Esterification of Long-Chain Acids and Alcohols Catalyzed by Ferric

Oct 21, 2008 - The esters of aromatic carboxylic acids with cetyl alcohol and bulky steroid alcohols, including cholesterol, with C8−C18 fatty acids...
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Ind. Eng. Chem. Res. 2008, 47, 8631–8638

8631

Esterification of Long-Chain Acids and Alcohols Catalyzed by Ferric Chloride Hexahydrate Noboru Ieda, Kshudiram Mantri, Yasuyuki Miyata, Akiyoshi Ozaki, Kenichi Komura, and Yoshihiro Sugi* Department of Materials Science and Technology, Faculty of Engineering, Gifu UniVersity, Gifu 501-1193, Japan

A variety of multivalent metal salt, many of them are hydrates, were screened as catalysts for the esterification of fatty acids and alcohols. These salts included chlorides, nitrates, sulfates, and acetates of Fe3+, Al3+, Ga3+, In3+, ZrO2+, HfO2+, Zn2+, Co2+, Ni2+, Mn3+, Cr3+, and Cu2+. Ferric salts, particularly, FeCl3 · 6H2O, were the most active among the salts screened. The esters of primary C10-C18 fatty acids and alcohols were obtained quantitatively from equimolar mixtures in the presence of FeCl3 · 6H2O (substrate/catalyst (S/C; mol/ mol) ) 200, reaction period ) 6 h, in refluxing mesitylene). Esters of isostearic acid and C10–C18 fatty alcohols were obtained with large quantities and prolonged reaction periods. The esters of aromatic carboxylic acids with cetyl alcohol and bulky steroid alcohols, including cholesterol, with C8-C18 fatty acids, were obtained in high yield. The cationic cluster formed by hydrolysis of the ferric cation is proposed to be the catalytically active species. Such a catalysis is proposed to occur through the activation of the carboxylic acid by ligand exchange from water to the carboxylate moiety, followed by addition of the alcohol. 1. Introduction Fatty acid esters are used as raw materials for emulsifiers; oiling agents for foods, spin finishes, and textiles; lubricants for plastics, paints, and inks; additives for mechanical processing; emollients for personal care products; and surfactants and base materials for perfumes and medicines.1-4 They are also used as solvents, cosolvents, and oil carriers in the agricultural industry. Typically, these esters are synthesized directly from carboxylic acids and alcohols, or from carboxylate derivatives such as esters, amides, and acid halides, and alcohols.5-8 The direct condensation of carboxylic acids and alcohols can be achieved by the use of large excesses of either carboxylic acid or alcohol, along with removal of generated water. The use of acid catalysts has been proposed for high yields of the desired esters. Often, these reactions employ mineral acids, such as sulfuric acid or phosphoric acid. Additionally, organic acids, such as p-toluenesulfonic acid, methanesulfonic acids, trifluoromethanesulfonic acid, heteropolyacids, such as tungstophopsphoric acid, silicophopsphoric acid, and rare earth metal triflates such as scandium and lanthanum triflates, are also used as esterification catalysts. These catalysts have inherent drawbacks, such as the requirement for excess reagents, corrosiveness, high susceptibility to water, difficulty in catalyst recovery and reuse, and posing environmental hazards. Recently, many research groups have investigated homogeneous and heterogeneous catalysts for the esterification of equimolar carboxylic acids and alcohols.9-41 Yamamoto and Ishihara reported direct ester condensation of equimolar carboxylic acids and alcohols using Hf4+ and Zr4+ chlorides,18-21 Zr4+-Fe3+, -Ga3+, and -Sn4+ binary metal complexes,22,23 and boron-derived complexes.24,25 Ishihara also reported that bulky diarylammonium arenesulfonate26-29 and DMAP30,31 are effective catalysts for the esterifications. Tanabe et al. have described the use of areneammonium triflates as catalysts for the esterification of acids and alcohols.32,33 Sambri et al. described Zn(ClO4)2 · 6H2O-catalyzed condensations of nearequimolar quantities of acids and alcohols without solvent.34 * To whom correspondence should be addressed. Tel.: +81-58-2932597. Fax: +81-58-293-2653. E-mail: [email protected].

Nie et al. reported a novel polymer-supported sulfonimide, 10-(4′-perfluorobutylsulfonaminosulfonylphenyl)decylpolystyrene, for esterification of equimolar carboxylic acids and alcohols.36 The use of acidic ionic liquids has also been proposed for esterification reactions.37 These liquids show high catalytic activities; however, they are expensive, synthetically tedious to prepare, and not easy for recycling and reuse for practical applications. There have been a few proposals for the esterification of relatively high molecular weight acids and alcohols.38-41 As such, our group has been interested in examining the “green” synthesis of esters with long-chain carboxylic acids and/or alcohols. Previously, we have reported that multivalent metal salts, many of them are hydrates, have high catalytic activities for the esterification of fatty acids and alcohols.38-41 Herein, we discuss the catalytic performances of multivalent metal salts, particularly FeCl3 · 6H2O, in the esterification of C10-18 fatty acids and alcohols. These catalysts are also applied to the synthesis of esters of benzoic acid and cholesterol with longchain alkyl moieties. 2. Experimental Section 2.1. Chemicals. Stearic acid (1-octadecanoic acid), palmitic acid (1-hexadecanoic acid), myristic acid (1-tetradecanoic acid), lauric acid (1-dodecanoic acid), capric acid (1-decanoic acid), isostearic acid (2-heptylundecanoic acid), stearyl alcohol (1octadecanol), cetyl alcohol (1-hexadecanol), myristyl alcohol (1-tetradecanol), lauryl alcohol (1-dodecanol), capryl alcohol (1-decanol), 2-tetradecanol, 2-dodecanol, and 2-decanol were purchased from Tokyo Kasei Kogyo Co. Ltd., Japan. Oleic acid (Z-9-octadecenoic acid), elaidic acid (E-9-octadecenoic acid), linoleic acid (Z,Z-9,12-octadecandienoic acid), cholesterol, ergosterol, and stigmasterol were purchased from Sigma-Aldrich Inc. 2-Hexadecanol was supplied by from Acros Organics. m-Xylene, mesitylene, and tetralin were purchased from Nacalai Tesque, Japan. Diethylbenzene (o-:m-:p- ) 5:66:29; average ethyl number in benzene ring ) 2.014) was supplied from

10.1021/ie800957b CCC: $40.75  2008 American Chemical Society Published on Web 10/15/2008

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Nippon Steel Chemicals Ltd. All metal salts were obtained from Nakalai Tesque, Japan. All chemicals were used without further purification. 2.2. Product Analysis. Products were analyzed by gas chromatography (GC; Shimadzu Gas Chromatograph 14A equipped with FID, Ultra-1 capillary column (25 m × 0.3 mm; 0.33 µm thick layer)). 1H and 13C NMR spectra were recorded at 400 and 100 MHz, respectively, on a Varian Inova 400 spectrometer. Elemental analyses of all esters were carried out at the Center for Organic Elemental Microanalysis, Kyoto University, Japan. 2.3. Esterification. All esterification reactions were conducted in a single necked round-bottomed flask (100 mL) equipped with a Teflon-coated magnetic stir bar and a Dean-Stark apparatus surmounted with a reflux condenser. An equimolar mixture of substrates (acid and alcohol, 6 mmol) and catalyst (FeCl3 · 6H2O, 0.0082 g, 0.03 mmol) in 40 mL of solvent (benzene, toluene, m-xylene, mesitylene, diethylbenzene, and tetralin) was charged to the round-bottomed flask. The mixture was heated to reflux, and water generated by the reaction was subsequently removed. After 12 or 24 h, the reaction mixture was cooled to ambient temperature. GC analysis was employed to determine the conversion and product yield. Analysis of the products of the esterification of steroid alcohols was carried out by 1H NMR by the comparison of area of the 2-H of the substrate and product esters. Product purification was carried out by column chromatography using silica gel (70-230 mesh), eluting with 10% ethyl acetate in hexane. Analytical data of typical product esters are listed as follows: Decyl Palmitate. IR (KBr): 1731 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.88 (br t, 6H), 1.26 (br s, 38H), 1.58-1.63 (br m, 4H), 2.27-2.31 (t J ) 7.5 Hz, 2H), 4.04-4.07 (t, J ) 6.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ ) 14.11, 22.67, 25.03, 25.93, 28.65, 29.16, 29.25, 29.27, 29.30, 29.36, 29.47, 29.53, 29.60, 29.64, 29.68, 31.89, 31.92, 34.42, 64.40, 174.04. Elemental analysis. Calcd for C26H52O2: C, 78.72; H, 13.21. Found: C, 79.02; H, 12.96. Lauryl Palmitate. IR (KBr): 1732 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.85-0.89 (br m, 6 H), 1.25-1.29 (br s, 42 H), 1.59-1.62 (br m, 4 H), 2.28 (t, J ) 7.5 Hz, 2 H), 4.04 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.32, 22.91, 25.26, 26.16, 28.88, 29.39, 29.48, 29.50, 29.58, 29.59, 29.70, 29.76, 29.80, 29.83, 29.86, 29.88, 29.92, 32.15, 34.63, 64.60, 174.22. Elemental analysis. Calcd for C28H56O2: C, 79.18; H, 13.29. Found: C, 79.17; H, 13.52. Myristyl Palmitate. IR (KBr): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.85-0.89 (br m, 6 H), 1.25-1.30 (br s, 46 H), 1.59-1.65 (br m, 4 H), 2.28 (t, J ) 7.5 Hz, 2 H), 4.04 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.33, 22.92, 25.26, 26.17, 28.88, 29.39, 29.49, 29.50, 29.59, 29.71, 29.76, 29.81, 29.83, 29.88, 29.91, 29.92, 32.15, 34.63, 64.61, 174.22. Elemental analysis. Calcd for C30H60O2: C, 79.58; H, 13.36. Found: C, 79.53; H, 13.66. Cetyl Palmitate. IR (KBr): 1734 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.86-0.89 (br m, 6 H), 1.24-1.30 (br s, 50 H), 1.55-1.65 (br m, 4 H), 2.28 (t, J ) 7.5 Hz, 2 H), 4.04 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.33, 22.92, 25.26, 26.17, 28.88, 29.39, 29.49, 29.50, 29.59, 29.70, 29.76, 29.80, 29.83, 29.88, 29.92, 32.15, 34.64, 64.61, 174.24. Elemental analysis. Calcd for C32H64O2: C, 79.93; H, 13.41. Found: C, 80.02; H, 13.45. Stearyl Palmitate. IR (KBr): 1731 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.86-0.90 (br m, 6 H), 1.26-1.30 (br s, 54 H), 1.57-1.65 (br m, 4 H), 2.29 (t, J ) 7.5 Hz, 2 H), 4.05

(t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.33, 22.92, 25.26, 26.17, 28.88, 29.39, 29.49, 29.50, 29.59, 29.71, 29.76, 29.81, 29.83, 29.88, 29.93, 32.15, 34.64, 64.61, 174.24. Anal. Calcd for C34H68O2: C, 80.24; H, 13.47. Found: C, 80.29; H, 13.63. Cetyl Decanoate. IR (KBr): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.88 (br t, 6H), 1.26 (br s, 38H), 1.58-1.63 (br m, 4H), 2.27-2.31 (t, J ) 7.5 Hz, 2H), 4.04-4.07 (t, J ) 6.7 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ ) 14.10, 22.66, 22.69, 25.03, 25.94, 28.65, 29.16, 29.26, 29.28, 29.37, 29.43, 29.53, 29.58, 29.65, 29.68, 29.70, 31.59, 31.87, 31.92, 34.40, 64.37, 173.98. Anal. Calcd for C26H52O2: C, 78.72; H, 13.21. Found: C, 78.46; H, 12.98. Cetyl Laurate. IR (KBr): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.85-0.88 (br m, 6 H), 1.22-1.29 (br s, 42 H), 1.56-1.62 (br m, 4 H), 2.28 (t, J ) 7.5 Hz, 2 H), 4.04 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.32, 22.91, 25.26, 26.16, 28.88, 29.38, 29.48, 29.50, 29.58, 29.69, 29.75, 29.80, 29.83, 29.88, 29.90, 29.91, 32.13, 32.14, 34.63, 64.61, 174.23. Anal. Calcd for C28H56O2: C, 79.18; H, 13.29. Found: C, 79.21; H, 13.54. Cetyl Myristate. IR (KBr): 1731 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.85-0.89 (br m, 6 H), 1.23-1.27 (br s, 46 H), 1.57-1.62 (br m, 4 H), 2.28 (t, J ) 7.5 Hz, 2H), 4.04 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.33, 22.91, 25.26, 26.16, 28.88, 29.39, 29.48, 29.50, 29.58, 29.70, 29.76, 29.80, 29.83, 29.87, 29.90, 29.92, 34.64, 64.61, 174.24. Anal. Calcd for C30H60O2: C, 79.58; H, 13.36. Found: C, 79.31; H, 13.39. Cetyl Stearate. IR (KBr): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.85-0.89 (br m, 6 H), 1.22-1.29 (br s, 54 H), 1.56-1.62 (br m, 4 H), 2.28 (t. J ) 7.5 Hz, 2 H), 4.04 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.11, 22.68, 25.03, 25.93, 28.64, 29.15, 29.25, 29.27, 29.35, 29.47, 29.52, 29.57, 29.60, 29.65, 29.69, 31.92, 34.41, 64.39, 174.02. Anal. Calcd for C34H68O2: C, 80.24; H, 13.47. Found: C, 80.08; H, 13.76. Decyl Isostearate. IR (film): 1728 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.88 (br t, 6H), 1.19 (d, J ) 6.2 Hz, 3H), 1.25-1.30 (br s, 44H), 1.38-1.48 (br m, 4H), 1.56-1.61 (br m, 4H), 2.25-2.30 (m, 2H), 4.89-4.94 (m, 1H). 13C NMR (100 MHz, CDCl3): δ ) 14.08, 20.12, 22.64, 22.66, 25.46, 27.47, 29.26, 29.31, 29.32, 29.46, 29.54, 29.56, 29.58, 31.81, 31.88, 32.64, 32.71, 35.97, 46.09, 70.39, 176.34. Anal. Calcd for C28H56O2: C, 79.18; H, 13.29. Found: C, 79.56; H, 13.06. Lauryl Isostearate. IR (film): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.87 (br t, 6 H), 1.26 (br s, 45 H), 1.39-1.44 (br m, 2 H), 1.56-1.64 (br m, 4 H), 2.27-2.32 (m, 1 H), 4.06 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.07, 22.63, 22.67, 26.00, 27.48, 28.72, 29.16, 29.56, 29.30, 29.35, 29.50, 29.53, 29.55, 29.57, 29.59, 29.63, 29.66, 31.80, 31.89, 31.91, 32.57, 45.86, 64.10, 176.64. Anal. Calcd for C30H60O2: C, 79.58; H, 13.36. Found: C, 79.74; H, 13.55. Myristyl Isostearate. IR (film): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.87 (br t, 6 H), 1.25 (br s, 49 H), 1.38-1.46 (br m, 2 H), 1.56-1.63 (br m, 4 H), 2.27-2.34 (m, 1 H), 4.06 (t, J ) 6.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.05, 14.07, 22.67, 26.00, 27.48, 28.73, 29.17, 29.26, 29.31, 29.36, 29.51, 29.53, 29.57, 29.60, 29.66, 29.68, 31.81, 31.90, 31.92, 32.57, 45.86, 64.09, 176.63. Anal. Calcd for C32H64O2: C, 79.93; H, 13.41. Found: C, 80.23; H, 13.44. Cetyl Isostearate. IR (film): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.86-0.89 (br m, 9 H), 1.22-1.29 (br s, 50 H), 1.40-1.44 (br m, 2 H), 1.57-1.62 (br m, 4 H), 2.30-2.32 (br

Ind. Eng. Chem. Res., Vol. 47, No. 22, 2008 8633

m, 1 H), 4.06 (t, J ) 6.5 Hz, 1 H). C NMR (100 MHz, CDCl3): δ ) 14.09, 22.64, 22.68, 26.00, 27.49, 28.74, 29.17, 29.27, 29.37, 29.54, 29.58, 29.67, 29.71, 31.59, 31.82, 31.90, 31.93, 32.58, 45.88, 64.11, 176.67. Anal. Calcd for C34H68O2: C, 80.24; H, 13.47. Found: C, 80.14; H, 13.20. Stearyl Isostearate. IR (film): 1735 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.88 (br t, 9H), 1.26 (br s, 54H), 1.39-1.44 (br m, 4H), 1.56-1.65 (br m, 4H), 2.27-2.34 (m, 1H), 4.04-4.08 (t, J ) 6.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ ) 14.10, 22.64, 22.68, 26.00, 27.48, 28.73, 29.17, 29.27, 29.31, 29.37, 29.51, 29.54, 29.56, 29.61, 29.67, 29.71, 31.81, 31.90, 31.93, 32.58, 45.87, 64.11, 176.68. Anal. Calcd for C36H68O2: C, 80.53; H, 13.52. Found: C, 80.61; H, 13.85. 2-Decyl Palmitate. IR (film): 1730 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.88 (br t, 6H), 1.19 (d, J ) 6.6 Hz, 3H), 1.25-1.30 (br s, 40H), 1.44-1.49 (br m, 4H), 1.54-1.63 (br m, 4H), 2.24-2.31 (m, 2H), 4.87-4.92 (m, 1H). 13C NMR (100 MHz, CDCl3): δ ) 14.07, 14.09, 20.00, 22.65, 22.68, 25.11, 25.41, 29.14, 29.23, 29.29, 29.36, 29.45, 29.48, 29.50, 29.60, 29.65, 29.68, 31.85, 31.92, 34.74, 35.95, 70.66, 173.51. Anal. Calcd for C26H52O2: C, 78.72; H, 13.21. Found: C, 79.04; H, 13.29. 2-Dodecyl Palmitate. IR (KBr): 1736 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.87-0.89 (br m, 6 H), 1.20 (d, J ) 6.3 Hz, 3 H), 1.22-1.29 (br s, 40 H), 1.45-1.65 (br m, 4 H), 2.25 (t, J ) 7.4 Hz, 2 H), 4.89-4.90 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ ) 14.07, 19.99, 22.67, 25.10, 25.41, 29.28, 29.33, 29.36, 29.45, 29.48, 29.55, 29.56, 29.60, 29.65, 29.69, 31.90, 70.65, 173.47. Anal. Calcd for C28H56O2: C, 79.18; H, 13.29. Found: C, 79.46; H, 13.21. 2-Tetradecyl Palmitate. IR (KBr): 1723 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.85-0.88 (br m, 6 H), 1.17 (d, J ) 6.2 Hz, 3 H), 1.22-1.30 (br s, 44 H), 1.38-1.65 (br m, 4 H), 2.25 (t, J ) 7.4 Hz, 2 H), 4.84-4.91 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ ) 14.32, 20.23, 22.91, 25.34, 25.64, 29.38, 29.52, 29.58, 29.68, 29.71, 29.78, 29.81, 29.83, 29.88, 29.91, 32.15, 34.99, 36.18, 70.92, 173.77. Anal. Calcd for C30H60O2: C, 79.58; H, 13.36. Found: C, 79.31; H, 13.12. 2-Hexadecyl Palmitate. IR (KBr): 1723 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.85-0.88 (br m, 6 H), 1.18 (d, J ) 6.2 Hz, 3 H), 1.22-1.30 (br s, 48 H), 1.38-1.65 (br m, 4 H), 2.25 (tr, J ) 7.4 Hz, 2 H), 4.84-4.92 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ ) 14.33, 20.24, 22.91, 25.34, 25.64, 29.38, 29.52, 29.59, 29.68, 29.71, 29.78, 29.81, 29.83, 29.88, 29.92, 32.15, 34.99, 36.18, 70.92, 173.78. Anal. Calcd for C32H64O2: C, 79.93; H, 13.41. Found: C, 79.70; H, 13.28. 2-Decyl Isostearate. IR (film): 1735 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.88 (br t, 9H), 1.26 (br s, 40H), 1.39-1.44 (br m, 4H), 1.56-1.65 (br m, 4H), 2.27-2.34 (m, 1H), 4.04-4.08 (t, J ) 6.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ ) 14.08, 22.63, 22.67, 25.93, 27.48, 28.72, 29.17, 29.26, 29.31, 29.51, 29.53, 29.55, 29.57, 31.81, 31.89, 32.57, 45.87, 64.10, 176.66. Anal. Calcd for C28H56O2: C, 79.18; H, 13.29. Found: C, 79.35; H, 13.54. Cetyl Oleiate. IR (film): 1740 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.87 (br t, 6 H), 1.26 (br s, 46 H), 1.58-1.63 (br m, 4 H), 1.98-2.03 (br m, 4 H), 2.28 (br t, 2 H), 4.05 (tr, J ) 6.7 Hz, 2 H), 5.32-5.35 (br m, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.07, 22.67, 25.00, 25.93, 27.14, 27.20, 28.65, 29.09, 29.12, 29.16, 29.25, 29.31, 29.35, 29.51, 29.57, 29.65, 29.68, 29.75, 31.90, 31.91, 34.36, 64.35, 129.70, 129.94, 173.86. Anal. Calcd for C34H66O2: C, 80.56; H, 13.12. Found: C, 80.82; H, 13.13. 13

Cetyl Elaidate. IR (KBr): 1735 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.88 (br t, 6 H), 1.26 (br s, 46 H), 1.58-1.63 (br m, 4 H), 1.98-2.03 (br m, 4 H), 2.28 (br t, 2 H), 4.05 (t, J ) 6.6 Hz, 2 H), 5.32-5.35 (br m, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.09, 22.68, 25.01, 25.94, 28.66, 28.95, 29.12, 29.18, 29.25, 29.31, 29.35, 29.48, 29.52, 29.57, 29.65, 29.67, 29.69, 31.90, 31.92, 32.54, 32.60, 34.40, 64.39, 130.21, 130.45, 173.96. Anal. Calcd for C34H66O2: C, 80.56; H, 13.12. Found: C, 80.28; H, 13.07. Cetyl Linoleate. IR (film): 1740 cm-1. 1H NMR (400 MHz, CDCl3): δ ) 0.87 (br t, 6 H), 1.25 (br s, 44 H), 1.58-1.63 (br m, 4 H), 1.98-2.02 (br m, 4 H), 2.27 (br t, 2 H), 4.05 (t, J ) 6.6 Hz, 2 H), 5.32-5.34 (br m, 2 H). 13C NMR (100 MHz, CDCl3): δ ) 14.04, 22.66, 24.98, 25.91, 27.13, 27.18, 28.65, 29.08, 29.11, 29.15, 29.24, 29.30, 29.35, 29.51, 29.56, 29.64, 29.66, 29.68, 29.74, 31.89, 31.91, 34.33, 64.30, 129.67, 129.90, 173.77. Anal. Calcd for C34H64O2: C, 80.89; H, 12.78. Found: C, 80.61; H, 13.06. Cholesteryl Palmitate. mp: 80-81 °C. IR (KBr): 1742 cm-1. 1 H NMR (500 MHz, CDCl3): δ ) 0.67 (3H, s), 0.82-0.92 (12H, m), 0.92-0.99 (2H, m), 1.00 (3H, s), 1.02-1.18 (6H, m), 1.2 (28H, br s), 1.28-1.38 (6H, m), 1.40-1.61 (10H, m), 1.83 (3H, m), 1.94-2.04 (2H, m), 2.25 (2H, t, J ) 7.6 Hz), 2.36 (2H, m), 4.6 (1H, m), 5.4 (1H, br d). 13C NMR (125 MHz, CDCl3): δ ) 11.9, 14.2, 18.8, 19.4, 21.1, 22.6, 22.8, 22.9, 23.9, 24.4, 25.2, 27.9, 28.1, 28.3, 29.2, 29.3, 29.4, 29.5, 29.6, 29.7, 29.8, 31.9, 32.0, 34.8, 35.9, 36.3, 36.7, 37.1, 38.2, 39.6, 39.8, 42.4, 50.1, 56.2, 56.8, 73.7, 122.7, 139.8, 173.4. Anal. Calcd for C43H76O2: C, 82.63; H, 12.26. Found: C,82.73; H, 12.18. Ergosteryl Stearate. mp: 108-109 °C. IR (KBr): 1742 cm-1. 1 H NMR (500 MHz, CDCl3): δ ) 0.62 (3H, s), 0.78-0.92 (14H, m), 0.92 (2H, s), 1.02 (3H, br d), 1.24 (40H, s), 1.46 (1H, m), 1.58 (4H, m), 1.64-1.78 (2H, m), 1.82-1.94 (4H, m), 1.96-2.08 (2H, m), 2.25-2.95 (2H, m), 2.30-2.38 (1H, m), 2.40-2.52 (1H, m), 4.7 (1H, m), 5.20-5.50 (2H, m), 5.3 (1H, br s), 5.5 (1H, br s). 13C NMR (125 MHz, CDCl3): δ ) 12.1, 14.2, 16.3, 17.7, 19.7, 20.0, 21.1, 21.2, 22.8, 23.1, 25.1, 28.2, 28.4, 29.2, 29.3, 29.4, 29.5, 29.6, 29.7, 29.8, 32.0, 33.2, 35.0, 36.8, 37.2, 38.0, 39.1, 40.5, 42.9, 46.1, 54.6, 55.7, 72.5, 116.4, 120.2, 132.1, 135.6, 138.7, 141.5, 173.4. Anal. Calcd for C46H78O2: C, 83.32; H, 11.86. Found: C, 83.57; H, 12.13. Stigmasteryl Palmitate. mp: 106-107 °C. IR (KBr): 1741 cm-1. 1H NMR (500 MHz, CDCl3): δ ) 0.67 (3H, s), 0.7-0.9 (14H, m), 1.0 (9H, m), 1.1-1.2 (3H, m), 1.3 (28H, br s), 1.38-1.74 (14H, m), 1.83 (2H, m), 1.92-2.08 (2H, m), 1.92-2.08 (2H, m), 2.27 (2H, d, J ) 7.2 Hz), 2.30 (2H, br d), 4.6 (1H, m), 5.0 (1H, dd, J ) 9.0, 15.2 Hz), 5.1 (1H, dd, J ) 8.3, 11.0 Hz), 5.3 (1H, br d). 13C NMR (125 MHz, CDCl3): δ ) 12.1, 12.3, 14.2, 19.1, 19.4, 21.1, 21.2, 21.3, 22.8, 24.4, 25.2, 25.5, 27.9, 29.0, 29.2, 29.3, 29.4, 29.5, 29.7, 29.8, 31.9, 32.0, 34.8, 36.7, 37.1, 38.2, 39.7, 40.6, 42.3, 50.1, 51.3, 56.0, 56.9, 73.7, 122.6, 129.4, 138.4, 139.8, 173.4. Anal. Calcd for C45H78O2: C, 83.01; H, 12.07. Found: C, 82.76; H, 11.94. 3. Results and Discussion 3.1. Catalyst Screening. Figure 1 shows influences of the type of metal chloride hydrates on the esterification of palmitic acid and cetyl alcohol using multivalent metal chlorides. The reactions were carried out at substrate/catalyst (S/C) ) 200 (mol/ mol) for 6 h in refluxing mesitylene, where water formed by the reaction was removed as azeotropic mixtures. Among the metal salts, FeCl3 · 6H2O and GaCl3 provided particularly high activities for the esterification reaction, InCl3 · 4H2O and ZnCl2 provided moderate activities, and AlCl3 · 6H2O, ZrOCl2 · 8H2O,

8634 Ind. Eng. Chem. Res., Vol. 47, No. 22, 2008 Table 1. Influences of Type of Metal Salt in Esterification of Palmitic Acid and Cetyl Alcohol Catalyzed by Metal Saltsa

3+

Fe Al3+ In3+ ZrO2+ Zn2+ Co2+ Ni2+ Cu2+

chloride

nitrate

sulfate

acetate

98 36 70 28 43 31 21 24

73 36 68 37 41 31 23 15

67 22 34 42 19 18 19 31

60 68 39 41 18 16

a Reaction conditions: palmitic acid, 6 mmol; cetyl alcohol, 6 mmol; catalyst, 0.03 mmol; mesitylene, 40 mL; reaction period, 6 h. The reaction was carried out under refluxing mesitylene.

Figure 1. Catalytic activity of metal chlorides in the esterification of palmitic acid and cetyl alcohol. Reaction conditions: palmitic acid, 6 mmol; cetyl alcohol, 6 mmol; catalyst, 0.03 mmol; solvent mesitylene, 40 mL; reflux; reaction period, 6 h. The reaction was carried out in refluxing mesitylene.

Figure 3. Influence of solvent on the esterification of palmitic acid and cetyl alcohol catalyzed by FeCl3 · 6H2O. Reaction conditions: palmitic acid, 6 mmol; solvent, 6 mmol; the solvent, 40 mL. The reaction was carried out under refluxing mesitylene. 9, Mesitylene; 0, m-xylene; b, toluene; O, benzene.

Figure 2. Influence of the type of metal salts on the esterification of palmitic acid and cetyl alcohol. Reaction conditions: palmitic acid, 6 mmol; cetyl alcohol, 6 mmol; catalyst, 0.03 mmol; mesitylene, 40 mL. The reaction was carried out under refluxing mesitylene. 9, FeCl3 · 6H2O; 0, GaCl3; 4, InCl3 · 6H2O; 2, AlCl3 · 6H2O; b, ZrOCl2 · 8H2O; O, HfOCl2 · 8H2O.

HfOCl2 · 8H2O, and CoCl2 · 6H2O provided low activities. Almost no activity was observed with other metal halides, CrCl3 · 6H2O, MnCl2 · 6H2O, NiCl2 · 6H2O, CuCl2 · 6H2O, MgCl2, CaCl2, and NaCl. ZrOCl2 · 8H2O and HfOCl2 · 8H2O, which are among the most active catalysts in previous work,38 provided significantly lower activities for the esterification reaction relative to FeCl3 · 6H2O. The conventional acid catalyst, H2SO4, had a high catalytic activity of 93% under our conditions. Figure 2 shows the influence of the type of metal salts on the reaction period in the esterification of palmitic acid and cetyl alcohol. These results highlight the efficient catalyst performances of FeCl3 · 6H2O and GaCl3 over a short reaction time. InCl3 · 4H2O provided a medium level of activity, completing the esterification in 24 h. AlCl3 · 6H2O, ZrOCl2 · 8H2O, and HfOCl2 · 8H2O provided lower initial activities, and the reactions were not complete after 24 h. These results indicate that it is important to note the initial activities when discussing overall catalytic activities. Herein, activities are discussed over a 6-h reaction period.

Table 1 summarizes the influences of the type of metal salts on the esterification of palmitic acid and cetyl alcohol. The esterification reaction progressed in the presence of a variety of metal salts; chlorides provided the highest activities, while nitrates, sulfates, and acetates provided high to moderate activities. Some differences were observed among metal salts, although the order of the activity was similar to that of the chlorides. These results suggest that the cationic metal moieties play important roles in the catalytically active species. Among the multivalent metal salts, FeCl3 · 6H2O provided the highest catalyst activities in the esterification of palmitic acid and cetyl alcohol in refluxing mesitylene. As such, further research was focused on studying FeCl3 · 6H2O as the optimal esterification catalyst. 3.2. Catalytic Properties of FeCl3 · 6H2O in the Esterification of Fatty Acids and Alcohols. Figure 3 shows the influences of the reaction period on aromatic hydrocarbon solvents under refluxing conditions, in the esterification of palmitic acid and cetyl alcohol. Catalytic activities were increased with an increase in boiling point of the solvent; the boiling points of aromatic hydrocarbon are keys for the completaion of the reaction. The reaction was complete within 6 h in mesitylene and within 24 h in m-xylene. However, only 65% and 10% conversion were obtained in toluene and benzene, respectively, after 24 h. The use of diethylbenzene and tetralin, under refluxing conditions, resulted in faster completion of the reaction, likely due to the higher reaction temperatures.

Ind. Eng. Chem. Res., Vol. 47, No. 22, 2008 8635

Figure 4. Influence of the amount of FeCl3 · 6H2O on the esterification of palmitic acid and cetyl alcohol. Reaction conditions: palmitic acid, 6 mmol; cetyl alcohol, 6 mmol; FeCl3 · 6H2O, 0.03 mmol; mesitylene, 40 mL. The reaction was carried out under refluxing mesitylene. S/C: 9, 50; 0, 100; b, 200; O, 1000; 2, 2000. Table 2. Esterification of Normal Acids with Primary Alcohols with Different Carbon Chain Lengths Catalyzed by FeCl3 · 6H2Oa entry

acid

1 2 3 4 5

palmitic palmitic palmitic palmitic palmitic

acid acid acid acid acid

(C16) (C16) (C16) (C16) (C16)

6 7 8 4 9

capric acid (C10) lauric acid (C12) myristic acid (C14) palmitic acid (C16) stearic acid (C18)

alcohol

yield (%)

capryl alcohol (C10) lauryl alcohol (C12) myristic alcohol (C14) cetyl alcohol (C16) stearyl alcohol (C18)

100 91 96 91 94

cetyl cetyl cetyl cetyl cetyl

alcohol alcohol alcohol alcohol alcohol

(C16) (C16) (C16) (C16) (C16)

90 97 98 91 94

a Reaction conditions: acid, 6 mmol; alcohol, 6 mmol; catalyst, 0.03 mmol; mesitylene, 40 mL; reaction period, 6 h. The reaction was carried out under refluxing mesitylene.

Figure 4 show the influences of the reaction period on the catalytic activities with varying substrate/catalyst (S/C; mol/ mol) in the esterification of palmitic acid and cetyl alcohol. The reaction with S/C ) 200 was complete within 6 h, while a decrease in catalyst amounts significantly increased the requisite reaction period. From these results, we chose S/C ) 200 for further research. 3.3. Influences of Chain Length of Acids and Alcohols Catalyzed by FeCl3 · 6H2O. Table 2 summarizes the influences of chain lengths of fatty acids and alcohols on the esterifications. High yields of the desired esters were obtained with a change of chain length of alcohols (C10-C18) with palmitic acid, and with a change of chain length of the fatty acids (C10-C18) with cetyl alcohol. It is interesting that the catalytic activities of FeCl3 · 6H2O do not depend significantly on the chain length of acids and alcohols. 3.4. Esterification of Unsaturated Fatty Acids with Cetyl Alcohol Catalyzed by FeCl3 · 6H2O. Figure 5 shows the influences of reaction periods on catalytic activities by varying the S/C in the esterification of oleic acid and cetyl alcohol. The reaction with S/C ) 200 was complete within 6 h, while a decrease in catalyst quantities resulted in longer requisite reaction periods, analogous to the experiments described above. As such, we again selected S/C ) 200 for further research.

Figure 5. Influence of the amount of FeCl3 · 6H2O on the esterification of oleic acid with cetyl alochol. Reaction conditions: oleic acid, 6 mmol; cetyl alcohol, 6 mmol; mesitylene, 40 mL. The reaction was carried out under refluxing mesitylene. S/C: 9, 50; 0, 100; b,200; O, 1000; 2, 2000. Table 3. Esterification of Unsaturated Acid with Cetyl Alcohol Catalyzed by FeCl3 · 6H2Oa entry

acid

yield (%)

1 2 3

oleic acid elaidic acid linoleic acid

94 95 97

a Reaction conditions: acid, 6 mmol; alcohol, 6 mmol; catalyst, 0.03 mmol; mesitylene, 40 mL; reaction period, 6 h. The reaction was carried out under refluxing mesitylene.

Table 3 summarizes the esterification of unsaturated acids, specifically elaidic and linoleic acids, with cetyl alcohol in refluxing mesitylene over 6 h (S/C ) 200). The esterification of these acids afforded the corresponding esters in 80-90% overall yields within 6 h. It is interesting to note that isomerization of the double bonds did not occur under the relatively harsh reaction conditions, likely due to the weak acidity of the active species derived from FeCl3 · 6H2O. 3.5. Esterification of Branched Acids and Alcohols Catalyzed by FeCl3 · 6H2O. Figure 6 shows the influence of the reaction period on the catalytic activities by varying the substrate/catalyst (S/C) in the esterification of palmitic acid and 2-dodecanol. The esterification did not occur without the catalyst, and the reactivities of 2-alkanols with C10-C16 were significantly less relative to the reaction of the corresponding primary fatty alcohols under the same conditions. Large quantities of catalyst were necessary for the completion of the reaction. The use of catalyst with S/C ) 13-100 provided yields between 80 and 90% within 6 h in refluxing mesitylene; however, with the use of smaller catalyst loadings the reaction did not complete even in 24 h. As such, we selected S/C ) 17 for further research on 2-alkanol. Table 4 summarizes the influence of chain length of the 2-alkanols on the esterification of palmitic acid in refluxing mesitylene over 6 h (S/C ) 17). The esterification proceeded to only 11% conversion without the catalyst, and the inherent reactivities of the 2-alkanols were significantly lower relative to the corresponding primary alcohols, even in the presence of FeCl3 · 6H2O under the same reaction conditions. The esterification provided up to 80-90% yields in the presence of large quantities of catalyst within 6 h.

8636 Ind. Eng. Chem. Res., Vol. 47, No. 22, 2008 Table 6. Esterification of Aromatic Acids with Cetyl Alcohol and Palmitic Acid with Aromatic Alcohols Catalyzed by FeCl3 · 6H2Oa

Figure 6. Influence of the amount of FeCl3 · 6H2O on the esterification of palmitic acid and 2-dodecanol. Reaction conditions: palmitic acid, 6 mmol; 2-dodecanol, 6 mmol; mesitylene, 40 mL. The reaction was carried out under refluxing mesitylene. S/C: 9, 13; 0, 17; b, 25; O, 50; 2, 100; 4, 200. Table 4. Esterification of Palmitic Acid with Secondary Alcohols Catalyzed by FeCl3 · 6H2Oa entry

alcohol

yield (%)

1 2 3 4

2-decanol (2-C10) 2-dodecanol (2-C12) 2-tetradecanol (2-C14) 2-hexadecanol (2-C16)

84 87 80(11b) 89

a Reaction conditions: acid, 6 mmol; alcohol, 6 mmol; catalyst, 0.36 mmol; mesitylene, 40 mL; reaction period, 6 h. The reaction was carried out under refluxing mesitylene. b Without using catalyst.

Table 5. Esterification of Isostearic Acid with Primary and Secondary Alcohols Catalyzed by FeCl3 · 6H2Oa entry

alcohol

yield (%)

1 2 3 4 5

capryl alcohol (C10) lauryl alcohol (C12) myristic alcohol (C14) cetyl alcohol (C16) stearyl alcohol (C18)

80 85 86 87 79

6 7 8

2-decanol (2-C10) 2-dodecanol (2-C12) 2-tetradecanol (2-C14)

9 10 8

a Reaction conditions: acid, 6 mmol; alcohol, 6 mmol; catalyst, 0.12 mmol; mesitylene, 40 mL; reaction period, 24 h. The reaction was carried out under refluxing mesitylene.

Table 5 summarizes the esterification of isostearic acid (1) with primary alcohols and 2-alkanols in refluxing mesitylene over 24 h (S/C ) 50). The reaction of isostearic acid with primary C10-C18 alcohols provided 90-100% yield after 24 h, while it took longer for reaction completion relative to the reaction of palmitic acid with C10-C18 alcohols. These lower reactivities of isostearic acid are likely due to the steric hindrance of the acid toward catalyst and alcohol. The esterification of isostearic acid with C10-C16 2-alkanols did not proceed significantly, resulting only in yields below 10%, again likely due to steric hindrance issues.

entry

acid

1 2 3 4 5 6 7 8

benzoic acid p-nitrobenzoic acid o-nitrobenzoic acid p-chlorobenzoic acid o-chlorobenzoic acid p-cyanobenzoic acid p-anisic acid p-toluic acid

cetyl cetyl cetyl cetyl cetyl cetyl cetyl cetyl

9 10 11 12 13 14 15

palmitic palmitic palmitic palmitic palmitic palmitic palmitic

phenol 2-chlorophenol 4-chlorophenol 2-nitrophenol 4-nitrophenol benzyl alcohol 3-phenylpropanol

acid acid acid acid acid acid acid

alcohol

(C16) (C16) (C16) (C16) (C16) (C16) (C16)

alcohol alcohol alcohol alcohol alcohol alcohol alcohol alcohol

yield (%) (C16) (C16) (C16) (C16) (C16) (C16) (C16) (C16)

93 96 43 37 51 17 76 90 no reaction trace trace no reaction no reaction 85 98

a Reaction conditions: acid, 6 mmol; alcohol, 6 mmol; catalyst, 0.12 mmol; mesitylene, 40 mL; reaction period, 6 h. The reaction was carried out under refluxing mesitylene.

3.6. Esterification of Benzoic Acid with Fatty Alcohols by FeCl3 · 6H2O. Table 6 summarizes the esterification of aromatic acids with cetyl alcohol and of aromatic alcohols with palmitic acid in refluxing mesitylene over 6 h (S/C ) 50). The reaction occurred smoothly under our conditions, although the reactivities of benzoic acid varied with each aromatic substituent. Benzoic acid and p-chlorobenzoic acid provided high reactivities, resulting in excellent yields of the corresponding esters. However, the yield of the ester of o-chlorobenzoic acid was only 51%. The reaction of p-anisic acid and p-toluic acid with cetyl alcohol provided 80-90% of the corresponding esters. These results suggest the electronic properties of the carboxylic acid moieties do not significantly influence reactivities. However, o-nitrobenzoic, p-nitrobenzoic, and p-cyanobenzoic acids were poorly reactive, due, in part, to their poor solubilities in mesitylene even under refluxing conditions. Table 6 summarizes the esterification of alcohols bearing phenyl groups with palmitic acid. Phenol, 2-chlorophenol, 4-chlorophenol, and nitrophenols did not provide the desired esters. This suggests that FeCl3 · 6H2O cannot catalyze the esterification of phenols. However, benzyl alcohol and 3-phenylpropanol provided the corresponding esters in high yield. 3.7. Esterification of Steroid Alcohols with Fatty Acids by FeCl3 · 6H2O. FeCl3 · 6H2O was the most active catalyst for the esterification of steroid alcohols with fatty acids, among metal salts examined.42 We examined the catalyst loadings for the esterification of cholesterol and stearic acid in the presence of FeCl3 · 6H2O. Increasing the S/C from 50 to 200 resulted in a decrease in the yield from 93% to 20%. From these results, we chose S/C ) 100 for the esterification of steroids with fatty acids. Table 7 shows the influences of chain lengths of fatty acids on the esterification of the steroid alcohols, cholesterol (2), ergosterol (3), and stigmasterol (4) in the presence of FeCl3 · 6H2O. The esterification proceeded efficiently for all fatty acids, resulting in the formation of the corresponding fatty acid esters of steroid alcohols, 2, 3, and 4; FeCl3 · 6H2O provided esters with high yields irrespective of chain length. 3.8. Catalytically Active Species in the Esterification. It is interesting to note that multivalent metal salt, many of them are hydrates, impart high catalytic activities on the esterification of bulky molecules. The metal salts are susceptible to forming metal hydroxides, resulting in the formation of cationic metal clusters under the appropriate conditions.43 Notably, the metal

Ind. Eng. Chem. Res., Vol. 47, No. 22, 2008 8637 Table 7. Influence of Chain Length of Fatty Acid with Steroid Alcohols Catalyzed by FeCl3 · 6H2Oa entry

alcohol

1 2 3 4 5 6

cholesterol cholesterol cholesterol cholesterol cholesterol cholesterol

(2) (2) (2) (2) (2) (2)

7 8 9 10 11 12

ergosterol ergosterol ergosterol ergosterol ergosterol ergosterol

13 14 15 16 17 18

stigmasterol stigmasterol stigmasterol stigmasterol stigmasterol stigmasterol

(3) (3) (3) (3) (3) (3) (4) (4) (4) (4) (4) (4)

acid

yield (%)

octanoic acid (C8) decanoic acid (C10) lauric acid (C12) myristic acid (C14) palmitic acid (C16) stearic acid (C18)

>88 (97) >99 >99 94 77 (96) 89 (>99)

octanoic acid (C8) decanoic acid (C10) lauric acid (C12) myristic acid (C14) palmitic acid (C16) stearic acid (C18)

>99 >99 84 (>99) >99 86 (>99) 57 (>99)

octanoic acid (C8) decanoic acid (C10) lauric acid (C12) myristic acid (C14) palmitic acid (C16) stearic acid (C18)

90 97 >99 96 90 80 (97)

a Reaction conditions: FeCl3 · 6H2O, 0.06 mmol; acid and alcohol, 6.0 mmol; mesitylene, 40 mL; reaction period, 12 h. Numbers in parentheses are yields after 24 h. The reaction was carried out under refluxing mesitylene.

salts of Zr4+, Al3+, and Fe3+ are readily hydrolyzed to hydroxides, forming the corresponding cationic clusters. Although there is not enough evidence for this formation in the present work, we propose that the cluster may be the catalytically active species. These clusters are not as acidic as the conventional mineral acids, and they are only stable in the presence of water as a coordinated ligand. We therefore propose that the carboxylic acid moieties of the fatty acids are activated by replacing a bridged water coordinated to the ferric cation, followed by attack of the alcohol moieties to form the esters. This hypothesis is supported by the observation that no transesterification of cetyl and myristyl palmitates with capryl alcohol occurs under our conditions. This suggests that the interaction of the carboxylic acid moieties against the metal enter is an important key for the catalysis. It is interesting that FeCl3 · 6H2O provides high catalytic activities. Cationic clusters from ferric chloride are readily agglomerated to higher order clusters, and they typically precipitate in the absence of stabilizers.43 This is different from other metal halides, such as ZrOCl2 · 8H2O, which form definite cationic clusters, such as [Zr4(OH)8(H2O)16]8+.44 Although there is no formation of precipitate, the agglomerated Fe3+ clusters should be formed and dispersed in the reaction solution under our conditions. Interestingly, no Tyndall phenomena, characteristic phenomena of colloids, were observed in our reaction

mixtures. This suggests that the ferric clusters are not of high molecular weight under our conditions due to the stabilization of the carboxylic acid moieties. Further research, such as the identification of the specific ferric species, is necessary for the clarification of this proposed mechanism. We are currently examining the characterization of Fe3+ clusters by MALDI TOF mass spectroscopy, and these results will be reported in due course. The clusters formed by the hydrolysis of metal salts as discussed previously are dispersed as colloids in the reaction solution. However, the ferric species dispersed in the reaction solution were removed effectively by adsorption on activated charcoal, and the esters can be easily obtained as pure products by a conventional work up. 4. Conclusion In the present work, multivalent metal salts, many of them are hydrates, were screened as catalysts for the esterification of fatty acids and alcohols, and FeCl3 · 6H2O and GaCl3 were the most active among the salts. Esters with bulky moieties were obtained from an equimolar mixture of corresponding acids and alcohols. Esters of primary fatty acids and alcohols with C10-C18 were obtained quantitatively from their equimolar mixtures in the presence of small quantities of catalyst (substrate/catalyst (S/C; mol/mol) ) 200). Esters with branched alkyl moieties were obtained by using large quantities of catalyst and prolonged reaction periods. However, esters with bulky moieties in both acid and alcohol, such as isostearic acid and 2-alkanol, were not obtained under our conditions. The esters of bulky steroid alcohols, such as cholesterol, ergosterol, and stigmasterol with C8-C18 fatty acids were obtained in high yields. Esters of benzoic acid with C8-C10 fatty alcohols were also obtained effectively in the presence of FeCl3 · 6H2O. We have proposed that a cationic cluster, formed by hydrolysis of the ferric cation, acts as the catalytically active species. Catalysis is initiated by the activation of the carboxylic acid by ligand exchange from water to carboxylate, and it is followed by nucleophilic attack of the alcohols. Further aspects, particularly on the scope of the reactions, catalytic active species, and practical applications, are under investigation. The details will be published in the near future. Acknowledgment A part of this work was financially supported by a Grantin-Aid for Scientific Research (B) 19310060, The Ministry of Education, Culture, Sports, Science and Technology. K.M. is grateful to the Japan Society for the Promotion of Science (JSPS) for a postdoctoral fellowship. Literature Cited (1) Fatty Acids in Industry: Processes, Properties, DeriVatiVes, Applications; Johnson, R. W., Fritz, E., Eds.;Marcel Dekker: New York, 1988. (2) Srivastava, A. K.; Monohar, R.; Shukla, J. P. Refractive indices, order parameter and principal polarizability of cholesteric liquid crystals and their mixtures. Mol. Cryst. Liq. Cryst. 2006, 454, 627. (3) Bunjes, H.; Rades, T. J. Thermotropic liquid crystalline drugs. J. Pharm. Pharmacol. 2005, 57, 807. (4) Ginsburg, G. S.; Atkinson, D.; Small, D. M. Physical properties of cholesteryl esters. Prog. Lipid Res. 1985, 23, 135. (5) Larock, R. C. ComprehensiVe Organic Transformations; VCH: New York, 1989; p 966. (6) Benz, G. ComprehensiVe Organic Syntheses; Trost, R. M., Flemings, I., Eds.; Pergamon: Oxford, 1991; Vol. 6, Chapter 2.3, pp 381-417.

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ReceiVed for reView June 18, 2008 ReVised manuscript receiVed August 16, 2008 Accepted August 25, 2008 IE800957B