Zinc/ammonium formate: a chemoselective and cost-effective protocol for the reduction of azides to amines

Abstract

Reduction of the azide moiety to an amine constitutes a synthetically important process, and, since many azides can be prepared with regio-and stereocontrol, subsequent reduction permits a controlled introduction of the amine function. It has been used extensively in carbohydrate and nucleoside chemistry. Although quite a number of methods have been reported for this reductive process, 1-6 LiAlH 4 and Pd/C-H 2 are the most commonly used reagents systems. However, despite of their potential utility these methods often suffer from certain inconveniences such as, incompatibility with other functionalities and protecting groups, use of expensive and hazardous reagents, drastic reaction conditions, long reaction times and tedious product isolation procedure.Ammonium formate is proved to be a versatile hydrogen donor for the catalytic hydrogen transfer reductions of wide variety of functionalities. 7-9 However, most of the ammonium formate reductions are achieved by the use of expensive catalysts like Pd/C, Ru/Ca, Pd/CaCO 3 , Ru/C and Raney Ni. As part of our endeavour to develop low cost metals as catalyst for transfer reduction of important organic functional groups, 10-15 it was found that zinc can efficiently catalyse the reduction of several functionalities. 12-15 We now report a rapid, selective and cost-effective method for the reduction of azides to corresponding primary amines using catalytic transfer hydrogenation with ammonium formate as the hydrogen source, in the presence of commercial zinc dust.Azides were treated with zinc and ammonium formate in methanol to give corresponding amines in good to excellent yields (85-95%) at room temperature (Scheme 1). Under the present reaction conditions many other functionalities like halogens, acids, esters, methoxy etc. are tolerated. Several structurally varied azides are reduced to amines within 5 to 10 minutes, and the results are summarised in Table 1. The course of reaction was monitored by TLC and IR spectra and the products were characterised by comparison of their TLC, IR spectra, 1 H NMR spectra and melting points with authentic samples. A control experiment was carried out using azido compounds with ammonium formate, but without zinc, does not yield the desired product.In earlier reports, catalytic transfer hydrogenation of azides to primary amines had been achieved with the systems Pd-C/ammonium formate 16 and Pd-C/hydrazine. 2 But these systems requires longer reaction time and expensive catalyst. Further, palladium lacks industrial potentiality due its pyrophoric nature. Thus, zinc/ammonium formate appears to be a mild and efficient reagent for the rapid reduction of azides to corresponding amines in high yields. Moreover, the easy availability of the reagent, operational simplicity, chemoselectivity and cost-effectiveness make this procedure extremely attractive. ExperimentalReduction of azides. general procedure: A suspension of azide (10 mmol), ammonium formate (20 mmol) and zinc (2 equiv.) in methanol (10ml) was stirred at room temperature, under nit...

Efficient Reduction of Nitroarenes over Nickel‐Iron Mixed Oxide Catalyst Prepared from a Nickel‐Iron Hydrotalcite Precursor

“…The usual catalysts used in the hydrazine reduction of nitroarenes are zinc, [3] magnesium, [4] FeCl 3 ·6 H 2 O-activated carbon, [5] ironA C H T U N G T R E N N U N G (III) oxide [6] and iron oxide hydroxide. [7] Recently magnesium-iron mixed oxide prepared from a magnesium-iron hydrotalcite-like precursor has also been reported as an effective catalyst for the hydrazine reduction of aromatic nitro compounds.…”

Streamlined Routes to Phenacyl Azides and 2,5‐Diarylpyrazines Enabled by Deep Eutectic Solvents

“…To the best of our knowledge, there is only one case of reduction reported in a low melting mixture: the catalytic hydrogenation of methyl α‐cinnamate run in the melt citric acid‐dimethyl urea using the Wilkinson's catalyst (15 mol %) (90 °C, 1 atm H 2 ) A survey of conditions was undertaken to optimise this step in the above DES. A complex mixture always formed when azide 2a was treated at r.t. with Zn/ammonium formate, Zn/HCl, Zn/NH 4 Cl, Ph 3 P, or d ‐glucose/KOH as reducing agents (Table , entries 1–5). Pleasingly, when SnCl 2 · 2H 2 O was alternatively used the reduction of the azide moiety to the corresponding α‐amino ketone this time took place, but the latter spontaneously underwent dimerisation/cyclisation in the same eutectic mixture leading to the isolation of 2,5‐diphenylpyrazine 4a as the sole product in 48 % yield (Table , entry 6).…”

Ammonium Formate

“…The selective reduction of nitro compounds to the corresponding amines via catalytic transfer hydrogenation using ammonium formate has been extensively studied. 49- 53 The reduction can also be performed conveniently using ionic liquids as safe and recyclable media. 50 The use of mesoporous PdMCM-41 as catalyst is advantageous as it is relatively stable, non-hazardous, and possesses high surface area.…”