Categories: C=O Bond Formation >
Synthesis of amides
Name Reactions
Recent Literature
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.
A copper(II)-promoted denitrogenation/oxidation reaction of α-azido ketones
and TEMPO as an oxidant provides primary α-ketoamides. α-Azido ketones were
denitrogenated in situ to form an imino ketone intermediate, which underwent a
radical addition process and radical migration to form α-ketoamides.
A.-J. Wang, C.-Y. She, Y.-D. Zhang, L.-H. Zhao, W.-M. Shu, W.-C. Yu, J. Org. Chem., 2022, 87,
16099-16105.
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.
X. Xin, D. Xiang, J. Yang, Q. Zhang, F. Zhou, D. Dong, J. Org. Chem., 2013,
78, 11956-11961.
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.
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.
Preparation of One-Carbon Homologated Amides from Aldehydes or Primary
Alcohols
M. K. Gupta, Z. Li, T. S. Snowden, Org. Lett., 2014,
16, 1602-1605.