440 Acta Chim. Slov. 2008, 55, 440–447 Short communication Synthesis of ฿-aminoalcohols Catalyzed by ZnO Mona Hosseini-Sarvari* Department of Chemistry, Shiraz University, Shiraz 71454, I. R. Iran Fax: +98(711)2280926 * Corresponding author: E-mail: hossaini@susc.ac.ir Received: 17-11-2007 Abstract Zinc oxide (ZnO) catalyses the nucleophilic opening of epoxide rings by amines leading to the efficient synthesis of ฿-aminoalcohols. The reaction works well with aromatic and aliphatic amines in short reaction times and in the absence of any solvent. Exclusive trans stereoselectivity is observed for cyclic epoxides. Furthermore, the catalyst can be reused for several times without any significant loss of catalytic activity. Keywords: ZnO, epoxides, amines, solvent-free conditions, ฿-aminoalcohols 1. Introduction Epoxides are versatile synthetic intermediates and a variety of reagents are known for the epoxide ring opening.1 The resulting products of epoxide aminolysis are important bioisosteres, which appear in several FDA approved drugs.2 Opening of epoxides with amines developed in the past few years mainly involved monohaptic nucleophiles and the use of different catalysts such as metal triflates,3 metal halides,4 polymer supported catalysts,5 montmoril-lonite K10,6 metal salts,7 and different reaction media such as fluoroalcohols,8a ionic liquids,8b and water3b,c or solvent-free conditions (SFC).4c,9 Even though these procedures have considerably improved the scope of this reaction, they are associated with certain limitations. For example, metal triflates and halides either deactivated the Lewis acid catalyst as a consequence of the formation of a stable complex between the metal ion and the amine or require prolonged reaction times (of about 12 h). Only Zn(II) salts in acetonitrile4b were in some cases truly effective catalysts but they completely failed with bihaptic nucleophiles such as 2-picolylamine because the highly azaphilic Zn(II) cation forms a stable complex with the amine. Work-up with such Lewis acids, which are often used in stoichiometric quantities, is difficult due to the formation of emulsions. Furthermore, these catalysts are of no use with deactivated amines and are inconvenient for handling. In some cases reagents are expensive. Finally, hexafluoropropan-2-ol and [bmim]BF4 were not effective in the aminolysis with alkyl amines.8a,b Therefore it seems highly desirable to find a simple, efficient, econo- mical and inexpensive protocol for ฿-aminoalcohols synthesis via epoxide ring opening. In the light of stringent and growing environmental regulations, the chemical industry needs to re-examine the most important synthetic processes and to develop more eco-compatible synthetic methodologies.9 To this purpose heterogeneous catalysis plays a fundamental role, mainly due to its economic and environmental advantages (i.e. minimum execution time, low corrosion, waste minimization, recycling of the catalyst, easy transport and disposal of the catalyst).10 Another important goal in green chemistry is represented by the elimination of volatile organic solvents, in fact solvent-free organic reactions make syntheses simpler, save energy, and prevent solvent waste, hazards, and toxicity.11 Of course the combination of heterogeneous catalysis with the use of solvent-free conditions represents a suitable way toward the so-called ideal synthesis. Because the revision of the fundamental synthetic reactions under solvent-free conditions (SFC) has been the subject of our research in recent years,12 we have recently examined the catalytic activity of zinc oxide (ZnO) in organic synthe-sis.13 ZnO is a non-toxic, inexpensive and non-hygroscopic white powder. It is an important material with a wide Scheme 1 Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ... Acta Chim. Slov. 2008, 55, 440–447 441 ranging application as a catalyst for a number of organic syntheses. So, we wish to report here some efficient ZnO-catalyzed preparations of ฿-aminoalcohols under solvent-free conditions by conventional heating in an oil bath (Scheme 1). Furthermore, ZnO can be re-used up to five times. 2. Results and Discussion In order to delineate the standard operating conditions, cyclohexene oxide (7-oxabicyclo[4.1.0]heptane, 1a) (1 mmol) was treated with 2-picolylamine (2a) (1 mmol) un- der solvent-free conditions in the presence of a catalytic amount of ZnO (5 mol%) at 70 ฐC in an oil bath. Complete conversions took place in 2 h leading to a quantitative yield of the 2-(2-picolylamine)cyclohexanol (3a). The catalyst was recovered by filtration after diluting the reaction mixture with ethyl acetate and was reused repeatedly without any significant loss of catalytic activity. The inexpensive and commercially available catalyst ZnO could now be applied under optimized conditions for the reaction of 1a with variously substituted aromatic and aliphatic amines (Table 1). The reaction protocol is simple and does not require dry glassware and reagents. This is very important for scaling-up the process. The final amino Table 1: ZnO catalyzed synthesis of ฿-aminoalcohols by condensation reaction of 1a with amines (2) Entry Substrate Product Time (h) Yieldb,c (%) 2a 3a 98 2b 3b 98 2c 3c 3.5 92 2d 3d 93 2e 3e 90 2f 3f 92 2g 3g 3.5 90 2h 3h 90 a) All products were characterized by 1H NMR, IR and mass spectral data which were found to be identical with those described in ref. 3,4; for compound 3a see 3d, for 3b,c,f,u see 4c, for 3d see 6, for 3e see 14, for 3h see 4a, for 3j see 4g, for 3n see 3c, for 3s see 15, and for 3t see 16. b) A ra-cemic aminocyclohexanol was obtained. c) Yields for the isolated compounds. d) Reaction was carried out on 100 mmol scale. 1 2 3 4 5 6 7 8 Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ... 442 Acta Chim. Slov. 2008, 55, 440–447 Entry Substrate Product Time (h) Yieldb,c (%) 2i 3i 95 10 2j 3j 98 11 2k 3k 90 12 21 31 93 13 2m 3m 4.5 85 14 2n 3n 36 50 15 2o 3o 30 50 16 2p 3p 80 17 2q 3q 70 18 PhNHPh 2r 3r 30 50 19 (CH3)2CHNHCH(CH3)2 2s 3s 85 20 CH3CH2CH2NH2 2t 3t 94 9 Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ... Acta Chim. Slov. 2008, 55, 440–447 443 Entry Substrate Product Time (h) Yieldb,c (%) 21 2u 3u 90 22 2v 3v 90 23 2w 3w 90 24 2x 3x 80 25 2b 3b 90d alcohols were isolated with high purity (> 99%) and in good yields (50–98%). The results summarized in Table 1 reveal that excellent yields were obtained with aromatic and aliphatic amines and in each case the resulting racemic 2-aryl/alkylami-nocyclohexanol was obtained with exclusive trans diaste-reoselectivity as detected by 1H NMR spectroscopic analysis. Primary and secondary amines react very rapidly. Aniline and its derivatives with electron donating substituents also react quite fast. However, anilines with electron withdrawing substituents, as well as sterically hindered anilines, react very slowly, and aminolysis required prolonged reaction times. The most important contribution is probably the success in the aminolysis of cyclo-hexene epoxide with diphenylamines (entries 17, 22, 23). This represents the first catalytic method for the synthesis of ฿-aminoalcohols derived from diarylamines. These products can be useful for preparation of macrocyclic Table 2: ZnO-catalyzed ring opening of 1,2-epoxides 1b–d with 2-picolylamine (2a) under solvent-free conditions Entry 1,2-Epoxide Product Time (h) Yielda (%) lb 3y 96b lc 3z 95 Id 3a' 93 a) Yields for the isolated compounds. b) 1H NMR, IR and mass spectral data were found to be identical with those described in ref. 3d. Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ... 1 2 3 444 Acta Chim. Slov. 2008, 55, 440–447 compounds. The conversion of aniline into 2-aryl/alkyla-minocyclohexanol on a 100 mmol scale (entry 25) proceeded just as well as the 1 mmol reaction. Then, ZnO catalyzed conditions were extended to a variety of 1,2-epoxides (Table 2). All the reactions were fast and completely ฿- or C2-regioselective. Excellent chemo-selectivity was achieved with epichlorohydrin (entry 3, Table 2) resulting in 93% yield of the aminoalcohol corresponding to the nucleophilic attack at the terminal carbon of the epoxide moiety. No product arising from nuc-leophilic displacement of the chlorine could be detected through MS analysis of the reaction mixture. The re-usability and catalytic activity of ZnO was studied in this system. The catalyst can be so easily separated by dispersing the reaction mixture in ethyl acetate, so that the recovery and re-use of ZnO could be very convenient. As shown in Table 3, the yields of 2-(2-picolylami-ne)cyclohexanol (3a) only slightly decreases after the reuse of ZnO for five times. Table 3: Re-use of ZnO Number of use Yield (%) Recovery of ZnO (%) 1 98 96 2 94 95 3 92 95 4 92 93 5 90 90 Structurally, the ZnO crystal is described schematically as a number of alternating planes composed of four-fold coordinated O2– and Zn2+ ions. As shown in Scheme 2, we propose the following mechanism for the reaction: first, ZnO activates the epoxide with its Lewis acid site (Zn2+) to give intermediate I and this is followed by a nucleophi-le (amine) attack to I to give II and III, respectively. 3. Experimental Progress of the reactions was monitored by the use of silica gel polygrams SIL G/UV 254 plates. IR spectra were recorded on Perkin Elmer 781 and on Impact 400 D Ni-colet FTIR spectrometers. NMR spectra were recorded on Bruker DPX 250 MHz instrument and mass spectra on Shimadzu QP 1100 EX spectrometer using EI 70 eV modes. Microanalyses were performed on a Perkin Elmer 240-B microanalyzer. 3. 1. General Procedure A mixture of ZnO (5 mol %, 0.04 g), amine (1 mmol) and 1,2-epoxide (1 mmol) were heated and stirred in an oil bath at 70 ฐC. The progress of the reaction was monitored by TLC (eluent: n-hexane : EtOAc = 80 : 20). After the reaction was complete, ethyl acetate (2 ื 10 mL) was added to the reaction mixture and ZnO was removed by filtration. The organic solvent was then evaporated and the crude product was obtained. This was further purified by column chromatography. The structures of the products were confirmed by 1H NMR, 13C NMR and comparison with authentic samples obtained commercially or prepared by reported methods. 2-(3-Toluidino)cyclohexanol (3d):6 Oily liquid. 1H NMR (CDCl3) 8 7.02 (1H, s), 6.39-6.60 (3H, m), 3.46 (2H, brs, NH, OH), 3.19-3.27 (1H, m), 3.02-3.08 (1H, m), 2.21 (3H, s), 2.00-2.05 (2H, m), 1.61-1.69 (2H, m), 1.17-1.35 (4H, m); 13C NMR (CDCl3) 8 21.5, 23.7, 25.0, 31.0, 33.4, 59.9, 75.6, 111.5, 115.6, 118.5, 128.7, 139.0, 148.0; MS m/z 205 [M+]. Anal. Cald. for C13H19NO: C, 76.06; H, 9.33. Found: C, 76.03; H, 9.30. 2-(3-Methoxyphenylamino)cyclohexanol (3e):14 Oily liquid. 1H NMR (CDCl3) 8 7.06 (1H, s), 6.21-6.31 (3H, m), 3.73 (3H, s), 3.33 (2H, brs, NH, OH), 3.27 (1H, ddd, J = 4.0, 5.7, 4.4 Hz), 3.08 (1H, ddd, J = 4.0, 5.7, 4.4 Hz), 2.05-2.11 (2H, m), 1.65-1.73 (2H, m), 1.02-1.65 (4H, m); 13C NMR (CDCl3) 8 23.9, 24.9, 30.9, 32.6, 55.1, 59.9, 73.1, 100.3, 103.1, 107.2, 130.0, 149.3, 160.7; MS m/z 221 [M+]. Anal. Cald. for C13H19NO2: C, 70.56; H, 8.65. Found: C, 70.52; H, 8.63. 2-(2-Bromophenylamino)cyclohexanol (3g): Oily liquid. 1H NMR (CDCl3) 8 7.40-7.46 (1H, m), 7.16-7.18 (1H, m), 6.74-6.85 (1H, m), 6.56-6.60 (1H, m) 3.20 (2H, brs, NH, OH), 4.19-4.35 (1H, m), 3.38-3.41 (1H, m), 2.04-2.10 (2H, m), 1.67-1.74 (2H, m), 1.13-1.43 (4H, m); 13C NMR (CDCl3) 8 24.0, 24.4, 31.5, 32.7, 59.7, 74.1, 112.9, 118.3, 123.4, 128.3, 132.5, 144.9; MS m/z 270 [M+]. Anal. Cald. for C12H16BrNO: C, 53.35; H, 5.97. Found: C, 53.33; H, 5.95. O- ZnO ffi-Zn* O2- R-NH^ fY ฉ NH2R ^^^ 1 0-Zn2+ O2- NHR OH ZnO Scheme 2 II III Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ... Acta Chim. Slov. 2008, 55, 440–447 445 2-(3-Bromophenylamino)cyclohexanol (3h):4a Oily liquid. :H NMR (CDC13) ๔ 6.93-6.99 (IH, m), 6.75-6.79 (2H, m), 6.53-6.58 (IH, m), 4.15 (2H, brs, NH, OH), 3.42 (IH, m), 3.25-3.30 (IH, m), 2.98-3.03 (2H, m), 1.64-1.73 (2H, m), 1.01-1.31 (4H, m); 13C NMR (CDC13) ๔ 24.4, 24.6, 31.6, 33.1, 56.9, 73.9, 115.7, 117.8, 120.4, 124.3, 129.8, 148.4; MS m/z 270 [M+]. Anal. Cald. for C12H16BrNO: C, 53.35; H, 5.97. Found: C, 53.31; H, 5.96. 2-(4-Fluorophenylamino)cyclohexanol (3i): Oily liquid. :H NMR (CDCI3) ๔ 6.84-6.91 (2H, m), 6.63-6.69 (2H, m), 3.67 (2H, brs, NH, OH), 3.30-3.34 (IH, m), 2.88-3.01 (IH, m), 2.07-2.10 (2H, m), 1.70-1.75 (2H, m), 1.04-1.35 (4H, m); 13C NMR (CDC13) ๔ 23.9, 24.5, 31.2, 33.3, 58.4, 73.0, 115.1 (d, JCF = 37.5 Hz), 116.5 (d, JCF = 6.3 Hz), 143.4, 156.4 (d, JCF = 239.0 Hz); MS m/z 209 [M+]. Anal. Cald. for C12H16FNO: C, 68.88; H, 7.71. Found: C, 68.85; H, 7.70. 2-(3-Hydroxyphenylamino)cyclohexanol (3k): Oily liquid. :H NMR (CDC13) ๔ 7.06 (IH, s), 6.18-6.27 (3H, m), 4.68 (3H, brs, NH, OH, Ar-OH), 3.26-3.29 (IH, m), 3.01-3.04 (IH, m), 1.99-2.02 (2H, m), 1.59-1.65 (2H, m), 1.18-1.26 (4H, m); 13C NMR (CDC13) ๔ 25.4, 26.2, 31.2, 33.4, 62.9, 72.3, 105.7, 109.2, 111.7, 130.4, 143.3, 148.2; MS m/z 207 [M+]. Anal. Cald. for C12H17N02: C, 69.54; H, 8.27. Found: C, 69.42; H, 8.27. l-{4-[(2-Hydroxycyclohexyl)amino]phenyl}etheno- ne (31): solid; m.p. 79 ฐC. :H NMR (CDC13) ๔ 7.76 (2H, d, J = 3.2 Hz), 6.56 (2H, d, J = 3.2 Hz), 4.30 (2H, brs, NH, OH), 3.43-3.55 (IH, m), 3.24-3.28 (IH, m), 2.48 (3H, s), 2.07-2.12 (2H, m), 1.69-1.79 (2H, m), 1.18-1.34 (4H, m); 13C NMR (CDC13) ๔ 23.9, 24.2, 24.6, 31.4, 33.5, 58.9, 74.2, 112.1, 113.6, 130.8, 152.3, 196.6; MS m/z 233 [M+]. Anal. Cald. for C14H19N02: C, 72.07; H, 8.21. Found: C, 72.06; H, 8.20. 4-(2-Hydroxycyclohexylamino)benzoic acid (3m): solid; m.p. 167 ฐC. :H NMR (CDC13) ๔ 7.85 (2H, d, J = 2.3 Hz), 6.62 (2H, d, J = 2.3 Hz), 5.29 (IH, s, C02H), 4.94 (2H, brs, NH, OH), 3.23-3.43 (2H, m), 1.95-2.10 (2H, m), 1.69-1.85 (2H, m), 1.02-1.47 (4H, m); 13C NMR (CDC13) ๔ 24.2, 24.4, 30.3, 32.9, 61.2, 74.2, 113.7, 118.3, 132.2, 151.5, 171.1; MS m/z 235 [M+]. Anal. Cald. for C13H17N03: C, 66.36; H, 7.28. Found: C, 66.32; H, 7.25. 2-(3-Cyanophenylamino)cyclohexanol (3o): Oily liquid. :H NMR (CDC13) ๔ 6.96 (IH, m), 6.80 (2H, d, J = 1.4 Hz), 6.54-6.59 (IH, m), 3.32 (2H, brs, NH, OH), 3.30-3.32 (IH, m), 3.05-3.07 (IH, m), 2.06-2.07 (2H, m), 1.66-1.72 (2H, m), 1.16-1.33 (4H, m); 13C NMR (CDC13) ๔ 23.7, 24.7, 31.3, 33.5, 59.5, 74.3, 111.2, 116.0, 118.2, 121.1, 124.9, 129.9, 148.3; MS m/z 216 [M+]. Anal. Cald. for C13H16N20: C, 72.19; H, 7.46. Found: C, 72.13; H, 7.45. 2-[2-(Trifluoromethyl)phenylamino]cyclohexanol (3p): Oily liquid. :H NMR (CDC13) ๔ 7.16-7.35 (2H, m), 6.52-6.81 (2H, m), 4.10^1.27 (IH, m), 3.23-3.30 (IH, m), 3.19 (2H, brs, NH, OH), 1.88-1.92 (2H, m), 1.52-1.57 (2H, m), 1.07-1.15 (4H, m); 13C NMR (CDC13) ๔ 24.2, 24.5, 31.2, 33.4, 55.9, 59.5, 121.4 (q, JCF = 257.9 Hz), 113.3 (q, JCF= 37.7 Hz), 116.9 (2xq, JCF= 12.5 Hz), 126.4 (q, JCF= 4.6 Hz), 132.9, 145.9 (q, JCF= 4.6 Hz); MS m/z 259 [M+]. Anal. Cald. for C13H16F3NO: C, 60.22; H, 6.22. Found: C, 60.20; H, 6.20. 2-({6-[(2-Hydroxycyclohexyl)amino]pyridin-2-yl}amino)cyclohexanol (3q): Oily liquid. :H NMR (DM-SO-d6) 8 7.24-7.41 (2H, m), 6.97 (IH, t, J = 1.5 Hz), 5.50-5.70 (4H, m), 5.36 (4H, brs, NH, OH), 2.30-2.48 (4H, m), 1.42-1.55 (4H, m), 1.04-1.27 (8H, m); 13C NMR (DMSO-d6) ๔ 23.7, 24.2, 31.1, 34.1, 56.0, 73.3, 95.1, 138.4, 158.3; MS m/z 305 [M+]. Anal. Cald. for C17H27N302: C, 66.85; H, 8.91. Found: C, 66.82; H, 8.90. 2-(Diphenylamino)cyclohexanol (3r): Oily liquid. :H NMR (CDC13) ๔ 6.67-7.32 (10H, m), 4.13^1.54 (IH, m), 3.02-3.23 (IH, m), 3.01 (IH, brs, OH), 2.34-2.48 (2H, m), 1.72-1.84 (2H, m), 1.12-1.34 (4H, m); 13C NMR (CDC13) ๔ 24.4, 25.9, 32.1, 33.4, 60.2, 74.1, 119.2, 120.6, 126.2, 146.4; MS m/z 267 [M+]. Anal. Cald. for C18H21NO: C, 80.86; H, 7.92. Found: C, 80.84; H, 7.90. 2-(Diisopropylamino)cyclohexanol (3s):15 Oily liquid. :H NMR (CDC13) ๔ 3.56-3.73 (IH, m), 3.42-3.60 (2H, m), 3.34-3.39 (IH, m), 3.37 (IH, brs, OH), 1.14-2.25 (20H, m); 13C NMR (CDC13) ๔ 19.3, 23.7, 23.8, 29.9, 32.9, 46.5, 67.5, 72.8; MS m/z 199 [M+]. Anal. Cald. for C12H25NO: C, 72.31; H, 12.64. Found: C, 72.30; H, 12.61. 2-(Propylamino)cyclohexanol (3t):16 Oily liquid. :H NMR (CDC13) ๔ 4.56 (2H, brs, NH, OH), 4.31^1.33 (IH, m), 4.13 (2H, dd, J = 7.2, 7.2 Hz), 3.60-3.61 (IH, m), 2.18-2.27 (2H, m), 2.04-2.08 (3H, s), 1.72-1.78 (2H, m), 1.22-1.33 (6H, m); 13C NMR (CDC13) ๔ 14.1, 21.0, 24.1, 24.5, 30.9, 33.1, 60.4, 72.7, 87.0; MS m/z 157 [M+]. Anal. Cald. for C9H19NO: C, 68.74; H, 12.18. Found: C, 68.72; H, 12.10. 2-(4-{4-[(2-Hydroxycyclohexyl)amino]phe-noxy}anilino)cyclohexanol (3v): Oily liquid. :H NMR (CDC13) ๔ 6.78 (4H, d, J = 8.8 Hz), 6.59 (4H, d, J = 8.8 Hz), 3.44 (4H, brs, NH, OH), 3.29 (2H, ddd, J = 8.9, 3.6, 9.8 Hz), 2.99 (2H, ddd, J = 8.9, 3.6, 9.8 Hz), 2.01-2.03 (4H, m), 1.68-1.80 (4H, m), 1.00-1.36 (8H, m); 13C NMR (CDC13) ๔ 24.3, 24.8, 32.4, 33.3, 60.8, 74.0, 115.0, 119.0, 143.4, 150.2; MS m/z 396 [M+]. Anal. Cald. for C24H32N203: C, 72.70; H, 8.13. Found: C, 72.70; H, 8.10. 2-(4-{4-[(2-Hydroxycyclohexyl)amino]benzyl}ani-lino)cyclohexanol (3w): Oily liquid. :H NMR (CDC13) Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ... 446 ______________________________________Acta Chim. Slo 8 6.80 (4H, d, J = 5.9 Hz), 6.43 (4H, d, J = 5.9 Hz), 3.90-3.98 (2H, m), 3.59 (2H, s), 3.44 (4H, brs, NH, OH), 2.88-3.15 (2H, m), 0.84-1.87 (16H, m); 13C NMR (CDCl3) 8 20.8, 24.2, 30.8, 31.3, 40.0, 60.3, 73.8, 114.2, 129.4, 143.2, 146.0; MS m/z 394 [M+]. Anal. Cald. for C25H34N2O2: C, 76.10; H, 8.69. Found: C, 76.10; H, 8.67. 7-(2-Hydroxycyclohexyl)-5,6,7,8,9,10-hexahydro-2H-1,13,4,7,10-benzodioxatriazacyclopentadecine-3,ll(4H,12H)-dione (3x): Oily liquid. 1H NMR (CDCl3) 8 8.03 (2H, s, NH), 6.96-7.01 (2H, m), 6.85-6.91 (2H, m), 4.51 (4H, s), 4.32 (1H, brs, OH), 3.49 (4H, t, J = 5.4 Hz), 3.33-3.36 (1H, m), 3.18-3.20 (1H, m), 2.92-2.96 (4H, t, J = 5.4 Hz), 1.96-2.02 (2H, m), 1.69-1.80 (2H, m), 1.25-1.30 (4H, m); 13C NMR (CDCl3) 8 24.0, 24.8, 32.1, 32.7, 38.0, 47.3, 66.8, 73.2, 120.0, 122.0, 165.0, 168.1, 168.6; MS m/z 391 [M+]. Anal. Cald. for C20H29N3O5: C, 61.36; H, 7.47. Found: C, 61.33; H, 7.45. l-Phenoxy-2-[(2-pyridylmethyl)amino]-l-ethanol (3z): Oily liquid. 1H NMR (CDCl3) 8 8.20-8.43 (1H, m), 7.50-7.78 (1H, m), 7.03-7.16 (4H, m), 6.71-6.84 (3H, m), 5.60 (2H, brs, NH, OH), 3.78-4.05 (5H, m), 2.70-2.88 (2H, m); 13C NMR (CDCl3) 8 53.2, 59.0, 68.9, 70.0, 114.5, 121.0, 122.2, 122.8, 129.3, 137.0, 148.9, 158.4, 158.6; MS m/z 258 [M+]. Anal. Cald. for C15H18N2O2: C, 69.74; H, 7.02. Found: C, 69.75; H, 7.01. l-Chloro-3-[(2-pyridylmethyl)amino]-2-propanol (3a’): Oily liquid. 1H NMR (CDCl3) 8 9.07 (1H, d, J = 5.9 Hz), 7.70 (1H, d, J = 5.9 Hz), 7.27-7.32 (2H, m), 5.61 (2H, brs, NH, OH), 3.97-4.01 (2H, m), 3.54 (2H, s), 2.76-3.01 (3H, m); 13C NMR (CDCl3) 8 46.5, 54.2, 54.3, 70.2, 122.7, 122.9, 135.0, 148.6, 169.1; MS m/z 200 [M+]. Anal. Cald. for C9H13ClN2O: C, 53.87; H, 6.53. Found: C, 53.86; H, 6.52. 4. Conclusions In conclusion, we have described a novel and highly efficient solvent-free protocol for the synthesis of ฿-ami-noalcohols using non-toxic and inexpensive ZnO powder. Our method is superior to other existing methods as: (i) there is no need for toxic and waste-producing Lewis acids, (ii) work-up is simple, (iii) the reaction procedure does not require any specialized equipment, (iv) zinc oxide powder can be re-used and (v) solvent-free conditions are appropriate. 5. Acknowledgment I gratefully acknowledge the support of this work by the Shiraz University. 2008, 55, 440–447 6. References 1. (a) H. Sharghi, A. Hassani-Nejad, M. A. Nasseri, New J. Chem. 2004, 28, 946–951 and references therein. (b) H. Sharghi, H. Naeimi, Bull. Chem. Soc. Jpn. 1999, 72, 1525– 1531. (c) B. Tamami, N. Iranpoor, R. Rezaei, Synth. Commun. 2004, 35, 2789–2795. (d) N. Iranpoor, H. Firouzabadi, A. Safavi, M. Shekarriz, Synth. Commun. 2002, 32, 2287–2293. (e) H. Firouzabadi, N. Iranpoor, A. A. Jafari, S. Makarem, J. Mol. Cat. A: Chemical 2006, 250, 237–242. 2. In 1995, thirteen of the top two hundred drugs ranked by prescription volume were ethanolamine-based compounds (source: Pharmacy Times, April 1996). 3. (a) G. Sekar, V. K. Singh, J. Org. Chem. 1999, 64, 287–289. (b) T. Ollevier, G. Lavie-Compin, Tetrahedron Lett. 2004, 45, 49–52. (c) N. Azizi, M. R. Saidi, Tetrahedron 2007, 63, 888–892. (d) F. Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro, J. Org. Chem. 2004, 69, 7745–7747. 4. (a) L. R. Reddy, M. A. Reddy, N. Bhanumathi, K. R. Rao, New J. Chem. 2001, 25, 221–222. (b) L. Durแn Pach๓n, P. Gamez, J. J. M. van Brussel, J. Reedijk, Tetrahedron Lett. 2003, 44, 6025–6027. (c) A. Chakraborti, A. Kondaskar, Te -trahedron Lett. 2003, 44, 8315–8319. (d) J. R. Rodrํguez, A. Navarro, Tetrahedron Lett. 2004, 45, 7495–7498. (e) G. Sun-darajan, K. Vijayakrishna, B. Varghese, Tetrahedron Lett. 2004, 45, 8253–8256. (f) M. Mujahid Alam, R. Varala, E. Ra-mu, S. R. Adapa, Lett. Org. Chem. 2006, 3, 187–190. (g) F. Carr้e, R. Gil, J. Collin, Tetrahedron Lett. 2004, 45, 7749–7751. 5. V. R. Yarapathy, S. Mekala, B. V. Rao, S. Tammishetti, Catalysis Commun. 2006, 7, 466–471. 6. A. K. Chakraborti, A. Kondskar, S. Rudrawar, Tetrahedron 2004, 60, 9085–9091. 7. (a) P.-Q. Zhao, L.-W. Xu, C.-G. Xia, Synlett, 2004, 5, 846–850. (b) M. Curini, F. Epifano, M. C. Marcotullio, O. Rosati, Eur. J. Org. Chem. 2001, 4149–4152. 8. (a) U. Das, B. Crousse, V. Kesavan, D. Bonnet-Delpon, J.-P. B้gu้, J. Org. Chem. 2000, 65, 6749–6751. (b) J. S. Yadav, B. V. S. Reddy, A. K. Basak, A. Venkat Narsaiah, Tetrahedron Lett. 2003, 44, 1047–1050. 9. (a) A. Corma, Chem. Rev., 1995, 95, 559–614. (b) J. H. Clark, D. J. Macquarrie, Chem. Soc. Rev. 1996, 25, 303–310. 10. R. Sheldon, A. Dakka, J. Catal. Today 1994, 19, 215–245. 11. K. Tanka, Solvent-free Organic Synthesis, Wiley-VCH, Weinhein, 2003. 12. (a) H. Sharghi, M. Hosseini-Sarvari, Synlett 2001, 99–101. (b) H. Sharghi, M. Hosseini-Sarvari, Tetrahedron 2002, 58, 10323–10328. (c) H. Sharghi, M. Hosseini-Sarvari, Synthesis 2003, 243–246. (d) M. Hosseini-Sarvari, Acta Chim. Slov. 2007, 54, 345–359. (e) M. Hosseini-Sarvari, H. Sharg-hi, S. Etemad, Chinese J. Chem. 2007, 25, 1563–1567. 13. (a) M. Hosseini-Sarvari, H. Sharghi, J. Org. Chem. 2004, 69, 6953–6956. (b) M. Hosseini-Sarvari, H. Sharghi, Synthesis 2002, 1057–1060. (c) M. Hosseini-Sarvari, Synthesis 2005, 787–790. (d) M. Hosseini-Sarvari, H. Sharghi, Tetrahedron 2005, 61, 10903–10907. (e) M. Hosseini-Sarvari, H. Sharg- Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ... Acta Chim. Slov. 2008, 55, 440–447 447 hi, J. Org. Chem. 2006, 71, 6652–6654. (f) M. Hosseini-Sar- 15. M. Chini, P. Crotti, F. Macchia, Tetrahedron Lett. 1990, 31, vari, H. Sharghi, Phos. Silicon. Sulf. 2007, 182, 2125–2130. 4661–4664. 14. E. Rafiee, S. Tangestaninejad, M. H. Habibi, V. Mirkhani, 16. Y. Yashida, S. Inoue, Chem. Lett. 1978, 2, 139–140. Synth. Commun. 2004, 34, 3673–3681. Povzetek Povzetek: Cinkov oksid (ZnO) katalizira nukleofilno odpiranje epoksidnih obro~ev z amini, kar predstavlja u~inkovito sintezo ฿-aminoalkoholov. Reakcija dobro poteka z aromatskimi in alifatskimi amini s kratkimi reakcijskimi ~asi in brez dodatkov topila. Pri cikli~nih epoksidih reakcija poteka z izklju~no trans stereoselektivnostjo. Katalizator je mo`-no ve~krat ponovno uporabiti brez ob~utnej{ih izgub katalitske aktivnosti. Hosseini-Sarvari: Synthesis of ฿-aminoalcohols Catalyzed by ZnO ...