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Synthesis of amides
A simple ruthenium catalyst mediates a direct coupling between an alcohol and an amine with the liberation of two molecules of dihydrogen. The active catalyst is generated in situ from an easily available ruthenium complex, an N-heterocyclic carbene and a phosphine. The reaction allows primary alcohols to be coupled with primary alkylamines to afford secondary amides in good yields.
L. U. Nordstrřm, H. Vogt, R. Madsen, J. Am. Chem. Soc., 2008, 130, 17672-17673.
An in situ generated catalyst from readily available RuH2(PPh3)4, an N-heterocyclic carbene (NHC) precursor, NaH, and acetonitrile showed high activity for the amide synthesis directly from either alcohols or aldehydes with amines.
S. Muthaiah, S. C. Ghosh, J.-E. Jee, C. Chen, J. Zahng, S. H. Hong, J. Org. Chem., 2010, 75, 3002-3006.
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.
A visible-light-driven photoredox-catalyzed nonaqueous oxidative C-N cleavage of N,N-dibenzylanilines provides 2° amides. The protocol also enables the conversion of 2-(dibenzylamino)benzamide to quinazolinones in the presence of (NH4)2S2O8 as an additive.
N. Neerathilingam, M. B. Reddy, R. Anandhan, J. Org. Chem., 2021, 86, 15117-15127.
An efficient, metal-free domino protocol for the synthesis of benzamides from ethylarenes proceeds through the formation of triiodomethyl ketone intermediate in the presence of iodine as the promoter and TBHP as an oxidant followed by nucleophilic substitution with aqueous ammonia. This operationally simple, functional-group-tolerant tandem approach provides an easy access to the broad range of biologically important benzamides.
K. S. Vadagaonkar, H. P. Kalmode, S. Prakash, A. C. Chaskar, Synlett, 2015, 26, 1677-1682.
A combination of 1,1,1,3,3,3-hexafluoroispropanol (HFIP) and H2O2 enables a straightforward synthesis of N,N-disubstituted formamides from imines in very good yields via an oxidation-rearrangement sequence under smooth reaction conditions.
N. Llopis, P. Gisbert, A. Baeza, J. Org. Chem., 2020, 85, 11072-11079.
Macroporous Amberlyst A26 OH catalyzes a selective hydration of nitriles to primary amides as well as a base-catalyzed synthesis of 2-substituted 4(1H)-quinazolinones via reaction of 2-aminobenzonitrile with carbonyl compounds in H2O-EtOH.
F. Tamaddon, F. Pouramini, Synlett, 2014, 25, 1127-1131.
The enhanced activity of a "donor-acceptor"-type catalyst, which is readily prepared from (DPPF)PtCl2, PMe2OH, and AgOTf, permits the hydration of a wide range of nitriles and cyanohydrins to proceed at 40°C with excellent turnover numbers.
X. Xing, C. Xu, B. Chen, C. Li, S. C. Virgil, R. H. Grubbs, J. Am. Chem. Soc., 2018, 140, 17782-17789.
Potassium tert-butoxide acts as a nucleophilic oxygen source during the hydration of a broad range of nitriles to give the corresponding amides under mild, anhydrous conditions. The easily scalable reaction provides an efficient and economically affordable synthetic route to amides in excellent yields without any transition-metal catalyst or any special experimental setup.
G. C. Midya, A. Kapat, S. Maiti, J. Dash, J. Org. Chem., 2015, 80, 4148-4151.
Sodium perborate in acetic acid is an effective reagent for the oxidation of aromatic aldehydes to carboxylic acids, iodoarenes to (diacetoxyiodo)arenes, azines to N-oxides, and various sulphur heterocycles to S,S-dioxides. Nitriles undergo smooth oxidative hydration to amides when aqueous methanol is employed as solvent.
A. McKillop, D. Kemp, Tetrahedron, 1989, 45, 3299-3306.
Ru(OH)x / Al2O3 acts as a heterogeneous catalyst for the hydration of activated and unactivated nitriles in water. This reaction can be performed with high selectivity and conversion to give amides. Furthermore, catalyst/product separation is easy and Ru(OH)x / Al2O3 is recyclable.
K. Yamaguchi, M. Matsushita, N. Mizuno, Angew. Chem. Int. Ed., 2004, 43, 1576-1580.
In a sustainable, robust, reliable, and scalable flow chemistry process for the hydration of nitriles, an aqueous solution of the nitrile is passed through a column containing commercially available amorphous manganese dioxide. A broad range of products are obtained simply by concentration of the output stream without any other workup steps. The protocol shows a high level of chemical tolerance.
C. Battilocchio, J. M. Hawkins, S. V. Ley, Org. Lett., 2014, 16, 1060-1063.
The use of acetaldoxime as the water source in the presence of a Rh catalyst allows the conversion of various nitriles to amides under neutral and anhydrous conditions. The reaction displays excellent compatibility with acid or base labile and hydrolytically labile functional groups.
J. Lee, M. Kim., S. Chang, H.-Y. Lee, Org. Lett., 2009, 11, 5598-5601.
A copper-catalyzed amidation of arylboronic acids with nitriles provides an efficient and complementary methodology for the synthesis of a broad range of N-arylamides.
H. Huang, Z.-T. Jiang, Y. Wu, C.-Y. Gan, J.-M. Li, S.-K. Xiang, C. Feng, B.-Q. Wang, W.-T. Yang, Synlett, 2016, 27, 951-955.
A photoinduced oxidative formylation of N,N-dimethylanilines with molecular oxygen in the absence of an external photocatalyst provided formamides in good yields under mild reaction conditions.
S. Yang, P. Li, Z. Wang, L. Wang, Org. Lett., 2017, 19, 3386-3389.
CpRuCl(PPh3)2 catalyzes reactions of terminal alkynes with primary and secondary amines to afford the corresponding amides in the presence of 4-picoline N-oxide. The reactions occur in chlorinated solvent and aqueous medium, showing applications in peptide chemistry.
A. Álvarez-Pérez, M. A. Esteruelas, S. Izquierdo, J. A. Varela, C. Saá, Org. Lett., 2019, 21, 5346-5350.
An operationally simple, palladium-catalyzed three-component reaction between terminal alkynes, isonitriles, and sodium carboxylates provides N-acyl propiolamide derivatives under mild conditions.
Y. He, Y. Wang, X. Liang, B. Huang, H. Wang, Y.-M. Pan, Org. Lett., 2018, 20, 7117-7120.
In a metal-free, selective oxidation of cyclic secondary and tertiary amines for the formation of lactams, molecular iodine facilitates both chemoselective and regioselective oxidation of C-H bonds directly adjacent to a cyclic amine. The reaction offers mild conditions, functional group tolerance, and a broad substrate scope.
R. J. Griffiths, G. A. Burley, E. P. A. Talbot, Org. Lett., 2017, 19, 870-873.
Various enamines were photocatalytically cleaved to produce amide products under simple visible-light irradiation from a 45 W household light bulb via photosensitized formation of a singlet oxygen intermediate and a subsequent [2+2] cycloaddition event.
J. Li, S. Cai, J. Chen, Y. Zhao, D. Z. Wang, Synlett, 2014, 25, 1626-1628.
N-Sulfonyl ketenimine formation followed by a probable 1,3-OAc migration ([3,3]-sigmatropic rearrangement) enables a synthesis of trans-α,β-unsaturated N-tosylamides from readily accessible propargyl acetates and sulfonyl azides in the presence of CuI as catalyst. The reaction is very general and affords products at ambient temperature with excellent diastereoselectivity in good yields.
Y. K. Kumar, G. R. Kumar, M. S. Reddy, J. Org. Chem., 2014, 79, 823-828.
In an NBS-promoted allyloxyl addition-Claisen rearrangement-dehydrobromination cascade reaction, more than 20 substituted alkynylsulfonamides were reacted with allyl alcohols to generate (2Z)-2,4-dienamides in good yields. Theoretical calculations suggested that a [3,3] sigmatropic rearrangement be the rate-limiting step.
R. Ding, Y. Li, C. Tao, B. Cheng, H. Zhai, Org. Lett., 2015, 17, 3994-3997.
An efficient decarbonylative coupling of α-keto acids and ynamides with extrusion of CO enables the synthesis of a broad range of β-keto imides under mild reaction conditions.
R. Chen, L. Zeng, B. Hoang, Y. Shen, S. Cui, Org. Lett., 2018, 20, 3377-3380.
The reaction of sulfoxonium ylides with primary or secondary amines afforded α-ketothioamides in the presence of elemental sulfur, whereas α-ketoamides were produced when I2 and TBHP were present. This simple, scalable reaction proceeded well at room temperature, tolerated a range of functional group, and generated the corresponding products in very good yields.
T. N. Chaubey, P. J. Borpatra, A. Sharma, S. K. Pandey, Org. Lett., 2022, 24, 8062-8066.
A facile and efficient route for the homogeneous and highly stereoselective monohydration of substituted methylenemalononitriles to (E)-2-cyanoacrylamides is catalyzed by copper(II) acetate in acetic acid containing 2% water. The protocol is suitable for the monohydration of dicyanobenzenes and 2-substituted malononitriles.
X. Xin, D. Xiang, J. Yang, Q. Zhang, F. Zhou, D. Dong, J. Org. Chem., 2013, 78, 11956-11961.
A palladium(II)-catalyzed transfer hydration of various aldehyde- and ketone-derived cyanohydrins provides α-mono- and α,α-disubstituted-α-hydroxyamides by using carboxamides as water donors under mild conditions.
T. Kanda, A. Naraoka, H. Naka, J. Am. Chem. Soc., 2019, 141, 825-830.
A wide range of aldoximes has been converted into the corresponding amides in high yield and selectivity using the ruthenium-based catalyst Ru(PPh3)3(CO)H2/dppe/TsOH with catalyst loading as low as 0.04 mol%.
N. A. Owston, A. J. Parker, J. M. J. Williams, Org. Lett., 2007, 9, 3599-3601.
[Ir(Cp*)Cl2]2 catalyzes the rearrangement of oximes to furnish amides. An iridium-catalyzed transfer hydrogenation between alcohols and styrene and the subsequent formation of an oxime allows the conversion of alcohols into amides in a one-pot process.
N. A. Owston, A. J. Parker, J. M. J. Williams, Org. Lett., 2007, 9, 73-75.
In the presence of hydrogen peroxide and trimethylsilyl chloride, thiocarbonyls desulfurize to the corresponding carbonyls in short reaction times with no side reactions and excellent selectivity. This process is a safe, operationally simple, and environmentally benign alternative for the desulfurization of thiocarbonyls.
K. Bahrami, M. M. Khodaei, M. Tajik, Synthesis, 2010, 4282-4286.
Desulfurization of thioamides was accomplished using a semicatalytic amount of Bu4NBr. The corresponding amides were obtained in high yields, with good functional group compatibility.
K. Inamoto, M. Shiraishi, K. Hiroya, T. Doi, Synthesis, 2010, 3087-3090.
The hydrogen peroxide-zirconium(IV) chloride reagent system is efficient and general for the conversion of thioamides to amides in short reaction times and good chemoselectivity, and allows a simple workup that precludes the use of toxic solvents.
K. Bahrami, M. M. Khodaei, Y. Tirandaz, Synthesis, 2009, 369-371.
Several amides were obtained in high yields by an efficient method from the corresponding imines which are readily prepared from aldehydes. This procedure involves the oxidation of aldimines with m-CPBA and BF3ˇOEt2. In this reaction, the product is strongly influenced by the electron releasing capacity of the aromatic substituent (Ar).
G. An, M. Kim, J. Y. Kim, H. Rhee, Tetrahedron Lett., 2003, 44, 2183-2186.