It is widely known that most of primary amines are biologically active compounds or the important building blocks for the syntheses of biologically active compounds, such as aminobenzlactam 1^1a,1b,1c,1d aminobenzlactam 2^2a,2b and l-homophenylalanine 3^1a,3a,3b and so on. The reduction of azides to amines is of considerable importance for the introduction of primary amino group in organic synthesis because of the easy preparation of azide by regio and stereo controlled procedure⁴. Many common reagents for this purpose have been developed^5a,5b but some of them suffer from poor selectivity⁴ or using some environmentally unfriendly chemicals.^{6a,6b,6c,6d,6e,6f} The use of zinc and ammonium chloride has been well established in organic synthesis for the reduction of nitro group⁷, however, little attention has been focused on the reduction of azido group⁸. Herein, we will describe a facile method for the reduction of azides to amines or amides in good to excellent yield using zinc and ammonium chloride as reducing agent under mild condition.

Aminobenzlactam 1, a key intermediate for the synthesis of many biologically active compounds^1a,1b,1c,1d such as thromboxane synthase inhibitors, and benazepril hydrochloride, can be prepared by reduction of the corresponding azide 4. Initially, we tried to reduce 4 via hydrogenation over 10% and 5% palladium on carbon at room temperature under 1, 5 and 10 atm. hydrogen, a general method for the reduction of azides⁴, but the yields were always below 54% due to the incomplete conversion (Table 1, Entry 1). Hydrogen transfer reduction was tested for this transformation with ammonium formate as hydrogen donor⁹, in the presence of 10% palladium on carbon, but the reaction could not proceed completely, either, and only 43% yield was isolated (Table 1, Entry 2). Using 5% palladium on aluminum as catalyst and ammonium formate as hydrogen donor, resulted in more than 65% yield (Table 1, Entry 3). The combination of sodium borohydride and cobalt chloride, which was very efficient for the reduction of azides^5b, was also employed to reduce 4, but low yield of 45% was obtained (Table 1, Entry 4). The treatment of ferrum and ammonium chloride with 4 led to much higher yield of 73% (Table 1, Entry 5)¹⁰. However the conversion was still not complete even if the reaction was prolonged.

Considering zinc is more reactive than ferrum, we proposed that the combination of zinc and ammonium chloride was probably more efficient for the reduction of azides than that of ferrum and ammonium chloride. As we expected, the azide 4 was reduced to amine completely in a short time to provide 90% isolated yield (Table 1, Entry 6). The co-solvents of ethyl acetate and water, ethyl alcohol and water as well as ethyl acetate, ethanol and water were suitable for the reaction, which could be selected based on the solubility of azides.

To extend the scope of the reducing reagent of zinc and ammonium chloride for the reduction of other azides, a variety of azides prepared according to the literature^{4,11a,11b,11c,11d,11e} were tested for this transformation (Table 2). All of azides were reduced completely with zinc and ammonium chloride at refluxing or room temperature to readily give the corresponding amines or amides in good to excellent yields.

Moreover, this new reduction system of zinc and ammonium chlorides could tolerate some functional groups which were easily destroyed during hydrogenation, such as C=C bond, benzyl, and so on, thus the azides bearing such groups were reduced in high yields (Entries 2 and 4). The reductions of Aroyl azide, arylsulphonyl azides were performed at room temperature to afford the corresponding amides smoothly in over 94% yields (Entries 5 and 6). Aryl azide was also reduced in excellent yield (98%, Entry 7). For the reduction of the optically active azide, no racemization was observed (Entry 8).

In summary, using zinc and ammonium chloride to reduce a broad spectrum of azides to amines or amides in good to excellent yields was first presented, which might provide a facile alternative for the reduction of azides to amines and amides under a mild condition.