Nitriles are versatile organic precursors in the synthesis of amines,amides,aldehydes,carboxylic acids,esters,and ketones, which are also key raw materials for agricultural chemicals,dyes, pharmaceuticals,and functional materials ^[1]. Furthermore,the cyano group is present in numerous bioactive molecules ^[2]. Two of the most classic methods for the preparation of aliphatic nitriles and aromatic nitriles are,respectively,the nucleophilic substitution reaction of alkyl halides with highly toxic inorganic cyanides ^[3] and the Sandmeyer reactions ^[4]. However,the most convenient and attractive method for the synthesis of nitriles is the dehydration of aldoximes,owing to their easy availability and avoiding the use of highly toxic inorganic cyanides. To date,lots of methods have been developed to effect the conversion of aldoximes to nitriles ^[5]. However,some of these methods suffer from the use of moisture-sensitive,highly expensive,and toxic or hazardous reagents,and some of them suffer from tedious work-up procedure. Therefore the search for more convenient and effective methods for dehydration of aldoximes is still desirable.

Perfluoroalkanosulfonyl fluoride (R_fSO₂F,such as n-C₄F₉SO₂F and n-C₈F₁₇SO₂F) is a kind of commercially available and cost effective reagent. R_fSO₂F is non-toxic and moisture-tolerant. In R_fSO2F-induced reactions,the by-product is water-soluble perfluoroalkanesulfonic acid anion,which makes their work-up procedure very easy to handle; on the other hand,perfluoroalkanesulfonic acid salt R_fSO₃^-M⁺ is also a kind of highly valued surfactant,and if needed,perfluoroalkanesulfonic acid can be easily isolated from the aqueous layer by adjusting its pH value with aqueous hydrochloric acid solution after work-up procedure. On the basis of the excellent leaving ability of perfluorosulfonate anion (in comparison with p-toluenesulfonate anion and methanesulfonate anion) ^[6] and the ease of reaction of perfluoroalkanosulfonyl fluoride with alcohol in the presence of a base,R_fSO2F has been developed and used as an excellent hydroxyl groupactivating reagent for fluorination of alcohols ^[7],for cyclodehydration of chiral vicinal diols ^[8],N-acylamino alcohols,β-hydroxy sulfonamides and β-hydroxy thioamides ^[9]. Very recently, perfluoroalkanosulfonyl fluoride-induced Beckmann rearrangement of α,β-unsaturated ketoximes in alkaline media leading to the smooth formation of enamides was reported by us ^[10]. However, to the best of our knowledge,the reaction of perfluoroalkanosulfonyl fluoride with aldoximes has not been investigated yet. Herein,we wish to report the results of dehydration of aldoximes to nitriles induced by perfluoroalkanosulfonyl fluoride in alkaline media (Scheme 1).

Scheme 1

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Scheme 1.n-C4F9SO2F-induced dehydration of aldoximes to nitriles.

The general procedure of n-C4F9SO2F-induced dehydration of a variety of aldoximes to nitriles: at room temperature,n-C4F9SO2F (20.0 mmol,2.0 equiv.) was slowly dropped via syringe into a solution of substrate 1a (10.0 mmol) and 1,8-diazabicyclo[ 5.4.0]undec-7-ene (DBU,50.0 mmol,5.0 equiv.) in CH₂Cl₂ (20 mL). The resulting solution was stirred at this temperature for 10 min. Evaporation under vacuum to remove volatile components offered residue which was purified through silica gel column chromatography (eluted with a mixture of petroleum ether and ethyl acetate),generating nitrile 2a in 95% yield. Colorless solid,mp 143-146 ℃. ¹H NMR (400 MHz,CDCl₃): δ 8.35 (d,2H,J = 8.0 Hz),7.88 (d,2H,J = 8.0 Hz); ¹³C NMR (101 MHz, CDCl₃): δ 150.01,133.43,124.26,118.31,116.74.

To optimize the reaction conditions,p-nitrobenzaldoxime (1a) was selected as a model substrate under various reaction conditions (Table 1). First,using dichloromethane as solvent and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base,we explored the effect of the molar ratio of n (1a): n (n-C₄F₉SO₂F): n (DBU) on dehydration at room temperature. When the molar ratio of 1a/n- C₄F₉SO₂F/DBU is 1:1.5:2,the yield of 2a is 46% with 40% of 1a recovered after 10 min (Table 1,entry 1); the longer reaction time did not improve the yield of 2a. When the ratio was increased to 1:2:5,the best result was obtained with the formation of 2a in 95% yield (entry 3). When the reaction was carried out at 0 ℃,a similar result was obtained; however when the reaction was run at reflux, some unidentified impurities formed. Solvent effects on dehydration were investigated (entries 4-8). Among screened solvents of acetonitrile,toluene,chloroform,dichloromethane,acetone and tetrahydrofuran,dichloromethane was found to be the best choice, and the use of the other solvents resulted in lower yields of 2a in the range of 72-90%. Several organic and inorganic bases,such as pyridine,triethylamine,DBU,K₂CO3,and NaOH were further tested,and the results showed that the use of DBU as base offered the best yield (entries 9-13). Finally both n-C₄F₉SO₂F and n-C₈F₁₇SO₂F showed imilar activity (entry 14). Therefore,the optimized reaction conditions for the dehydration of 1a are: CH₂Cl₂ as solvent,DBU as base,1a: n-C₄F₉SO₂F: DBU = 1:2:5,room temperature,and reaction time of 10 min.

Table 1

Table 1 Optimization of reaction conditions.a

Table 1 Optimization of reaction conditions.a

With the optimized reaction conditions in hand,a variety of aldoximes were subjected to the n-C4F9SO2F/DBU system for dehydration to explore the scope and limitations of the reaction. The results are presented in Table 2. All the aldoximes were smoothly converted to the corresponding nitriles in 70%-95% yields. The dehydration of pyridine-3-carbaldehyde oxime provided 3-cyanopyridine in 86% yield (entry 13). For comparison,the dehydration of pyridine-3-carbaldehyde oxime with AlCl₃⋅6H₂O/ KI/H₂O/CH₃CN system ^[11] and triphenylphosphine/I₂ system ^[12] provided 3-cyanoprridine in 69% yield (after refluxing at 80 ℃ for 6 h) and in 84% yield (at room temperature for 4 h),respectively. The method is applicable to aromatic,aliphatic,and heteroaryl aldoximes and is tolerant to a wide range of functional groups such as methoxy,hydroxyl,halide,and diethylamino groups. Electrondonating or electron-withdrawing group on the aromatic ring has little effect on the yield of the product. The work-up procedure is simple,just needing evaporation under vacuum to remove volatile components and subsequent purification of residue through silica gel column chromatography with a mixture of petroleum ether and ethyl acetate as eluent. All the products were confirmed by 1 HNMR and ¹³C NMR,IR and MS spectra,and the data were identical with literature records.

Table 2

Table 2 n-C4F9SO2F-Induced dehydration of a variety of aldoximes to nitriles.a

Table 2 n-C4F9SO2F-Induced dehydration of a variety of aldoximes to nitriles.a

In conclusion,an efficient method was developed for the dehydration of aldoximes in alkaline media and nitrile products were obtained in 70%-95% yields. Mild reaction conditions,simple work-up procedure,and high yields are advantages of the presented method.

The authors thank the National Natural Science Foundation of China (No. 21362022) for financial support.