A study of ruthenium tetroxide as an oxidant for alcohols

Cm&hydrateResearch

431

Ekevier Pubfishing Company. Amsterdam Printed in Belgium

A STUDY OF RUTHENIUM TETROXIDE AS AN OXIDANT FOR ALCOHOLS P. J. BEYNON, P. M. COLLINS, D. GARDINER,

AND

W. G. O~EREND

Chemistry Department, Birkbeck College. Malet Street, London, W.C.
I (Great Britain)

ZOth, 1967)

ABSTRACT

The oxidation of benzhydrol and partially protected sugars with ruthenium tetroxide has been studied and the stoichiometry of the reaction verified. Axial and equatorial hydroxyl groups on an otherwise protected pyranoid ring are oxidized with equal ease. The generation of the tetroxide with periodate and ruthenium dioxide has been confirmed to be an easy reaction, providing that the dioxide has been prepared by the precipitation process. INTRODUCTION

Recently, we introduced ruthenium tetroxide as an oxidant for partially protected carbohydrates’. This oxidant represented a considerable improvement on the methods then available for oxidizing alcoholic groups in partially protected pyranoid or furanoid rings. Although another method is now available*, which uses less expensive reagents, we still find ruthenium tetroxide to be the reagent of choice, when a good yield of clean product is quickly required. We were smrprised, therefore, to learn that some workers3 had found difficulties in preparing the tetroxide from the dioxide, uatil we experienced the same trouble4. 1 This problem has now been resolved. Ruthenium dioxide is available commercially in an anhydrous form, prepared by direct oxidation of ruthenium metal, and a hydrated form, with the probable composition Ru02*2H20, obtained by a precipitation process. The form required must be specified when purchasing, since rhe chemical catalogues list them both under one heading. Only the hydrated form is oxidizabie under the mild conditions that we used4*‘. It is noteworthy that the dioxide recovered from the oxidations described below was always easy to reoxidize. We now report on a detailed procedure for these oxidations and an examination of the stoichiometry of the reactions involved. RESULTS AND

DISCUSSION

Ruthenium tetroxide was formed by shaking a suspension of hydrated ruthenium dioxide with an aqueous solution of sodium periodate and extracting the tetroxide Carbohyd. Res., 6 (1968) 431-435

P. J. BEYNON,

432

P. M. COLLINS, D. GARDINBR,

W. G. OVBRBND

as a yellow solution into carbon tetrachloride. The stoichiometry of this conversion was determined by treating a weighed quantity of RuO,.2H,O with a measured excess of sodium periodate. Shaking was continued until all of the insoluble, black dioxide had been consumed. The RuO, was extracted by several washings with carbon tetrachloride. The residual aqueous solution was then examined spectroscopically@ in order to determine the amount of remaining sodium periodate. The results reported in the experimental section show the expected stoichiometry, depicted by equation (i). RuO,-2H,O+2NaIO,

-+ RuO,+2NaIO,

+2H,O

Ammonium persulphate, which has been shown7 to oxidize ruthenium salts, did not effect this conversion. Although RuO, can be obtained from RuO, by treatment with sodium hypochlorite8, the process is not efficient. The stoichiometry of the conversion of alcohols into ketones was then investigated because it is known9 that Ru”“’ can, in certain circumstances, be reduced to Rum or to Ru”’ rather than the more common1o Ru Iv . The benzhydrol-benzophenone conversion was selected for this study because the yield, based on the alcohol, is high”. Also, the amount of ketone formed in the crude product could be measured easily by ultraviolet spectroscopy. The method adopted was to treat a measured excess of the alcohol with carbon tetrachloride containing a known amount of ruthenium tetroxide. This was obtained by oxidizing a weighed sample of RuO,*2H,O with an excess of aqueous sodium periodate solution followed by extraction of the RuO, into carbon tetrachloride. The results recorded in Table I clearly show that the stoichiometry for this oxidation is that given by equation (ii). RuO,+2RR’CHOH

--, RuO,+2H,O+2RR’CO

(ii)

These results also show (see Entries 1 and 2 in Table I) that carbon tetrachloride is the solvent of choice for dissolving the alcohol. Entry 6 shows that acetone is a poor TABLE Entry a

I Alcohol

oxidized

(nzntoles)

Ketone

(mnwles)

by I nunole

Benzhydrol (4.08) Benzhydrol (4.63) Benzhydrol(3.85) Benzhydrol (3.84) Benzhydrol (3.95) Benzhydrol (3.93) 1 (3.92) 2 (3.99)

1.90 1.88 1.78 I A2 1.50 1.22 1.53 1.54

formed

of RuO4

Solcezr, 25 nd

cc14 cc14

CHKln, CHpC12 CHzCl-2 (CH3)2CO

CHaCln CH?Clo

=Entry 2 and 4: the extracts of ruthenium tetroxide were run into solvent, and the mixture was stirred for 5 min before addition of solid benzhydrol. Entry 5: as 2 and 4. but stirring was continued for 30 min before addition of benzhydrol. Carbohyd

Res.,

6 (1968)

431435

RUTHENIUM

‘I-ETROXIDE OXIDATIONS

433

solvent; dichloromethane is quite good, providing that the oxidant is not in contact with it for more than a few minutes (cf- Entries 3, 4, and 5). The behaviour of the oxidant towards methyl 4,6-O-benzylidene-Z-deoxy-aD-arabino-hexopyranoside (1)was then examined. Ultraviolet spectroscopy was not suitable for estimating the amount of glycopyranosidulose in the product, but n.m.r. spectroscopy was applicable, since the signals for the anomeric protons of the “0x0 sugar” and the parent alcohol were well separated. The benzylidene, one-proton singlet was used to represent lOO%, since its chemical shift was the same in both starting material and product. Compound 1 was picked because it is crystalline and therefore obtainable in a high state of purity. Its solubihty in carbon tetrachloride is low, and dichloromethane was therefore used. This drawback is aggravated by the relatively slow oxidation of compound 1 compared to benzhydrol. Thus, the result given in Entry 7, that only 1.53 moles of compound 1 are consumed by 1.0 mole of oxidant,

must be compared

time for the oxidation

with Entries 4 or 5 (probably

of compound

Entry 5, since the reaction

1,under the conditions used, approaches 30 min).

We conclude, therefore, that the stoichiometry for the oxidation of the hydroxyl group in partially protected sugars is that depicted in equation (ii), and that the loss of 0.47 mole of oxidant in the case of compound 1 is due mainly to oxidation of the

dichloromethane. OCHZ

/ PhCH Lo

0 d2 OH

/OCH2 PhCH OMe

1

10

0

0 OMe OH

2

Since equations (i) and (ii) indicate that no acid is produced, it appears that the necessity to add base in the catalytic RuO,/IO,oxidation3b must arise from carboxylic acids produced through oxidation and hydrolytic breakdown of some sugar molecules. Possibly, they could be produced partly from hydrolysis of lactones of the type described by Nutt ei al-l2 as arising from over oxidation by prolonged treatment with an excess of ruthenium tetroxide. We find’ that formation of such lactones proceeds slowly, but consecutively with simple oxidation, from the initial stages of the reaction. The oxidation of methyl 4,6-O-benzylidene-2-deoxy-c+D-ribo-hexopyranoside (2) is also noteworthy. The efficiency of this oxidation is again lowered by the use of dichloromethane, but the amount of carbonyl-group formation is virtually identical to that produced from compound 1. Thus, ruthenium tetroxide appears to oxidize axial and equatorial hydroxyl groups with equal ease, and, iu other work, we have shown that it oxidizes equally well endo and eso hydroxyl groups in 1,4:3,6dianhydrides13. EXPERIMENTAL.

Comersion

of rrrthenimn dioxide into ruthenium tetroxide. -

Precipitated

Curbohyd. Res., 5 (1968)

431-435

434

P. J. BEYNON,

P. M. COLLINS, D. GARDINER,

W. G. OVEREND

ruthenium dioxide (RuO,.2H,O) (0.1691 g, 0.001 mole) was added to an aqueous solution (50 ml) of sodium periodate (2.14 g, 0.01 mole). The mixture was shaken until all of the insoluble, black dioxide had been converted into tetroxide. The tetroxide was then removed by washing with carbon tetrachloride (25 ml x 3). The residual, aqueous solution was made up to a standard volume, and the residual periodate was found to be 0.008 mole by spectroscopic measurement. Oxidation of alcohok with ruthenium refroxide. (a) Benthydrol. Precipitated ruthenium dioxide (0.1691 g) was oxidized with an aqueous solution containing an excess of sodium periodate. The known amount of tetroxide so formed was quantitatively extracted into carbon tetrachloride (25 ml x 3) (the partition of RuO, between Ccl, and H,O is 6O:l). This solution of oxidant was added to a stirred solution of benzhydrol(O.004 mole) in carbon tetrachloride, dichloromethane, or acetone. After 10 min, the oxidation was complete, and the precipitated ruthenium dioxide was filtered off, and washed with solvent (25 ml x2). The combined colourless filtrates and washings were evaporated to small volume, transferred to a 250-ml volumetric flask, and diluted to standard volume with ethanol. The benzophenone in the crude product was estimated by measuring the absorbance at 333 nm, with a Unicam SP.500 spectrophotometer. In calibration experiments, benzophenone had &,,, 333 nm (E 155). Only a small correction for benzhydrol at this wavelength was necessary_ (b) Sugar derivatiues 1 or 2. The method was similar to that used in (a), except that dichloromethane was used as solvent for these compounds and the oxidation period was longer, Le., 30 min. A portion of the filtrate from this reaction was removed, and evaporated to give about 50 mg of crude product. This was dissolved in deuteriochloroform and examined with a Varian A-60 n.m.r. spectrometer over the range 250-350 Hz from tetramethylsilane at sweep width of 100 Hz. The benzylidene signal which appeared at T 4.42 for both starting material and oxidation produci, and the anomeric protons of compound 1 at z 5.20 (quartet) and oxidation product at ~4.86 (quartet) were integrated several times. The composition of the crude product was then estimated by comparing the size of the signals at ‘c 5.20 and 4.86 with the one-proton signal at T 4.42. ACKNOWLEDGMENT

The authors thank the Governors of Birkbeck College for financial support for this project. REFERENCES 1 P. J. BEYNON, P. M. COLLINS, and W. G. OVEREND, Proc. Chem. Sot., (1964) 342; P. J. BEYNON, P. M. COLLINS, P. T. DOGANGES, and W. G. OVEREND, J. Chem. SOL, (1966) 1131. 2 See references in W. W. EPSTEINand F. W. SXVEAT,Chem. Reu., 67 (1967) 247. 3 (u) Personal communications from Dr. B. BANNISTERof The Upjohn Co., U.S.A., and Professor A. B. FO.SI-ERof the Chester Beatty Research Institute, London; (b) V. M. PARIKH and J. K. N. JONES, Can. J. Chem., (1965) 3452. 4 P. J. BEY-NON,Ph. D. Thesis, University of London, 1967, p. 31. Corbohyd_ Res., 6 (1968) 431-435

RUTHENIUhf 5 6 7 8 9 10 11 12 13

TBTROXIDE

435

OXIDATIONS

JOHNSON AND MA~HEY Chemicals Ltd, U.K., and ALFA INORGANICS Inc., U.S.A. G. 0. ASPINALL AND R. J. FERRIER, Chem. Znd. (London), (1956) 1216. H. H. CADY AND R. E. CONNICK, J. Am. Chem. Ser., SO (1958) 2646. Observations in our laboratory by P. T. DOGANGES, B. FLAHJXRTY,AND R. A. KITCHEN. F. S. MARTIN, J. Chem. Sot., (1952) 2682, 3053. L. W~~HLER, P. BALZ, AND L. METZ, Z. Anorg. Chem., 139 (1924) 205. L. M. BERKOWITZ AND P. N. RI-LANDER, J_ Am. C/rem. Sot., 80 (1958) 6682. R. F. Nun, B. AVISON, F. W. HOLLY, AND E. WALTON, J. Am. Chem. Sot., 87 (1965) 3273. P. T. DOGANGES, Ph. D. Thesis, University of London, 1967. Carbohyd. Res., 6 (1968) 431435