Available online at www.sciencedirect.com Chinese Chemical Letters 23 (2012) 1103–1106 www.elsevier.com/locate/cclet Synthesis of a-aminonitriles using silica-bonded N-propylpiperazine sulfamic acid as a recyclable catalyst Tahere Rahi a, Mojtaba Baghernejad a, Khodabakhsh Niknam b,* a b Department of Chemistry, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran Received 11 April 2012 Available online 23 September 2012 Abstract a-Aminonitriles were synthesized via a one-pot three-component condensation of aldehydes, amines, and trimethylsilyl cyanide using silica-bonded N-propylpiperazine sulfamic acid (SBPPSA) as a recyclable solid acid at room temperature. SBPPSA showed much the same efficiency when used in consecutive reaction runs. # 2012 Khodabakhsh Niknam. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Silica-bonded N-propylpiperazine sulfamic acid; a-Aminonitriles; Aldehydes; Amines; Catalyst; Solid acid The addition of cyanide anion to imines (the Strecker reaction) [1] provides one of the most important and straightforward method for the synthesis of a-aminonitriles, which are useful intermediates for the synthesis of amino acids [2] and nitrogen containing heterocycles such as thiadiazoles and imidazoles. [3,4]. The classical Strecker reaction usually is carried out in aqueous solution and the work-up procedure is also tedious. Thus several modifications of Strecker reaction have been reported using a variety of cyanide reagents [5], such as diethyl phosphorocyanidate and a-trimethylsiloxy nitriles, as well as catalysts such as InCl3 [6], [bmim]BF4 [7], montmorillonite KSF clay [8], silica sulfuric acid [9], I2 [10], Fe(Cp)2PF6 [11], xanthan sulfuric acid [12], hydrophobic sulfonic acid based nanoreactors [13], silica-bonded S-sulfonic acid [14], and sulfamic acidfunctionalized magnetic Fe3O4 nanoparticles [15] under various reaction conditions. The use of trimethylsilyl cyanide is a safer and more effective cyanide anion source for the nucleophillic addition reactions of imines under mild conditions [16,17]. However, many of these methods involve the use of expensive reagents, harsh conditions, extended reaction times, and also require tedious workup leading to the generation of a large amount of toxic waste. Furthermore many of these catalysts are deactivated or sometimes decomposed by amines and water that exist during imine formation. In order to overcome these problems, recently one-pot procedures have been developed for this transformation [18]. Recently we prepared silica-bonded N-propylpiperazine sulfamic acid (SBPPSA) and used as a catalyst for the synthesis of 1,2,4,5-tetrasubstituted imidazoles [19] (Scheme 1). * Corresponding author. E-mail address: khniknam@gmail.com (K. Niknam). 1001-8417/$ – see front matter # 2012 Khodabakhsh Niknam. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. http://dx.doi.org/10.1016/j.cclet.2012.07.007 1104 T. Rahi et al. / Chinese Chemical Letters 23 (2012) 1103–1106 Scheme 1. Preparation of silica-bonded N-propylpiperazine sulfamic acid (SBPPSA). Scheme 2. Condensation of aldehydes, amines and trimethylsilyl cyanide catalyzed by SBPPSA. In continuation of our studies toward the preparation and applications of heterogeneous solid acid catalysts [19– 25], herein we wish to report a valid and an efficient procedure for the synthesis of a-aminonitriles via one-pot threecomponent condensation of aldehydes, amines and trimethylsilyl cyanide in the presence of SBPPSA as an inexpensive solid acid catalyst (Scheme 2). Initial studies were carried out on the condensation reaction between benzaldehyde and aniline with TMSCN in the presence of catalytic amounts of SBPPSA as a model reaction (Table 1). A blank experiment without catalyst the reaction did not proceed even after 24 h. The optimal amount of SBPPSA was 0.2 g (equal to 0.24 mmol of H+) per 1 mmol of aldehyde in ethanol at room temperature. Next, we prepared a range of a-aminonitriles under the optimized conditions (Table 2). Both aromatic and aliphatic aldehydes reacted with amines and TMSCN in the presence of SBPPSA in this one-pot three-component condensation to afford excellent yields of corresponding a-aminonitriles. Moreover, aldehydes with electron-withdrawing or electron-donating groups, i.e. 3-nitrobenzaldehyde or 4-methoxybenzaldehyde, and 3,4,5-trimethoxybenzaldehyde were converted into the corresponding a-aminonitriles 1d–1f in high yields (Table 2, entries 4–6). The acid sensitive substrate thiophene-2-carbaldehyde gave the expected a-aminonitrile 1g in very good yield (Table 2, entry 7). Aliphatic aldehydes such as 2-methylpropanal gave the corresponding product 1h in 76% yield Table 1 The reaction of benzaldehyde, aniline and TMSCN in the presence of different amounts of SBPPSA.a Entry The amounts of catalyst (g) Time (min) Yield (%) b 1 2 3 4 5 – 0.08 0.10 0.20 0.30 24 h 140 110 5 5 <10 58 69 90 90 a b Reaction conditions: benzaldehyde (1 mmol), aniline (1.5 mmol), TMSCN (1.5 mmol), EtOH (2 mL), and room temperature. Isolated yield. 1105 T. Rahi et al. / Chinese Chemical Letters 23 (2012) 1103–1106 Table 2 Preparation of various a-aminonitriles in the presence of SBPPSA in EtOH at room temperature.a Entry C6H5– 4-ClC6H4– 4-BrC6H4– 4-CH3OC6H4– 3,4,5-(MeO)3C6H2– 3-O2NC6H4– 2-Thionyl– (CH3)2CH– C6H5– 1 2 3 4 5 6 7 9 10 11 b c R2–NH2 Product C6H5– C6H5– C6H5– C6H5– C6H5– C6H5– C6H5– C6H5–CH2– HN O HN O 3,4-(CH3O)2C6H3– 3,4,5-(MeO)3C6H2– 12 a R1–CHO 4-Cl–C6H5– Time (min) Yield (%) b 90, 89, 89, 87, 85, 85 86 85 93 90 89 79 76 90 c Mp (8C) Lit. Mp (8C) 80–82 112–114 101–103 95–97 147–149 88–91 97–99 Colorless oil 69–71 81–83 [12] 111–112 [8] 99–100 [5] 94–95 [8] 147–149 [14] 89–92 [14] 98–100 [11] Colorless oil [6] 68–69 [6] 1a 1b 1c 1d 1e 1f 1g 1h 1i 5 5 5 30 5 30 50 5 5 1j 5 89 88–91 – 1k 5 90 145–148 – Reaction conditions: aldehyde (1 mmol), amine (1.5 mmol), TMSCN (1.5 mmol), SBPPSA (0.2 g), and EtOH (2 mL). Isolated yield. The recycled catalyst was used. (Table 2, entry 9). Primary amines such as aniline, 4-chloroaniline, benzyl amine, and secondary amine such as morpholine were accomplished these one-pot three-component condensation reactions in short reaction time at room temperature and very good yields. The condensation reaction between benzaldehyde and aniline with TMSCN was examined for the possibility of recycling SBPPSA under the optimized conditions. Upon completion, the reaction mixture was filtered and washed with warm ethanol. The product was recrystallized from hot ethanol. The recovered catalyst was dried and reused for subsequent runs. The recycled catalyst could be reused five times without any additional treatment. SBPPSA showed much the same efficiency when used in six consecutive reactions runs (Table 2, entry 1). Finally, a comparative study of SBPPSA with other recently reported catalysts for condensation of benzaldehyde and aniline with TMSCN as a model compound was made which revealed that SBPPSA is an equally efficient and reusable catalyst (Table 3). In conclusion, heterogeneous conditions, green solvent, easy and clean work-up, high yields and recovery of the catalyst makes this method practical for the synthesis of a-aminonitriles. 1. General procedure, synthesis of a-aminonitriles A mixture of aldehyde (1 mmol), amine (1.2 mmol), trimethylsilyl cyanide (1.2 mmol) and SBPPSA (0.2 g, equal to 0.24 mmol of H+) in EtOH (2 mL) was stirred at room temperature for appropriate time (Table 2). After completion of the reaction, as indicated by TLC, the reaction mixture was filtered and the remaining washed with warm ethanol Table 3 Comparison of the result of condensation reaction of benzaldehyde, aniline and TMSCN in the presence of different catalysts based on silica. Entry Catalyst Catalyst loading (g) Conditions Time (min) Yield (%)a Ref. 1 2 3 4 5 6 7 Montmorillonite KSF clay Silica sulfuric acid Xanthene sulfuric acid SBA-15 supported sulfonic acid SBSSA Sulfamic acid Fe3O4 nanoparticles SBPPSA 1.0 0.095 (0.25 mmol) 0.1 (0.06 mmol) 0.031 (0.017 mmol) 0.2 (0.066 mmol) 0.02 (0.006 mmol) 0.2 (0.24 mmol) rt rt rt 50 8C rt rt rt 210 360 65 5 30 10 5 90 88 97 100 94 97 90 [8] [9] [12] [13] [14] [15] Present work a Isolated yield. 1106 T. Rahi et al. / Chinese Chemical Letters 23 (2012) 1103–1106 (3  5 mL). After cooling, the corresponding a-aminonitrile products were obtained which purified by recrystallization from hot ethanol. The recovered catalyst was dried and reused for subsequent runs. All the products were characterized by comparison of their IR, 1H NMR and 13C NMR spectroscopic data and their melting points with reported values [5–18,26]. Silica-bonded N-propylpiperazine sulfamic acid (SBPPSA) was prepared according to our previously reported procedure [19]. Acknowledgment We are thankful to the Islamic Azad University Research Council for the partial support of this work. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] A. Strecker, Ann. Chem. Pharm. 75 (1850) 27. J. March, Advanced Organic Chemistry, 4th ed., Wiley, New York, 1995, p. 965. L.M. Weinstock, P. Davis, B. Handelsman, R. Tull, J. Org. Chem. 32 (1967) 2823. W.L. Matier, D.A. Owens, W.T. Comer, et al. J. Med. Chem. 16 (1973) 901. A.A.S. El-Ahl, Synth. Commun. 33 (2003) 989. B.C. Ranu, S.S. Dey, S. Hajra, Tetrahedron 58 (2002) 2529. J.S. Yadav, B.V.S. 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Catal. 32 (2011) 1477. K. Niknam, D. Saberi, M. Baghernrjad, Chin. Chem. Lett. 20 (2009) 1444. K. Niknam, D. Saberi, M. Sadegheyan, et al. Tetrahedron Lett. 51 (2010) 692. K. Niknam, N. Jafarpour, E. Niknam, Chin. Chem. Lett. 22 (2011) 69. K. Niknam, A. Hasaninejad, M. Arman, Chin. Chem. Lett. 21 (2010) 399. Data for new compounds. (3,4-Dimethoxyphenyl)-morpholin-4-yl-acetonitrile 1j: white solid; recrystallized from ethanol; mp: 88–91 8C; IR (KBr, cm 1): 2925 (s), 2810 (s), 2320 (m), 1610 (m), 1585 (m), 1510 (vs), 1465 (s), 1418 (s), 1340 (s), 1320 (s), 1279 (s), 1250 (s), 1235 (vs), 1158 (s), 1140 (s), 1115 (vs), 1020 (s), 1000 (s), 865 (vs), 779 (s). 1H NMR (400 MHz, CDCl3): d 2.46–2.55 (m, 4H), 3.60–3.70 (m, 4H), 3.82 (s, 3H), 3.84 (s, 3H), 4.69 (s, 1H), 6.80 (d, 1H, J = 8.3 Hz), 6.94 (d, 1H, J = 2.0 Hz), 7.03 (dd, 1H, J1 = 8.0 Hz, J2 = 2.0 Hz). 13C NMR (100 MHz, CDCl3): d 49.91, 55.97, 56.02, 62.10, 66.69, 110.72, 110.83, 115.40, 120.47, 124.81, 149.28, 149.56. Elemental analysis: calcd: C, 64.10; H, 6.92; N, 10.68. Found: C, 63.89; H, 6.88; N, 10.51. (4-chlorophenylamino)-(3,4,5-trimethoxyphenyl)-acetonitrile 1k: white solid; recrystallized from ethanol; mp: 145–148 8C; IR (KBr, cm 1): 3380 (vs), 2950 (m), 2910 (s), 2807 (m), 2340 (m), 1590 (vs), 1500 (vs), 1458 (s), 1418 (s), 1338 (s), 1310 (s), 1279 (s), 1240 (s), 1230 (vs), 1180 (m), 1081 (m), 999 (s), 810 (s), 720 (s). 1H NMR (400 MHz, CDCl3): d 3.87 (s, 3H), 3.88 (s, 6H), 4.12 (d, 1H, J = 8.4 Hz), 5.32 (d, 1H, J = 8.0 Hz), 6.72 (d, 2H, J = 8.8 Hz), 6.78 (s, 2H), 7.24 (d, 2H, J = 8.8 Hz). 13C NMR (100 MHz, CDCl3): d 50.42, 56.23, 60.89, 104.22, 115.35, 117.97, 125.05, 128.94, 129.45, 138.64, 143.33, 153.77. Elemental analysis: calcd. C, 61.36; H, 5.15; N, 8.42. Found: C, 61.13; H, 5.12; N, 8.28.