Journal of Oleo Science Copyright ©2010 by Japan Oil Chemists’ Society J. Oleo Sci. 59, (11) 607-613 (2010) Amidation of Alcohols with Nitriles under Solvent-free Conditions Using Molecular Iodine as a Catalyst Yoshio Kasashima1＊ , Atsushi Uzawa1, Kahoko Hashimoto2, Yu Yokoyama3, Takashi Mino3, Masami Sakamoto3 and Tsutomu Fujita3 1 Education Center, Faculty of Engineering, Chiba Institute of Technology (2-1-1shibazono, Narashino-shi, Chiba 275-0023, JAPAN) 2 Department of Life Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology (2-17-1 Tsudanuma, Narashino-shi, Chiba 275-0016, JAPAN) 3 Graduate School of Engineering, Chiba University (1-33 Yayoi-cho, Inage-ku, Chiba-shi, Chiba 263-8522, JAPAN) Abstract: The reactions of alcohols with nitriles under solvent-free conditions, using molecular iodine as a catalyst, were investigated. The reaction of 1-phenylethanol with propanenitrile produced the amide N-(1- phenylethyl)propanamide, by dehydration and tautomerization, in 71% yield, under the following conditions: temperature＝90℃, alcohol:iodine molar ratio＝1:0.2, alcohol:nitrile molar ratio＝1:5, and reaction time＝5 h. The amidation reactivity depended on the stability of the cationic intermediate formed from the alcohol. The reaction of (−)-borneol with benzonitrile produced a racemic amide in 83% yield. Key words: iodine, solvent-free, amidation, borneol 1 INTRODUCTION spectrometer（JASCO, Easton, MD, USA）. Gas chromatog- Compounds with amide linkages are important in the raphy/mass spectra（GC-MS）were recorded on a Shimadzu chemical industry. The Ritter reaction, which is the reac- GCMS-QP5050A（Shimadzu, Kyoto, Japan）［column: JW tion of alcohols with nitriles, is one method of producing Scientifi c DB-5ms（30 m×0.25 mm, 0.25 μm fi lm）, Agilent, amides1-5）. However, the catalysts used in this reaction are Santa Clara, CA, USA］. Optical rotations were measured generally strong acids or heavy-metal compounds, which on a JASCO DIP-370. X-ray measurements were made on a are very expensive and/or toxic. In the present study, io- Bruker axs-SMART APEX II at －100℃. dine was investigated as a catalyst for the reaction of alco- hols with nitriles. Recently, iodine has been investigated as 2.2 Materials a potential efficient catalyst in several organic reactions 1-Phenylethanol（1）was synthesized as follows: because it has low toxicity6-18）. In this study, we also inves- Acetophenone（6.02 g, 50 mmol）and ethanol（50 mL） tigated solvent-free conditions, from the viewpoint of were placed in a fl ask and the mixture was stirred. Sodium “green chemistry”. borohydride（3.88 g, 102 mmol）was added and the mixture was stirred at 0℃ for 1 d. After evaporation, diethyl ether （50 mL）and then 6M aqueous HCl were added. The mix- ture was then extracted twice with 100 mL of diethyl ether. 2 EXPERIMENTAL The organic layer was washed with 100 mL of aqueous so- 2.1 General dium hydrocarone solution, dried with anhydrous sodium Melting points were measured on a Shibata micro melt- sulfate, and evaporated. The product was purifi ed by col- ing point apparatus（Shibata, Tokyo, Japan）, and were un- umn chromatography with hexane/ethyl acetate（4/1）as the corrected. NMR spectra were obtained using a 400 MHz or eluent. A total of 4.38 g（36.0 mmol; 72％ yield）of 1 was 300 MHz FT-NMR spectrometer（JEOL JNM-LA-400, JEOL, obtained. Tokyo, Japan, or Bruker DPX-300, Bruker, Billerica, MA, USA）with Me4Si as the internal standard and CDCl3 as the 2.3 Amidation solvent. IR spectra were recorded on a JASCO FT/IR-230 A typical procedure is as follows: ＊Correspondence to: Yoshio Kasashima, Education Center, Faculty of Engineering, Chiba Institute of Technology, 2-1-1shibazono, Narashino-shi, Chiba 275-0023, JAPAN E-mail: [email protected] Accepted May 21, 2010 (received for review March 29, 2010) Journal of Oleo Science ISSN 1345-8957 print / ISSN 1347-3352 online http://www.jstage.jst.go.jp/browse/jos/ 607 Y. Kasashima, A. Uzawa1, K. Hashimoto et al. 13 Compound 1（121 mg, 1.0 mmol）, propanenitrile（2）（272 m）, 7.74（2H, d, J＝8.9 Hz）; C-NMR（CDCl3）δ: 21.8, 49.1, mg, 5.0 mmol）and iodine（50.0 mg）were place in a reaction 55.4, 113.7, 126.2, 126.8, 127.4, 128.7, 128.7, 143.3, 162.1, tube, and the tube was sealed. The mixture was stirred at 166.0; IR（KBr）: 3335, 1628 cm－1; EI-MS m/z（rel intensi- 90℃ for 5 h. Diisopropyl ether（3 mL）was added, and then ty）: 255（M＋, 27） a 20％ aqueous solution of sodium thiosulfate（5 mL）was 2.3.7 N（- 2-Octyl）benzamide（10） 1 added to the reaction mixture to remove the iodine. The White crystals, mp 66-67℃. H-NMR（CDCl3）δ: 0.88（3H, mixture was then extracted three times with 20 mL of di- t, J＝6.6 Hz）,1.29（3H, t, J＝7.0 Hz）, 1.22-1.56（10H, m）, isopropyl ether. The organic layer was washed with 100 mL 4.12-4.26（1H, m）, 5.87（1H, bs）, 7.40-7.52（3H, m）, 13 of water, dried with anhydrous sodium sulfate, and evapo- 7.74-7.76（2H, m）; C-NMR（CDCl3）δ: 14.1, 21.1, 22.6, 26.0, rated. The product was purified by column chromatogra- 29.2, 31.8, 37.1, 45.8, 126.8, 128.5, 131.2, 135.1, 166.8; IR phy with hexane/ethyl acetate（10/1）as the eluent. A total （KBr）: 3292, 2923, 2851, 1635 cm－1; EI-MS m/z（rel inten- of 124 mg（0.70 mmol; 71％ yield）of N（- 1-phenylethyl）pro- sity）: 233（M＋, 9） panamide（3）was obtained. The GC-MS purities of all prod- 2.3.8 N-Cyclohexylbenzamide（11） 1 ucts were above 98％. White crystals, mp 137-138℃. H-NMR（CDCl3）δ: The spectroscopic data of the product from 1 is as fol- 1.13-1.30（3H, m）, 1.36-1.50（2H, m）, 1.62-1.79（3H, m）, lows: 2.01-2.06（2H, m）, 3.92-4.04（1H, m）, 6.02（1H, bs）, 13 2.3.1 N（- 1-Phenylethyl）propanamide（3） 7.39-7.51（3H, m）, 7.74-7.77（2H, m）; C-NMR（CDCl3）δ: 1 White crystals, mp 55-56℃. H-NMR（CDCl3）δ: 1.16（3H, 24.9, 25.5, 33.2, 48.6, 126.8, 128.5, 131.2, 135.1, 166.6; IR t, J＝7.6 Hz）, 1.49（3H ,d, J＝6.9 Hz）, 2.21（2H ,q, J＝7.6 （KBr）: 3318, 3240, 2929, 2851, 1627 cm－1; EI-MS m/z（rel Hz）, 5.14（1H, qd, J＝6.9, 7.3 Hz）, 5.67（1H, bs）, 7.24-7.37 intensity）: 203（M＋, 30） 13 （5H, m）; C-NMR（CDCl3）δ: 9.77, 21.7, 29.7, 48.5, 126.1, 2.3.9 N-tert-Butylbenzamide（12） －1 1 127.2, 128.6, 143.3, 172.7; IR（KBr,）; 3330, 2972, 1651 cm ; White crystals, mp 135-136℃. H-NMR（CDCl3）δ: 1.48 EI-MS m/z（rel intensity）: 177（M＋, 46） （9H, s）, 5.95（1H, s）, 7.39-7.48（3H, m）, 7.71-7.73（2H, m）; 13 2.3.2 N（- 1-Phenylethyl）acetamide（4） C-NMR（CDCl3）δ: 28.8, 51.6, 126.7, 128.4, 131.0, 135.9, 1 －1 White crystals, mp 70-71℃. H-NMR（CDCl3）δ: 1.49（3H , 166.9; IR（KBr）: 3325, 2965, 1636 cm ; EI-MS m/z（rel in- d, J＝6.8 Hz）, 1.99（3H , s）, 5.13（1H, qd, J＝6.8, 7.3 Hz）, tensity）: 177（M＋, 18） 13 5.73（1H , bs）, 7.24-7.37（5H, m）; C-NMR（CDCl3）δ: 21.7, 2.3.10 N-Benzylbenzamide（13） 1 23.4, 48.7, 126.2, 127.4, 128.6, 143.1, 169.0; IR（KBr）: 3282, White crystals, mp 92-94℃. H-NMR（CDCl3）δ: 4.65（2H, 1647 cm－1; EI-MS m/z（rel intensity）: 163（M＋, 41） d, J＝5.7 Hz）, 6.43（1H, bs）, 7.20-7.53（8H, m）, 7.78-7.81 13 2.3.3 2-Cyano-N（- 1-phenylethyl）acetamide（5） （2H, m）; C-NMR（CDCl3）δ: 44.1, 126.9, 127.6, 127.9, 1 White crystals, mp 100-101℃. H-NMR（CDCl3）δ: 1.53 128.6, 128.8, 131.5, 134.3, 138.1, 167.3; IR（KBr）: 3289, （3H, d, J＝7.0 Hz）, 3.31（2H , s）, 5.09（1H, qd, J＝7.0, 7.2 3060, 1638 cm－1; EI-MS m/z（rel intensity）: 211（M＋, 64） 13 Hz）, 6.45（1H, bs）, 7.26-7.39（5H, m）; C-NMR（CDCl3）δ: 2.3.11 （±） -exo-N-Isobornylbenzamide（15） 1 21.4, 25.9, 49.9, 114.7, 126.1, 127.8, 128.9, 141.8, 160.0; IR White crystals, mp 125-126℃. H-NMR（CDCl3）δ: 0.88 （KBr）: 3278, 3067, 2975, 2921, 2257, 1648 , cm－1; EI-MS （3H, s）, 0.92（3H, s）, 1.01（3H, s）, 1.19-1.25（1H, m）, m/z（rel intensity）: 188（M＋, 54） 1.33-1.42（1H, m）, 1.59-1.82（4H, m）, 1.93-2.00（1H, m）, 2.3.4 N（- 1-Phenylethyl）benzamide（6） 4.08-4.15（1H, m）, 6.08（1H, bs）, 7.40-7.49（3H, m）, 1 13 White crystals, mp 113-115℃.