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Reactions >> Protecting Groups >> Stability

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, 100C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100C
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.


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.


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.