Greener Oxidation of Alcohols, Glycosides and Sulfides - ACS

Chapter 6

Downloaded by UNIV OF MICHIGAN ANN ARBOR on February 18, 2015 | http://pubs.acs.org Publication Date (Web): December 16, 2014 | doi: 10.1021/bk-2014-1186.ch006

Greener Oxidation of Alcohols, Glycosides and Sulfides Mo Hunsen* Department of Chemistry, Kenyon College, 310 Tomsich Hall, 200 North College Road, Gambier, Ohio 43022, United States *E-mail: [email protected]

Catalytic reactions significantly contribute towards the development of sustainable chemistry approaches that do not harm the environment. We have been actively developing novel catalytic reactions including enzyme catalyzed polymerization and green oxidation reactions. While chromium reagents have proven to be powerful and versatile oxidizing agents, their carcinogenicity makes them less attractive for any large scale or industrial applications. We have developed greener reactions for preparation of aldehydes, ketones, and carboxylic acids directly from alcohols. Our method is also useful for selective oxidative ring-opening of glycosides and for oxidation of sulfides to sulfones. In these reactions, we use pyridinium chlorochromate (PCC) as a catalyst together with a co-oxidant that is used to regenerate the catalyst. As a co-oxidant, we show that the electrolytically recyclable periodic acid works very well. Hence, using PCC as a catalyst, instead of a stoichiometric amount, we are able to reduce the amount of chromium waste generated by up to a 100 fold while still maintaining the power and versatility of chromium oxidation reactions.

Introduction Oxidation reaction is an important tool in the transformation of organic compounds (1). There are a number of methods available in the literature. For © 2014 American Chemical Society In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


example, Jones’ reagent (2) or chromium trioxide in sulfuric acid is a classic condition for preparation of ketones from secondary alcohols and carboxylic acids from primary alcohols. Jones condition is not suitable for preparation of aldehydes due to further oxidation of the aldehydes into carboxylic acids,. A milder reagent, pyridinium chlorochromate (PCC), was later developed by the Corey group (3). PCC was successfully used to prepare aldehydes from primary alcohols and ketones from secondary alcohols. However, the search for greener processes for oxidation of organic compounds is still an active area of investigation. We have been developing greener alternatives to existing oxidation methods (4–6). We describe here a method for catalytic oxidation reactions of various organic compounds using periodic acid as the co-oxidant and pyridinium chlorochromate (PCC) as the catalyst. We have also carried out some of the oxidation reactions using other chromium reagents including chromium trioxide (CrO3), pyridinium fluorochromate (PFC) and the results are comparable. Due to its reasonable price and long shelf life, our preferred catalyst is PCC and this work focuses on using PCC with periodic acid to oxidize alcohols, sulfides, and carbohydrates.

Results and Discussion 1. Catalytic Oxidation of Alcohols to Aldehydes & Ketones Chromium (VI) is a known carcinogen (7–10) and this limits its utility in large scale applications. We sought to maintain the power of chromium oxidation reactions while reducing the amount of toxic waste that is generated. To do that, we have identified that periodic acid (H5IO6) is a suitable co-oxidant maintaining chromium at a higher oxidation state. As such using 2 mol% of PCC with respect to the substrates, alcohols, and one equivalent of periodic acid we have successfully oxidized primary alcohols to aldehydes and secondary alcohols to ketones (Schemes 1 and 2) (6). As shown below, our approach is mild and it enabled the oxidation of a variety of aliphatic and aromatic alcohols including those with electron withdrawing groups, electron donating groups, and benzylic as well as homobenzylic alcohols. Furthermore, it is worth noting that sensitive functional groups such as the cyclopropyl and propargyl groups were not affected by the reaction condition. However, in cases where an electron withdrawing group is attached to the aromatic ring of benzyl alcohols, we have observed that some further oxidation into carboxylic acids has occurred resulting in moderate yields (Scheme 2).

118 In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


Scheme 1. PCC catalyzed oxidation of alcohols to ketones.

Scheme 2. PCC catalyzed oxidation of alcohols to aldehydes.

We hypothesize that a chlorochromatoperiodate complex forms in the reaction mixture (Scheme 3) resulting in PCC staying at a higher oxidation state throughout the reaction. This hypothesis is consistent with our observation that no green coloration of the reaction mixture was seen during the reaction suggesting the absence of Cr (III) species (Scheme 3).



Scheme 3. Proposed mechanism for the PCC catalyzed oxidation of alcohols to aldehydes and ketones.

While our approach is useful for preparation of aldehydes, our attempt to prepare an ortho dialdehyde surprisingly gave an important lactone, phthalide. Phthalides and their analogs have shown interesting biological activities including antifungal and cytotoxic activities (11, 12). These lactones also have potential utility in polymer chemistry as they make interesting substrates for ring opening polymerization of lactones to polyesters (13, 14). One possible explanation could be the initial formation of a monoaldehyde that reacts with the intramolecular hydroxymethyl group to form a hemiacetal that is then oxidized to the observed lactone (Scheme 4).

Scheme 4. PCC catalyzed oxidation of an ortho diol to a lactone. 120 In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


2. Catalytic Oxidation of Alcohols Directly to Carboxylic Acids Direct oxidation of alcohols to carboxylic acids is a very useful transformation in organic chemistry. Intrigued by some further oxidation of aldehydes into carboxylic acids we have observed during our preparation of aldehydes from primary alcohols, we pursued direct oxidation of alcohols to carboxylic acids. We attempted the direct oxidation by using two equivalents of periodic acid with a catalytic amount of PCC (2 mol% with respect to substrates) and we were delighted to see that primary alcohols could be oxidized quantitatively into carboxylic acids (5). As shown in Scheme 5 below, our approach is rather versatile and it enabled oxidation of a variety of primary alcohols. Our method worked smoothly for direct oxidation of electron poor as well as electron rich benzylic and homobenzylic alcohols (Scheme 5). Aliphatic alcohols and diols were also effortlessly oxidized to the corresponding carboxylic acids in high yields.

Scheme 5. PCC catalyzed oxidation of primary alcohols directly to carboxylic acids.

3. Selective Oxidative Ring-Opening of Glycosides With the goal of developing a method for oxidatively ring-opening glycosides, we have further investigated our catalytic oxidation approach. Previously, excess chromium trioxide has been shown to oxidatively open glycoside rings (15). However, the carcinogenicity of chromium reagents prohibits any large or wide scale applications of this very useful transformation. As discussed above, our strategy involves maintaining the power of chromium reagents but using these reagents catalytically. Hence, the problem then becomes identifying co-oxidants that will regenerate the catalyst under the ring cleavage condition. Previously, we have reported the preparation of a novel polyketoester directly from cellulose in a one-pot acetylation and oxidation approach (Scheme 6) (16). 121 In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


Scheme 6. Preparation of a polyketoester directly from cellulose in a one-pot acetylation and oxidation protocol.

In the above reaction, we have discovered that periodic acid is still a viable co-oxidant for the purpose of regenerating the catalyst efficiently under the reaction conditions shown above (Scheme 6). It is worth mentioning that the byproduct iodic acid could be re-oxidized to periodic acid by electrolysis. Eventhough electrochemical manufacturing of chemicals costs energy, there are promising improvements that could make it more attractive in the Chemical Industry (17). In addition, by using less than two equivalents of periodic acid, we have shown that preparation of a copolymer with polyglycoside and polyketoester segments is possible through a limited ring opening of glycosides. Here the oxidation of glycosides stops when all periodic acid that regenerates the catalyst is consumed. Further investigation is in progress to determine the scope and limitation of this oxidation reaction especially when other than 1-4 linkages are present. Most interestingly, this catalytic oxidation reaction selectively oxidized βglycosides while the α-glycosides were not amenable to the ring opening observed for the β-glycosides (Scheme 7). While 1-O-methyl β-D-glucose tetraacetate is oxidized to the corresponding ketoester, the corresponding α-glycoside did not generate a ketoester. One possible cause for this difference is the difference in the stereoelectronic environment around the anomeric carbon. Compared to the previous harsh reaction condition used by others (15), where excess chromium trioxide was used to carry out the oxidation of glycosides, our approach is milder and more attractive. We anticipate that our method might be useful in selective skeletal modification of complex carbohydrates which are more likely to contain both α- and β-linkages as well as different types of glycosidic linkages (e.g. 14 versus 1-2). Further investigation in this direction is in progress and will be reported in due course. Furthermore, other groups have shown that the above type of ketoesters could be converted to iminocyclitols (Figure 1) - that are important glycosidase inhibitors and relevant in the treatment of diabetes, cancer, and immune diseases – via reductive amination reactions (18–24). Since our approach generates significantly lower amount of chromium waste compared to previous methods, we anticipate that it will make the scale up for preparation of iminocyclitols from ketoesters more attractive. 122 In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


Scheme 7. PCC catalyzed oxidative ring-opening of glycosides with periodic acid.

Figure 1. Iminocyclitols - important class of glycosidase inhibitors 4. Oxidation of Sulfides to Sulfoxides and Sulfones Oxidation of sulfides to sulfoxides and sulfones is another area of interest in developing green organic chemistry methodologies. There are some interesting approaches for these transformations in the literature but many of these methods have limited substrate scope (25–30). In this regard, we have investigated the strengths and limitations of our approach by using a variety of sulfides and varying the amount of the co-oxidant. When one equivalent of periodic acid was used with a catalytic amount of PCC (2 mol% with respect to substrates), the results for the formation of sulfoxides are mixed (Scheme 8 and Table 1). For some of the sulfides, a mixture of sulfoxides and sulfones were obtained and we have indicated the mole % ratio in Table 1. We have observed some degree of further oxidation to sulfones both for sulfides with electron donating groups (entries 3, 4, and 7) and those with electron withdrawing groups (entries 2, 5, and 6). The percent yield for entry 7 was relatively low due to the water solubility of the product and we recommend that alternative work up approaches be pursued in such a case. Since the oxidation of sulfides to sulfoxides is in general not difficult to carry out and there are various methods to do that, we were not disappointed with the results but we were rather curious about the possibility of oxidizing sulfides directly to sulfones with our catalytic approach. Indeed, we were pleased to observe that our method delivers sulfones almost quantitatively directly from sulfides (Scheme 9 and Table 2). Sulfides with electron withdrawing substituents (entries 2, 5, and 6) as well as those with electron donating substituents (entries 3 and 4) were oxidized smoothly to their corresponding sulfones. Interestingly, a hydroxymethyl group remained intact during the oxidation of sulfides (entry 7 in Tables 1 and 2), but some of the product was lost during workup due to its water 123 In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.

solubility and we recommend that alternative work up approaches be pursued in such a case.


Scheme 8. Oxidation of sulfides to sulfoxides.

Table 1. Oxidation of sulfides to sulfides.


Scheme 9. Oxidation of sulfides to sulfones.


Table 2. Oxidation of sulfides to sulfones

Conclusions In summary, we have developed a versatile method for oxidation of a variety of organic compounds including alcohols, sulfides, and carbohydrates. Our approach of using a catalytic amount of PCC with periodic acid as the co-oxidant is useful in the preparation of aldehydes, ketones, carboxylic, acids, sulfones, and ketoesters of glycosides.


Experimental


Oxidation of 1-O-Methyl 2,3,4,6-tetra-O-acetyl-β-D-glucose Is Representative for Oxidative Ring Opening of Glycosides To a mixture of 50 mL acetic acid, 5 ml acetic anhydride, and 0.90 g (2.5 mmol) of 1-O-methyl 2,3,4,6-tetra-O-acetyl-β-D-glucose was added (in ice bath) 2.28 g ( 10 mmol) of H5IO6 and 0.022 g PCC (2 mol%). The reaction mixture was stirred in ice-bath for 1 h and at r.t. overnight. The iodic acid precipitate was recovered by filtration under vacuum and the solvents were evaporated under reduced pressure using a rotary evaporator. The residue was dissolved in 100 mL ethyl acetate, and washed with brine and saturated aq. NaHSO3. respectively. It was then dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to give methyl 2,3,4,6-tetra-O-acetyl-D-xylo-hex-5-ulosonate (0.84 g, 90%). The 1H- and 13C- NMR spectra of the product was identical to those reported by Angyal (15) and Pistia (20).

Synthesis of Methyl Phenyl Sulfoxide (Table 1, entry 3) Is Representative for Preparation of Sulfoxides To 30 mL of acetonitrile was added 1.21 g (5.3 mmol) of H5IO6 and stirred vigorously at r.t. for 15 min. Methyl phenyl sulfide (0.621 g, 5 mmol) was then added (in ice-water bath) followed by addition of 22 mg (2 mol %) PCC in 10 mL acetonitrile (in two portions) and the reaction mixture was stirred at r.t. for 4 h. The reaction mixture was then diluted with 100 mL ethyl acetate and washed with 1:1 brine : water, saturated aq. Na2S2O3 solution, and brine, respectively. It was then dried over anhydrous Na2SO4 and concentrated at reduced pressure to give the sulfoxide (0.69 g, 98 % Yield). The products are known compounds and they were characterized by comparing their NMR spectra with those reported by Aldrich and with authentic samples.

Synthesis of Dibenzothiophene Sulfone (Table 2, entry 1) Is Representative for Preparation of Sulfones To 30 mL of acetonitrile was added 1.21 g (5.3 mmol) of H5IO6 and stirred vigorously at r.t. for 15 min. Dibenzothiophene (0.461 g, 2.5 mmol) was then added (in ice-water bath) followed by addition of 22 mg (2 mol %) PCC in 10 mL acetonitrile (in two portions) and the reaction mixture was stirred at r.t. for 4 h. The reaction mixture was then diluted with 100 mL ethyl acetate and washed with 1:1 brine : water, saturated aq. Na2S2O3 solution, and brine, respectively. It was then dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the sulfone (0.513 g, 95 % Yield). The products are known compounds and they were characterized by comparing their NMR spectra with those reported by Aldrich and with authentic samples. 126 In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.

Acknowledgments MH thanks Kenyon College, The Henry Dreyfus Foundation, and HHMI for the generous funding.

References


1. 2. 3. 4. 5. 6. 7. 8. 9.

10. 11. 12. 13. 14. 15. 16.

17. 18. 19. 20. 21. 22. 23.

Hudlicky, M. Oxidations in Organic Chemistry; ACS Monograph Series 186; American Chemical Society: Washington, DC, 1990; pp 1−46. Bowden, K.; Heilbron, I. M.; Jones, E. R. H.; Weedon, B. C. L. J. Chem. Soc. 1946, 39–45. Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 2647–2460. Hunsen, M. J. Fluorine Chem. 2005, 126, 1356–1360. Hunsen, M. Synthesis 2005, 2487–2490. Hunsen, M. Tetrahedron Lett. 2005, 46, 1651–1653. Nickens, K. P.; Patierno, S. R.; Ceryak, S. Chem.-Biol. Interact. 2010, 188, 276–288. Costa, M. Crit. Rev. Toxicol. 1997, 27, 431–442. Thompson, C. M.; Proctor, D. M.; Haws, L. C.; Hebert, C. D.; Grimes, S. D.; Shertzer, H. G.; Kopec, A. K.; Hixon, J. G.; Zacharewski, T. R.; Harris, M. A. Toxicol. Sci. 2011, 123, 58–70. Wise, S. S.; Holmes, A. L.; Qin, Q.; Xie, H.; Katsifis, S. P.; Thompson, W. D.; Wise, J. P., Sr. Chem. Res. Toxicol. 2010, 23, 365–372. Karmakar, R.; Pahari, P.; Mal, D. Chem. Rev. 2014, 114, 6213–6284. Rukachaisirikul, V.; Rodglin, A.; Sukpondma, Y.; Phongpaichit, S.; Buatong, J.; Sakayaroj, J. J. Nat. Prod. 2012, 75, 853–858. Hunsen, M.; Abul, A.; Xie, W.; Gross, R. Biomacromolecules 2008, 9, 518–522. Hunsen, M.; Azim, A.; Mang, H.; Wallner, S. R.; Ronkvist, A.; Xie, W.; Gross, R. A. Macromolecules 2007, 40, 148–150. Angyal, S. J.; James, K. Aust. J. Chem. 1970, 23, 1209–1221. Hunsen, M. In Materials, Chemicals and Energy from Forest Biomass; Argyropoulos, D. S., Ed.; ACS Symposium Series 954; American Chemical Society: Washington, DC, 2007; pp 247−259. Botte, G. G. Interface 2014, 23, 46. Asano, N.; Nash, R. J.; Molyneux, R. J.; Fleet, G. W. J. Tetrahedron: Asymmetry 2000, 11, 1645–1680. Watson, A. A.; Fleet, G. W.; Asano, N.; Molyneux, R. J.; Nash, R. J. Phytochemistry 2001, 56, 265–295. Pistia, G.; Hollingsworth, R. I. Carbohydr. Res. 2000, 328, 467–472. Heck, M.-P.; Vincent, S. P.; Murray, B. W.; Bellamy, F.; Wong, C.-H.; Mioskowski, C. J. Am. Chem. Soc. 2004, 126, 1971–1979. Kajimoto, T.; Liu, K. K. C.; Pederson, R. L.; Zhong, Z.; Ichikawa, Y.; Porco, J. A., Jr.; Wong, C. H. J. Am. Chem. Soc. 1991, 113, 6187–6196. Mitchell, M. L.; Lee, L. V.; Wong, C.-H. Tetrahedron Lett. 2002, 43, 5691–5693. 127 In Green Technologies for the Environment; Obare, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.


24. Moris-Varas, F.; Qian, X.-H.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 76477652. 25. Engberts, J. B. F. N. In The Chemistry of Sulphones and Sulphoxides; Patai, S., Rappoport, Z., Stirling, C., Ed.; John Wiley and Sons: Chichester, UK, 1988; Vol. 107, pp 165−278. 26. Lakouraj, M. M.; Abdi, H.; Hasantabar, V. J. Sulfur Chem. 2011, 32, 435–441. 27. Priebe, W.; Grynkiewicz, G. Tetrahedron Lett. 1991, 32, 7353–7356. 28. Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X.-Q.; Noyori, R. Tetrahedron 2001, 57, 2469–2476. 29. Simpkins, N. S. In Sulphones in organic synthesis; Tetrahedron organic chemistry series 10; Pergamon Press: Oxford, UK, 1993; Vol. 10, pp 5−50. 30. Rozen, S.; Bareket, Y. J. Chem. Soc., Chem. Commun. 1994, 1959–1959.


Greener Oxidation of Alcohols, Glycosides and Sulfides - ACS

Recommend Documents