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An improved procedure for oxidation of carbohydrate derivatives with ruthenium tetraoxide
456
CARJ3OHYJXATE
RESEARCH
Note
An improved procedure for oxidation with ruthenium tetraoxide B. T. LAWKON, W. A. SZAREK,
Department (Received
of Chemistry,
AND
of carbohydrate
derivatives
J. K. N. JONES
Queen’s University,
Kingston,
Ontario (Canada)
January 14th, 1969)
The biological importance of ketoses and their utility in the synthesis of ‘branched-chain and amino sugars has led in recent years to several studies of procedures for oxidation of partially substituted carbohydrates. Work in this laboratory’ has centered on the ruthenium tetraoxide oxidation method, which was introduced to carbohydrate chemistry by Overend and co-workers2. The method has been applied to carbohydrates O-substituted with methoxycarbonyl, benzoyl, benzylidene, isopropylidene, and methylene groups, and to alkyl glycosides and 1,6-anhydro sugars l-‘. The procedure reported by Overend and co-workers2*6 involves two steps, generation of the oxidant with sodium periodate and ruthenium dioxide, and oxidation of the alcohol with the tetraoxide. Prolonged treatment of some aldofuranose derivatives with an excess of ruthenium tetraoxide has been reported3 to yield Iactones by an oxygen-insertion reaction of the glycosuioses formed initially. In our original procedureI, the two steps are combined; a solution of the carbohydrate in chloroform or carbon tetrachloride is treated with a catalytic amount of ruthenium dioxide (20 mg/g of sugar), and a 5% aqueous solution of sodium periodate (1.3 equivalents) is added with vigorous stirring and control to pH 6-7 (sodium hydrogen carbonate). As a result of requests frcm several workers, we now report a modification of this procedure in connection with some oxidation studies that demonstrate the stability of additional functional groups (see Table I) towards ruthenium tetraoxide. In the improved procedure, the problem of over-oxidation is minimized by use of the sparingly soluble potassium periodate, and the pH is controlled by the addition in bulk of a determined quantity of potassium carbonate. Ruthenium dioxide is formed from ruthenium trichloride (British Drug Houses Ltd.) by the precipitation method described by Miiller and Schwabe’. For oxidation of “isolated” secondary hydroxyl groups to ketones in protected sugar derivatives, the compound is dissolved in ethanol-free chloroform to give an approximately 15% solution, and an equal volume of water is added. For each mole of substrate, 0.24 mole of anhydrous potassium carbonate, 1.3 moles ofpotassium periodate, and a catalytic amount (N 0.05 mole) of ruthenium dioxide are then added. The reaction mixture is stirred vigorously, and the progress of the oxidation is followed by t.1.c. *. At the end of the reaction, the mixture is treated Carbohyd- Res., 1G (1969) 456458
? %
2 . ;; h 5; 3
P w $. A
1,2:5,6-di-O-isopropylidcnc-ct-o-~~b~hexos-3-uloses methyl 4,6-O-benzylidenc-2-O-p-tolylsulfonyl-a-rwihohexopyranosid-3.uloseo-” methyl 4,6-O-benzylidene-2-deoxy~-o-rhreo-liexopyranosid-3uloses*6 methyl 2,3-di-O-methyl-6-O-~tolylsulfonyl-co-xylohcxopyranosid-4-ulose”** methyl 2,3-di-O-benzoyl-~-L-r/lreo-pentopyranosid-~uloscb~~
1,2:5,6-Di-O-isopropylidene-a-D-glucofuranose Methyl 4,6-O-benzylidene-2-O-p-tolylsulfonyl-#-o-plucopyranosidcs
93
83
89
go-95 85
Yield, %
._
OSyrupy product, characterized as the crystalline (2,4_dinitrophenyl)hydrazone. lrlb be published; see ref. 16, CCharacterized by conversion into methyl #-D-xylopyranoside.
Methyl 2,3-di-0-benzoyl-P-t.-arabinopyranosidel4Js
Methyl 2,3-di-O-methyl-6-O-~tolylsulfonyl-a-o-~lucopyranoside~~
Methyl 4,6-O-benzylidcne-2-dcoxy-rw-o-/~suo-hexopyranosides~~~
Product
Substrate
OXIDATION OF CARDOHYDRATE DERIVATIVES WITH RUTHENIUM TETRAOXIDE
TABLE I
458
NOTE
with isopropyl alcohol to reduce residual ruthenium tetraoxide. The mixture is filtered, and the aqueous layer is extracted with chloroform. The conibined extracts are dried, and concentrated to give the oxidized product. The oxidations listed in Table I have been achieved with this improved procedure. ACKNOWIJZDGMENL-
The authors thank the National Research Council of Canada for financial support of this research. REFERENCES 1 V. M. PARIKH AND J. K. N. JONES, Gun. J. C/rem., 43 (1965) 3452. 2 P. J. BEYNON, P. M. COLLINS, AND W- G. OVE~~ND, Proc. Chem. Sot., (1964) 342; P. J. BEYNON, P. M. COLLINS, P. T. DOGANGES, ANJJ W. G. OVEREND, J. Chem. Sot. (C), (1966) 1131. 3 R. F. Nurr, B. AmsoN. F. W. HOLLY, AND E. WALTON, J. Amer. Chem. Sot.. 87 (1965) 3273; R. F. Nun-, M. J. DICKMSON, F. W. HOLLY, AND E. WALTON, J. Org. Chem., 33 (1968) 1789. 4 D. HORTON AND J. S. JEWELL, Carbohyd. Res.. 2 (1966) 251; 5 (1967) 149. 5 G. B. HOWAFXH, W. A. S-K, AND J. K. N. JONES, Cheer. Commun., (1968) 62; Curbohyd. Res., 7 (1968) 284. 6 P. J. BEYNON, P. M. COLLINS, D. GAXDMER, AND W. G. OVEREND, Carbohyd. Res.. 6 (1968) 431. 7 E. MUELLERAND K. SCHWABE, 2. Elektrochem., 35 (1929) 171; Gmelins Hundbuch der Anorgunischen Cbemie (8. A&age), 63, Rufhenium, Veriag Chemie, G.m.b.H., Berlin. 1938, p. 26. 8 G. J_ ROBERTSON AND C. F. GRIFFITH, 1. Chem. Sot., (1935) 1193. 9 B. R. BAKER AND D. H. Buss. J. Org. Chem., 30 (1965) 2304. 10 K. ONODERA, S. HIRANO, AND N. KASHIMJRA, Curbohyd. Res., 6 (1968) 276. 11 G. B. HOWARTH, W. A. SZAREK, AND J. K. N. JONES, Cm. J. Chem., 46 (1968) 3375. 12 A. B. FOSTER, W. G. OVEREND, AND M. STACEY, J. Chem. Sot., (1951) 974. 13 N. K. KOCHETKOV AND A. I. Usov, Tetrahedron, 19 (1963) 973. 14 E. J. Rmsr, L. V. FISHER, AND L. GOODMAN, 1. Org. Chem., 32 (1967) 2541. 15 A. J. DICK, Ph. D. Thesis, Queen’s University (1967). 16 B. T. LAWTON. W. A. SZARJZK,AND J. K. N. JONES, to be published. *If oxidation is incomplete, further amounts of potassium carbonate, ruthenium dioxide may be added in the specified ratio. Cwbohyd.
Res., 10 (1969) 456-458
potassium periodate,
and
CARJ3OHYJXATE
RESEARCH
Note
An improved procedure for oxidation with ruthenium tetraoxide B. T. LAWKON, W. A. SZAREK,
Department (Received
of Chemistry,
AND
of carbohydrate
derivatives
J. K. N. JONES
Queen’s University,
Kingston,
Ontario (Canada)
January 14th, 1969)
The biological importance of ketoses and their utility in the synthesis of ‘branched-chain and amino sugars has led in recent years to several studies of procedures for oxidation of partially substituted carbohydrates. Work in this laboratory’ has centered on the ruthenium tetraoxide oxidation method, which was introduced to carbohydrate chemistry by Overend and co-workers2. The method has been applied to carbohydrates O-substituted with methoxycarbonyl, benzoyl, benzylidene, isopropylidene, and methylene groups, and to alkyl glycosides and 1,6-anhydro sugars l-‘. The procedure reported by Overend and co-workers2*6 involves two steps, generation of the oxidant with sodium periodate and ruthenium dioxide, and oxidation of the alcohol with the tetraoxide. Prolonged treatment of some aldofuranose derivatives with an excess of ruthenium tetraoxide has been reported3 to yield Iactones by an oxygen-insertion reaction of the glycosuioses formed initially. In our original procedureI, the two steps are combined; a solution of the carbohydrate in chloroform or carbon tetrachloride is treated with a catalytic amount of ruthenium dioxide (20 mg/g of sugar), and a 5% aqueous solution of sodium periodate (1.3 equivalents) is added with vigorous stirring and control to pH 6-7 (sodium hydrogen carbonate). As a result of requests frcm several workers, we now report a modification of this procedure in connection with some oxidation studies that demonstrate the stability of additional functional groups (see Table I) towards ruthenium tetraoxide. In the improved procedure, the problem of over-oxidation is minimized by use of the sparingly soluble potassium periodate, and the pH is controlled by the addition in bulk of a determined quantity of potassium carbonate. Ruthenium dioxide is formed from ruthenium trichloride (British Drug Houses Ltd.) by the precipitation method described by Miiller and Schwabe’. For oxidation of “isolated” secondary hydroxyl groups to ketones in protected sugar derivatives, the compound is dissolved in ethanol-free chloroform to give an approximately 15% solution, and an equal volume of water is added. For each mole of substrate, 0.24 mole of anhydrous potassium carbonate, 1.3 moles ofpotassium periodate, and a catalytic amount (N 0.05 mole) of ruthenium dioxide are then added. The reaction mixture is stirred vigorously, and the progress of the oxidation is followed by t.1.c. *. At the end of the reaction, the mixture is treated Carbohyd- Res., 1G (1969) 456458
? %
2 . ;; h 5; 3
P w $. A
1,2:5,6-di-O-isopropylidcnc-ct-o-~~b~hexos-3-uloses methyl 4,6-O-benzylidenc-2-O-p-tolylsulfonyl-a-rwihohexopyranosid-3.uloseo-” methyl 4,6-O-benzylidene-2-deoxy~-o-rhreo-liexopyranosid-3uloses*6 methyl 2,3-di-O-methyl-6-O-~tolylsulfonyl-co-xylohcxopyranosid-4-ulose”** methyl 2,3-di-O-benzoyl-~-L-r/lreo-pentopyranosid-~uloscb~~
1,2:5,6-Di-O-isopropylidene-a-D-glucofuranose Methyl 4,6-O-benzylidene-2-O-p-tolylsulfonyl-#-o-plucopyranosidcs
93
83
89
go-95 85
Yield, %
._
OSyrupy product, characterized as the crystalline (2,4_dinitrophenyl)hydrazone. lrlb be published; see ref. 16, CCharacterized by conversion into methyl #-D-xylopyranoside.
Methyl 2,3-di-0-benzoyl-P-t.-arabinopyranosidel4Js
Methyl 2,3-di-O-methyl-6-O-~tolylsulfonyl-a-o-~lucopyranoside~~
Methyl 4,6-O-benzylidcne-2-dcoxy-rw-o-/~suo-hexopyranosides~~~
Product
Substrate
OXIDATION OF CARDOHYDRATE DERIVATIVES WITH RUTHENIUM TETRAOXIDE
TABLE I
458
NOTE
with isopropyl alcohol to reduce residual ruthenium tetraoxide. The mixture is filtered, and the aqueous layer is extracted with chloroform. The conibined extracts are dried, and concentrated to give the oxidized product. The oxidations listed in Table I have been achieved with this improved procedure. ACKNOWIJZDGMENL-
The authors thank the National Research Council of Canada for financial support of this research. REFERENCES 1 V. M. PARIKH AND J. K. N. JONES, Gun. J. C/rem., 43 (1965) 3452. 2 P. J. BEYNON, P. M. COLLINS, AND W- G. OVE~~ND, Proc. Chem. Sot., (1964) 342; P. J. BEYNON, P. M. COLLINS, P. T. DOGANGES, ANJJ W. G. OVEREND, J. Chem. Sot. (C), (1966) 1131. 3 R. F. Nurr, B. AmsoN. F. W. HOLLY, AND E. WALTON, J. Amer. Chem. Sot.. 87 (1965) 3273; R. F. Nun-, M. J. DICKMSON, F. W. HOLLY, AND E. WALTON, J. Org. Chem., 33 (1968) 1789. 4 D. HORTON AND J. S. JEWELL, Carbohyd. Res.. 2 (1966) 251; 5 (1967) 149. 5 G. B. HOWAFXH, W. A. S-K, AND J. K. N. JONES, Cheer. Commun., (1968) 62; Curbohyd. Res., 7 (1968) 284. 6 P. J. BEYNON, P. M. COLLINS, D. GAXDMER, AND W. G. OVEREND, Carbohyd. Res.. 6 (1968) 431. 7 E. MUELLERAND K. SCHWABE, 2. Elektrochem., 35 (1929) 171; Gmelins Hundbuch der Anorgunischen Cbemie (8. A&age), 63, Rufhenium, Veriag Chemie, G.m.b.H., Berlin. 1938, p. 26. 8 G. J_ ROBERTSON AND C. F. GRIFFITH, 1. Chem. Sot., (1935) 1193. 9 B. R. BAKER AND D. H. Buss. J. Org. Chem., 30 (1965) 2304. 10 K. ONODERA, S. HIRANO, AND N. KASHIMJRA, Curbohyd. Res., 6 (1968) 276. 11 G. B. HOWARTH, W. A. SZAREK, AND J. K. N. JONES, Cm. J. Chem., 46 (1968) 3375. 12 A. B. FOSTER, W. G. OVEREND, AND M. STACEY, J. Chem. Sot., (1951) 974. 13 N. K. KOCHETKOV AND A. I. Usov, Tetrahedron, 19 (1963) 973. 14 E. J. Rmsr, L. V. FISHER, AND L. GOODMAN, 1. Org. Chem., 32 (1967) 2541. 15 A. J. DICK, Ph. D. Thesis, Queen’s University (1967). 16 B. T. LAWTON. W. A. SZARJZK,AND J. K. N. JONES, to be published. *If oxidation is incomplete, further amounts of potassium carbonate, ruthenium dioxide may be added in the specified ratio. Cwbohyd.
Res., 10 (1969) 456-458
potassium periodate,
and