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Silica Gel Supported Jones Reagent (SJR)

A Simple And Efficient Reagent For Oxidation Of Benzyl Alcohols To Benzaldehydes

Synthetic Communications 31(9), 1389-1397 (2001)

Introduction

Oxidation of alcohols to carbonyl compounds is one of the most important reactions in organic chemistry. Chromium(VI) reagents are widely utilized in the oxidation of alcohols to carbonyl compounds. Jones reagent is the best known of these Cr(VI) reagents for oxidation of secondary alcohols to ketones. However, it fails to produce satisfactory results for oxidation of primary alcohols, including benzyl alcohols to the corresponding aldehydes1. Difficulty in the above oxidation reaction arises due to the fact that aldehydes react with water and alcohols under acidic aqueous media employed in the Jones oxidation procedure, producing hydrates and hemiacetals, which are then oxidized to carboxylic acids12, and esters3 respectively. A number of Cr (VI) based reagents or procedures have been developed to avoid these problems11-15. Most of these reported reagents are complexes of an amine and Cr(VI)oxide. Unfortunately, these procedures produce slow reactions5,8,9,11,14, and require meticulous and time-consuming preparative methods8,11,13. Recently, employment of solid supported chromium (VI) reagents in the oxidation of alcohols to carbonyl compounds has generated interest. In most cases, solid-supported reagents have been found superior to the non supported reagents. Solid supports modify activity of the reagent, improve selectivity, and, more importantly, make product isolation easier. There are some isolated reports on oxidation of benzyl alcohols to benzaldehydes with solid supported chromium(VI) reagents9,15-22. However, these solid supported chromium reagents require difficult and laborious preparation9,16,17,21, activation by subjecting the supported reagents to high temperature for prolonged periods of time20,21, have a longer reaction time20,21, produce low yields17,18, and require elevated temperature for the reaction to work15-17. Herein, we report a systematic study of the oxidation of benzyl alcohols to benzaldehydes with a new reagent prepared by supporting Jones reagent on silica gel (SJR). It is noteworthy that SJR does not suffer from many of the undesired properties associated with previously reported solid supported chromium reagents.

As a part of our on going study of organic reactions on solid supports22-25, we are reporting the first successful use of Jones reagent supported on silica gel (SJR) for the oxidation of benzyl alcohols to the corresponding benzaldehyd es. The SJR can be prepared in few minutes by mixing a known amount of Jones reagent and chromatographic grade silica gel. Activation of the reagent prior to use is not required to effect oxidation of alcohols. One of the advantages of this reagent is that the amount of chromium(VI) oxidant present on the silica gel is known precisely. For other reported solid supported chromium reagents, the amount of chromium(VI) loaded on the support needs to be determined by a method such as titration. We have found SJR is capable of oxidizinga wide range of benzyl alcohols efficiently and selectively to the corresponding benzaldehydes (see the Tab.). According to this method, stirring a heterogeneous mixture of a benzyl alcohol and SJR in methylene chloride at room temperature carries out oxidation of benzyl alcohols. The reaction takes less than 15 min to complete. Products are isolated by a simple filtration of the reaction mixture and washingthe solid residue with methylene chloride. Evaporation of methylene chloride from the filtrate under vacuum produces product that is often pure by NMR and TLC. Byproducts of the Jones reagent are adsorbed on the silica gel and are removed during the filtration. The reaction is very fast and does not require any special care or conditions to prevent overoxidation. The procedure produces an excellent yield of benzaldehydes. No significant amount of carboxylic acid or ester is detected in the product. However, we have found that if the product is not separated from the excess reagent after the reaction is over, the aldehyde is slowly oxidized to the corresponding carboxylic acid. Products containing impurities were purified by radial chromatography using a Chromatotron instrument.

The Cr(VI) and Cr(III) compounds remain on the silica gel support and never leach into the methylene chloride solvent during the reaction or during washing of the solid residue with methylene chloride after the reaction is complete. We observed that when the magnetic stirrer is turned off, the orange silica gel supported Jones reagent (SJR) settles, producinga colorless liquid layer on the top of an orange solid at the bottom of the flask. Also dark green color, a typical color of Cr(III) salts produced in the Jones reaction, was absent in the filtered solution. In addition, proton NMR produced sharp and narrow peak, and chemical shift values were as expected. The presence of paramagnetic chromium compounds in the products would broaden and shift the positions of the NMR peaks. The above observations indicated the absence of Cr(III) and/or Cr(VI) compounds in the product.

The electronic nature of the group present on aromatic ring has no detrimental effect on this oxidation procedure. The presence of electron donating (1b, 1c, 1d, 1f, and 1h) as well as electron-withdrawing (1g, 1i, and 1j) groups on the benzene ring produced very similar results. However, oxidation of 2,3-dimethoxybenzyl alcohol 2c produced a lower yield of the corresponding aldehyde, and 2,5-dimethoxybenzyl alcohol 2e produced a mixture of unidentified inseparable products. We anticipated complication in these oxidation reactions, since both 1,2- and 1,4-dimethoxybenzes are known to undergo oxidation to benzoquinone with Jones reagent1.

Preparation and utilization of SJR in the oxidation reaction requires very little handling of the toxic chromium reagent. Therefore, the possibility for workers to come into contact with the reagent is minimum. The amount of toxic waste produced in this procedure is significantly smaller than the acetone-aqueous media employed in the traditional Jones oxidation procedure. Moreover, the solid nature of the waste makes for easy disposal. Overall, this procedure is safer to carry out and also environmentally safer. We have found that, in addition to methylene chloride, chloroform and hexane can also be used as the solvent in this reaction. However, if hexane is employed as the solvent, the solid residue should be washed with a polar solvent such as methylene chloride or ethyl acetate to obtain higher yields. Flexibility in the choice of solvents makes SJR more attractive than the traditional Jones reagent. Also the higher yields, greater selectivity, ease of preparation, ease of use, safety, and long life26 of SJR make this reagent clearly superior to all previously reported Cr (VI) reagents utilized in the oxidation of benzyl alcohols to the corresponding benzaldehydes.

# Starting Material Product Yield
a Benzylalcohol Benzaldehyde 85%
b 2-Methoxybenzylalcohol 2-Methoxybenzaldehyde 100%
c 2,3-Dimethoxybenzylalcohol 2,3-Dimethoxybenzaldehyde 82%
d 2-Methylbenzylalcohol 2-Methylbenzaldehyde 98%
e 2,5-Dimethoxybenzylalcohol Complex Mixture
f 4-Methoxybenzylalcohol 4-Methoxybenzaldehyde 99%
g 4-Nitrobenzylalcohol 4-Nitrobenzaldehyde 99%
h 4-Methylbenzylalcohol 4-Methylbenzaldehyde 98%
i 2-Chlorobenzylalcohol 2-Chlorobenzaldehyde 90%
j 4-Chlorobenzylalcohol 4-Chlorobenzaldehyde 99%

The results of our studies in progress indicated that SJR, in addition to the oxidation of benzyl alcohols to benzaldehydes, can be utilized in the following transformations; oxidation of secondary alcohols to ketones oxidation of primary alcohols to aldehydes with some limitations: oxidative regeneration of carbonyl compounds from oximes; oxidation of aldehydes to carboxylic acids; oxidation of hydroquinones to quinines and oxidation of sulfides to sulfones. We have also found that the above reactions can be promoted by a catalytic amount of Jones reagent utilizing a stoichiometric oxidant to regenerate Cr(VI) both supported on silica gel. The results we have so far show that all of the above SJR-promoted reactions, except oxidation of primary alcohols to aldhydes, produce excellent results. Oxidation of primary alcohols to aldehydes produced moderate to good yields due to overoxidation of alcohols to carboxylic acids that we have not been able to control so far.Upon completion, results of these later studies will be published.

Experimental

All reaction mixtures were stirred with a Teflon coated magnet. Methylene chloride was used as received from the supplier without any further purification. Benzyl alcohols were purchased from Aldrich, Acros, and Lancaster Chemical Companies in the USA and were used without further purification. Jones reagent (8M) was prepared according to the literature method1. Silica gel used in the oxidation reactions, as solid support, was MN-Kieselgel 60 (0.04–0.063mm mesh size) supplied by Fisher Scientific. Analytical thin-layer chromatography was done on pre-coated silica gel plates with 254nm fluorescent indicator (Merck #5715) and developed in a 1:9 mixture of ethyl acetate-hexane solvent system. Compounds were visualized by UV lamp and/or by staining either with a p-anisaldehyde/sulfuric acid or phosphomolybdic acid. All products were identified by comparing spectroscopic data with values reported in the literature and those of the authentic samples.

Representative Procedure

Dry silica gel (5 g) was placed in a 100-mL round-bottom flask containing a magnetic stirring bar and fitted with a rubber septum. Jones reagent (1.5mL, 12 mmol) was added slowly from a syringe to the vigorously stirred silica gel. After complete addition of the reagent, stirring continued until a free-flowing orange powder was obtained (less than 5 min). Methylene chloride (25 mL) was added to the above flask. A solution of benzyl alcohol 1a (396 mg, 3.66 mmol) in methylene chloride (5 mL) was added slowly from a syringe through the rubber septum to the stirred heterogeneous mixture. The orange SJR turned dark green/brown immediately. After complete disappearance of the starting benzyl alcohol as indicated by TLC (10 min), the reaction mixture was filtered through a sintered glass funnel, the solid residue was washed with methylene chloride (75 mL) and the washings were added to the filtrate. Solvent was removed from the solution under vacuum to produce a colorless oil (331.6 mg, 85.3% yield) which was pure benzaldehyde according to NMR and IR data.

 

References

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  26. Identical results obtained for the oxidation of benzyl alcohols to benzaldehydes using either freshly prepared SJR or SJR that was stored longer than four months in a flask filled with a rubber septum in the hood under ambient light.
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  28. Spectral data (1H and 13C) are identical to those of the commercially available authentic compound.