Acetamides
Ac-NR2
T. W. Green, P. G. M. Wuts, Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 550-555, 740-743.
Stability
H2O: | pH < 1, 100°C | pH = 1, RT | pH = 4, RT | pH = 9, RT | pH = 12, RT | pH > 12, 100°C |
Bases: | LDA | NEt3, Py | t-BuOK | Others: | DCC | SOCl2 |
Nucleophiles: | RLi | RMgX | RCuLi | Enolates | NH3, RNH2 | NaOCH3 |
Electrophiles: | RCOCl | RCHO | CH3I | Others: | :CCl2 | Bu3SnH |
Reduction: | H2 / Ni | H2 / Rh | Zn / HCl | Na / NH3 | LiAlH4 | NaBH4 |
Oxidation: | KMnO4 | OsO4 | CrO3 / Py | RCOOOH | I2, Br2, Cl2 | MnO2 / CH2Cl2 |
Protection of Amino Groups
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.
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.
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.
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.
[Ni(quin)2] catalyzes the N-formylation and N-acylation
of amines using N,N-dimethylformamide and N,N-dimethylacetamide in
the presence of imidazole in good yields. The protocol shows broad substrate
scope for aliphatic, aromatic, and heterocyclic amines.
R. B. Sonawane, N. K. Rasal, S. V. Jagtap, Org. Lett.,
2017, 19, 2078-2081.
Other Syntheses of Acetamides
Hypervalent Iodine(III)-Mediated Decarboxylative Ritter-Type Amination
Leading to the Production of α-Tertiary Amine Derivatives
K. Kiyokawa, T. Watanabe, L. Fra, T. Kojima, S. Minakata, J. Org. Chem.,
2017, 82, 11711-11720.
Zinc(II) catalyzes a single-step protocol for the Beckmann rearrangement
using hydroxylamine-O-sulfonic acid (HOSA) as the nitrogen source in
water. This environmentally benign and operationally simple method efficiently
produces secondary amides under open atmosphere in a pure form after basic
aqueous workup.
S. Verma, P. Kumar, A. K. Khatana, D. Chandra, A. K. Yadav, B. Tiwari, J. L.
Jat, Synthesis, 2020, 52,
1841-1846.
Deprotection
Imidoyl chlorides, generated from secondary acetamides and oxalyl chloride,
enable a selective and practical deprotection sequence. Treatment of these
intermediates with propylene glycol enables the rapid release of
amine hydrochloride salts in good yields without epimerization of the amino
center. The hydrochloride salts can be isolated or carried forward for subsequent chemistry.
S. G. Koenig, C. P. Vandenbossche, H. Zhao, P. Mousaw, S. P. Singh, R. P. Bakale, Org. Lett., 2009,
11, 433-436.
Transition-metal-free catalytic protocols for controlled reduction of amide
functions using cheap and bench-stable hydrosilanes as reducing agents enable
the selective reduction of unactivated C-O bonds in amides. By altering the
hydrosilane and solvent, the C-N bonds selectively breaks via a
deacylative cleavage.
W. Yao, L. He, D. Han, A. Zhong, J. Org. Chem., 2019, 84,
14627-14635.
A combination of KOH and BEt3 catalyzes a deaminative
hydroboration of acyl-iminodibenzyl derivatives, including nonheterocyclic
carboxamides, to the corresponding amines. This novel transition-metal-free
methodology was also applied to the hydroboration/reduction of aldehydes.
W. Yao, J. Wang, A. Zhong, J. Li, J. Yang,
Org. Lett., 2020, 22, 8086-8090.
Conversion of Acetamides to Other Functional Groups
Imidoyl chlorides, generated from secondary acetamides and oxalyl chloride,
enable a selective and practical deprotection sequence. Treatment of these
intermediates with propylene glycol and warming enables the rapid release of
amine hydrochloride salts in good yields without epimerization of the amino
center.
S. G. Koenig, C. P. Vandenbossche, H. Zhao, P. Mousaw, S. P. Singh, R. P. Bakale, Org. Lett., 2009,
11, 433-436.