Organic Process Research & Development 2006, 10, 941−943
Production of Piperonal, Vanillin, and p-Anisaldehyde via Solventless Supported Iodobenzene Diacetate Oxidation of Isosafrol, Isoeugenol, and Anethol Under Microwave Irradiation Heiddy Marquez Alvarez,*,† Dayse P. Barbosa,†,§ Alini Tinoco Fricks,† Donato A. G. Aranda,‡ Ricardo H. Valde´s,‡,§ and O. A. C. Antunes*,†,§ Instituto de Quı´mica, UFRJ, CT Bloco A 641, Cidade UniVersita´ ria, Rio de Janeiro RJ 21941-590, Brazil, Escola de Quı´mica, UFRJ, Rio de Janeiro, 21941-590 Brazil, Nu´ cleo de Pesquisas de Produtos Naturais, UFRJ, CCS Bloco H, Cidade UniVersita´ ria, Rio de Janeiro, RJ 21941-590, Brazil
Abstract: A novel experimental procedure to obtain carbonyl compounds under microwave irradiation from activated olefins and supported iodobenzene diacetate is described. By varying the reaction conditions it is possible to generate the corresponding aldehydes in reasonable-to-excellent yields and selectivities. The methodology is simple, clean, and reproducible and presents short reaction times. Using isosafrol, isoeugenol, and anethol it was possible to produce piperonal, vanillin and p-anisaldehyde, respectively.
Introduction The oxidation of olefins to carbonyl compounds is an important reaction in organic synthesis and several methods are available to accomplish this conversion under a variety of reaction conditions.1 In recent years, organic reactions on solid supports assisted by microwave irradiation have gained special attention because of their enhanced selectivity, milder reaction conditions, and associated ease of manipulation.2 Iodosobenzene (PhIO)3 and iodobenzene diacetate [PhI(OAc)2]4 are commonly used single oxygen atom donors in * Corresponding authors. (H.M.A.) E-mail:
[email protected]; telephone: +55 21 25627248; fax: +55 21 25627559. E-mail: (O.A.C.A.): E-mail:
[email protected]; telephone: +55 21 25627818; fax: +55 21 25627559. † Instituto de Quı´mica, UFRJ. ‡ Escola de Quı´mica, UFRJ. § Nu ´ cleo de Pesquisas de Produtos Naturais. (1) (a) Choudary, B. M.; Reddy, P. N. J. Mol. Catal. A 1995, 103, L1-L3. (b) Gekhman, A. E.; Stolarov, I. P.; Moiseeva, N. I.; Rubaijlo, V. L.; Vargaftik, M. N.; Moiseevi, I. I. lnorg. Chim. Acta 1998, 275-276, 453-461. (c) Benhaliliba, H.; Derdour, A.; Bazureau, J.-P.; Texier-Bouilet, F.; Hamefin, J. Tetrahedron Lett. 1998, 39, 541-542. (d) Costa, P. R. R. Quı´m. NoVa 2000, 23(3), 357-369. (2) (a) Palombi, L.; Bonadies, F.; Scettri, A. Tetrahedron 1997, 53, 1586715876. (b) Varma, R. S.; Dahiya, R. Tetrahedron Lett. 1997, 38, 20432044. (c) Varma, R. S.; Dahiya, R. Tetrahedron Lett. 1998, 39, 13071308. (d) Bogdal, D.; L -ukasiewicz, M. Synlett 2000, 1, 143-145. (e) Alvarez, H. M.; Plutı´n, A. M; Rodrı´guez, Y.; Perez, E.; Loupy, A. Synth.Commun. 2000, 30, 1067-1069. (f) Alvarez, H. M.; Perez, E.; Plutı´n, A. M; Morales, M.; Loupy, A. Tetrahedron Lett. 2000, 41, 1753-1755. (g) Varma, R. S. Pure Appl. Chem. 2001, 73, 193-198. (h) Shaabani, A.; Bazgir, A.; Teimouri, F.; Lee, D. G. Tetrahedron Lett. 2002, 43, 51655167. (i) Loupy, A. C. R. Chim. 2004, 7, 103-112. (j) Graebin, C. S.; Lima, V. L. E. Quim. NoVa 2005, 28, 73-76. (k) Loupy, A. Top. Curr. Chem. 1999, 206, 153. (l) Loupy, A., Ed. MicrowaVes in Organic Synthesis; Wiley-VCH: New York, 2003. (m) Lidstro¨m, P., Tierney, J.P., Eds. MicrowaVe Assisted Organic Synthesis; Blackwell: Oxford, 2004. (n) Stadler, A.; Yousefi, B. H.; Dallinger, D.; Walla, P.; Van der Eycken, E.; Kaval, N.; Kappe, C. O. Org. Process Res. DeV. 2003, 7, 707. (o) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250-6284. 10.1021/op060117t CCC: $33.50 © 2006 American Chemical Society Published on Web 08/16/2006
catalytic oxygenation reactions. However, polymeric PhIO is insoluble in most organic media. PhIO is prepared by the hydrolysis of PhI(OAc)2 which is soluble in most organic solvents.5 Recently, several groups reported the direct use of PhI(OAc)2 as a terminal oxidant, for example in the oxidation of alcohols to carbonyl compounds using alumina-supported PhI(OAc)2 under microwave irradiation,6 chemoselective oxidation of alcohols by CrIII(salen)X,4a and oxygenation of olefins by iron(III)-porphyrin catalysis in the presence of a small amount of water in organic solvent.7 Whereas the epoxidation of alkenes metalloporphyrins/ PhI(OAc)2 is already known, the selective cleavage of CdC double bonds leading to aldehydes, ketones, or carboxylic acids has thus far never (to our knowledge) been reported so far. Due to the fact that piperonal, p-anisaldehyde, and vanillin are used extensively within the flavor and fragrance industry and because the present process includes, among other routes, ozonolysis followed by ozonide reduction with sulphur or zinc, a highly energy-demanding and environmentally unfriendly process, we describe in the present paper the oxidation of isopropenylbenzenes to the corresponding aldehydes using solventless supported PhI(OAc)2 as reaction media. Results and Discussion The oxidation of piperonal, p-anisaldehyde, and vanillin to the corresponding aldehydes using solventless supported PhI(OAc)2 as reaction media was carried out (Scheme 1). (3) (a) Samsel, E. G.; Srinivasan, K.; Kochi, J. K. J. Am. Chem. Soc. 1985, 107, 7606-7617. (b) Srinivasan, K.; Kochi, J. K. Inorg. Chem. 1985, 24, 4671-4679. (c) Bressan, M.; Morvillo, A. Inorg. Chem. 1989, 28, 950953. (d) Meunier, B. Chem. ReV. 1992, 92, 1411. (e) Ryan, K. M.; Bousquet, C.; Gilheany, D. G. Tetrahedron Lett. 1999, 40, 3613-3616. (f) Guimara˜es, C. A.; Santos, M. C.; Moraes, M. Quı´m. NoVa 2004, 27, 199-205. (4) (a) Adam, W.; Hajra, S.; Herderich, M.; Saha-Mo¨ller, C. R. Org. Lett. 2000, 2, 2773-2776. (b) Karthikeyan, G.; Perumal, P. T. Synlett 2003, 14, 22492250. (c) Li, Z.; Xia, C.-G.; Ji, M. Appl. Catal., A 2003, 252, 17-21. (d) Park, S.-E.; Song, W. J.; Ryu, Y. O.; Lim, M. H.; Song, R.; Kim, K. M.; Nam, W. J. Inorg. Biochem. 2005, 99, 424-431. (5) (a) Sharefkin, J. G.; Saltzman, H. Org. Synth. 1963, 5, 660. (b) Sharefkin, J. G.; Saltzman, H. Org. Synth. 1963, 5, 658. (6) (a) Collman, J. P.; Chien, A. S.; Eberspacher, T. A.; Brauman, J. I. J. Am. Chem. Soc. 2000, 122, 11098-11100. (b) Varma, R. S.; Dahiya, R.; Saini, R. K. Tetrahedron Lett. 1997, 38, 7029-7032. (7) In, J.-H.; Park, S.-E.; Song, R.; Nam, W. Inorg. Chim. Acta 2003, 343, 373-376. Vol. 10, No. 5, 2006 / Organic Process Research & Development
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Scheme 1. Oxidation of isopropenylbenzenes with PhI(OAc)2-zeolite (NaY) under microwave irradiation
Table 1. Oxidation of isosafrol PhI(OAc)2 (mmol)/ support (g) or solvent (mL) t (min) T (°C) conv (%) 0.5/6 CH2Cl2 0.8/3 CH2Cl2 0.8/6 CH3CN 0.8/6 CH3CN 0.8/6 CH3CN 0.8/1 g Al2O3 0.8/1 g Al2O3 0.8/1 g Al2O3 0.8/0.2 g NaY 0.8/0.5 g NaY 0.8/1 g NaY a
5 30 5 10 30 3 5 30 5 5 5
50 84a 100 100 110 110 110 140 130 140 170
3 11 7 7 21 25.5 61 75 89 72 100
selectivity (%) 2a
byproducts
29 100 36 40 90 96 69 57 91 55 62
15 (3a), 55 (4a) 17 (3a), 37 (4a) 19 (3a), 39 (4a) 6 (3a), 4 (4a) 4 (4a) 5 (3a), 26 (5a) 12 (3a), 31 (5a) 9 (3a) 45 (3a), 5 (5a)
37 psi.
Figure 1. Oxidation of isosafrol with PhI(OAc)2.
The analysis of the products obtained after workup revealed the formation of carbonyl compounds as summarized in Table 1. This table shows the more significant results obtained in the oxidation of isosafrol under microwaves, using solventless PhI(OAc)2/Al2O3 and/or PhI(OAc)2/ NaY. As it can be seen, the use of CH2Cl2 or CH3CN as solvents led to poor conversions. Alternatively, considerably better conversions were obtained with solventless PhI(OAc)2 on Al2O3 (entries 7 and 8) and zeolite NaY (entries 9, 10, and 11). The interaction of the support with PhI(OAc)2 would generate in situ PhIO (more active oxygen donor). Due to the higher water content in NaY than in Al2O3, the in situ formation of iodosobenzene by hydrolysis of PhI(OAc)2 (Figure 1) is more favorable on this support. The larger surface area presented by the zeolite can also play an important role in this comparison, probably inhibiting polymerization of PhIO inside of pores. 942
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In view of our results and also on the basis of earlier results with microwave reactions on solid mineral supports,2e,f which normally afford cleaner products, we repeated the reaction using isopropenylbenzenes with supported PhI(OAc)2. Figure 2 shows the comparison between the oxidation products of different activated propenylbenzenes (mainly aldehydes). The reaction proceeded smoothly providing 91% yield piperonal, 62% p-anisaldehyde, and 43% vanillin, using NaY-supported PhI(OAc)2 and 61% yield piperonal, 59% to p-anisaldehyde and 35% to vanillin, using Al2O3-supported PhI(OAc)2. The smaller yields observed in the oxidation of isoeugenol could be related to further oxidation of vanillin to other byproducts. NaY-supported PhI(OAc)2 appears to be a better choice since the reactions, in addition to better yielding, are cleaner and faster. The best protocol involves mixing of the isopropenylbenzene with 2 equiv of PhI(OAc)2 on NaY (or Al2O3) and irradiation of the reaction mixture in a microwave reactor for the specified time (5 min) under solventless conditions. This rapid procedure avoids the overoxidation of isopropenylbenzene to the corresponding carboxylic acid. The microwave irradiations were performed under controlled conditions that make the procedure highly safe, reliable, and reproducible. Single-mode irradiation with monitoring of temperature, pressure, and irradiation power versus time was used throughout. The discussion on the so-called microwave effect is now an old one. Microwave (MW) irradiation is a rapid way of achieving a desired temperature, sometimes without solvent disturbance.2 This question was very well addressed by Stadler and Kappe in a Biginelli reaction, for example.8 Of course, one can claim the same thermal effect in an oil bath. However, in this case very long induction periods are needed,
Figure 2. Oxidation of isopropenylbenzene with PhI(OAc)2.
and presently, environmental considerations prevent the indiscriminate use of oil baths as well as of unnecessary solvents. A careful mass and energy balance sometimes is needed.9 The industrial use of this process deserves further studies. For example, a NOVARTIS group is working on rationalizing the energy working under the solvent boiling point temperature.10 Other groups are currently working on scaling up under batch11 or continuous process conditions including the use of microreactors.12 Although still tricky, solid-state technology is now widely applied in fermentations13 and polymers14 and must be adapted to these solvent-free reactions. In terms of green chemistry it must be emphasized that, although the byproduct iodobenzene cannot be considered friendly to waste or treat, it can be easily recycled upon oxidation with peracetic acid to the original oxidant, iodosobenzene.15 Experimental Equipment. The reactions were monitored utilizing highresolution gas chromatography. A model HP5890 was used with a HP 1 WCOT column (25 m × 0.32 mm i.d.). H2 was used as carrier gas at a flow rate of 3.0 mL/min (96 cm/s) with a pressure of 20 psi. The initial temperature was set at 100 °C and the final at 250 °C at a rate of 3 °C/min. The injector was held at 150 °C, and the detector, at 240 °C. The injection was operated at splitless mode for 0.2 µL of injected solution. To confirm, a GC-MS model 5973HP equipped with HP5 capillary column (30 m × 0.25 mm, 0.25 µm film thickness) was used using Helium as carrier gas with a flow rate of 1 mL/min (32 cm/s). The oven temperature was programmed starting from 80 to 260 °C at 3 °C/min. The injector was hold at 150 °C, and the interface, at 240 °C. Mass spectra were obtained (electron impact (8) Stadler, A.; Kappe, C. O. J. Chem. Soc., Perkin Trans. 2 2000, 13631368. (9) (a) Lancaster, M. Green Chemistry: An Introductory Course; Royal Society of Chemistry: London, 2002. (b) Luyben, W. L.; Wenzel, L. A. Chemical Process Analysis: Mass and Energy Balances: Prentice Hall: New York, 1988. (10) (a) Bose, A. K.; Ganguly, S. N.; Manhas, M. S.; Guha, A.; Pombo-Villars, E. Tetrahedron Lett. 2006, 47, 4605. (b) Bose, A. K.; Ganguly, S. N.; Manhas, M. S.; Rao, S.; Speck, J.; Pekelny, U.; Pombo-Villars, E. Tetrahedron Lett. 2006, 47, 1885. (c) Sorensen, U. S.; Pombo-Villars, E. Tetrahedron 2005, 61, 2697. (11) (a) Nuchter, M.; Muller, U.; Ondruschka, B.; Tied, A.; Lautenschlager, W. Chem. Eng. Technol. 2003, 26, 1207. (b) Nuchter, M.; Ondruschka, B.; Bonrath, W. Gum, A. Green Chem. 2004, 6, 128. (c) Pitts, M. R.; McCormack, Whittall, J. Tetrahedron 2006, 62, 4705. (12) (a) Comer, E.; Organ, M. G. Chem. Eur. J. 2005, 11, 7223. (b) Comer, E.; Organ, M. G. J. Am. Chem. Soc. 2005, 127, 8160. (13) Couto, S. R.; Sanroman, M. A. J. Food Eng. 2006, 76, 291. (14) Papaspyrides, C. D.; Vouyiouka, S. N.; Bletsos, I. V. Polymer 2006, 47, 1020. (15) (a) Sharefkin, J. G.; Saltzman, H. Organic Syntheses; Wiley and Son: New York, 1973; Collect. Vol. V, p 660. (b) Sharefkin, J. G.; Saltzman, H. Org. Synth. 1963, 43, 62. (16) (a) Santos, A. S.; Pereira, N., Jr.; da Silva, I. I.; Antunes, O. A. C. Appl. Biochem. Biotechnol. 2003, 107, 649. (b) Santos, A. S.; Pereira, N., Jr.; Silva, I. M.; Sarquis, M. I. M.; Antunes, O. A. C. Process Biochem. 2004, 39, 2269.
mode) at 70 eV (EI). Scan mode (1 scan/min; acquisition m/z: 40-400). Reactions were carried out with a single-mode cavity Discover Microwave synthesizer (CEM Corporation, NC) producing continuous irradiation at 2455 MHz and an infrared temperature control system. Typical Procedures. The oxidation of isosafrol to piperonal16 is representative of the general procedure employed. Isosafrol (0.065 g, 0.4 mmol) and PhI(OAc)2 (0.26 g, 0.8 mmol) on NaY (0.2 g, silica/alumina ratio ) 4, surface area ) 580 m2/g) or alumina (1 g, γ-alumina, 180 m2/g) are mixed thoroughly on a vortex mixer. The reaction mixture is placed in the microwave reactor and irradiated for a period of 5 min. (WARNING: HEATING OF PhI(OAc)2 CAN GENERATE HOT SPOTS UNDER MICROWAVE IRRADIATION. TO AVOID ANY EXPLOSION RISK THE STABILITY OF THE REAGENT MUST BE INVESTIGATED UNDER THESE CONDITIONS IF A SCALE-UP IS TO BE DONE.) The reactions were carried out in open 125 mL flasks at ambient pressure or in closed, conical vessels under pressure. In both cases P and T were monitored. On completion of the reaction, followed by TLC examination (hexane/AcOEt, 9:1, v/v), the product is extracted with dichloromethane and washed with aqueous sodium bicarbonate solution. The organic phase is separated, dried over magnesium sulfate, and filtered, and the crude product is analyzed by GC-MS. The chromatographic analysis of the sample presented peaks at 8.7 (1a), 11.8 (4a), 7.4 (2a), and 12.8 (3a), as compared with authentic samples. Conclusion In conclusion, we have described an efficient oxidation procedure for the preparation of various important aldehydes in reproducible conditions, under MW irradiation, avoiding the use of ozone and sulphur or zinc, of course with benign consequences. The advantages of this environmentally benign and safe protocol include simple reaction conditions, short reaction times, and easy workup and use of commercial oxidants. Using isosafrol, isoeugenol, and anethol it was possible to produce piperonal, vanillin and p-anisaldehyde, respectively Acknowledgment Dedicated to Professor A. Loupy for his outstanding contributions on Microwave in Organic Synthesis. This work was supported by grants from FAPERJ, CAPES, and CNPq, Brazilian scientific foundations. Microwave equipment was kindly provided by CEM Discover, Sa˜o Paulo, Brazil. Note Added after ASAP Publication. In the version published on the Web August 16, 2006, iodobenzene diacetate was misspelled. The misspellings have been corrected in the version published on the Web August 24, 2006, and in the print issue. Received for review June 15, 2006. OP060117T
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