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A Simple Method For Reductive Acylation Of Azides
Using Aluminium Iodide And Acetic Anhydride

Synthetic Communications 32(23), 3625–3628 (2002)

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A combination of aluminium iodide and acetic anhydride selectively converts a variety of azides to their corresponding acetamides in good to excellent yields without perturbing many active functionalities such as ether, ester, nitro etc.

Introduction of an amino group into a carbon backbone, especially in the field of the synthesis of natural products, is usually performed through the substitution of azide anion for halogen like substitutents, followed by reduction of azide functionality. Although numerous reports1 on the conversion of azides to amines are available in literature, an extensive literature survey could provide only a few methods2 for direct conversion of azides to acylamines.

Keeping in view of developing a mild and chemoselective reagent system, an attempt has been made to exploit the utility of relatively less explored and inexpensive reagent, AlI3 and acetic anhydride for direct conversion of azides to acetamides. A number of observations reveal that when an azide in acetonitrile is refluxed for about half an hour with this reagent system, it undergoes excellent conversion to acetamides. To the best of my knowledge, no such reagent system has so far been reported for the reductive acylation of azide.


Typical Procedure

A freshly prepared solution of 1.3 g AlI3 (prepared by refluxing 1.2 g aluminium foil and 17 g iodine in 40mL dry acetonitrile till color of the solution became pale yellow) in acetonitrile was added to a refluxing solution of phenyl azide (1.3 g, 14.24 mmol) and acetic anhydride (2 mL) in acetonitrile (2 mL) and allowed to reflux until completion while monitoring the reaction by TLC (Primary azides 30 min, Secondary 60 min, sterically hindered 90 min). The temperature of the reaction mixture was allowed to cool down to RT, and diluted with CHCl3 (10mL), washed successively with aqueous Na2S2O3 solution (20mL) and brine. The organic layer was separated, dried (over Na2SO4) and evaporated to get the crude which was purified by column chromatography (EtOAc/hexane 3:2). Yields 70-90%.

Although AlI3 is an established ether cleaving agent3,the AlI3–acetic anhydride combination is found to have little effect on ether and ester functionalities under this reaction condition. Therefore this method carries the preferences to the existing ones for being mild, selective and cheap. This method provides a straightforward procedure for conversion of azides to their corresponding acetamides in excellent yield avoiding amino reduction and carboxylactivati on usually required for two steps conversion.

In conclusion, this reagent system describes one step conversion of azides to acetamides using a easily made, cheap but excellent reagent system.


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