In this work, we report an efficient and facile preparation of diphenylmethylethers (benzydryl ethers, DPM-ethers) from benzhydrol and alcohols or phenols. Wells-Dawson heteropolyacid (H6P2W 18O62.24H2O), bulk or supported on silica showed catalytic activity for DPM-ethers preparation in toluene, at 60-80°C, in 0.5-1.5h. In these conditions twelve diphenylmethylethers of alcohols and phenol were obtained which excellent yields (78-96%). The heterogeneous reaction conditions provided a very simple, environmentally friendly, clean, economical and selective protocol, for the preparation of unsymmetrical ethers. The catalyst is easily recycled and reused without loss of the catalytic activity.Facultad de Ciencias Agrarias y ForestalesCentro de Investigación y Desarrollo en Ciencias Aplicada

Autino, Juan Carlos

Baronetti, Graciela T.

Bideberripe, Hernán Pablo

Romanelli, Gustavo Pablo

Ruiz, Diego Manuel

Thomas, Horacio Jorge

Baronetti, Graciela Teresita

Servicio de Difusión de la Creación Intelectual

General Papers ARKIVOC 2007 (i) 1-8Silicagel-supported H6P2W18O62.24H2O: a reusable catalyst to prepare diphenylmethyl (DPM) ethersGustavo P. Romanellia,b*, Diego M. Ruiza,b, Hernán P. Bideberripea, Juan C. Autinob, Graciela T. Baronetti/ and Horacio J. ThomasaaCentro de Investigación y Desarrollo en Ciencias Aplicadas “Dr. J. J. Ronco” (CINDECA), Departamento de Química, Facultad de Ciencias Exactas, UNLP-CONICET. Calle 47 N° 257, B1900AJK La Plata, Argentina bCátedra de Química Orgánica, Facultad de Ciencias Agrarias y Forestales, UNLP. Calles 60 y 119, B1904AANLa Plata, ArgentinacDepartamento de Ingeniería Química, Facultad de Ingeniería, Universidad de Buenos Aires. Ciudad Universitaria, C1428BG Buenos Aires, ArgentinaE-mail: gpr(d,química. unlp. edu. arAbstractIn this work, we report an efficient and facile preparation of diphenylmethylethers (benzydryl ethers, DPM-ethers) from benzhydrol and alcohols or phenols. Wells-Dawson heteropolyacid (H6P2Wi8O62.24H2O), bulk or supported on silica showed catalytic activity for DPM-ethers preparation in toluene, at 60-80°C, in 0.5-1.5h. In these conditions twelve diphenylmethylethers of alcohols and phenol were obtained which excellent yields (78-96%). The heterogeneous reaction conditions provided a very simple, environmentally friendly, clean, economical and selective protocol, for the preparation of unsymmetrical ethers. The catalyst is easily recycled and reused without loss of the catalytic activity.Keywords: H^WigC^ ST^O, silicagel-supported catalyst, DPM-ethers, protecting groups, alcohols, phenolsIntroductionThe use of heteropolyacids (HPAs) as catalysts for organic chemistry synthetic processes has been developed for important industries related to fine chemicals, such as flavor, pharmaceutical and food industries. Heteropolyacids are more active catalysts than conventional mineral acids. They have many advantages over liquid acid catalysts: higher acid strengths and thermal stabilities; they are noncorrosive, environmentally benign, cheap and reusable and require less waste disposal.1ISSN 1424-6376 Page 1 ARKAT USA, Inc.General Papers ARKIVOC 2007 (i) 1-8We have recently studied the catalytic activity for the heteropolyacid H6P2W18O62-24H2O with Wells-Dawson structure. We have already used this catalyst for performing the tetrahydropyranylation of alcohols and phenols and their detetrahydropyranylation,2 cleavage of MOM-ethers of phenols,3 preparation of acylals,4 and coumarin synthesis via the Pechmann reaction.5On the other hand, the correct choice of an efficient protecting group is often decisive for successfully synthesizing a complex molecule.6 Protection of the hydroxy functional group is an important procedure7'8'9 in multistep organic synthesis. The preparation of DPM ethers is one of the popular methods in view of their low cost and high stability towards a variety of reagents. Additionally, DPM ethers and DPM groups are found as part of the structure of pharmacological active compounds.10A wide variety of reagents are available for the preparation of DPM ethers such as diphenylmethyl chloride or bromide in the presence of a base,11 diphenylmethanol in the presence of concentrated sulfuric12 or p-toluenesulfonic13 acids, xenon di fluoride.14 diphenylmethyldiazomethane,15 diphenylmethylphosphate-trifluoroacetic acid,16 ytterbium triflate-ferric chloride17 and other ferric or ferrous salts.103 More recently Varma has described a suitable method using Nafion-H as a reusable catalyst.18In continuation of our work on the catalytic properties of Wells-Dawson heteropolyacids, herein we report the use of bulk or silica-supported Wells-Dawson acid as a reusable, heterogeneous catalyst for an efficient DPM-ether preparation over a wide variety of alcohols and phenols.Results and DiscussionThe catalytic activity of the bulk Wells-Dawson acid (WD) and that of Wells-Dawson acid containing 40% by weight of the acid (WDWSiCh) was tested in the preparation of DPM-ethers (Scheme in Table 1). The protection reaction was studied using different alcohols and phenols as substrates, and diphenylmethanol for introducing the DPM group. In all cases, toluene was used as solvent.Initially we conducted blank experiments without the presence of WD. No product was detected when 1 mmol of methanol and 1 mmol of benzhydrol were warmed at 60°C for 5 h. When the mixture of methanol and benzhydrol was warmed under identical conditions but in the presence of silica (support), benzhydrol was the only product detected by TLC.The preparation of DPM-ethers starting from methanol and benzydrol was tested under a variety of conditions (temperature and solvent), using the bulk catalyst. The reaction gives higher yields in toluene solution compared to the use of chloroform. The reaction was complete in 1 h at 60°C and in 4 h at 40°C, affording DPM ether in 93% (entry 1), and 78% (entry 2), respectively. No reaction was detected at room temperature (entry 3). Similarly benzhydrol and ISSN 1424-6376 Page 2 ARKAT USA, Inc.General Papers ARKIVOC 2007 (i) 1-8n-butanol were warmed in toluene at 70°C for 1 h with a catalytic amount of WD to give 83% of the DPM-ether (entry 5).Table 1. Preparation of DPM-ethers from alcohols and phenols using both bulk and silica-supported P2Wi8O62H6.24H2OOH OR1% P2W18062H6 ■ 24 H20Toluene, 70°CROHAlcohol Entry Time (h) Yield (%) WD Entry Time (h) Yield (%)WD40/SÌO2Methanol Ia 1 93 15a 1 94(94,93)d2b 4 783C 10 -Isopropanol 4a 1 91 16a 1 85n-Butanol 5 1 83 17 1 85'/b/V-Butanol 6 1.5 87 18 1.5 86Allylic Alcohol 7 1 89 19 1.5 89Benzyl alcohol 8 0.5 84 20 0.5 832-Phenethyl alcohol 9 1 81 21 1 81Benzhydrol 10 1 95 22 0.5 96Phenol 11 1 84 23 1 84(85,85)d4-Methyl-phenol 12 1 85 24 1 853- Methyl-phenol 13 1 83 25 1 844-Nitro-phenol 14 1 81 26 1 80a60°C, b40°C, c20°Cd In parentheses, yields obtained in the first and second reuse of the catalyst.Other primary, secondary, tertiary, allylic, and benzylic alcohols were also protected in the same way in short reaction times, the yields of DPM-ethers being higher than 81% (entries 4-10). The reactivity trend of this reaction for different alcohols was found to be benzylic > allylic = primary = secondary > tertiary.Primary and secondary alcohols give good to very good yields of DPM ethers (see Table 1, entries 1, 5, 9 and 4, 10). Likely, benzyl, allyl, and /c/7-butyl alcohols (entries 8, 7, 6) gave good yields, although the reaction times were somewhat different, between 0.5 and 1.5 h under the selected experimental conditions.We applied similar reaction conditions for the protection of substituted phenols. The reactions proceeded efficiently with good yields and the nature of the substituents seems to have no effects on the conversion rates (see Table 1, entries 11-14).ISSN 1424-6376 Page 3 ARKAT USA, Inc.General Papers ARKIVOC 2007 (i) 1-8In view of the obtained results when the bulk catalyst was employed, we used WD4o/Si02 for comparative purposes; very similar yields were obtained in comparable reaction times (entries 15-24). Furthermore, use of the supported catalyst allows an easy separation and recovery for its immediate reutilization.Recycling of the catalyst was studied for the reaction between methanol and benzydrol using WTWSiCh. The procedure was repeated twice without any significant loss of activity, as the catalyst remained active even after the third cycle (93% yield, entry 15). Similar results were obtained for DPM-ether of phenol (85% yield, entry 23).Experimental SectionGeneral Procedures. Commercially available alcohols and phenols Aldrich or Fluka were distilled or recrystallized before use. Melting points of the compounds were determined in open capillary tubes and are uncorrected. Boiling points were read from a thermometer in the microdistillation head and are reported uncorrected. 'H-RMN spectra (CDCI3) were recorded on Bruker 200 MHz spectrometer using TMS as internal standard. Low-resolution mass spectra were recorded on a Perkin Elmer GC-MS model (Q-MASS 910). Spectral data agree with the expected values. Elemental microanalyses were performed in F & M instrument. The purity determination of the products was accomplished by GC analysis on a Perkin Elmer instrument and TLC on silica gel 60 F254 plates, for co-inj ection with authentic samples prepared by known methods. The purity established by GLC, was better than 97% in all the cases.Catalyst preparationsThe Dawson acid (H6P2Wi8O62.24H2O.) was prepared by the Drechsel method19'20 from a a/p K6P2Wi8O62.10H2O isomer mixture. This Dawson-type salt was prepared according to the technique reported by Lyon et al.21. Concentrated H3PO4 in a 4:1 acid/salt ratio was added to a boiling aqueous solution of Na2WO4.2H2O, and the mixture was kept boiling in a reflux system for 8 h. The salt was precipitated by adding KC1, then purified by recrystallization and cooled overnight to 278 K. The product, which is a mixture of the a and P isomers, was filtered, washed and then vacuum-dried for 8 h.The acid was obtained from an aqueous solution of a/p K6P2Wi8O62.10H2O salt, which was treated with ether and concentrated HC1 (37%) solution. The Dawson acid so released formed an addition compound with the ether, which allows it to be separated from the solution. After obtaining the ether solution with the acid, the ether was eliminated by flowing dry air and the remaining solution was placed in a vacuum-desiccator until crystallization.Silica-supported Wells-Dawson acids (WD40/SÍO2) was prepared by wet impregnation Grace Davison silica (Grade 59, specific area= 250 m2/g) with an aqueous solution of the synthesized WD acid. A catalyst containing 40 wt% of WD was prepared. After impregnation, samples were dried at room temperature in a vacuum-dessicator for 8 h.ISSN 1424-6376 Page 4 ARKAT USA, Inc.General Papers ARKIVOC 2007 (i) 1-8Typical procedure for the preparation of DPM-ethers of alcoholsA mixture of alcohol (1 mmol), diphenylmethanol (1 mmol), and P2Wi8O62H6-24H2O (1% mmol, approx. 40 mg of bulk catalyst, or 100 mg of the silica-supported one) was stirred at the indicated temperature and time (see Table 1), in toluene (5 mL). The reaction mixture was diluted with toluene (15 mL), and the catalyst was filtered off, then the solution was washed with water (2x10 mL), dried with anhydrous Na2SO4, the solvent was evaporated, and the residue was purified by column chromatography (silicagel, ethyl acetate:hexanes) to afford pure DPM- ethers.Benzhydryl methyl ether. Colorless oil (94%); bp: 150-151°C (20 Torr) (lit bp: 147-148°C (17 Torr)22; 'H-NMR 5h (200 MHz, CDCk, TMS): 3.49 (3H, s), 5.37 (1H, s) 7.30-7.41 (10H, m); MS (El), 70 eV, m/z (rel. intensity): 198 (65) [M+], 167 (97), 152 (22), 121 (100), 105 (70); Anal Calcd. For C14H14O: C 84.81, H 7.12; Found: C 84.78, H 7.08.Benzhydryl isopropyl ether. Colorless oil (91%); bp: 160-162°C (20 Torr) (lit. bp: 156- 159.5°C (15 Torr)16; 'H-NMR 5h (200 MHz, CDCk TMS): 1.20 (6H, d, J=6Hz), 3.67 (1H, sp, J=6Hz), 5.30 (s, 1H), 7.15-7.25 (10H, m); Anal Calcd. For Ci6Hi8O: C 84.92, H 8.02; Found: C 84.90, H 8.02.Benzhydryl n-butyl ether. Colorless oil (85%); bp: 165-166 °C (10 Torr) (lit. bp: 166-167.5°C (10 Torr)16; 'H-NMR 5h (200 MHz, CDC13, TMS): 0.92 (t, 3H, 6Hz), 1.30-160 (m, 4H), 3.45 (t, 2H, 6Hz), 5.34 (s, 1H), 7.10-7.30 (m, 10H); MS (El), 70 eV, m/z (rel. intensity): 240 (10) [M+], 183 (5), 167 (100), 153 (21), 107 (37), 105 (28); Anal Calcd. For Ci7H20O: C 84.96, H 8.39; Found: C 84.92, H 8.40.Benzhydryl Lbutyl ether. White needles (87%); mp: 50-51 °C (Methanol) (lit. mp: 50°C (Methanol)24; 'H-NMR 5h (200 MHz, CDC13, TMS): 1,20 (s, 9H), 5.34 (s, 1H), 7.11-7.31 (m, 10H); MS (El), 70 eV, m/z (rel. intensity): 240 (1) [M+], 222 (66), 207 (70), 178 (25), 165 (29), 91 (60); Anal Calcd. For Ci7H20O: C 84.96, H 8.39; Found: C 84.93, H 8.42.Benzhydryl allyl ether. Colorless oil (89%); bp: 125-126 °C (1 Torr) (lit. bp: 120°C (0.2 Torr)23; 'H-NMR 5h (200 MHz, CDC13, TMS): 3.81 (d, 2H, J=3Hz), 5.20 (m, 2H), 5.42 (s, 1H), 6.01 (m, 1H), 7.15-722 (m, 10H); MS (El), 70 eV, m/z (rel. intensity): 224 (5) [M+], 182 (49), 168 (58), 167 (100), 166 (56), 105 (85); Anal Calcd. For Ci6Hi6O: C 85.68, H 7.18 ; Found: C, 85.66 H 7.22.Benzhydryl benzhyl ether. White needles (84%); mp: 49-51 °C (Ethanol) (lit. mp: 51 °C (Ethanol)24; 'H-NMR 5h (200 MHz, CDC13, TMS): 4.50 (s, 2H), 5.40 (s, 1H) 7.10-7.35 (m, 15H); MS (El), 70 eV, m/z (rel. intensity): 274 (1) [M+], 183 (91), 167 (98), 152 (25), 105 (72), 91 (100); Anal Calcd. For C20Hi8O: C 87.56, H 6.61 ; Found: C, 87.59 H 6.64.Benzhydryl phenethyl ether. Colorless oil (81%); bp: 135-136 °C (1 Torr) (lit. no data)25. 'H- NMR §H (200 MHz, CDC13, TMS): 2.71 (t, 2H, 6Hz), 3.50 (t, 2H, 6Hz), 5.42 (s, 1H), 7.12-7.35 (m, 15H); MS (El), 70 eV, m/z (rel. intensity): 288 (9) [M+], 183 (18), 167 (100), 152 (15), 105 (18), 91 (10); Anal Calcd. For C2iH20O: C 87.46, H 6.99 ; Found: C, 87.47 H 6.97.ISSN 1424-6376 Page 5 ARKAT USA, Inc.General Papers ARKIVOC 2007 (i) 1-8Dibenzhydril ether. White needles (96%); mp: 106-107°C (Benzene) (lit. mp: 107-107.5°C (Ethanol)19; *H-NMR SH (200 MHz, CDCk TMS): 5.40 (s, 2H), 7.20-7.39 (m, 20H); Anal Calcd. For C26H22O: C 89.11, H 6.32 ; Found: C, 89.12 H 6.32.Typical procedure for the preparation of DPM-ethers of phenolsA mixture of phenol (1 mmol), diphenylmethanol (1 mmol), and P2Wi8O62H6-24H2O (1% mmol, approx. 40 mg, bulk or 100 mg supported on silica) was stirred at the indicated temperature and time (see Table 1), in toluene (5 mL). The reaction mixture was diluted with toluene (15 mL), the catalyst was filtered off, and then the solution was washed with 1 M NaOH (10 mL) and water (2 x 10 mL), dried with anhydrous Na2SC>4, solvent was evaporated, and the residue purified by column chromatography (silicagel, ethyl acetate:hexanes) to afford pure DPM-ethers.Benzhydryl phenyl ether. White needles (85%); mp: 53-54 °C (Methanol) (lit. mp: 52-54°C)26. 'H-NMR 6h (200 MHz, CDC13, TMS): 5.50 (s, 1H), 6.93 (m, 3H), 7.12-7.38 (m, 12H); MS (El), 70 eV, m/z (rel. intensity): 260 (85) [M+], 183 (65), 181 (100), 165 (80), 152 (28), 115 (15); Anal Calcd. For Ci9Hi6O: C 87.65, H 6.19; Found: C, 87.63, H 6.17.Benzhydryl 4-methylphenyl ether. White needles (85%); mp: 74-75 °C (Methanol) (lit. mp: 74.5-75.5°C)27 'H-NMR 5h (200 MHz, CDC13, TMS): 2.20 (s, 3H), 5.50 (s, 1H), 6.71 (d, 2H, J=8Hz), 6.97 (d, 2H, J=8Hz). 7.17-7.36 (m, 10H); MS (El), 70 eV, m/z (rel. intensity): 274 (10) [M ], 260 (5), 196 (40), 152 (25), 115 (15), 51 (100); Anal Calcd. ForC20Hi8O: C 87.56, H 6.61; Found: C, 87.53, H 6.59.Benzhydryl 3-methylphenyl ether. White needles (84%); mp: 121-122°C (Methanol) (lit. mp: 124°C)28. 'H-NMR 6h (200 MHz, CDC13, TMS): 2.20 (s, 3H), 5.50 (s, 1H), 6.91 (m, 3H), 7.15- 7.36 (m, 11H); MS (El), 70 eV, m/z (rel. intensity): 274 (10) [M+], 260 (15), 196 (50), 181 (51) 165 (30), 152(20), 115 (15), 51 (100); Anal Calcd. For C20Hi8O: C 87.56, H 6.61; Found: C, 87.52, H 6.60.Benzhydryl 4-nitrophenyl ether. Yellow needles (81%); mp 117-118°C (Methanol) (lit mp: no data)29. 'H-NMR 5h (200 MHz, CDC13, TMS): 5.50 (s, 1H), 6.91 (d, 2H, J=8Hz), 7.15-7.36 (m, 10H), 8.2 (d, 2H, J=8Hz); Anal Calcd. For Ci9Hi5O: C 74.74, H 4.95, N 4.59; Found: C, 74.76, H 4.93, N 4.58.Recycling of the catalyst. The filtered catalyst was washed with toluene (2x5 mL), dried under vacuum and then reused.ConclusionsThe present method describes an efficient and simple alternative for the preparation of DPM- ethers of alcohols and phenols. This method has the advantages of simplicity in operation and mild reaction conditions, low cost, very good yields, and environment friendliness compared to homogeneous catalysis procedures. Moreover, this procedure introduces a practical and viable technology for the synthesis of DPM-ethers.ISSN 1424-6376 Page 6 ARKAT USA, Inc.General Papers ARKIVOC 2007 (i) 1-8AcknowledgementsWe thank Agencia Nacional de Promoción Científica y Tecnológica (Argentina), Fundación Antorchas, Universidad Nacional de La Plata, and CONICET for financial support. We thank to Mr. Norberto Firpo for performing the CG-MS analysis.References1. (a) Okuhara, T.; Mizuno, N.; Misono, M. Adv. Catal. 1996, 41, 221. (b) Firouzabadi, H.; Iranpoor, N.; Amani, K.; Nowrouzi, F. J. Chem. Soc., Perkin Trans. 1 2002, 2601 and references cited herein.2. Romanelli, G.; Autino, J.; Baronetti, G.; Thomas, H. Molecules 2001, 6, 1006.3. Romanelli, G.; Baronetti, G.; Thomas, H.; Autino, J. Tetrahedron Lett. 2002, 43, 7589.4. Romanelli, G.; Thomas, H.; Baronetti, G.; Autino, J. Tetrahedron Lett. 2003, 44, 1301.5. Romanelli, G.; Bennardi, D.; Ruiz, D.; Baronetti, G.; Thomas, H.; Autino, J. Tetrahedron Lett. 2004, 45, 8935.6. Sharma, G.; Mahalingam, A. J. Org. Chem. 1999, 64, 8943.7. Naik, S.; Kavala, V.; Gopinath, R.; Patel, B. K. Arkivoc 2006, 119.8. Kavala, V.; Kumar Samal, A.; Patel, B. K. Arkivoc 2005, 20.9. Kagaiah, K.; Reddy, B. V. S.; Sreenu, D.; VerkatNarsaiah, R:, Arkivoc 2005, 192.10. (a) Namboodiri, V.; Varma, R. Tetrahedron Lett. 2002, 43, 4593 and references cited herein.(b) Green, T.; Wuts, P. Protective Group in Organic Synthesis, 3rd Edn.; Wiley & Sons: New York, 1999.11. Dobson, D.; Todd, A.; Gilmore, J. Synth. Commun. 1991, 21, 601.12. Sugsawa, S.; Fujiwara, K. Org. Synth. Coll. 1963, 4, 72.13. Parades, R.; Perez, R. Tetrahedron Lett. 1998, 39, 2037.14. Stavber, S.; Zupan, M. Tetrahedron Lett. 1993, 34, 4355.15. Kolovos, M.; Froussios, C. Tetrahedron Lett. 1984, 25, 3909.16. Lapatsanis, L. Tetrahedron Lett.1978,19, 3943.17. Sharma, G; Prasad, T.; Mahalingam, A. Tetrahedron Lett. 2001, 42, 759.18. Stanescu, M.; Varma, R. Tetrahedron Lett. 2002, 43, 7307.19. Baronetti, G. T.; Briand, L.; Sedran, U.; Thomas, H. Appl. Catal. A: General 1998, 172, 265.20. Jander, G.; Banthien, H. Z. Z. Anorg. Allg. Chem. 1936, 229, 142.21. Lyon, D. K.; Miller, W. K.; Novet, T.; Domadle, P. J.; Evitt, E.; Jonson, D. C. V.; Finke, R.G. J. Am. Chem. Soc. 1991,113, 7209.22. Rutherford, K. G.; Marner, O. A.; Prokipcak, J. M.; Jobin, R. A. Can. J. Chem. 44, 1966, 44, 2337.23. Petrov, V.; Stephenson, O.; Thomas, A. J. J. Pharm. and Pharmacol, 1956, 8, 666.24. Ghenciulescu, A.; Necsoiu, I.; Nenitzescu, G. Revue Rom.Chim. 1969, 14, 1553.ISSN 1424-6376 Page 7 ARKAT USA, Inc.General Papers ARKIVOC 2007 (i) 1-825. Olah, G. A.; Welch, J. J Am. Chem. Soc. 1978, 100, 5396.26. Wittig, G; Happe, W. Ami. 1947, 557, 205.27. Wittig, G.; Clausnizer, R. Ami. 1954, 558, 145.28. Lapkin, 1.1.; Belanovich, M. I. Zh. Obshch. Khim. 1961, 31, 3182.29. Barti, J.; Steenken, S.; Mayr, H.; McClelland, R. A. J. Am.Chem. Soc. 1990,112, 6918.ISSN 1424-6376 Page 8 ARKAT USA, Ine.

Silicagel-supported H6P2W18O62.24H2O: A reusable catalyst to prepare diphenylmethyl (DPM) ethers

SEDICI - Repositorio de la UNLP

General Papers ARKIVOC 2007 (i) 1-8
Silicagel-supported H6P2W18O62.24H2O: a reusable catalyst to 
prepare diphenylmethyl (DPM) ethers
Gustavo P. Romanellia,b*, Diego M. Ruiza,b, Hernán P. Bideberripea, Juan C. Autinob, 
Graciela T. Baronetti/ and Horacio J. Thomasa
aCentro de Investigación y Desarrollo en Ciencias Aplicadas “Dr. J. J. Ronco” (CINDECA), 
Departamento de Química, Facultad de Ciencias Exactas, UNLP-CONICET. Calle 47 N° 257, 
B1900AJK La Plata, Argentina 
bCátedra de Química Orgánica, Facultad de Ciencias Agrarias y Forestales, UNLP. Calles 60 y 
119, B1904AANLa Plata, Argentina
cDepartamento de Ingeniería Química, Facultad de Ingeniería, Universidad de Buenos Aires. 
Ciudad Universitaria, C1428BG Buenos Aires, Argentina
E-mail: gpr(d,química. unlp. edu. ar
Abstract
In this work, we report an efficient and facile preparation of diphenylmethylethers (benzydryl 
ethers, DPM-ethers) from benzhydrol and alcohols or phenols. Wells-Dawson heteropolyacid 
(H6P2Wi8O62.24H2O), bulk or supported on silica showed catalytic activity for DPM-ethers 
preparation in toluene, at 60-80°C, in 0.5-1.5h. In these conditions twelve diphenylmethylethers 
of alcohols and phenol were obtained which excellent yields (78-96%). The heterogeneous 
reaction conditions provided a very simple, environmentally friendly, clean, economical and 
selective protocol, for the preparation of unsymmetrical ethers. The catalyst is easily recycled 
and reused without loss of the catalytic activity.
Keywords: H^WigC^ ST^O, silicagel-supported catalyst, DPM-ethers, protecting groups, 
alcohols, phenols
Introduction
The use of heteropolyacids (HPAs) as catalysts for organic chemistry synthetic processes has 
been developed for important industries related to fine chemicals, such as flavor, pharmaceutical 
and food industries. Heteropolyacids are more active catalysts than conventional mineral acids. 
They have many advantages over liquid acid catalysts: higher acid strengths and thermal 
stabilities; they are noncorrosive, environmentally benign, cheap and reusable and require less 
waste disposal.1
ISSN 1424-6376 Page 1 ARKAT USA, Inc.
General Papers ARKIVOC 2007 (i) 1-8
We have recently studied the catalytic activity for the heteropolyacid H6P2W18O62-24H2O 
with Wells-Dawson structure. We have already used this catalyst for performing the 
tetrahydropyranylation of alcohols and phenols and their detetrahydropyranylation,2 cleavage of 
MOM-ethers of phenols,3 preparation of acylals,4 and coumarin synthesis via the Pechmann 
reaction.5
On the other hand, the correct choice of an efficient protecting group is often decisive for 
successfully synthesizing a complex molecule.6 Protection of the hydroxy functional group is an 
important procedure7'8'9 in multistep organic synthesis. The preparation of DPM ethers is one of 
the popular methods in view of their low cost and high stability towards a variety of reagents. 
Additionally, DPM ethers and DPM groups are found as part of the structure of pharmacological 
active compounds.10
A wide variety of reagents are available for the preparation of DPM ethers such as 
diphenylmethyl chloride or bromide in the presence of a base,11 diphenylmethanol in the 
presence of concentrated sulfuric12 or p-toluenesulfonic13 acids, xenon di fluoride.14 
diphenylmethyldiazomethane,15 diphenylmethylphosphate-trifluoroacetic acid,16 ytterbium 
triflate-ferric chloride17 and other ferric or ferrous salts.103 More recently Varma has described a 
suitable method using Nafion-H as a reusable catalyst.18
In continuation of our work on the catalytic properties of Wells-Dawson heteropolyacids, 
herein we report the use of bulk or silica-supported Wells-Dawson acid as a reusable, 
heterogeneous catalyst for an efficient DPM-ether preparation over a wide variety of alcohols 
and phenols.
Results and Discussion
The catalytic activity of the bulk Wells-Dawson acid (WD) and that of Wells-Dawson acid 
containing 40% by weight of the acid (WDWSiCh) was tested in the preparation of DPM-ethers 
(Scheme in Table 1). The protection reaction was studied using different alcohols and phenols as 
substrates, and diphenylmethanol for introducing the DPM group. In all cases, toluene was used 
as solvent.
Initially we conducted blank experiments without the presence of WD. No product was 
detected when 1 mmol of methanol and 1 mmol of benzhydrol were warmed at 60°C for 5 h. 
When the mixture of methanol and benzhydrol was warmed under identical conditions but in the 
presence of silica (support), benzhydrol was the only product detected by TLC.
The preparation of DPM-ethers starting from methanol and benzydrol was tested under a 
variety of conditions (temperature and solvent), using the bulk catalyst. The reaction gives 
higher yields in toluene solution compared to the use of chloroform. The reaction was complete 
in 1 h at 60°C and in 4 h at 40°C, affording DPM ether in 93% (entry 1), and 78% (entry 2), 
respectively. No reaction was detected at room temperature (entry 3). Similarly benzhydrol and 
ISSN 1424-6376 Page 2 ARKAT USA, Inc.
General Papers ARKIVOC 2007 (i) 1-8
n-butanol were warmed in toluene at 70°C for 1 h with a catalytic amount of WD to give 83% of 
the DPM-ether (entry 5).
Table 1. Preparation of DPM-ethers from alcohols and phenols using both bulk and silica-
supported P2Wi8O62H6.24H2O
OH OR
1% P2W18062H6 ■ 24 H20
Toluene, 70°C
ROH
Alcohol Entry Time (h) Yield (%) WD Entry Time (h) Yield (%)
WD40/SÌO2
Methanol Ia 1 93 15a 1 94(94,93)d
2b 4 78
3C 10 -
Isopropanol 4a 1 91 16a 1 85
n-Butanol 5 1 83 17 1 85
'/b/V-Butanol 6 1.5 87 18 1.5 86
Allylic Alcohol 7 1 89 19 1.5 89
Benzyl alcohol 8 0.5 84 20 0.5 83
2-Phenethyl alcohol 9 1 81 21 1 81
Benzhydrol 10 1 95 22 0.5 96
Phenol 11 1 84 23 1 84(85,85)d
4-Methyl-phenol 12 1 85 24 1 85
3- Methyl-phenol 13 1 83 25 1 84
4-Nitro-phenol 14 1 81 26 1 80
a60°C, b40°C, c20°C
d In parentheses, yields obtained in the first and second reuse of the catalyst.
Other primary, secondary, tertiary, allylic, and benzylic alcohols were also protected in the 
same way in short reaction times, the yields of DPM-ethers being higher than 81% (entries 4-10). 
The reactivity trend of this reaction for different alcohols was found to be benzylic > allylic = 
primary = secondary > tertiary.
Primary and secondary alcohols give good to very good yields of DPM ethers (see Table 1, 
entries 1, 5, 9 and 4, 10). Likely, benzyl, allyl, and /c/7-butyl alcohols (entries 8, 7, 6) gave good 
yields, although the reaction times were somewhat different, between 0.5 and 1.5 h under the 
selected experimental conditions.
We applied similar reaction conditions for the protection of substituted phenols. The 
reactions proceeded efficiently with good yields and the nature of the substituents seems to have 
no effects on the conversion rates (see Table 1, entries 11-14).
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General Papers ARKIVOC 2007 (i) 1-8
In view of the obtained results when the bulk catalyst was employed, we used WD4o/Si02 for 
comparative purposes; very similar yields were obtained in comparable reaction times (entries 
15-24). Furthermore, use of the supported catalyst allows an easy separation and recovery for its 
immediate reutilization.
Recycling of the catalyst was studied for the reaction between methanol and benzydrol using 
WTWSiCh. The procedure was repeated twice without any significant loss of activity, as the 
catalyst remained active even after the third cycle (93% yield, entry 15). Similar results were 
obtained for DPM-ether of phenol (85% yield, entry 23).
Experimental Section
General Procedures. Commercially available alcohols and phenols Aldrich or Fluka were 
distilled or recrystallized before use. Melting points of the compounds were determined in open 
capillary tubes and are uncorrected. Boiling points were read from a thermometer in the 
microdistillation head and are reported uncorrected. 'H-RMN spectra (CDCI3) were recorded on 
Bruker 200 MHz spectrometer using TMS as internal standard. Low-resolution mass spectra 
were recorded on a Perkin Elmer GC-MS model (Q-MASS 910). Spectral data agree with the 
expected values. Elemental microanalyses were performed in F & M instrument. The purity 
determination of the products was accomplished by GC analysis on a Perkin Elmer instrument 
and TLC on silica gel 60 F254 plates, for co-inj ection with authentic samples prepared by known 
methods. The purity established by GLC, was better than 97% in all the cases.
Catalyst preparations
The Dawson acid (H6P2Wi8O62.24H2O.) was prepared by the Drechsel method19'20 from a a/p 
K6P2Wi8O62.10H2O isomer mixture. This Dawson-type salt was prepared according to the 
technique reported by Lyon et al.21. Concentrated H3PO4 in a 4:1 acid/salt ratio was added to a 
boiling aqueous solution of Na2WO4.2H2O, and the mixture was kept boiling in a reflux system 
for 8 h. The salt was precipitated by adding KC1, then purified by recrystallization and cooled 
overnight to 278 K. The product, which is a mixture of the a and P isomers, was filtered, washed 
and then vacuum-dried for 8 h.
The acid was obtained from an aqueous solution of a/p K6P2Wi8O62.10H2O salt, which was 
treated with ether and concentrated HC1 (37%) solution. The Dawson acid so released formed an 
addition compound with the ether, which allows it to be separated from the solution. After 
obtaining the ether solution with the acid, the ether was eliminated by flowing dry air and the 
remaining solution was placed in a vacuum-desiccator until crystallization.
Silica-supported Wells-Dawson acids (WD40/SÍO2) was prepared by wet impregnation Grace 
Davison silica (Grade 59, specific area= 250 m2/g) with an aqueous solution of the synthesized 
WD acid. A catalyst containing 40 wt% of WD was prepared. After impregnation, samples were 
dried at room temperature in a vacuum-dessicator for 8 h.
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Typical procedure for the preparation of DPM-ethers of alcohols
A mixture of alcohol (1 mmol), diphenylmethanol (1 mmol), and P2Wi8O62H6-24H2O (1% mmol, 
approx. 40 mg of bulk catalyst, or 100 mg of the silica-supported one) was stirred at the 
indicated temperature and time (see Table 1), in toluene (5 mL). The reaction mixture was 
diluted with toluene (15 mL), and the catalyst was filtered off, then the solution was washed with 
water (2x10 mL), dried with anhydrous Na2SO4, the solvent was evaporated, and the residue 
was purified by column chromatography (silicagel, ethyl acetate:hexanes) to afford pure DPM- 
ethers.
Benzhydryl methyl ether. Colorless oil (94%); bp: 150-151°C (20 Torr) (lit bp: 147-148°C (17 
Torr)22; 'H-NMR 5h (200 MHz, CDCk, TMS): 3.49 (3H, s), 5.37 (1H, s) 7.30-7.41 (10H, m); 
MS (El), 70 eV, m/z (rel. intensity): 198 (65) [M+], 167 (97), 152 (22), 121 (100), 105 (70); Anal 
Calcd. For C14H14O: C 84.81, H 7.12; Found: C 84.78, H 7.08.
Benzhydryl isopropyl ether. Colorless oil (91%); bp: 160-162°C (20 Torr) (lit. bp: 156- 
159.5°C (15 Torr)16; 'H-NMR 5h (200 MHz, CDCk TMS): 1.20 (6H, d, J=6Hz), 3.67 (1H, sp, 
J=6Hz), 5.30 (s, 1H), 7.15-7.25 (10H, m); Anal Calcd. For Ci6Hi8O: C 84.92, H 8.02; Found: C 
84.90, H 8.02.
Benzhydryl n-butyl ether. Colorless oil (85%); bp: 165-166 °C (10 Torr) (lit. bp: 166-167.5°C 
(10 Torr)16; 'H-NMR 5h (200 MHz, CDC13, TMS): 0.92 (t, 3H, 6Hz), 1.30-160 (m, 4H), 3.45 (t, 
2H, 6Hz), 5.34 (s, 1H), 7.10-7.30 (m, 10H); MS (El), 70 eV, m/z (rel. intensity): 240 (10) [M+], 
183 (5), 167 (100), 153 (21), 107 (37), 105 (28); Anal Calcd. For Ci7H20O: C 84.96, H 8.39; 
Found: C 84.92, H 8.40.
Benzhydryl Lbutyl ether. White needles (87%); mp: 50-51 °C (Methanol) (lit. mp: 50°C 
(Methanol)24; 'H-NMR 5h (200 MHz, CDC13, TMS): 1,20 (s, 9H), 5.34 (s, 1H), 7.11-7.31 (m, 
10H); MS (El), 70 eV, m/z (rel. intensity): 240 (1) [M+], 222 (66), 207 (70), 178 (25), 165 (29), 
91 (60); Anal Calcd. For Ci7H20O: C 84.96, H 8.39; Found: C 84.93, H 8.42.
Benzhydryl allyl ether. Colorless oil (89%); bp: 125-126 °C (1 Torr) (lit. bp: 120°C (0.2 
Torr)23; 'H-NMR 5h (200 MHz, CDC13, TMS): 3.81 (d, 2H, J=3Hz), 5.20 (m, 2H), 5.42 (s, 1H), 
6.01 (m, 1H), 7.15-722 (m, 10H); MS (El), 70 eV, m/z (rel. intensity): 224 (5) [M+], 182 (49), 
168 (58), 167 (100), 166 (56), 105 (85); Anal Calcd. For Ci6Hi6O: C 85.68, H 7.18 ; Found: C, 
85.66 H 7.22.
Benzhydryl benzhyl ether. White needles (84%); mp: 49-51 °C (Ethanol) (lit. mp: 51 °C 
(Ethanol)24; 'H-NMR 5h (200 MHz, CDC13, TMS): 4.50 (s, 2H), 5.40 (s, 1H) 7.10-7.35 (m, 
15H); MS (El), 70 eV, m/z (rel. intensity): 274 (1) [M+], 183 (91), 167 (98), 152 (25), 105 (72), 
91 (100); Anal Calcd. For C20Hi8O: C 87.56, H 6.61 ; Found: C, 87.59 H 6.64.
Benzhydryl phenethyl ether. Colorless oil (81%); bp: 135-136 °C (1 Torr) (lit. no data)25. 'H- 
NMR §H (200 MHz, CDC13, TMS): 2.71 (t, 2H, 6Hz), 3.50 (t, 2H, 6Hz), 5.42 (s, 1H), 7.12-7.35 
(m, 15H); MS (El), 70 eV, m/z (rel. intensity): 288 (9) [M+], 183 (18), 167 (100), 152 (15), 105 
(18), 91 (10); Anal Calcd. For C2iH20O: C 87.46, H 6.99 ; Found: C, 87.47 H 6.97.
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General Papers ARKIVOC 2007 (i) 1-8
Dibenzhydril ether. White needles (96%); mp: 106-107°C (Benzene) (lit. mp: 107-107.5°C 
(Ethanol)19; *H-NMR SH (200 MHz, CDCk TMS): 5.40 (s, 2H), 7.20-7.39 (m, 20H); Anal 
Calcd. For C26H22O: C 89.11, H 6.32 ; Found: C, 89.12 H 6.32.
Typical procedure for the preparation of DPM-ethers of phenols
A mixture of phenol (1 mmol), diphenylmethanol (1 mmol), and P2Wi8O62H6-24H2O (1% mmol, 
approx. 40 mg, bulk or 100 mg supported on silica) was stirred at the indicated temperature and 
time (see Table 1), in toluene (5 mL). The reaction mixture was diluted with toluene (15 mL), the 
catalyst was filtered off, and then the solution was washed with 1 M NaOH (10 mL) and water (2 
x 10 mL), dried with anhydrous Na2SC>4, solvent was evaporated, and the residue purified by 
column chromatography (silicagel, ethyl acetate:hexanes) to afford pure DPM-ethers.
Benzhydryl phenyl ether. White needles (85%); mp: 53-54 °C (Methanol) (lit. mp: 52-54°C)26. 
'H-NMR 6h (200 MHz, CDC13, TMS): 5.50 (s, 1H), 6.93 (m, 3H), 7.12-7.38 (m, 12H); MS (El), 
70 eV, m/z (rel. intensity): 260 (85) [M+], 183 (65), 181 (100), 165 (80), 152 (28), 115 (15); 
Anal Calcd. For Ci9Hi6O: C 87.65, H 6.19; Found: C, 87.63, H 6.17.
Benzhydryl 4-methylphenyl ether. White needles (85%); mp: 74-75 °C (Methanol) (lit. mp: 
74.5-75.5°C)27 'H-NMR 5h (200 MHz, CDC13, TMS): 2.20 (s, 3H), 5.50 (s, 1H), 6.71 (d, 2H, 
J=8Hz), 6.97 (d, 2H, J=8Hz). 7.17-7.36 (m, 10H); MS (El), 70 eV, m/z (rel. intensity): 274 (10) 
[M ], 260 (5), 196 (40), 152 (25), 115 (15), 51 (100); Anal Calcd. ForC20Hi8O: C 87.56, H 6.61; 
Found: C, 87.53, H 6.59.
Benzhydryl 3-methylphenyl ether. White needles (84%); mp: 121-122°C (Methanol) (lit. mp: 
124°C)28. 'H-NMR 6h (200 MHz, CDC13, TMS): 2.20 (s, 3H), 5.50 (s, 1H), 6.91 (m, 3H), 7.15- 
7.36 (m, 11H); MS (El), 70 eV, m/z (rel. intensity): 274 (10) [M+], 260 (15), 196 (50), 181 (51) 
165 (30), 152(20), 115 (15), 51 (100); Anal Calcd. For C20Hi8O: C 87.56, H 6.61; Found: C, 
87.52, H 6.60.
Benzhydryl 4-nitrophenyl ether. Yellow needles (81%); mp 117-118°C (Methanol) (lit mp: no 
data)29. 'H-NMR 5h (200 MHz, CDC13, TMS): 5.50 (s, 1H), 6.91 (d, 2H, J=8Hz), 7.15-7.36 (m, 
10H), 8.2 (d, 2H, J=8Hz); Anal Calcd. For Ci9Hi5O: C 74.74, H 4.95, N 4.59; Found: C, 74.76, 
H 4.93, N 4.58.
Recycling of the catalyst. The filtered catalyst was washed with toluene (2x5 mL), dried under 
vacuum and then reused.
Conclusions
The present method describes an efficient and simple alternative for the preparation of DPM- 
ethers of alcohols and phenols. This method has the advantages of simplicity in operation and 
mild reaction conditions, low cost, very good yields, and environment friendliness compared to 
homogeneous catalysis procedures. Moreover, this procedure introduces a practical and viable 
technology for the synthesis of DPM-ethers.
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General Papers ARKIVOC 2007 (i) 1-8
Acknowledgements
We thank Agencia Nacional de Promoción Científica y Tecnológica (Argentina), Fundación 
Antorchas, Universidad Nacional de La Plata, and CONICET for financial support. We thank to 
Mr. Norberto Firpo for performing the CG-MS analysis.
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English

Silicagel-supported H6P2W18O 62.24H2O: A reusable catalyst to prepare diphenylmethyl (DPM) ethers

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Silicagel-supported H6P2W18O 62.24H2O: A reusable catalyst to prepare diphenylmethyl (DPM) ethers

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