Dimethylsulfoxide (DMSO) oxidizes benzyl ethers into corresponding benzaldehydes at 110°; the reaction is accelerated by 49​% aq. HBr.  The conditions work well for different aryl-​substituted benzyl ethers.  This protocol is inert toward dialkyl ethers

Pasha, M.A.

Ramesh Naik, .

ePrints@Bangalore University

Full Terms & Conditions of access and use can be found athttp://www.tandfonline.com/action/journalInformation?journalCode=lsyc20Download by: [Bangalore University] Date: 25 August 2016, At: 00:11Synthetic CommunicationsISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20Novel and Efficient Oxidation of Benzyl Ethers toBenzaldehydes by DMSO/49% Aq. HBrRamesh Naik & M. A. PashaTo cite this article: Ramesh Naik & M. A. Pasha (2007) Novel and Efficient Oxidation of BenzylEthers to Benzaldehydes by DMSO/49% Aq. HBr, Synthetic Communications, 37:10, 1723-1726,DOI: 10.1080/00397910701266042To link to this article:  http://dx.doi.org/10.1080/00397910701266042Published online: 22 May 2007.Submit your article to this journal Article views: 116View related articles Citing articles: 3 View citing articles Novel and Efficient Oxidation of BenzylEthers to Benzaldehydes by DMSO/49%Aq. HBrRamesh Naik and M. A. PashaDepartment of Chemistry, Central College Campus, BangaloreUniversity, Bangalore, IndiaAbstract: Dimethylsulfoxide (DMSO) oxidizes benzyl ethers into corresponding ben-zaldehydes at 1108C; the reaction is accelerated by 49% aq. HBr. The conditions workwell for different aryl-substituted benzyl ethers. This protocol is inert toward dialkylethers.Keywords: benzaldehydes, benzyl ethers, DMSO/49% aq. HBrINTRODUCTIONInvestigation from our laboratory has revealed the new paradigms fordimethylsulfoxide (DMSO) in effecting the oxidation of benzylic substrates.We successfully employed the oxidation of primary benzyl amines tobenzoic acids by DMSO/aq. HBr/NaNO2.[1] In context of our ongoingprogram, we sought to develop DMSO-based synthetic technology overbenzyl ethers to their corresponding benzaldehydes under acidic conditions.Although a few methods to achieve the oxidation of benzyl ethers areknown, none are both simple and effective. The reported methods involveuse of reagents such as expensive UF6,[2] metallic nitrates,[3] experimentallyincontinent reagents in a common laboratory such as HOF . CH3CNcomplex,[4] and dimethyldioxirane,[5] which requires a specially designedReceived in India October 17, 2006Address correspondence to M. A. Pasha, Department of Chemistry, Central CollegeCampus, Bangalore University, Bangalore 560 001, India. E-mail: m_af_pasha@yahoo.co.inSynthetic Communicationsw, 37: 1723–1726, 2007Copyright# Taylor & Francis Group, LLCISSN 0039-7911 print/1532-2432 onlineDOI: 10.1080/003979107012660421723apparatus and reagents for its preparation. The only method that offers a goodyield of benzaldehyde is the use of HNO3[6] at 08C in dichloromethane(DCM). The disadvantage encountered in this method is the formation ofnitrated product at elevated temperature.RESULTS AND DISCUSSIONAs we noted, the inherent reactivity of DMSO under acidic conditions is suffi-cient for oxidation of benzyl ethers. To explore the DMSO-based syntheticparadigm of oxidation, a quick experiment was done with benzyl methylether as our prime substrate. On heating benzyl methyl ether with DMSOand 49% aq. HBr at 1108C for 4 h, partial conversion of the substrate into ben-zaldehyde occurred (gas chromatography (GC)). On continuous heating for anadditional 3 h, complete conversion of the substrate to benzaldehyde wasachieved. After workup, the crude product was purified on silica-gel columnchromatography and characterized by 1H NMR, GC-MS, and IR spectralanalysis by comparing with that of authentic benzaldehyde (Scheme 1).To optimize the reaction conditions, we demonstrated the reaction ofbenzyl methyl ether under different acidic conditions such as con. HCl, con.H2SO4, H3PO4, CH3COOH, CF3COOH, and 49% aq. HBr. Among these,only 49% aq. HBr gave the pure product with excellent yields at 1108C.This protocol has been successesfully employed for a variety of substitutedbenzyl ethers compiled in Table 1; in all cases, excellent yields ofcorresponding benzaldehydes were obtained. A noteworthy feature is that theelectron-releasing groups like -OH, -OCH3, -CH3 accelerate the reaction con-siderably (Table 1, entries 4–6), and in contrast electron-withdrawing groupslike -NO2 and -Cl retard the rate of the reaction (Table 1, entries 8–10).Another interesting feature is the presence of an aryl group on the other sideof the benzyl ether (Table 1, entry 3) utilized longer duration to give the titlecompound with the formation of phenol. When dibenzyl ether was subjectedto the standard reaction conditions, as expected, the reaction needed a longduration (15 h) with the formation of 2 equivalents of benzaldehyde.A similar type of mechanism holds good for this protocol as predicted inour previous communication for the oxidation of benzyl amines to benzoicacids[1] (Scheme 2).In conclusion, we have developed a novel protocol for the oxidation ofbenzyl ethers to the corresponding benzaldehydes in excellent yields.Scheme 1. Oxidation of benzyl ethers.R. Naik and M. A. Pasha1724EXPERIMENTALMelting points were determined on a Buchi melting-point apparatus. IR, 1HNMR, and 13C NMR GC-MS spectra were recorded on Nicolet 400 DFT-IR spectrophotometer, 400-MHz Bruker spectrometer, and ShimadzuGC-MS QP 5050A respectively. Benzyl ethers were prepared by reportedmethods and purified and characterized thoroughly before use.Table 1. Oxidation of benzyl ethers into benzaldehydes byDMSO and aq. HBr.Entry Ethers Time (h) Yield (%)a1 7 852 10 803 48 784 4 925 6 866 5 947 10 868 14 889 15 8910 12 84aIsolated yields.Scheme 2. Mechanism for the oxidation of benzyl ethers.Oxidation of Benzyl Ethers 1725General Procedure for Oxidation of Benzyl Ethers by DMSOPromoted by 49% Aq. HBrA solution of 4-methoxybenzylmethyl ether (2.0 g, 13.15 mmol), DMSO(10 mL), and 49% HBr (3.0 mL, 17.80 mmol) was heated to 1108C untilcomplete conversion was achieved as monitored by thin-layer chromato-graphy (TLC). Brine (30 mL) was then added, neutralized with saturatedNaHCO3, and extracted with dichloromethane (3  15 mL). The combinedDCM extract was again washed with brine (2  10 mL), dried over anhyd.Na2SO4, and concentrated. The resulting crude mixture was purified bysilica-gel column chromatography to get 4-methoxybenzaldehyde (1.61 g,90% yield).ACKNOWLEDGMENTRamesh Naik acknowledges the Bangalore University for financial assistanceand the Deptartment of Organic Chemistry and NMR Research Center, IndianInstitute of Science, Bangalore, for recording NMR spectra.REFERENCES1. Pasha, M. A.; Ramesh, N. DMSO/NaNO2/49% HBr: A novel and powerful oxidantfor the direct conversion of primary benzylamines to benzoic acids. Synth. Commun.2005, 36, 165–168.2. Olah, G. A.; Welch, J. Synthetic methods and reactions, 46: Oxidation of organiccompounds with uranium hexafluoride in haloalkane solutions. J. Am. Chem. Soc.1978, 100, 5396–5402.3. Nishiguchi, T.; Bougauchi, M. Convenient oxidative cleavage of ethers by metallicnitrates supported on silica gel. J. Org. Chem. 1989, 54, 3001–3002.4. Rozen, S.; Dayan, S.; Bareket, Y. Oxidative cleavage of methyl ethers using theHOF . CH3CN complex. J. Org. Chem. 1995, 60, 8267–8269.5. Van HeerdenDixon, J. T.; Holzapfel, C. W. Direct transformation of steroidal ethersinto ketones by dimethyldioxirane. Tetrahedron Lett. 1992, 33, 7399–7402.6. Strazzolini, P.; Runcio, A. Oxidation of benzyl alcohols and ethers to carbonylderivatives by nitric acid in dichloromethane. Eur. J. Org. Chem. 2003, 526–536.R. Naik and M. A. Pasha1726

Novel and efficient oxidation of benzyl ethers to benzaldehydes by DMSO​/49​% aqueous HB

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Novel and efficient oxidation of benzyl ethers to benzaldehydes by DMSO/49% aqueous HB

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Novel and efficient oxidation of benzyl ethers to benzaldehydes by DMSO​/49​% aqueous HB

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Novel and efficient oxidation of benzyl ethers to benzaldehydes by DMSO/49% aqueous HB