The Reaction of Vinyl Ethers with Carbo Hydrates

I This dissertation has been microfilmed exactly as received 69-11,687 PAREKH, Girlsh Girdhar, 1939- THE REACTION OF VINYL ETHERS WITH CARBO HYDRATES. The Ohio State University, Ph.D., 1968 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan THE REACTION OF VINYL ETHERS WITH C/JtDOHYDRATES DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Girish Girdhar Parekh, B.So.(Hons.), M.Sc. ******* The Ohio State University 1968 Approved by Adviser Department of Chemistry ACKNOWLEDGMENT I aia grateful to Professor M. L. Wolfrom for suggesting the problem and the advice given throughout the research period. I wish to acknowledge the helpful suggestions from Dr. S. S. Bhattacharjeo and the cooperation of other colleagues. The work was supported by Grant No. 12-14.-100-7652(71), from the U. S. Department of Agriculture, Northern Regional Research Laboratory, Peoria, Illinois, to The Ohio State Uni versity Research Foundation (Project 1856). i i VITA November 11, 1939 ..........................Born - Bombay 56, India i 9 6 0 ................................................... B.Sc.(Hons.), The University of Bombay, Bombay 1, India 1960-1963 ........................................... Research Fellow, Institute of Science , Bombay 1, India 1963 .................................................... M.Sc., The University of Bombay, Bombay 1, India 1963-1964 ........................................... Research chemist, Lyka Labora to rie s, Bombay 57, India 1964-1968 ........................................... Research Assistant under Professor M. L. Wolfrom, Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, U.S.A. ill CONTENTS Page ACKHO'ÆiDGKiST.............................................. i i VITA.......................................................................................................... i i i LIST OF TABLES................................................................................ v ii INTRODUCTION MU STATEMENT OF PROBLEM......................... 1 HISTORICAL ..... .................................................................... 11 Vinyl ethers ....................................................... 11 1. Synthesis 2. Reactions 3. Protection of hydroxyl group Chemical synthesis of l-thioglycosides .... 28 1. Direct acid-catalyzed glyc03i dation 2. Preparation from dithioacetals 3. Synthesis from glycosyl halides 4. Synthesis from l-thioaldosides DISCUSSION OF RESULTS ................................................................ 45 Part I ................................................................................. 45 Part I I ............................................................................ 61 EXPERIMENTAL..................................................................................... 69 Part I ................................................................................. 69 Reaction of ethyl vinyl ether with D-galactose diethyl dithioacetal (56^ Reaction of isopropyl vinyl ether with D-galactose diethyl dithioacetal (56) iv CONTENTS (Continued) Page Reaction of ter-butyl vinyl ether •with D-galactose diethyl dithioacetaü. (j^) . 71 Desulfurization of 5,6-0-ethylidene D-galactose diethyl dithioacetal (57) Periodate Oxidation Periodate oxidation of 5,6-0-ethylidene 1-deoxy-D-galactitol (5S) Preparation of 6-0-(l-ethoxyethyl)-D- galactose diethyl dithioacetal (6o) Acid-catalyzed reaction of 6-0-(l-ethoxyethyl)-D-galactose diethyl dithioacetal (60) Partial deiner captai at ion of 5,6-0-ethylidcne- D-galactose diethyl dithioacetal (57) Synthesis of ethyl 5,6-0-ethylidene-l-thio- a-D-galactofuranoside (62) Preparation of methyl 6-0-tetrahydro-2H- pyran-2-yl-a-D-glucopyranoside (67) Conversion of methyl 6-0-tetrahydro-2H- pyran-2-yl-a-D-glucopyranoside to 2,3,4“ tri-0-methyl-N-phenyl-p-D-glucopyranosyl- emine “ • - Preparation of methyl 6-0-(tetrahydro-2H- pyran-2-yl)-a-D-glucopyranoside from methyl 2,3,4-tri-O-acetyl-a-D-glucopyranoside ” Part I I ..........................................................................................82 Synthesis of l,2:3,A-“di-0-benzylidene-6- 0-(l-methoxyphenylethyl)-a-D-galactopyranose (tô) Synthesis of diphcnylmethyl vinyl ether Synthesis of l,2:3,4-di-0-benzylidono-6-0- (l-diphenylraethoxyethyl)-D-D-galactopyranose (62) CONÏülN'K (Continued) Page Reaction of starch viith vinyl e t h e r s .................... 84 Determination of degree of substitution SU14KMY ........................................................................................................ 88 BIBLIOGRAPHY ......................................................................................... 91 Vi TABLES Table No. Page 1. Partial deinercaptalation of 5,6-0- ethylidene--D-galactose diethyl- dithioacetal (^V.) .......................................... 56 2. Reaction of starch with vinyl ethers ....................... ^2 3 . D. S. of starch acetals ..................................................... 55 CHo I ^ /(.. Starch acetals (Starch-O-GHOR)-physical p r o p e r t i e s ........................................................................ VI1 INTRODUCTION and STATEMENT OF PROBLEM In carbohydrate derivatives, it is frequently necessary to protect hydroxyl and amino groups; the methods used to protect these groups are often similar and protective groups used for one may be applicable to the other. In transformations of sugars, there are mainly three types of protective groups most commonly employed; ethers, mixed acetals, and esters. There are a number of review articles (1-3) • (1) B. Helferich, Adv. Carbohydrate Chem., 3., 79 (1948). (2)A. N. DeBelder, ib id .. 20, 219 (1965). (3) J . F. W. McOraie, Adv. Org. Chem., 2, 216 (1963). Until recently, alkyl ethers have not found much favor as protective groups mainly because of the comparatively drastic con ditions required for their cleavage ( 4). The discovery that methyl (4) R. L. Burwell, Chem. Rev,, 615 (1954). ethers can be cleaved under very mild conditions by boron trichloride or boron tribromide (5) has led to the use of such ethers in the (5) T. G. Bonner, E. J. Bourne, and S. McNally, J . Ghein. Soc., 2929 (i960 ). fie ld of carbohydrates (6). For the f ir s t time Long and coworkers (7) (6) A. B. Foster, D. Horton, N. Sa].im, M. Stacey, and J . M. Webber, ib id .. 2587 (i960). (7) M. S. Evans, F. N, Parrish, and L. Long, J r ., Carbohydrate Res., 2, A53 (1967). studied the formation of cyclic acetals of sugars by reactions with ketone dimethyl acetals. The acetal exchange reactions were carried out with 2,2-dimethoxypropano (2), 2,2-dln’.ethoxy-3,3-dir;iO’bylbutane, acetophenone dimethyl acetal, and ben%ophcnono dimethyl acetal on methyl o-Ë-glucopy’ranoside (l) , in N,N-dimethylforinaiTiide in the presence of p,~toluenesulfonic acid as catalyst, whereby the 4,6- acetals (3,) of the sugar with minor amounts of other products were isolated. A typical reaction was formulated as an equilibrium mixture of the two acetals, as shown below. In the case of the reaction with benzophenone dimethyl acetal, the 4,6-acetal was ob tained in low yield, which was explained as due to the sterically hindered axial phenyl group in the resulting methyl 4,6-0-(diphenyl- methylidene)-c-D-glucopyranoside ( 3). The major product was the monoacetal, methyl 6-0-(diphenylmethoxymethyl)-a-D-glucopyranoside ( 4), CHgOn OCH + ZCH^CH HO \0 OCH, OCH 1 2 1 The monoacetal (A) vjas converted partially into the 4,6-acotal (^) under acid-cataly sis, as shovin below. ?h OH OCH OH OCH k The use of alkyl vinyl ethers to protect hydroxyl or amino groups has occasionally been done but their potential usefulness •in the fie ld of carbohydrates has not been investigated. Tchoubar prepared (8) mixed acetals of simple alkyl vinyl and ethers and (8) B. Tchoubar, Compt, rend., 237, 1006 (1953). showed their stability against anionic reagents, Sims and co workers (9) made use of alkyl vinyl ethers to protect the hydroxyl (9 ) H. J. Sims, H. B. Parseghian, and P. L. deBenville, J , Org. Chem., 2^, 724 (1958). 4 groups of cyanohydrins in the synthesis of o.-hydroxyguanaiiiines. Barker and covioikers (lO) prepared acetals of sucrose by the reac- (lO) S, A, Barker, J . S. Briraacoiribe, J. A. O'aravis, and J. M. Williams, J. Chem, Soc., 3158 (1962). tion of sucrose uith alkyl vinyl ethers under acid catalysis. 3,4- Dihydro-2H-pyran, a cyclic vinyl ether, has been extensively used in the field of steroids (11) to protect hydrozcyl groups as their (11) G. Djcrassi, "Steriod Reactions," Holden-Day, In c., San Francisco, (1963), p. 76. tetrahydropyran-2-yl derivatives. The use of dihydropyran to pro tect hydroxyl groups in transformations of sugars is quite recent, Paul f ir s t shewed (12) that dihydropyran reacts with anhydrous (12) a. Paul, Bull. Soc. Chim., 1, 978 (1934). methanol under acid catalysis to yield a mixed acetal. Wood and Kramer (13) extended this reaction to a number of alcohols and phenols, (13) G. F, Wood and D. Kramer, J . Amer. Chem. Soc., 2246 (1947 ). They found that the vinyl ether adds to primary, secondary, and tertiary alcohols in the presence of an acid catalyst. This reac tion is also found to take place in the presence of acid catalysts such as hydrochloric acid ( 13), p-toluenesulfonic acid (14), (14) D. Robertson, J . Org, Chem,, 25, 931 (i960). phosphorus oxychloride (15), polyphosphoric acid (l6) , and Air.berlite (15) G. Greenhough, H. K. Henbest, and E. Jones, J. Chem. Soc.,

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The Reaction of Vinyl Ethers with Carbo­ Hydrates

The Reaction of Vinyl Ethers with Carbo Hydrates