The Synthesis and Application of Polymer-Supported Hypervalent

A project for an organic chemistry laboratory course for chemistry and biochemistry majors has been developed in which a polymer-supported hypervalent...
0 downloads 0 Views 736KB Size
In the Laboratory

The Synthesis and Application of Polymer-Supported Hypervalent Iodine Reagent in the Organic Chemistry Laboratory Jinsong Zhang* and Jason A. Phillips Department of Chemistry and Biochemistry, California State University, Chico, Chico, California 95929-0210 *[email protected]

Redox reactions are an important topic throughout all areas of chemistry. Many traditional oxidizing agents used in organic chemistry include the heavy metals, silver (1), copper (2), chromium (3), iron (4), manganese (5), cerium (6), and osmium (7), all of which are potential environmental pollutants and are toxic to biological systems. Many of these oxidizing agents have low chemoselectivity: for example, Jones' oxidizing agent1 tends to oxidize 1° alcohols to carboxylic acids instead of aldehydes (8). Others, such as potassium permanganate, have low tolerance for other functional groups (9). Hypervalent iodine reagents (Figure 1) offer multiple advantages in oxidation reactions, as they have less toxicity, excellent ability to control oxidation states of products, broad tolerance of other functional groups, and involve extremely mild reaction conditions compared to the traditional heavy metal oxidizing agents (10). The first hypervalent iodine reagent, (dichloroiodo)benzene, 1, was prepared in 1886 by Willgerodt (11). Iodosobenzene2 (PhIO)n, 2, and [bis(acyloxy)iodo]benzenes, 3 and 4, are the most frequently used aryl-λ3-iodane (ArIL2) reagents (12-14). Aryl-λ5-iodane (ArIL4) reagents include Dess-Martin periodinane, 5 (15), and IBX (1-hydroxy-1,2benziodoxol-3(1H)-one 1-oxide, abbreviated as o-iodoxybenzoic acid, 6) (16). In recent years, IBX has been widely employed as an oxidizing agent (17- 22). In the past decade, solid-phase organic chemistry has become popular due to the easy workup and regeneration of solidphase reagents. A number of polymer-supported IBX reagents have been developed (Figure 2). In reagent 7, IBX was immobilized on polystyrene (Scheme 1) through a phenoxide and chloromethylated polystyrene resin (Merrifield's resin, 13) (23, 24). Reagent 8 was prepared from iodination of the aromatic ring on poly(p-methylstyrene) followed by oxidation (25). Reagent 9 uses mesoporous aminopropylsilica gel as a solid support (26). To date, there has been only one application of a hypervalent iodine reagent in this Journal, the oxidation of menthol using Dess-Martin periodinane 5 (27). Examples of using solidsupported oxidizing agents include oxidation of primary alcohols with silver(I) carbonate on diatomaceous earth (Fetizon's reagent) (28); oxidation of 2° alcohols using polymer, silica gel, diatomaceous earth, molecular sieves, or alumina supported chromium(VI) reagents (29); and oxidation of benzoin to benzil using alumina-supported active MnO2 (30). In principle some of the above reagents may be reused, but in practice they typically are not. In this experiment, a synthesis of polymer-supported IBX reagent was carried out, followed by testing the reagent's ability to

_

oxidize various primary, secondary, benzylic, allylic, and propargyl alcohols. Rademann's synthesis of the IBX resin (Scheme 1 (23)) was adopted, but the reaction conditions were modified to make it more appropriate for an undergraduate laboratory experiment. The sequence of reactions was successfully carried out by chemistry and biochemistry majors as one of their second-semester organic chemistry laboratory projects. The experiment takes 6-8 weeks for a lab that meets twice a week for 3 h per class. Hazards This sequence of reactions involves the use of such caustic chemicals as concentrated sulfuric acid, glacial acetic acid, methanesulfonic acid, potassium trimethylsilanoxide, and tetrabutylammonium Oxone, which all can be harmful to the eyes and respiratory tract and can cause burns to skin. Solvents, including diethyl ether, ethyl acetate, hexanes, methanol, and tetrahydrofuran, are highly flammable, toxic if ingested, and harmful to skin and eyes. Dichloromethane is carcinogenic. All other chemicals involved, including the alcohols used for oxidation, are either toxic, harmful, or irritants. All reactions and workups including flash chromatography are carried out in the fume hoods. Results and Discussion Preparation of polymer-supported IBX is summarized in Scheme 1, including diazotization and subsequent iodination of an aromatic amine, Fischer esterification, Williamson ether synthesis, saponification, and oxidation to make the hypervalent iodine reagent. The reaction conditions were modified from the Rademann (23) procedure to lower cost and to ensure appropriate scheduling for the laboratory class. For instance, in attaching compound 12 to Merrifield's resin 13 to synthesize 14, K2CO3 ($65.20/kg, Acros) was used instead of Cs2CO3 ($42.30/ 25 g, Acros) and the reaction conditions were changed from extensive heating (80 °C for 3 h) to milder conditions (80 °C for 1 h followed by stirring at room temperature for 48 h for completion of the reaction) so that students would be able to work up the reaction during the following class period. The yields under these modified conditions were comparable to those obtained by running the reactions following the literature procedure. The oxidative activity of polymer-supported IBX, 7, (i.e., the “yield” of the last three steps in Scheme 1) was determined by reacting 7 with an excess quantity of benzyl alcohol (16a) (Scheme 2). The reaction was monitored by both TLC and

_

r 2010 American Chemical Society and Division of Chemical Education, Inc. pubs.acs.org/jchemeduc Vol. 87 No. 9 September 2010 10.1021/ed100239c Published on Web 07/08/2010

_

Journal of Chemical Education

981

In the Laboratory

GC-MS and was found to be complete within 2 h. Even though the reaction mechanism is still being debated, the stoichiometry between alcohol and IBX has been shown to be 1:1 (22a, 31). The oxidative activity of the polymer-supported IBX, determined by the students by GC-MS analysis of unreacted benzyl alcohol and benzaldehyde, was 0.28-0.47 mmol/g, consistent with literature oxidative activity (23). Based on the loading of chlorine on Merrifield's resin (13) (1 mmol/g), the yield of the last three steps in synthesizing polymer-supported IBX was 28-47%. Each student picked one or two alcohols out of a diverse collection of primary, secondary, allylic, benzylic, and propargylic alcohols (Table 1) and carried out an oxidation reaction using the polymer-supported IBX reagent (7) they prepared themselves (Scheme 3). The percent conversion of the reactions was determined with GC-MS. Most alcohols converted to aldehydes and ketones in good to excellent percent conversions (Table 1). The reduced polymer-supported product (15) obtained in reactions of Schemes 2 and 3 was collected, washed extensively with diethyl ether and dichoromethane, dried under vacuum, and reoxidized using tetrabutylammonium Oxone (as shown in the last step of Scheme 1). The oxidative activity of newly regenerated 7 was again determined by the students by reaction with an excess quantity of benzyl alcohol, 16a (Scheme 2), and reported to be 0.14-0.58 mmol/g, comparable to the previous crop of 7 (0.28-0.47 mmol/g).

Figure 1. Common hypervalent iodine reagents.

Figure 2. Polymer-bound IBX reagents. Scheme 1. Preparation of Polymer-Supported IBXa

a (a) Typical student yields. (b) Oxone: 2KHSO5 3 KHSO4 3 K2SO4. (c) Yield was determined according to the oxidative activity of 7 compared to the loading of Cl atom on the polystyrene 13.

Scheme 2. Reaction of Polymer-Supported IBX with an Excess Quantity of Benzyl Alcohol To Determine the Oxidative Activity of the Polymer

982

Journal of Chemical Education

_

Vol. 87 No. 9 September 2010

_

pubs.acs.org/jchemeduc

_

r 2010 American Chemical Society and Division of Chemical Education, Inc.

In the Laboratory Table 1. Results of the Treatment of Various Alcohols with Polymer-Supported IBX 7

a Reduced quantity of polymer-supported IBX was added to the reaction mixture because of an student calculation error. b Reaction was carried out in a sealed tube. c Percent conversion is determined by GC-MS analysis by comparing the quantity of aldehyde or ketone with the corresponding alcohol.

Scheme 3. Oxidation of an Alcohol Using the Polymer-Supported IBX Reagent

Conclusion

Acknowledgment

This is the first time a polymer-supported hypervalent iodine reagent has been used in an undergraduate organic laboratory and published in this Journal. This experiment provides undergraduate chemistry and biochemistry majors an opportunity to work on a multistep synthesis involving polymer-based chemistry. Students have hands-on experience using reactions they learn in organic chemistry lecture and gain experience using TLC, flash chromatography, GC-MS, FTIR, and 1H NMR in the laboratory as well as conducting chemical reactions under inert gas conditions (see the supporting information for detailed experimental procedures).

This work was supported in part by a Research Corporation Cottrell College Science Award (#7720), a California State University Program for Education and Research in Biotechnology (CSUPERB) Faculty-Student Collaborative Research Seed Grant and start-up funds provided by the College of Natural Sciences of California State University, Chico. Thanks are also given to David B. Ball for obtaining the departmental high-field NMR spectrometer through a CCLI grant (#99-50413) from NSF. Thanks are given to the students in CHEM 370M classes who participated in this experiment during its development.

r 2010 American Chemical Society and Division of Chemical Education, Inc.

_

pubs.acs.org/jchemeduc

_

Vol. 87 No. 9 September 2010

_

Journal of Chemical Education

983

In the Laboratory

Notes 1. Jones' oxidizing agent is a solution of chromium trioxide in concentrated sulfuric acid. 2. The structure of iodosobenzene is unverified crystallographically. Its low solubility in most solvents and vibrational spectroscopy indicate that it is polymeric, consisting of I-O-I-O chains. The active agent in these oxo-transfer reactions is assumed to be the monomeric PhIdO.

Literature Cited 1. (a) Thomason, S. C.; Kubler, D. G. J. Chem. Educ. 1968, 45, 546– 547. (b) Jenkins, I. D. J. Chem. Educ. 1987, 64, 164. (c) Kemp, M. J. Chem. Educ. 1981, 58, 655–656. 2. Depreux, P.; Bethegnies, G.; Marcincal-Lefebvre, A. J. Chem. Educ. 1988, 65, 553. 3. (a) Mason, T. J. J. Chem. Educ. 1982, 59, 980–981. (b) Mason, T. J.; Turrell, J. A.; Went, C. W. J. Chem. Educ. 1985, 62, 344–345. (c) Finlayson, M. E.; Lee, D. G. J. Chem. Educ. 1971, 48, 473–474. (d) Jones, R. B.; Dreisbach, J. H. J. Chem. Educ. 1994, 71, 158. (e) Lunn, G.; Sansone, E. B. J. Chem. Educ. 1989, 66, 443–445. 4. Mucientes, A. E.; de la Pe~ na, M. A. J. Chem. Educ. 2006, 83, 1643–1644. 5. (a) Miles, B.; Nyarku, S. K. J. Chem. Educ. 1990, 67, 269–270. (b) Brown, K. C.; Chang, V. S.; Dar, F. H.; Lamb, S. E.; Lee, D. G. J. Chem. Educ. 1982, 59, 696–697. 6. Doyle, M. P. J. Chem. Educ. 1974, 51, 131–132. 7. Nichols, C. J.; Taylor, M. R. J. Chem. Educ. 2005, 82, 105–108. 8. Bowden, K.; Heilbron, I. M.; Jones, E. R. H. J. Chem. Soc. 1946, 39–45. 9. Fatiadi, A. Synthesis 1987, 85–127. 10. (a) Topics in Current Chemistry, Hypervalent Iodine Chemistry; Wirth, T., Ed.; Springer-Verlag: Berlin, 2003. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523–2584. 11. Willgerodt, C. J. Prakt. Chem. 1886, 33, 154. 12. (a) Moriarty, R. M.; Rani, N.; Condeiu, C.; Duncan, M. P.; Prakash, O. Synth. Commun. 1997, 27, 3273–3277. (b) Richter, H. W.; Cherry, B. R.; Zook, T. D.; Koser, G. F. J. Am. Chem. Soc. 1997, 119, 9614–9623. 13. Pohnert, G. J. Prakt. Chem. 2000, 342, 731. 14. Van de Water, R. W.; Hoarau, C.; Pettus, T. R. R. Tetrahedron Lett. 2003, 44, 5109–5113. 15. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277–7287. 16. Hartmann, C.; Meyer, V. Chem. Ber. 1893, 26, 1727. 17. (a) Magdziak, D.; Rodriguez, A. A.; Van De Water, R. W.; Pettus, T. R. R. Org. Lett. 2002, 4, 285–288. (b) Huang, Y.; Zhang, J.; Pettus, T. R. R. Org. Lett. 2005, 7, 5841–5844.

984

Journal of Chemical Education

_

Vol. 87 No. 9 September 2010

_

18. Corey, E. J.; Palani, A. Tetrahedron Lett. 1995, 36, 7945– 7948. 19. Wirth, T. Angew. Chem., Int. Ed. 2001, 40, 2812–2814. 20. Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic Press: San Diego, 1997. 21. (a) Frigerio, M.; Santagostino, S.; Sputore, S.; Palmisano, G. J. Org. Chem. 1995, 60, 7272–7276. (b) Frigerio, M.; Santagostino, S.; Sputore, S. J. Org. Chem. 1996, 61, 9272–9279. (c) Frigerio, M.; Santagostino, S. Tetrahedron Lett. 1995, 36, 8019–8022. 22. (a) Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y. L. J. Am. Chem. Soc. 2002, 124, 2245–2258. (b) Nicolaou, K. C.; Zhong, Y. L.; Baran, P. S. Angew Chem., Int. Ed. 2000, 39, 625– 628. 23. Sorg, G.; Mengel, A.; Jung, G.; Rademann, J. Angew. Chem., Int. Ed. 2001, 40, 4395–4397. 24. Reed, N. N.; Delgado, M.; Hereford, K.; Clapham, B.; Janda, K. D. Bioorg. Med. Chem. Lett. 2002, 12, 2047–2049. 25. Lei, Z.; Denecker, C.; Jegasothy, S.; Sherrinton, D. C.; Slater, N. K. H.; Sutherland, A. J. Tetrahedron Lett. 2003, 44, 1635– 1637. 26. (a) Mulbaier, M; Giannis, A. Angew. Chem., Int. Ed. 2001, 40, 4393–4394. (b) Mulbaier, M; Giannis, A. Arkivoc 2003, 228– 236. 27. Reed, N. A.; Rapp, R. D.; Hamann, C. S.; Artz, P. G. J. Chem. Educ. 2005, 82, 1053–1054. 28. Harwood, L. M.; Moody, C. J.; Percy, J. M. Experimental Organic Chemistry, 2nd ed.; Blackwell Science: Malden, MA,1999; pp 513-515. 29. (a) Mayo, D. W.; Pike, R. M.; Trumper, P. K. Microscale Organic Laboratory, 3rd ed.; Wiley: New York, 1994; pp 400-405. (b) Doxsee, K. M.; Hutchison, J. E. Green Organic Chemistry; Thomson: Belmont, CA, 2004; pp 197-200. (c) Burglass, A. J.; Waterhouse, J. S. J. Chem. Educ. 1987, 64, 371–372. (d) Taber, D. F.; Wang, Y.; Liehr, S. J. Chem. Educ. 1996, 73, 1042–1043. (e) Luzzio, F. A.; Fitch, R. W.; Moore, W. J.; Mudd, K. J. J. Chem. Educ. 1999, 76, 974–975. 30. Crouch, R. D.; Holden, M. S.; Burger, J. S. J. Chem. Educ. 2001, 78, 951–952. 31. Su, J. T.; Goddard, W. A., III. J. Am. Chem. Soc. 2005, 127, 14146– 14147.

Supporting Information Available Detailed student procedures; instructor's notes including materials and chemicals lists; 1H NMR spectra of 11 and 12; FTIR spectra of 14, 15, 7; and GC-MS chromatographs of conversions of 16a-24a to 16b-24b. This material is available via the Internet at http://pubs. acs.org.

pubs.acs.org/jchemeduc

_

r 2010 American Chemical Society and Division of Chemical Education, Inc.