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Practical synthesis of methyl 4-O-methyl- and methyl 4-O-benzyl-α-D -glucopyranoside
CARBOHYDRATE RESEARCH
PRACTICAL METHYL
465
SYNTHESIS
OF METHYL
4-O-METHYL-
AND
4-O-BENZYL-CZ-D-GLUCOPYRANOSIDE
J.W.VAN<=LEVE
AND
CR
RUSSELL
Northern Regional Research Laboratory +, Peoria, Illinois 61604 (U. S. A.) (Received April 26th, 1972; accepted’in revised form July 3rd, 1972)
ABSTRACT
Gram amounts of pure, crystalline methyl 4-U-methyland methyl 4-O-benzyla-D-glucopyranoside have been prepared from methyl 4,6-O-benzylidene-a-~-glucopyranoside in 40% overall yields by a method that appears to constitute a practical synthesis of methyl 4-0-alkyl-a-~glucopyranosides. 1NTRODUCTION
Investigations of the structure and chemical reactivity of starch have often benefited from insights provided by parallel studies of model compounds. Thus our interest in the reactivity of starch towards grafting reagents under various conditions could be served, it appeared, by studies of the chemical behavior of methyl 4-0-
aikyl-a-D-glucopyranosides
under the same conditions.
The simplest model compound analogous to the a-D-(144)-linked D-gIucose residues of starch is methyl PO-methyl-a-D-glucopyranoside (1).This compound, from which 4-O-methyl-D-glucose has been derived’ *‘, has been prepared by four methods: (a) reduction of methyl (methyl PO-methyl-a&D-glucopyranosid)uronate derived from mesquite gum or wood hemicellulosel, (b) methylation of methyl 2,3-di0-acetyl-3n** or(c) methyl 2,3-di-O-benzyL6O-trityl-a-D-glucopyranoside 3e followed, in each case, by removal of blocking groups, and (6) benzylation of amylose with subsequent methanolysis, methylation, and debenzylation4. As practical methods for the preparation of 1,these earlier procedures are of limited value for various reasons: (a) the product is impure2, (b) the yield is low and purification is laborious3e~4, or *This is a laboratory of the Northern Marketing and Nutrition Research Division, Agricultural Research Service, U. S. Department of Agriculture. Mention of firm names or trade products does not imply that they are endorsed or recommended by the U. S. Department of Agriculture over other firms or similar products not mentioned. **Two attempts have been made to prepare 1 by methylation of this intermediate. Purdie methylation was accompanied by acetyl migration and, after removal of blocking groups, the product, at first thought to be 1 (ref. 3b), was later proved to be methyl 2-O-methyl-cr-D-glucopyranoside”. Subsequently Deferrari and his associatesgd introduced diazomethane-boron trifiuoride etherate as a reagent for methylating partially acetylated sugars without acyl migration. With this reagent Trimnell et uI.~~ succeeded in preparing 1 ingood yield from the above intermediate. Carbohyd.
Res., 25 (1972) 465-473
PRACTICAL s YNl-HESIS OF GLUCOPYRANCXZDES
473
The crystalline product was filtered off, washed with a little heptane, and dried by aspiration_ A small second crop, obtained from the mother liquor, was combined with the first to give 2 (0.94 g, 93% based on 12,43% based on 3) having m.p. 127.5128.5” and [c&’ + 131” (c 2, water), + 146” (c 2.2, methanol). Anal.Calc. for C,,H,006: C, 59.1; H, 7.1. Found: C, 59.2; H, 7.2. ACKNOWLEDGMENT
We thank Mr. C. H. VanEtten and his associates, Mmes. Clara E. McGrew and Bonita R. Heaton, for the microchemical analyses. REFERENCES 1 F. SMITH, J. Chem. Sot., (1951) 2646; P. A. J. GORIN, Can. J. Cbem., 35 (1957) 595. 2 J. KENNERAND G.N.RIcHARDS, J. Chem.Soc.,(1955) 1810. 3 (a) D. TRIMNELL, W.M. DOANE,C.R.RUSSELL,AND C.E.Rxs-r,Cwbolryri. Res., 11(1969)504; (b) R. L. WHISTLER AND S.J. KAZENIAC, J. Amer. Chem. Sot., 76 (1954) 3044; (c) R. L. WHISTLER AND S. J. JCAZENIAC,ibid., 76 (1954) 5812; (d) J. 0. DEFERRARI,E. G. GROS, AND I. M. E. THIEL, Methods Curbohyd. Chem., 6 (1972) 365; (e) R. L. WHISTLER, E. G. LINKE, AND S. J. KAZENIAC, J. Amer. Chem. Sot., 78 (1956) 4704. 4 3. N. BEMILLER, C. L. COLLINS,E. R. DOYLE, AND R. E. WING, Curbohyd. Res., 16 (1971) 480. S S.S. BHAITACHARJEE AND P. A.J.GoRIN, Can. J. Chem.,47 (1969)1195. 6 J. W. VAN CLEVE, Curbohyd. Res., 17 (1971) 461. 7 R. GIGG AND C. D. WARREN, J. Chem. Sot. (C), (1968) 1903. 8 J. S. BRIMACOMBE, B. D. JONES, M. STACEY, AND J. J. WILLARD, Curbohyd. Res., 2 (1966) 167. 9 W-A. HAMMONDAND J.R. Wrm~ow,Imf. Eng. Chem.,25 (1933)111X 10 K. V. BHAT AND W. W. ZORBACH, Carbohyd. Res., 6 (1968) 69.
Curbohyd. Res., 25 (1972) 465473
PRACTICAL METHYL
465
SYNTHESIS
OF METHYL
4-O-METHYL-
AND
4-O-BENZYL-CZ-D-GLUCOPYRANOSIDE
J.W.VAN<=LEVE
AND
CR
RUSSELL
Northern Regional Research Laboratory +, Peoria, Illinois 61604 (U. S. A.) (Received April 26th, 1972; accepted’in revised form July 3rd, 1972)
ABSTRACT
Gram amounts of pure, crystalline methyl 4-U-methyland methyl 4-O-benzyla-D-glucopyranoside have been prepared from methyl 4,6-O-benzylidene-a-~-glucopyranoside in 40% overall yields by a method that appears to constitute a practical synthesis of methyl 4-0-alkyl-a-~glucopyranosides. 1NTRODUCTION
Investigations of the structure and chemical reactivity of starch have often benefited from insights provided by parallel studies of model compounds. Thus our interest in the reactivity of starch towards grafting reagents under various conditions could be served, it appeared, by studies of the chemical behavior of methyl 4-0-
aikyl-a-D-glucopyranosides
under the same conditions.
The simplest model compound analogous to the a-D-(144)-linked D-gIucose residues of starch is methyl PO-methyl-a-D-glucopyranoside (1).This compound, from which 4-O-methyl-D-glucose has been derived’ *‘, has been prepared by four methods: (a) reduction of methyl (methyl PO-methyl-a&D-glucopyranosid)uronate derived from mesquite gum or wood hemicellulosel, (b) methylation of methyl 2,3-di0-acetyl-3n** or(c) methyl 2,3-di-O-benzyL6O-trityl-a-D-glucopyranoside 3e followed, in each case, by removal of blocking groups, and (6) benzylation of amylose with subsequent methanolysis, methylation, and debenzylation4. As practical methods for the preparation of 1,these earlier procedures are of limited value for various reasons: (a) the product is impure2, (b) the yield is low and purification is laborious3e~4, or *This is a laboratory of the Northern Marketing and Nutrition Research Division, Agricultural Research Service, U. S. Department of Agriculture. Mention of firm names or trade products does not imply that they are endorsed or recommended by the U. S. Department of Agriculture over other firms or similar products not mentioned. **Two attempts have been made to prepare 1 by methylation of this intermediate. Purdie methylation was accompanied by acetyl migration and, after removal of blocking groups, the product, at first thought to be 1 (ref. 3b), was later proved to be methyl 2-O-methyl-cr-D-glucopyranoside”. Subsequently Deferrari and his associatesgd introduced diazomethane-boron trifiuoride etherate as a reagent for methylating partially acetylated sugars without acyl migration. With this reagent Trimnell et uI.~~ succeeded in preparing 1 ingood yield from the above intermediate. Carbohyd.
Res., 25 (1972) 465-473
PRACTICAL s YNl-HESIS OF GLUCOPYRANCXZDES
473
The crystalline product was filtered off, washed with a little heptane, and dried by aspiration_ A small second crop, obtained from the mother liquor, was combined with the first to give 2 (0.94 g, 93% based on 12,43% based on 3) having m.p. 127.5128.5” and [c&’ + 131” (c 2, water), + 146” (c 2.2, methanol). Anal.Calc. for C,,H,006: C, 59.1; H, 7.1. Found: C, 59.2; H, 7.2. ACKNOWLEDGMENT
We thank Mr. C. H. VanEtten and his associates, Mmes. Clara E. McGrew and Bonita R. Heaton, for the microchemical analyses. REFERENCES 1 F. SMITH, J. Chem. Sot., (1951) 2646; P. A. J. GORIN, Can. J. Cbem., 35 (1957) 595. 2 J. KENNERAND G.N.RIcHARDS, J. Chem.Soc.,(1955) 1810. 3 (a) D. TRIMNELL, W.M. DOANE,C.R.RUSSELL,AND C.E.Rxs-r,Cwbolryri. Res., 11(1969)504; (b) R. L. WHISTLER AND S.J. KAZENIAC, J. Amer. Chem. Sot., 76 (1954) 3044; (c) R. L. WHISTLER AND S. J. JCAZENIAC,ibid., 76 (1954) 5812; (d) J. 0. DEFERRARI,E. G. GROS, AND I. M. E. THIEL, Methods Curbohyd. Chem., 6 (1972) 365; (e) R. L. WHISTLER, E. G. LINKE, AND S. J. KAZENIAC, J. Amer. Chem. Sot., 78 (1956) 4704. 4 3. N. BEMILLER, C. L. COLLINS,E. R. DOYLE, AND R. E. WING, Curbohyd. Res., 16 (1971) 480. S S.S. BHAITACHARJEE AND P. A.J.GoRIN, Can. J. Chem.,47 (1969)1195. 6 J. W. VAN CLEVE, Curbohyd. Res., 17 (1971) 461. 7 R. GIGG AND C. D. WARREN, J. Chem. Sot. (C), (1968) 1903. 8 J. S. BRIMACOMBE, B. D. JONES, M. STACEY, AND J. J. WILLARD, Curbohyd. Res., 2 (1966) 167. 9 W-A. HAMMONDAND J.R. Wrm~ow,Imf. Eng. Chem.,25 (1933)111X 10 K. V. BHAT AND W. W. ZORBACH, Carbohyd. Res., 6 (1968) 69.
Curbohyd. Res., 25 (1972) 465473