Nitriles are well-known compounds due to their huge potential for applications in synthesis of various bioactive molecules ^{[1, 2, 3]}. They are viable precursors for preparation of a variety of nitrogen-containing functional compounds ^{[4, 5, 6, 7]}. In addition, nitriles are versatile and important building blocks of dyes,natural products,herbicides,agrochemicals,pharmaceuticals,and various fine chemicals ^{[8, 9, 10, 11]}. Therefore,developing a simple and flexible method for the preparation of such compounds is still needful.

Numerous approaches to the synthesis of nitriles are completely reviewed in literature. Conventionally used methods are the nucleophilic substitution reaction of alkyl halides with metal cyanides ^[12],dehydration of primary amides ^{[13, 14]} or aldoximes ^{[15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]} and oxidative transformation of primary alcohols ^{[27, 28, 29, 30, 31, 32]}, aldehydes ^{[33, 34, 35, 36]},alkyl halides ^{[37, 38, 39, 40]},primary aliphatic amines ^{[37, 38, 39, 40, 41, 42]} and primary azides ^{[43, 44]}. In addition Pd and Cu catalyzed cyanation of aryl halides was established for the synthesis of benzonitriles ^{[45, 46, 47]}. Furthermore transformation of esters to nitriles was reported ^{[48, 49, 50]}. Recently a mild ammoxidation method,which directly converts methyl arenes into aromatic nitriles,has been developed by using Pd(OAc)₂ and N-hydroxyphthalimide (NHPI) as the catalysts,and tert-butyl nitrite as the nitrogen source and oxidant ^[51]. More recently An NBS mediated nitriles synthesis through C=C double bond cleavage has been developed ^[52].

Undoubtedly,uses of expensive and toxic reagents are some disadvantages of reported methods. Herein an efficient and mild method for mentioned conversion using pentylpyridinium tribromide (PPTB) and aqueous ammonium acetate is reported (Scheme 1). To the best of our knowledge,this is the first report of the application of this reagent for the oxidative conversion of benzyl alcohols,benzyl amines,and benzaldehydes to the corresponding nitriles.

Scheme 1

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Scheme 1. Oxidative conversion of benzylic alcohols,amines and aldehydes to benzonitriles.

Chemicals were purchased from Fluka,Merck,and Aldrich chemical companies. Pentylpyridinium tribromide is a nonvolatile ionic liquid analog of bromine,which play a dual role as solvent and reagent and can be easily prepared from commercially available starting materials ^[53]. Thin layer chromatography (TLC) was performed on UV-active aluminum-backed plates of silica gel (TLC Silica gel 60 F254). Flash chromatography was performed using silica gel (60Å,230-400 mesh) with reagent grade solvents. NMR spectra were recorded on a Bruker Avance AQS 300 MHz using tetramethylsilane (TMS) as an internal standard. The products were characterized by comparison of their spectral,TLC and physical data with the authentic samples.

General procedure: To a mixture of amine,alcohol or aldehyde (1 mmol) and aqueous NH₄OAc (2.0 mL,45 mmol) in a roundbottomed flask was added pentylpyridinium tribromide (2.2 mmol for alcohols and amines and 1.1 mmol for aldehydes) gradually in several small portions at room temperature. The obtained mixture was stirred at 70 °C for appropriate time. When the reaction was complete (monitored by TLC),it was quenched at this temperature with H2O (10mL),aqueous Na₂SO₃ at 0 °C,and then itwas extractedwith Et2O (3 × 5 mL). The combined organic layers were washed with water,dried (MgSO4) and evaporated under vacuum to give benzonitriles in good yield. If necessary,the product was purified by column chromatography (silica gel, hexane-EtOAc,4:1).

Benzonitrile (4a): Colorless liquid. ¹H NMR (300 MHz,CDCl₃): d 7.68-7.65 (2H,m),7.61-7.58 (1H,m),7.51-7.45 (2H,m); ¹³C NMR (75 MHz,CDCl₃): δ 112.1,118.8,129.1,132.0,132.7; Elemental analysis calcd for C₇H₅N: C,81.55; H,4.85; N,13.59. Found: C, 81.52; H,4.87; N,13.61.

4-Methoxybenzonitrile (4b): White solid,mp 59-61 °C. 1H NMR (300 MHz,CDCl₃): δ 7.53 (d,2H,J = 8.4 Hz),7.28 (d,2H, J = 8.4 Hz),2.43 (s,3H); ¹³C NMR (75 MHz,CDCl₃): δ 162.8,134.1, 119.2,114.7,104.0,55.4; Elemental analysis calcd. for C₈H₇NO: C, 72.18; H,5.26; N,10.52. Found: C,72.17; H,5.28; N,10.51.

4-Methylbenzonitirle (4c): Colorless oil. ¹H NMR (CDCl₃, 300 MHz): δ 7.38 (d,2H,J = 8.0 Hz),7.15 (d,2H,J = 8.0 Hz),2.29 (s,3H); ¹³C NMR (75 MHz,CDCl₃): δ 143.4,131.7,129.6,118.8, 109.0,21.5; Elemental analysis calcd. for C₈H₇N: C,82.02; H,6.02; N,11.96. Found: C,81.99; H,6.04; N,11.97.

4-Chlorobenzonitrile (4d): White solid,mp 91-93 °C. ¹H NMR (300 MHz,CDCl₃): δ 7.58 (d,2H,J = 8.5 Hz),7.46 (d,2H,J = 8.5 Hz); ¹³C NMR (75 MHz; CDCl₃): δ 139.5,133.4,129.6,117.9,110.8; Elemental analysis calcd. for C₇H₄ClN: C,61.12; H,2.93; N, 10.18. Found: C,61.10; H,2.95; N,10.16.

3-Nitrobenzonitrile (4e): Colorless solid,mp 117-118 °C. 1H NMR (CDCl₃,300 MHz): δ 8.55-8.54 (m,1H),8.53-8.47 (m,1H), 8.01-7.99 (m,1H),7.76-7.74 (m,1H). ¹³C NMR (CDCl₃,75 MHz): d 148.3,137.6,130.7,127.4,127.2,116.5,114.2; Elemental analysis calcd. for C₇H₄N₂O₂: C,56.76; H,2.72; N,18.91; O,21.60. Found: C, 56.73; H,2.74; N,18.90; O,21.62.

4-Bromobenzonitrile (4f): White solid,mp 112-115 °C: 1H NMR (300 MHz,CDCl₃): δ 7.62 (d,2H,J = 8.5 Hz),7.51 (d,2H, J = 8.5 Hz); ¹³C NMR (75 MHz; CDCl₃): δ 133.3,132.4,127.8,117.9, 111.1. Elemental analysis calcd. for C₇H₄BrN: C,46.19; H,2.22; N, 7.70. Found: C,46.12; H,2.25; N,7.72. 3. Results and discussion

Pentylpyridinium tribromide is stable ionic liquid at room temperature with high molecular weight (MW = 389.95),less toxic than molecular bromine,nonvolatile,easy to handle and relatively cheap oxidant. Because of these properties,we decided to investigate the oxidative conversion of alcohols,amines and aldehydes to nitrile using this reagent in the presence of aqueous ammonium acetate. It is worthwhile to note that the ionic liquid pentylpyridinium bromide was recycled from the reaction mixture and the reagent was regenerated by the direct action of bromine.

In order to explore the optimum reaction conditions,benzyl alcohol was preferred as the model substrate. A mixture of benzyl alcohol and aqueous ammonium acetate solution was stirred under different conditions (Table 1). The results showed that reactions at room temperature provided low yields of benzonitrile, but increasing the amount of PPTB from 2 mmol to 2.2 mmol and increasing the temperature from room temperature to 70 °C gave a considerable improvement in the conversion. It should be mentioned that during all reactions care must be taken when adding PPTB to the substrate/ammonium acetate solution. Adding the PPTB in one portion would result in a relatively violent reaction. To avoid this problem PPTB was added carefully in several small portions.

Table 1

Table 1 Optimization of the amounts of PPTB/aq. NH4OAc for oxidative conversion of benzyl alcohol to benzonitrile at 70 8C.

Table 1 Optimization of the amounts of PPTB/aq. NH4OAc for oxidative conversion of benzyl alcohol to benzonitrile at 70 8C.

The current system was promoted for the direct conversion of aldehydes into nitriles,and the results are summarized in Table 2 (entries 6-11). It should be mentioned that required amount of PPTB for aldehydes is 1.1 mmol. Very good conversion of aldehydes to nitriles was obtained also these reactions were found to be faster compared to the alcohols.

Table 2

Table 2 Oxidative conversion of benzyl alcohols,benzyl amines and benzaldehydes to nitriles with PPTB/aq NH4OAc.

Table 2 Oxidative conversion of benzyl alcohols,benzyl amines and benzaldehydes to nitriles with PPTB/aq NH4OAc.

In addition,this reaction can be used to prepare nitriles in a onepot procedure from amines. In this case,the reaction can be carried out in a single step under the same conditions with PPTB (2.2 mmol) in aqueous ammonium acetate (3 mL,45 mmol) at 70 °C,benzylamine afforded benzonitrile within 1.5 h in 95% yield (Table 2,entry 12). Further,we examined the feasibility of this reaction for various substrates,and the results are summarized in Table 2 (entries 12-16). A probable mechanism for the conversion of substrates into benzonitriles is shown in Scheme 2.

Scheme 2

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Scheme 2. Proposed mechanism for the formation of nitriles.

In conclusion,the present reaction is simple and novel method for preparation of aromatic nitriles. Different benzyl derivatives of alcohols,amines and aryl aldehydes have been efficiently converted to their corresponding nitriles. The present method does not require any organic solvent and expensive catalysts. PPTB is a dark red stable room temperature ionic liquid and nonvolatile, low toxic than molecular bromine,easy to handle and relatively low cost oxidant. So it is more convenient to operate the reaction with PPTB.