole ring. The preparative procedure is highly tolerant of various functional groups.
T. Maehara, R. Kanno, S. Yokoshima, T. Fukuyama, Org. Lett., 2012, 14, 1946-1948.


The conversion of carboxylic acids to their corresponding acid chlorides occurs rapidly in the presence a tertiary amine base and 3,3-dichlorocyclopropenes via aromatic cation-activated nucleophilic acyl substitution. The effect of cyclopropene substituents on the rate of conversion is examined. Conditions were developed for the preparation of acid sensitive acid chlorides.
D. J. Hardee, L. Kovalchuke, T. H. Lambert, J. Am. Chem. Soc., 2010, 132, 5002-5003.


Aliphatic and/or aromatic esters were converted into the corresponding amides under mild conditions in good to excellent yields in the presence of tert-butoxide, water and air. The reaction is highly efficient, rapid, versatile, green and economical, and could find great practical application in organic synthesis, biochemistry, and industrial chemistry.
B. R. Kim, H.-G. Lee, S.-B. Kang, G. H. Sung, J.-J. Kim, J. K. Park, S.-G. Lee, Y.-J. Yoon, Synthesis, 2012, 44, 42-50.


The use of magnesium nitride as a convenient source of ammonia allows a direct transformation of esters to primary amides. Methyl, ethyl, isopropyl, and tert-butyl esters are converted to the corresponding carboxamides in good yields.
G. E. Veitch, K. L. Bridgwood, S. V. Ley, Org. Lett., 2008, 10, 3623-3625.


An iodine-NH3 • H2O system enables a direct transformation of aryl, heteroaryl, vinyl, or ethynyl methyl ketones or carbinols to the corresponding primary amides in good yields in aqueous media. A tandem Lieben-Haller-Bauer reaction mechanism is proposed.
L. Cao, J. Ding, M. Gao, Z. Wang, J. Li, A. Wu, Org. Lett., 2009, 11, 3810-3813.


ZrOCl2 • 8 H2O is a highly effective, water-tolerant, and reusable catalyst for the direct condensation of carboxylic acids and N,N′-dimethylurea under microwave irradiation to give the corresponding N-methylamides in moderate to excellent yields. ZrOCl2 • 8 H2O is a useful green catalyst due to its low toxicity, easy availability, low cost, ease of handling, easy recovery, good activity, and reusability.
D. Talukdar, L. Saikia, A. J. Thakur, Synlett, 2011, 1597-1601.


An operationally straightforward method for the amidation of aldehydes with economic ammonium chloride or amine hydrochloride salts enables the synthesis of various amides in good yield by using inexpensive copper sulfate or copper(I) oxide as a catalyst and aqueous tert-butyl hydroperoxide as an oxidant. Chiral amines can be used without detectable racemization.
S. C. Ghosh, J. S. Y. Ngiam, A. M. Seayad, D. T. Tuan, C. L. L. Chai, A. Chen, J. Org. Chem., 2012, 77, 8007-8015.


The use of diacetoxyiodobenzene in the presence of an ionic liquid enables a facile one-pot synthesis of a series of amides from aldehydes and amines at ambient temperature.
V. Prasad, R. R. Kale, B. B. Mishra, D. Kumar, V. K. Tiwari, Org. Lett., 2012, 14, 2936-2939.


A copper-catalyzed aerobic oxidative cross-dehydrogenative coupling (CDC) of amines with α-carbonyl aldehydes leads to various α-ketoamides compounds. Many types of amines are tolerant in this transformation. Wide substrate scope, and the use of air as oxidant and initiator make this transformation highly efficient and practical.
C. Zhang, X. Zong, L. Zhang, N. Jiao, Org. Lett., 2012, 14, 3280-3283.


The use of PhI=NTs/PhI=NNs as the nitrogen source in the presence of inexpensive iron(II) chloride + pyridine as the in situ formed precatalyst enables amidation of aldehydes under mild conditions at room temperature or microwave assisted conditions. The protocol is operationally straightforward and accomplished in good product yields and with complete chemoselectivity.
T. M. U. Ton, C. Tejo, S. Tania, J. W. W. Chang, P. W. H. Chan, J. Org. Chem., 2011, 76, 4894-4904.


N-Cbz-protected amino acids reacted with various aryl amines in the presence of methanesulfonyl chloride and N-methylimidazole in dichloromethane to give the corresponding arylamides in high yields without racemization under these mild conditions.
L. Mao, Z. Wang, Y. Li, X. Han, W. Zhou, Synlett, 2011, 129-133.


1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) catalyzes the amidation of acyl imidazoles. The rate acceleration is especially evident with traditionally unreactive, electron-deficient anilines. DBU offers safety and cost advantages over more commonly employed catalysts such as 1-hydroxybenzotriazole (HOBt).
C. Larrive-Aboussafy, B. P. Jones, K. E. Price, M. A. Hardink, R. W. McLaughlin, B. M. Lillie, J. M. Hawkins, R. Vaidyanathan, Org. Lett., 2010, 12, 324-327.


Malonic acid derivatives undergo unusually mild decarboxylation in the presence of N,N′-carbonyldiimidazole (CDI) at room temperature to generate a carbonyl imidazole intermediate in high yield. Subsequent reactions with various nucleophiles in an efficient one-pot process leads to amides, esters or carboxylic acids.
D. Lafrance, P. Bowles, K. Leeman, R. Rafka, Org. Lett., 2011, 13, 2322-2325.


Deprotonated 1,2,4-triazole is an active acyl transfer catalyst suitable for the aminolysis and transesterification of esters.
X. Yang, V. B. Birman, Org. Lett., 2009, 11, 1499-1502.


A N-heterocyclic carbene catalyzes the oxidative esterification of various aldehydes in the presence of 3,3',5'5-tetra-tert-butyldiphenoquinone to yield hexafluoroisopropylesters, which are useful active esters for in situ amide bond formation. This transition metal-free organocatalytic system also enabled a mild oxidative azidation of aldehydes.
S. De Sarkar, A. Studer, Org. Lett., 2010, 12, 1992-1995.


Amines are efficiently acylated by both cyclic and acyclic anhydrides in aqueous medium with sodium dodecyl sulfate (SDS) - without use of acidic or basic reagents. Various amines and anhydrides were reacted with equal ease. Chemoselective acylation in the presence of phenols and thiols has been achieved. No chromatographic separation is required for isolation of the acylated products.
S. Naik, G. Bhattacharjya, B. Talukdar, B. K. Patel, Eur. J. Org. Chem., 2004, 1254-1260.


Various alcohols, thiols, phenols, and amines can be acetylated using acetic anhydride in the presence of catalytic quantity of silver triflate. The method proceeds under mild conditions, does not involve cumbersome workup, and the resulting products are obtained in high yields within a reasonable time.
R. Das, D. Chakraborty, Synthesis, 2011, 1621-1625.


Phosphomolybdic acid (PMA) is a simple and efficient catalyst for the acetylation of structurally diverse alcohols, phenols, and amines. Acetylation reactions with acetic anhydride proceed in excellent yield in the presence of a catalytic amount of PMA at ambient temperature within a relatively short reaction time under solvent-free conditions.
S. T. Kadam, S. S. Kim, Synthesis, 2008, 267-268.


Copper(II) tetrafluoroborate efficiently catalyzes acetylation of structurally diverse phenols, alcohols, thiols, and amines with stoichiometric amounts of Ac2O under solvent-free conditions at room temperature. Acid-sensitive alcohols are smoothly acetylated without competitive side reactions.
A. K. Chakraborti, R. Gulhane, Shivani, Synthesis, 2004, 111-115.


Multivalent metal salts, such as ferric chloride and sulfate, are active and versatile catalysts for the amidation of aliphatic fatty acids with long-chain aliphatic amines.
Y. Terada, N. Ieda, K. Komura, Y. Sugi, Synthesis, 2008, 2318-2319.


Aliphatic, aromatic, and heteroaromatic carboxylic acids in the form of their salts condense with aryl isocyanates at room temperature with loss of carbon dioxide to give the corresponding amides in high yield. Application of the reaction to acyl isocyanates gives unsymmetric imides. The reaction is compatible with hydroxyl groups and both Fmoc and Boc protecting groups for amines.
K. Sasaki, D. Crich, Org. Lett., 2011, 13, 2256-2259.


2,2′-Dipyridyl diselenide catalyzes a direct reaction of carboxylic acids with azides and trimethylphosphine at room temperature. The mechanism of the process, which is not an aza-Wittig reaction, has been elucidated.
J. Burés, M. Martín, F. Urpí, J. Vilarrasa, J. Org. Chem., 2009, 74, 2203-2206.


2-Acyl-4,5-dichloropyridazin-3-ones served as stable, convenient and chemoselective N-acylating reagents for amines under neutral conditions.
Y.-J. Kang, H.-A Chung, J.-J. Kim, Y.-J. Yoon, Synthesis, 2002, 733-738.


The reaction of N,N-dialkylformamide dimethyl acetal with primary amides produces N'-acyl-N,N-dialkylformamidines as intermediates. In the presence of certain Lewis acid additives efficient acyl transfer occurs, providing new and useful methods for amide exchange such as transamidation.
T. A. Dineen, M. A. Zajac, A. G. Myers, J. Am. Chem. Soc., 2006, 128, 16406-16409.


A straightforward trimethylsilylation protocol activates a thiol acid for peptide bond formation at neutral pH using bistrimethylsilylacetamide (BSA). A unique reactivity of the generated O-silylthionoesters toward amines provides oxoamides.
W. Wu, Z. Zhang, L. S. Liebeskind, J. Am. Chem. Soc., 2011, 133, 14256-14259.


A novel amide bond formation strategy from simple thioacid and amine starting materials is mediated by unstable but very reactive S-nitrosothioacid intermediates. This fast reaction under mild conditions should be useful in synthesis.
J. Pan, N. O. Devarie-Baez, M. Xian, Org. Lett., 2011, 13, 1092-1094.


Thio FCMA intermediates, generated from the reactions of thioacids with isonitriles, are active acyl donors, that form amide bonds under neutral conditions.
Y. Rao, X. Li, S. J. Danishefsky, J. Am. Chem. Soc., 2009, 131, 12924-12926.


Microwave reactions of primary and secondary amines with imidoylbenzotriazoles gave various polysubstituted amidines in good yields. Convenient preparations of a variety of amides and imidoylbenzotriazoles have also been developed using microwave irradiation under mild conditions and short reaction times.
A. R. Katritzky, C. Cai, S. K. Singh, J. Org. Chem., 2006, 71, 3375-3380.


Various alcohols, phenols, amines and thiols may easily be converted into acetate derivatives by treatment with acetic anhydride in the presence of acetonyltriphenylphosphonium bromide in good yields at room temperature. With the same precatalyst, both aliphatic and aromatic aldehydes can be transformed into the corresponding gem-diacetates under reflux conditions.
A. T. Khan, L. H. Choudry, S. Ghosh, Eur. J. Org. Chem., 2005, 2782-2787.


Acyl halide-methanol mixtures are efficient reagents for the one-pot transformation of t-butyl carbamates into amides. This transformation can be carried out in the presence of a benzyloxycarbonyl group.
A. Nazih, D. Heissler, Synthesis, 2002, 203-206.


An efficient dynamic kinetic resolution of amines combines a ruthenium-catalyzed racemization with a lipase-catalyzed resolution. A variety of primary amines were transformed into one enantiomer of the amide in high yield and high enantioselectivity.
J. Paetzold, J. E. Bäckvall, J. Am. Chem. Soc., 2005, 127, 17620-17621.


A practical procedure for an efficient dynamic kinetic resolution of primary amines employs a palladium nanocatalyst as racemization catalyst, a commercial lipase as resolution catalyst, and ethyl acetate or ethyl methoxyacetate as acyl donor. Various amines and one amino acid amide have been resolved with good yields and high enantiomeric excesses.
M.-J. Kim, W.-H. Kim, K. Han, Y. K. Choi, J. Park, Org. Lett., 2007, 9, 1157-1159.


A practical procedure for an efficient dynamic kinetic resolution of primary amines employs a palladium nanocatalyst as racemization catalyst, a commercial lipase as resolution catalyst, and ethyl acetate or ethyl methoxyacetate as acyl donor. Various amines and one amino acid amide have been resolved with good yields and high enantiomeric excesses.
M.-J. Kim, W.-H. Kim, K. Han, Y. K. Choi, J. Park, Org. Lett., 2007, 9, 1157-1159.


A mild, versatile, copper-catalyzed three-component coupling of organoindium reagents with imines and acid chlorides provides α-substituted amides or N-protected amines in a single step with the sole byproduct being indium trichloride.
D. A. Black, B. A. Arndtsen, Org. Lett., 2006, 8, 1991-1993.


A simple, practical, and catalytic method for the N-formylation in the presence of molecular iodine as a catalyst under solvent-free conditions is applicable to a wide variety of amines. α-Amino acid esters can be converted without epimerization.
J.-G. Kim, D. O. Jang, Synlett, 2010, 2093-2096.


A simple, mild method for N-formylation in the presence of indium metal as a catalyst under solvent-free conditions is applicable to the chemoselective reaction of amines and α-amino acid esters without epimerization.
J.-G. Kima, D. O. Jang, Synlett, 2010, 1231-1234.


A mild, simple, and selective N-formylation of amines with formic acid in the presence of ZnO under solvent-free conditions gives products in excellent yields.
M. Hosseini-Sarvari, H. Sharghi, J. Org. Chem., 2006, 71, 6652-6654.


Various tertiary benzanilide derivatives were effectively synthesized in high yields from a broad range substituted benzoic acid and N-monoalkylated anilines using dichlorotriphenylphosphorane in chloroform. Allyl, Boc, MPM and the Z group were unaffected under these conditions.
I. Azumaya, T. Okamoto, F. Imabeppu, H. Takayanagi, Tetrahedron, 2003, 59, 2325-2331.


In the presence of sodium acetate, the reaction between 2,2,6-trimethyl-4H-1,3-dioxin-4-one and secondary or tertiary alcohols or primary or secondary amines could be carried out in refluxing tetrahydrofuran. Under these much milder conditions, side products were avoided, and β-keto esters and β-ketoamides were normally obtained in quantitative yields.
V. Sridharan, M. Ruiz, J. C. Menéndez, Synthesis, 2010, 1053-1057.


An amidation of unactivated esters with amino alcohols catalazyed by a stable nitrogen-heterocyclic carbene is described. The mechanism is discussed.
M. Movassaghi, M. A. Schmidt, Org. Lett., 2005, 7, 2373-2376.


LiNTf2 is able to activate cyclic esters towards ring opening with a stoichiometric amount of amines, thus leading to clean open-chain amides under mild conditions. The generality of the method was demonstrated by a range of selected lactones and amines.
C. Lalli, A. Trabocchi, G. Menchi, A. Guarna, Synlett, 2008, 189-192.


A small library of α,β-unsaturated oxindoles was prepared by an efficient microwave-assisted one-pot sequence comprising an aromatic substitution followed by an ionic Horner-Wadsworth-Emmons olefination.
A. Teichert, K. Jantos, K. Harms, A. Studer, Org. Lett., 2004, 6, 3477-3480.


Various alcohols, amines and N-hydroxylamines gave corresponding formylated adducts in high yields by treatment with 2,2,2-trifluoroethyl formate (TFEF). Chemoselective formylation of a primary amine could be readily achieved in the presence of an unprotected primary alcohol.
D. R. Hill, C.-N. Hsiao, R. Kurukulasuriya, S. Wittenberger, Org. Lett., 2002, 4, 111-113.


Deoxo-Fluor is a versatile and mild reagent for acyl fluoride generation and subsequent one-flask amide coupling. The conversion of acids to amides and Weinreb amides and the use of Deoxo-Fluor as peptide-coupling reagent have been explored. Products were isolated after facile purification in good yields.
J. M. White, A. R. Tunoori, B. J. Turunen, G. I. Georg, J. Org. Chem., 2004, 69, 2573-2576.


A stereoconservative protection and deprotection method of amino and carboxyl groups includes the generation of N-Phthaloyl N'-alkyl secondary amides from N-phthaloyl amino acids by using a mixed anhydride method. These secondary amides have been transformed by thermal rearrangement of the intermediate nitrosoamides to esters with retention of configuration and excellent yields.
D. M. Shendage, R. Froehlich, G. Haufe, Org. Lett., 2004, 6, 3675-3678.


A mild and efficient oxidative amidation of aldehydes uses amine HCl salts and tert-butyl hydroperoxide as an oxidant in the presence of a copper catalyst.
W.-J. Yoo, C.-J. Li, J. Am. Chem. Soc., 2006, 128, 13064-13065.


Formation of N-alkenyl alkynylamides by N-acylation of imines with alkynoyl chlorides and the subsequent cationic Au(I)/PPh3-catalyzed cycloisomerization allows a convergent and rapid assembly of substituted 2-pyridones.
H. Imase, K. Noguchi, M. Hirano, K. Tanaka, Org. Lett., 2008, 10, 3563-3566.