The nitrile functionality is one of the most elementary building blocks in chemistry,and has wide applications in synthetic chemistry and pharceuticals [1]. Conventional methods to construct nitriles involved the cyanation of halides [2, 3],the Sandmeyer reaction [4],dehydration of aryl oximes [5]. However, many of these methods suffer from the drawback of employing harsh reaction conditions,such as high temperature or pressure and large excess of reactants [6]. Therefore,the development of feasible and chemically economical approaches to synthesis of nitriles is highly required. Recently,Jiao and co-workers reported a copper catalyzed conversion of methylarenes to aryl nitriles,and successively,they realized the transformation of benzyl halides to aryl nitriles [7]. More recently,Prabhu and co-workers reported a convenient method to synthesize nitriles from primary azides catalyzed by copper iodide,and then achieved a selective oxidation of aliphatic primary azides to the corresponding nitriles in the presence of KI and TBHP [6, 8].
Electrochemical synthesis,an environmentally friendly process, has attracted much interest of chemists and great efforts have been made to gain excellent achievements in recent years [9]. Compared with the conventional redox process,the notable superiority of electrochemical conversion is a mass-free electron transfer between the electrode and the substrate during reactions,which making this method to be green and sustainable. In this context,we report an efficient and easy-to-handle method to synthesize aryl nitriles via a metal-free anodic oxidation process. A series of aryl nitriles were obtained in moderate to good yields directly from benzylic azides at room temperature. 2. Experimental
1H NMR spectra were recorded on a Bruker AVIII-400 spectrometer. Chemical shifts (in ppm) were referenced to tetramethylsilane in CDCl3 as an internal standard. 13C NMR spectra were obtained by using the same NMR spectrometers and were calibrated with CDCl3 (d 77.00 ppm). The spectral data and spectra of all compounds can be found in Supporting information.
Initial optimization studies were carried out by employing 1- (azidomethyl)naphthalene (1a) as a model substrate. In an electrochemical setup consisting of an undivided cell equipped with a pair of platinum electrodes,a mixture of 1a (0.5 mmol), electrolyte (0.25 mmol),and phrase transfer catalyst (PTC, 0.25 mmol) in different solvents (6 mL) was electrolyzed under galvanostatic conditions and stirred simultaneously for 4 h at room temperature (Table 1). First,the solvent of the reaction was optimized with K3PO4·3H2O as an electrolyte and TBAB as a PTC at a constant current of 20 mA (entries 1 and 2). However,no desired product was obtained. When the current of the reaction system was increased to 50 mA,the desired nitrile was obtained in 73% yield (entry 3). Nevertheless,increasing the current to 80 mA did not show any significant influence in enhancing the yield (entry 4). Subsequently,a series of electrolyte were optimized,and the results showed that K3PO4 was the best electrolyte (entries 3 vs. 5- 7). Finally,other PTCs were tested in this reaction,but only trace of desired nitrile was obtained (entries 8 and 9). Other typical reaction parameters,such as other organic solvent,reaction temperature and concentration of the reactant,were also investigated in this electrochemical transformation; however,no significant improvement in yield was obtained,so we do not discuss the relevant details here.
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Table 1 Optimization of the reaction conditions.a |
Under the optimized reaction condition,a series of substituted azides were investigated to test the generality of this catalytic system. As shown in Table 2,benzylic azides bearing both electrondonating and electron-withdrawing groups transformed into the corresponding nitriles smoothly in moderate to good yields (Table 2,entries 1-12). Interestingly,diazide derivative 1,4- bis(azidomethyl)benzene was oxidized into desired p-cyanobenzene (2l) in good yield (70%,Table 2,entry 11). Unexpectedly,when 1-(azidomethyl)-4-nitrobenzene was employed as the substrate, p-nitrobenzaldehyde 3 was obtained in 53% yield instead of the corresponding nitrile (Table 2,entry 13). This might because azides with strong electron-withdrawing groups undergo a hydrolyzation process more easily during reactions. Heterocyclic substituted azides failed to afford the corresponding products under the typical reaction condition (Table 2,entry 14).
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Table 2 The scope of electrochemical oxidation of azides to nitriles.a |
The plausible mechanism of this transformation is presented in Scheme 1. First,the aryl azide is electrochemically oxidized to the benzyl cation A in two steps [10, 11],and then the cation A undergoes Schmidt-type rearrangement [12] to afford the desired product aryl nitrile. During this process,if the intermediates A bearing a strong electron-withdrawing group,A could be attacked by water,resulting in the formation of aldehyde C [13]. This conversion is similar to Jiao and co-workers’ previous research,in which they achieved the transformation from benzyl halides to aryl nitriles by using DDQ as the oxidant [7].
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| Scheme 1.A proposed mechanism for the reaction. | |
In summary,we have developed a new method to synthesize aryl nitriles via a metal-free electrochemical oxidation process directly from primary benzylic azides. To the best of our knowledge,this is the first report of metal-free oxidation of benzylic azides to nitriles under electrochemical conditions. This electrochemical method is environmentally friendly and easy to handle,thus making it more attractive to aryl nitrile synthesis. Acknowledgment
This work was financially supported by the National Natural Science Foundation of China (Nos. 2127222,91213303,21172205, J1030412). Appendix A. Supplementary data
Supplementary data associated with this article can be found,in the online version,at http://dx.doi.org/10.1016/j.cclet.2014.04.024.
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