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Selective substitution of sucrose McKeown, George Gordon 1956-12-31

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SELECTIVE SUBSTITUTION OF SUCROSE GEORGE GORDON McKEOWN B.A., University of British Columbia, 19^0 M.Sc, University of British Columbia, 19£2 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in the Department of CHEMISTRY We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA September, 1956• In presenting t h i s t h e s i s i n p a r t i a l f u l f i l m e n t of the requirements f o r an advanced degree a t the U n i v e r s i t y of B r i t i s h Columbia, I agree th a t the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r reference and study. I f u r t h e r agree t h a t permission f o r extensive copying of t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the Head of my Department or by h i s r e p r e s e n t a t i v e . I t i s under stood that copying or p u b l i c a t i o n of t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be allowed without my w r i t t e n permission. Department of ^< The U n i v e r s i t y of B r i t i s h Columbia, Vancouver #, Canada. Date ABSTRACT Detritylation of tri-G-trityl-pent a-Q-acetyl sucrose with catalytic bydrogenolysis or graded hydrolysis with aqueous acetic acid gave in yields up to 60% a new crystal line penta-^acetyl sucrose derivative. Methylation of the pentaacetate with the Purdie reagents, followed by deacetylation and chromato graphic purification gave a sirupy tri-O-methyl sucrose which was shown to be l 1 , k9 6 ' -tri-Q-methyl sucrose by periodate oxidation and by hydrolysis to equal parts of U-Oj-methyl-D-glucose and 1, 6-di-O-methyl-D-fructose. The glucose derivative was identified by paper chromatography, specific rotation and by conversion to the known, crystalline osazone, and the structure of the new sirupy 1, 6-di-O-raethyl-D-fruetose was established by analysis, periodate oxidation, paper chromatographic behavior and the specific rotation. Deacetylation of tri-0-trityl-penta-O-acetyl sucrose gave an amorphous tri-O-trityl sucrose and methylation of this compound with the Purdie reagents, followed by detritylation with aqueous acetic acid gave a sirupy penta-O-methyl sucrose derivative, which was identified as 2, 3, 3', k9 h1 -penta-Cj- inethyl sucrose by hydrolysis to equal parts of the known 2, 3, . k -tri-O-methyl-D-glueose and 3, U -di-O-methyl-D-fructose. It was therefore established that the t r i t y l groups in the original tri-0-trityl-penta-O-acetyl sucrose occupied the three primary positions ( 1 6 and 6 *) in the sucrose molecule and that acetyl migration from Ch to in the glucose moiety had occurred during the synthesis of the tri-O-methyl sucrose* "Vinylation of It 2-3: h-di-Q-isopropylidene- D-galactose with vinyl acetate after the method of Adelraan gave after catalytic hydrogenation followed by removal of the acetone groups a 0,7% yield of sirupy 6-O-ethyl-D-galactose. The new galactose derivative was identified by comparison with an authentic sample synthesized by direct ethylation of 1; 2 -3* k -di-O- iaopropylidene-D-galactose. Preliminary studies of the vinylation of the new crystalline penta-O-acetyl sucrose are reported. The action of Dowex I on several acetates of non-reducing carbohydrates was found to result in deacetylation in nearly quantitative yields. Faculty of Graduate Studies P R O G R A M M E O F T H E FINAL ORAL EXAMINAT ION FOR THE DEGREE OF DOCTOR OF PHILOSOPHY of GEORGE GORDON McKEOWN B.A., University of British Columbia, 1950 M.Sc, University of British Columbia, 1952 T U E S D A Y , O C T O B E R 9, 1956, at 3:30 p.m. IN T H E CHEMISTRY LIBRARY C O M M I T T E E I N C H A R G E DEAN G . M . SHRUM, Chairman DEAN F. H . SOWARD W . A . BRYCE C. A. MCDOWELL G . G . S. DUTTON A . M . CROOKER L. D . HAYWARD W . J. POLGLASE R. D . JAMES G . M . VOLKOFF External Examiner: DR. R. A. LEMIEUX University of Ottawa SELECTIVE SUBSTITUTION,OF SUCROSE ABSTRACT Detritylation of tri-O-trityl-pentaiO-acetyl sucrose with catalytic hydrogeno- lysis or graded hydrolysis with aqueous acetic acid gave in yields up to 60% a new crystalline penta-O-acetyl sucrose derivative. Methylation of the pentaacetate with the Purdie reagents, followed by deacetylation and chromatographic purifi cation gave a sirupy tri-O-methyl sucrose which was shown to be l',4,6'-tri-0- methyl sucrose by periodate oxidation and by hydrolysis to equal parts of 4-0- methyl-D-glucose and 1,6-di-O-methyl-D-fructose. The glucose derivative was identified by paper chromatography, specific rotation and by conversion to the known, crystalline osazone, and the structure of the new sirupy 1,6-di-O-methyl- D-fructose was established by analysis; periodate oxidation, paper chromatogra phic behaviour and the specific rotation. Deacetylation of tri-O-trityl-penta-O-acetyl sucrose gave an amorphus tri- O-trityl sucrose and methylation of this compound with the .Purdie reagents, followed by detritylation with aqueous acetic acid gave a sirupy penta-O-methyl sucrose derivative,, which was. identified as 2,33', 4,4'-penta-0:methyl sucrose by hydrolysis to equal parts of the known 2,3,4-tri-O-methyl-D-glucose and 3,4- di-O-methyl-D-fructose. It was therefore established that the trityl groups in the original tri-O-trityl- penta-O-acetyl sucrose occupied the three primary positions (1', 6 and 6') in the sucrose molecule and that acetyl.migration from Q to C 0 in the glucose moiety had occurred during the synthesis of the tri-O-methyl sucrose. Vinylation of 1:2-3:4-diTO-/jcpropylidene-D-gaIactose with vinyl acetate after the method of Adelman gave after catalytic hydrogenation followed by re moval of the acetone groups a 0.7% yield of sirupy 6-O-ethyl-D-galactose. The new galactose derivative was identified by comparison with an authentic sample synthesized by direct ethylation of l:2-3:4-di-0-/Jopropylidene-D-galactose. Pre liminary studies of the vinylation of the new crystalline penta-O-acetyl sucrose are reported. The action of Dowex I on several acetates of non-reducing carbohydrates was found to result in deacetylation in nearly quantitative yields. PUBLICATIONS 1. Separation of Amaranth andTartrazine, McKeown, G. G., J. Assoc. Offic. Agr. Chemists, 37, 527-9 (1954). 2. Polarographic Reduction of Amaranth, McKeown, G. G. and Thomson, J. L., Can. J. Chem., 32, 1025-32 (1954). 3. A separation of the triphenylmethane food colors by column chromatog raphy, McKeown, G. G. and Thomson, J. L., J. Assoc. Offic. Agr. Chemists, 37, 917 (1954). 4. The Action of Pyridine on Dulcitol Hexanitrate, McKeown, G. G. and Hayward, L. D., Can. J. Chem., 33, 1392-98 (1955). 5. Selective Substitution in Sucrose, Parts I and II, to be published. G R A D U A T E STUDIES Field of Study: Chemistry f Drs. J. G. Hooley, C. Reid, Topics in Physical Chemistry I B. A . Dunell, M . Kirsch, L. W . Shemilt, [ W . A. Bryce, H . M . Daggett Topics in Inorganic Chemistry Drs. K . Starke and J. A . Harris Radiochemistry Drs. K . Starke and M . Kirsch Chemical Kinetics Drs. W . A . Bryce and J. Halpern Physical Chemistry of High Polymers Dr. B. A . Dunell _ . . _ . „ . ( Drs. L. D. Hayward, G. G. S. Dutton Topics in Organic Chemistry j a n d R M D a g g e t t Carbohydrates Dr. L. D . Hayward Cellulose, Lignin and Related Products Dr. L. D . Hayward Physical Organic Chemistry Dr. C. C. Lee Organic Analysis A . Werner Molecular Rearrangement Dr. A . Rosenthal Other Studies: Introduction to Quantum Mechanics Dr. O. Theimer Molecular Structure and Biological Function Dr. W . J. Polglase Outside Interests: Astronomy. ACKNOWLEDGEMENTS The writer wishes to express sincere thanks to Dr. L.D. Hayward for his ready encouragement and great interest in the direction of this investigation. Grateful acknowledgements are also made to the Sugar Research Foundation, Inc. for a grant, and to Canadian Industries, Ltd* for the award of a fellowship and to the Department of National Health and Welfare for educational leave* CONTENTS INTRODUCTION 1 HISTORICAL INTRODUCTION k DISCUSSION OF RESULTS 18 EXPERIMENTAL 1*8 A. Materials U8 Silver oxide U8 Palladized charcoal catalyst I4.8 Trityl chloride U8 Platinum oxide catalyst U8 Solvents and reagents k9 B. Analytical methods h$ Trityl k9 Acetyl k9 Alkcxyl h9 Carbon and hydrogen 1*9 Periodate oxidations 1+9 C. Tri-O-trityl-penta-O-acetyl Sucrose $0 Preparation at an elevated temperature 50 Preparation at room temperature J>1 D. Tri-O-trLtyl Sucrose 52 Direct tritylation of sucrose S>2 Deacetylation of tri-O-trityl-penta-O- ac etyl sucrose 53 Acetylation of tri-O-trityl sucrose 5U CONTENTS (continued) P^e Attempted catalytic detritylation of tri-O-trityl sucrose 55 E. Penta-O-acetyl Sucrose 55 Catalytic hydrogenation of tri-O-trityl- penta-O-acetyl sucrose 55 Graded hydrolysis of tri-O-trityl- penta-O-acetyl sucrose 59 Acetylation of penta-O-acetyl sucrose 59 F. Methylation of penta-O-acetyl sucrose 60 G. Tri-O-methyl sucrose 62 Deacetylation of methylated penta-O-acetyl sucrose 62 Chromatographic purification of the tri-O- methyl sucrose 62 Periodate oxidation of tri-O-methyl sucrose 63 Hydrolysis of tri-O-methyl sucrose 6k Chromatographic separation of the tri-O-methyl sucrose hydrolysis products "~ 65 H. k-O-methyl-D-glucose 66 I. 1, 6-Di-O-methyl-D-fructose 67 J, Methylation of tri-O-trityl sucrose . 69 K. Penta-O-methyl sucrose 72 Graded hydrolysis of methylated tri-O-trityl sucrose 72 Isolation of penta-O-methyl sucrose 75 Hydrolysis of penta-O-methyl sucrose 78 CONTENTS (continued) Page L. 2,3,U-Tri-0-methyl-D-glucose . 79 M. 3,U-Di-0-methyl-D-fructose 80 N . Attempted Vinylation of penta-O-acetyl sucrose 8 1 0 . Preparation of 1:2-3:U-di-O-isopropylidene- D-galactose 83 P. 6-Q-Etbyl-l s2-3 :li-di-Q-isopropylidene- D-galactose 81+ Q. 6-0-Ethyl-D- galactose 85 R. Vinylation of 1:2-3 tU-di-O-isopropylidene- P-galactose ~" 86 S* Deacetylation experiments with anion exchange resin 90 . CLAIMS TO ORIGINAL RESEARCH $k BIBLIOGRAPHY 96 TABLES Page I. Functional Derivatives of Sucrose 8 II. Progress of Methylation of Penta-O-acetyl Sucrose as followed by Paper Chromatography 2 6 III. Periodate Oxidation of Tri-O-methyl sucrose 63 IV. Periodate Oxidation of Sucrose 6U V. Hydrolysis of Sucrose 6k VI. Periodate Oxidation of 1,. 6-di-O-methyl-D-fructose 6 8 VII. Deacetylation of Sugar Acetates on a Column of Anion Exchange Resin 9 2 VIII. Elation of Deacetylated Compounds from the Resin Column 93 INTRODUCTION The object of this research was, in the larger view, to contribute toward the bringing together of sucrose as an inexpensive, abundantly available, pure organic chemical, and the vigorously expanding chemical industry as a potentially vast consumer. Sucrose i s produced on a scale of tens of millions of tons per year in a crystalline form of unrivalled purity for an industrial product. It has been calculated that the production could be practically trebled i n a relatively short period of time i f the occasion demanded and indeed international agreement has been necessary to curtail production i n order to avoid the economic difficulties resulting from a surplus. After many years of research no outlet of any importance other than its use as a food has been discovered for sucrose. If such an outlet could be developed the world's supply of utilizable carbon could be vastly increased. Our present source of utilizable carbon is lodged primarily i n the diminishing assets, coal and o i l . As these resources become exhausted, the perenially renewed products of plants such as sucrose w i l l inevitably rise to prime importance. In particular, two objectives were proposed for this research. The f i r s t of these was to carry out a precise study of the chemistry of sucrose: to prepare by unequivocal methods specifically substituted derivatives of sucrose and to thoroughly characterize such derivatives. Most of the previously 2 reported derivatives of sucrose have been mixtures of sometimes highly doubtful composition. The second objective was to investigate the usefulness of a new method of preparing vinyl ethers as applied to the carbohydrate field. The standard method for preparing vinyl ethers involves harsh reaction conditions not compatible with sensitive, complex substances such as carbohy drates. The new method on the other hand offered the promise of a mild route to a vinyl ether. It was desired to test the value of the new method and i f possible to prepare a selectively sub stituted vinyl ether of sucrose. Since the eight reactive centers on the sucrose molecule are hydrcxyl groups* three of which are primary, the proposed plan for preparing partially substituted derivatives was to firs t block the primary positions with t r i t y l groups (tri t y l chloride(triphenylmethyl chloride) has been shown to react preferentially with primary hydrcxyl groups), then acetylate or etherify the remaining positions and finally to remove the t r i t y l blocking group. By this route, one could theoretically prepare numerous selectively substituted penta-O-acyl-and alkyl - sucrose derivatives. The project was begun in this laboratory in 1953, under the direction of Dr. L.D. Hayward, by another worker, Mr. R.S.E. Serenius, who succeeded in preparing a key derivative, 3 tri -Oj-trityl-penta-0- acetyl sucrose i n a pure, crystalline form. Serenius also i n i t i a t e d studies on the detritylation of this compound. HISTORICAL INTRODUCTION The sugar cane seems to have originated i n North East India, in particular Bengal (1)* Probably sugar was fi r s t consumed by chewing the canes or drinking the pressed juice (2), however, i t was known around 300 A.D, i n certain parts of India, how to prepare solid cane sugar, at least for medical purposes ( 3 ) * The Arabs on conquering Iraq around 6k0 A.D* were introduced to sugar and planted cane i n Egypt (k) and later over North Africa, Sicily and Spain (£)• In lU°3 , Columbus brought sugar cane from the Canary Islands to San Domingo ( 6 ) * In America, because of favorable climatic conditions, the cultivation of cane spread rapidly and sugar grew into a world-wide commercial article (7)* Sucrose has been found to occur almost universally throughout the plant kingdom i n the leaves, roots, seeds, juices, flowers and fruits of plants. Sucrose was reported in a l l of the 281 species of phanerogams studied by Bourquelot and his associates (8). Commercially, the principal sources are the sugar cane which contains about 12 - 18% sucrose and the sugar beet which contains about 12 - 17%» Sucrose i s the most abundant fine organic c&ejmical produced today, on a scale of tens of millions of tons 5 per year (9). In 19U8, the world's production was 32 million long tons of which approximately two-thirds came from sugar cane and the remainder from sugar beets* The Americas produced more than a third of this total (10). The consumption of sucrose i s unfortunately limited almost entirely to its use as a food (11) and as the per capita consumption (about 100 pounds per year) i s surprisingly constant production must be curtailed to just meet the demand. In recent years there have been increasing efforts to find and develop new uses for this abundant natural product. A few of the types of investigation now i n progress are : the trans formation of sucrose into useful products by the chemical processes of oxidation, reduction, acid transformation and alkaline degradation; the production of useful derivatives of sucrose itself; and the conversion of sucrose into other products by fermentation processes (12). The determination of the structure and configur ation of sucrose ( I ) was a monumental task which extended over more than a century and involved contributions from such noted workers as Lavoisier, Dumas, Gay-Lussac, Liebig, Fischer, Raoult, Kiliani, Hudson, Haworth, Purdie, Irvine, Hirst, Purves and'many others. Although the structure and configuration of sucrose was 6 established with considerable certainty by 193U i t was not until 1953 that the fi r s t chemical synthesis of sucrose was achieved by Lemieux and Ruber (Ik). Their accomplishment marked a milestone in the history of carbohydrate chemistry. CH2OH I Sucrose i s a non-reducing disaccharide composed of an -D-glacopyranose residue and a /3 -D-fructo- furanose residue united through a double glycosidic linkage. The compound possesses eight reactive centers; the three primary and five secondary hydroxyl groups. As a consequence of the double glycosidic linkage- and idle lability of the furanose ring trtructure of the D-fructose moiety, sucrose is highly sensitive towards acid hydrolysis. Thus the ease of acid hydrolysis i s approximately 1500 times greater for sucrose than for any other disaccharide (15, 1 6 ) . This fact may well account for the scarcity of derivatives of sucrose. The molecule i s very stable to alkali as i s shown by 7 the fact that methylation of sucrose takes place in good yield in a solution of k0% sodium hydroxide (17 )• Since sucrose con tains only hydroxyl groups as reactive centers, the only possible derivatives are esters, ethers and (perhaps) acetals. A l i s t of the reported derivatives of sucrose is gixen i n TABLE I. From a consideration of the methods of preparation (non-selective partial acylation, non-selective partial etherification) of the majority of the partially sub stituted derivatives i t becomes obvious the products are of necessity complex mixtures. Furthermore, doubt must shadow the authenticity of any derivative prepared by means of acid catalysis in view of the known sensitivity of sucrose toward acid hydrolysis. Some examples are the preparation of the diethylidene derivative by the action of acetaldehyde and sulfuric acid on sucrose, and of the octanitrate derivative by mixed nitric and sulfuric acids. In a l l fairness, however, i t should be pointed out that i n most cases the authors neither claimed nor implied homogeneity for their products. Of the total number of derivatives, possibly- only four can be described as being adequately characterized homogeneous substances; the octamethyl, the octaacetyl, the trimethylpentaacetyl and the tritritylpentaacetyl derivatives. The preparation of the two last mentioned derivatives along with t r i t r i t y l sucrose wil l be described below in some detail as they have a direct bearing on the present research. 8 TABLE I FUNCTIONAL DERIVATIVES OF SUCROSE Derivative HU£. M S Analytical data dietbylidene (18) octaraethyl (17) sirup sirupjb.p. &7+70.18 115°C/ lO"^ nun* Calc. C,52.8£, H,8.U3; found 0,52.76, H,8.55j Calc. OCHo, 5U.62; found 5U-78; acetyl content after acety- lation 0.07 heptametbyl (19) t rimetbylpenta- acetyl (2^ dibenzyl (21) D + 52* amorphous (Calc. 0,59.77, H,6.£Lj found C, 59.73, H,6.1J4 pentabenzyl (21) o i l Calc. 0 , 7 1 . 2 1 , H,6.56$ found C,70.09, H,6.53 Hexabenzyl (22) o i l heptabenzyl (22) o i l octabenzyl , (22) benzyl- acetyl (22) 9 Derivative pentabenzcyl (23) hexabenzcyl (23) octabenzcyl (2U ) octakLs- (k-bromo- benzoyl) (25) octakis- (k-nitro- benzoyl) (26) octacinna- moyl (27) octanitrate (28) sulfuric acid (29) phosphoric acid (30) monacetyl (3D tetraacetyl (31) heptaacetyl ( 3 D nup_. amorphous amorphous M 2 Analytical data 60-63°C (+2 [*}*+yZ*6* moles of CClj) wxth 2 COL^ crystalline £K]D+k0.6o without CCl^ llk-117°C amorphous decomp. 150°C amorphous 87-88°G amorphous 85.5°C crystalline amorphous amorphous amorphous amorphous amorphous D +55.9°C C C IL i n crystals cont'g 2 moles of C C I L : Calc. 20.75, found 22.56, I8.83. In solvent free material, calc. G69.50, H, k.63j found C69.57, H, k.90 10 Derivative Analytical data octaacetyl (32) pentaallyl (33) heptaaUyl (3U) o c t a l l y l (3U) -methallyl (3U) -chloroallyl (3l+) acetyl- a l l y l (35) ethyl- a l l y l (35) bis-(2-bydraxy- ethyl) (36) octamesyl (37) octatosyl (37) l',6>, 6«- t r i t o s y l - 2,3,3 »,U,U'- pentaacetyl (37) 69-70°Cj 75° M+59.5°C C; 87°C; D poly-morphous , crystalline o i l o i l bip. 190-92°C/5u o n 2l£"C crystalline 86-9l+°C amorphous 82-86°C amorphous £8.5-61*0 amorphous Mjf*38,7° 9+1+1. 78° r^-j2U.9+53.3° calc. G$9.59, H 7.7U; found C59.21, H 7.58. calc. al3yl 1+6.2 found a l l y l 1+1+.3 calc. a l l y l 1+9.6; found alLyl 1+8.5 calc. G21+.8, H 3-93S26.5; found C21+.7, H 3 .92, S26.2 calc. C51.81+, H1+.1+5. S 16.27; found C51.U, H 1+.1+9, S 16.2 calc C50.86, H1+.93, S 9.I+6; found C51.0, H 5.21+, S 9.35 11 Derivative m 141 Analytical data t r i t r i t y l (36) t r i t r i t y l - pentaacetyl (39) 127-29°C amorphous 232.5-23U. f, 117+68,9' 5°c L * JD crystalline 1«, 6, 6«- 66-69°C tritosyl (37) amorphous calc. C77.1i9, H 6.045 found 077.07, H 6.19 calc. t r i t y l 56.6j found t r i t y l 56.7; calc. acetyl 16.8; found acetyl 16.8 calc. C k9.2 H k.97 S 11.9llj found Ck8.8, H k.89, S 12.k In 1935, E.G.y. Percival reported the preparation of 1', 6, 6' -tid-0-methyl-penta-O-acetyl sucrose (20). An addition compound of sucrose and potassium hydroxide was prepared (C-ioIkpQ,,. 3K0H) which was methylated with dimethyl sulfate and . x c " r 1 2 0 then acetylated to give a non-reducing colorless glass, [P£ J D a +£2° (c= 1 in acetone) which analysed correctly for a tri-O-methyl- penta-0-acetyl sucrose. After deacetylation and hydrolysis, a r - 1 20 sirupy mixture of methylated sugars was obtained, \J* J D »+19° (ca 1 i n water). The mixture was treated with methanol and hydrogen chloride and the product acetylated and distilled. Two apparently homogeneous fractions were obtained: (a) bath temperature lk6°/ 18 r* T 21 0.0k mm., n n l.kk75>, [^JD " + 2k° (c a 1 in chloroform) which 12 analysed correctly for a dimethyl methyl glycoside diacetate, and 20 r 1 2 1 (b) bath temperature 170-180%).03 mm., nD 1.U510, L ^ J D =+33.0° (c - 1.5 in chloroform) which analysed correctly for a mono methyl methyl glycoside triacetate. A portion of (a) was deacetylated and hydrolysed, during which period the optical rotation of the solution f e l l only slightly, to give a product which failed to give a crystalline ceazone on treatment with phenylhydragine and acetic acid. Another sample of fraction (a) was methylated with dimethyl sulfate and alkali to give tetra-O-methyl-methyl-D-fructofuranoside which was characterized by conversion by direct oxidation with nitric acid into crystalline, 2, 3, h9 6-tetra-O-methyl-D-fructofuronamide. Another portion of fraction (a) was oxidized directly with nitric acid to yield a lactol acid containing only one methoxyl residue. Oxidation of this product yielded 5- methyl- 2f -D-arabonolactone. The identity of fraction (b) was established by methylation and hydrolysis to crystalline 2,3,U,$-tetra-0-methyl- D-glucose and by hydrolysis to 6-0-met hyl-D- glue os e which was identified as i t s crystalline osazene. In 1929, K. Josephson reported the preparation of tri-O-trityl sucrose and tri-O-trityl-penta-0-acetyl sucrose (38). 13 Cane sugar, 3.k g«, and 8.k g. t r i t y l chloride in $0 ml. dried pyridine was heated for 2 hours on the steam bath. The solution was then poured into ice-water to precipitate a solid product which after drying weighed about 10 g. Purification was achieved by several precipitations from alcohol with water and finally by crystallization from ethyl acetate and petroleum ether: m.p. 127-129"} [*]D =+ 43.4°, + 44.3° (c* 2.kk, 1.58 i n alcohol)} carbon hydrogen analysis, found c • 77.07, H» 6.19, calculated for ^69%k%l» C l B 77»U9» 6.0k» Tritritylsucrose, 1 g., was dissolved in k ml. dried pyridine and 3 ml. acetic anhydride, let stand overnight at room temperature, then diluted with ice-water to yield a solid product which when air-dried weighed 1.05 g. This product was purified by a precipitation from alcohol with water and the dried product crystallized from absolute alcohol: the product "sintered at about 125-126° ••; L J 1 • +57° (c» l.k3 i n chloroform)} carbon hydrogen analysis, found c » 7k .11, H » 5.91, calculated for 019^016, c - 7k.lk, H » 5-83} t r i t y l analysis, found 97% of theoretical. In 195k, attempts to reproduce Josephson's results were made by R.S.E. Serenius and L.D. Hayward (39). These authors found that that the tritylation of sucrose according to the method of Josephson gaze an amorphous product waich could not be crystallized. They succeeded, however, in preparing crystalline tri*gdi-O-trityl-penta-0-acetyl sucrose by successive tritylation. 1U and acetylation in the same solution. A mixture of 1/10 mole of sucrose, 3/10 mole of t r i t y l chloride and 50 g. Drierite in 6.U moles of pyridine was heated with stirring for 3 hours at 75-80°C. After standing overnight 3*2 moles acetic anhydride was added and the mixture again let stand overnight. Precipitation i n ice-water gave an o i l which was separated and washed then cry stallized from tetrahydrofuran and ethanol: crude yield 30$ j m.p. 215-217°G. After recrystallization to constant melting point, the compound which formed i n colorless, hexagonal crystals melted at 232.5 - 23U.5°C, [** J D = + 68.9° (c = 2.UU9 i n chloroform), showed on analysis an acetyl and t r i t y l content correct for tri-O-trityl-penta-O-acetyl sucrose, and reduced Fehling's solution only after acid hydrolysis. Serenius and Hayward found that detritylation of tri-O-trityl-penta-0-acetyl sucrose by the method of Helferich and Klein (Uo) caused extensive degradation of the parent molecule. Thus when 1 mole of tri-O-trityl-penta-O-acetyl sucrose i n glacial acetic acid was treated with 3 moles of hydrogen bromide an immediate precipitation of t r i t y l bromide occurred. The precipitate was filtered off, the filtrate diluted with chloroform and washed with water. Evaporation of the acid-free, dried organic layer yielded a brownr.sirup which was found to be strongly reducing toward Fehling's solution and which could not be induced to yield a crystalline non-reducing product. 15 More promising results were obtained by Serenius and Hayward with the catalytic detritylation technique of Micheel (111). Catalytic hydrogenolysis using platinum oxide or palladized charcoal catalyst was found to cause detritylation of tri-O-trityl-penta-O-acetyl sucrose with the formation of t r i - cyclohexylmethane or tritane respectively. However, catalyst poisoning was found to be troublesome, causing the reaction to stop at a stage of pa r t i a l detritylation. To prepare a polymer of sucrose which i s to contain the intact molecule, two general.tapproaches are available. The f i r s t i s condensation polymerization i n which sucrose i s either condensed with i t s e l f with loss of water or as i s more feasible sucrose molecules are linked by means of an intermediate polyfunctional agent such as an aldehyde, or a polybasic acid. Numerous processes for preparing condensation polymers of sucrose are recorded i n the literature (1|2) and according to the des criptions of the products i n the patents, some were highly success f u l . However, commercial interests have apparently not been impressed since none of the processes has reached the production stage. The reason may be found i n the fact that the sucrose molecule i s highly sensitive to the action of heat and chemical reagents. Condensation polymerization i s at best a vigorous process and would be certain to cause some degree of degradation with the inevitable consequence of discoloration and unpredictable variation i n physical properties. 16 The second approach to the problem involves the preparation of a sucrose derivative substituted with groups capable of undergoing addition polymerization. This type of polymerization i s a relatively mild process and should not cause any significant amount of undesirable side-reactions. Three types of suitable unsaturated sucrose derivatives would be; an acrylic ester, an a l l y l ether, or a vinyl ether. The preparation and polymerization of a pentamethacrylate of glucose (1*3) has been described but the methacrylation of sucrose has not yet been reported. Ally l and substituted allyl ethers of sucrose (33* 34, 35) were prepared and polymerized by Nichols and Yanovski of the Eastern Regional Research Laboratory of the United States Department of Agriculture. Tetra-0-vinyl-<rt -methyl-D-glucoside has been prepared (44) but no vinyl ether of sucrose has been reported. Since 1937, the standard method of preparation of vinyl ethers has been that of Reppe (U5). The method involves a reaction between an alcohol and acetylene under high pressure and high temperature under the influence of a strongly basic catalyst. -The reaction has been applied with success to some of the more chemically-durable carbohydrate derivatives (46)5 for example, tetra-O-vinyl-irt -methyl-D-glucoside mentioned above was prepared by this method. A new method of vinylation which appeared to offer promise with alkali- and heat- sensitive compounds was 17 reported by Ade&man i n 1953 (<U7). He found that alcohols could be vinylated by treatment with vinyl acetate at low temperatures in the presence of catalytic amounts of mercuric acetate and sulfuric acid. A solution of methylglycolate i n excess vinyl acetate was cooled to -22° and treated with a catalytic amounts of mercuric acetate and sulfuric acid for 2.5 hours. The reaction mixture was then neutralized, washed, dried and distilled to yield (k0%) the v i i y l ether of methyl glycolate. With other alcohols studied, the yields of the corresponding vinyl ethers were lower, ethanol 8$, tetrahydrofurfuryl alcohol 25$, 1,5-pentanediol 30$. In 1955, Adelman reported on a similar type of vinyl ether preparation, transetherification between a vinyl ether and an alcohol occurring again at low temperature in the presence of mercuric acetate and sulfuric acid (l ;8). For example, vinyl ethyl ether was prepared through transetherification between ethanol and vinyl butyl ether in h2% yield. Under similar conditions, however, reaction between tetrahydrofurfurylalcohol and vinyl ethyl ether yielded only 9% of the desired vinyl tetrahydrofur furyl ether. 18 DISCUSSION OF RESULTS The investigations i n this thesis can be con veniently grouped into three phases: (i) the preparation of a penta-O-acetyl derivative of sucrose and subsequent trans formations j ( i i ) the preparation of a penta-O-methyl derivative of sucrose and subsequent transformationsj and ( i i i ) a study of the Adelman reaction (u7) as applied to partially substituted carbohydrate derivatives* In FIGURE I are presented the steps involved in the penta-O-acetyl sucrose study. Attempts to reproduce Josephson's (38) reported synthesis of crystalline tri-O-trityl sucrose by direct trity lation of sucrose resulted in a colorless glass which was shown to be a complex mixture containing tri-O-trityl sucrose* products of lower t r i t y l content, reducing sugar fragments and tritanol, from which the desired product could not be isolated* The dried mixture was of such high viscosity that i t could be pulverized to a powder which had a softening point of about 12£-30°C in the region of the melting point reported by Josephson for tri-O-trityl sucrose (127-129°C). Josephson reported an almost quantitative yield: i n the many tritylations carried out in this research, hydrolysis of the glycosidic linkage was found to always accompany the substitution reaction and i n no experiment was a yield higher 19 FIGURE I Sucrose 1 1', 6, 6'-tri-O-tiityl-penta-O-acetyl sucrose . " 1 2 , 3 , 3 ' , ht h'-penta-O-acetyl sucrose I " l 1 , U, 6 '-tri-O-methyl-penta-O-acetyl sucrose i l 1 , kt 6'-tri-O-methyl sucrose U-O-methyl-D-glucose 1, 6-di-O-methyl-D-fructose 20 than $0% achieved. Furthermore, 1', 6, 6 '-tri-Oj-trityl sucrose has been prepared by an indirect route and the constants are not in agreement with those reported by Josephson. Tri-0-trityl-penta-O-acetyl sucrose was pre pared by successive tritylation and acetylation i n the same solution (39, UO, U9)« A 3:1 molar ratio of t r i t y l chloride and sucrose was dissolved in anhydrous pyridine to give a colorless solution and heated to 6£°C for 2k hours. Excess acetic anhydride was then added and the mixture let stand at room temperature, for 7 hours. The now dark-red solution was poured into ice water causing the precipitation of a brown colored sirup which was separated, and crystallized from tetrahydrofuran-methanol to give a $0% yield of crude product. It was found that tritylation at a higher temperature caused a considerable degree of degradation; thus the reaction mixtures were dark colored, the mother liquors were strongly reducing toward Fehling's solution, the crude products had lower melting points and -the crude yields varied from 10 to $0%, A more convenient method of preparation was developed which gave consistently good yields of a high melting product. A 3:1 molar ratio of t r i t y l chloride and sucrose in anhydrous pyridine was let stand at room temperature in a stoppered flask for it8 hours with occasional shaking. Excess acetic anhydride 21 was then added and the pale-yellow solution let stand overnight in the refrigerator. A quantity of crystalline material, m.p. 175-77°C, which separated out at this stage was shown to be the double salt of tritanol and pyridinium hydrochloride (5cy?l) (reported m.p. 172-k°C), and was removed by filtration. The pale- yellow filtrate was poured with stirring into ice water causing the precipitation of a colorless, amorphous solid which was recovered by filtration, washed, dried and crystallized from chloroform- methanol to give a hg>% yield of colorless hexagonal crystals of tri-O-trityl-penta-O-acetyl sucrose of high purity. The mother liquor was shown to be reducing toward Fehling's solution. Two methods of detritylating the tri-O-trityl- penta-O-acetyl sucrose were investigated: low pressure catalytic hydrogenolysis (39, U l ) and graded hydrolysis with aqueous acetic acid (52, 5 3 ) . Since the t r i t y l ether (5u) and the double glycosidic linkage of sucrose (15, 16) are both notably sensitive to acid hydrolysis i t was expected that competitive reactions would occur. In a series of runs, fairly pure tri-O-trityl- penta-O-acetyl sucrose (5 times recrystaliized) i n glacial acetic acid was hydrogenated i n the presence of platinum oxide catalyst at 50°C. The reaction mixtures yielded varying quantities of tricyclohexylmethane melting at 57.5 - 58.0°C (55, 56), 22 partially detritylated starting material and a crystalline product melting at 218-19°C,{«<]D =+71.5° (c« 5«93 i n chloroform), which analysis indicated to be a partially saturated tri-O-trityl-penta- 0-acetyl sucrose. Under similar conditions, catalytic hydrogenoJysis with palladized charcoal catalyst yielded varying quantities of partially detritylated material, unreacted tri-O-trityl-penta-0- acetyl sucrose and triphenylmethane* Highly purified samples of tri-O-trityl-penta- 0-acetyl sucrose which had been recrystallized 12 to 18 times alternately from chloroform - petroleum ether and chloroforra- methanol were found to undergo complete detritylation giving yields of 27, 20, 38, 16, 23$ (platinum oxide) and 20$ (palladized charcoal) of crystalline pent a-O-acetyl sucrose. After recrystallization to constant melting point, the pure penta-O-acetyl sucrose which formed in colorless needle-like crystals melted sharply at 155-156° 0,1!* JD=+22»0° (c« 3.1 i n chloroform), and showed on analysis the acetyl content of a dihydrate. The compound reduced Fehling's solution only after acid hydrolysis. Acetylation of the pentaacetate gave in good yield octa-O-acetyl sucrose which melted at 86-88°C and showed no depression in melting point on admixture with an authentic specimen. 23 A more convenient method of preparing the penta- 0-acetyl sucrose was found i n a graded hydrolysis of the tri-O- "* (SZ> trityl-penta-O-acetyl sucrose with aqueous acetic acid. After optimum conditions of acid concentration and reaction time had been established, yields of 43-60$ of crystalline penta-O-acetyl sucrose which was identical with that obtained by the catalytic detrity lation were readily obtained. Tri-O-1rityl-penta-0-acetyl sucrose was dissolved in glacial acetic acid, the solution heated to boiling and a small quantity of water introduced. After 30 minutes refluxing the solution was cooled, the solvent evaporated and the residue • crystallized from chloroform-petroleum ether to give the desired - pentaacetate. Tritanol was recovered from the mother liquor. That hydrolysis of the sucrose derivatives took place simultaneously with the detritylation is shown by the facts that the mother liquors were strongly reducing toward Fehling's solution, and the yields of the pentaacetate depended markedly on the length of reflux time. After 120 minutes of refluxing no pentaacetate could be isolated from the reaction mixture. The graded hydrolysis method was preferred over the catalytic detritylation since a relatively less pure sample of starting material could be used, the hydrolysis required but a fraction of the time needed for a hydrogenation, and the use of an expensive catalyst was avoided. A sample of the pentaacetate after being repeatedly 2k recrystallized from neutral solvents showed a double melting point of 152-3° and 155-6° • It i s believed that some acetyl migration took place during the purification* since other samples when reciystaliized from solvents acidified with a trace of glac i a l acetic acid did not show the double melting point. I f the two assumptions are made: ( i ) that t r i  t ylation took place at the primary hydroxyl groups of sucrose according to Helferich's Rule (57) which i n fact has been demonstrated i n this research and i s described below, and ( i i ) that no acetyl migration took place during the detritylation, then the structure of the pentaacetate can be designated as 2, 3, 3 *» k, k ',-penta-Oj-acetyl sucrose (II). CH2OH C H/'H \ H II I A o J \ OAcQAc H / L_ o~J \H C G C I I H OAc The Purdie methylation of the penta-O-acetyl sucrose was undertaken for several reasons. At the time, the vinylation of penta-O-acetyl sucrose was being studied and i t was desired to find some means of determining the extent of vinylation, i f any* It was tentatively planned to hydrogenate the vinylation product, deacetylate and analyse the product for 0-ethyl sucroses by paper chromatography. The extent of the vinylation could then 25 qualitatively determined from the relative intensities of the spots for sucrose, mono-, di-, and tri-O-ethyl sucrose. However, since no information on the chromatographic behavior of any partially alkylated sucrose derivative was reported in the literature, i t was planned to use the Rf values of the mono-, di-, and tri-O- methyl sucroses, which would be formed i n the methylation, to serve as a guide* The penta-0-acetyl sucrose also offered an opportunity to study acetyl migration which has been reported to occur during Purdie methylations (58, 59, 60, 6l , 62, 63, 6k, 65). From the preferred conformation of the sucrose molecule (66), i t was predicted that migration would not occur i n the nearly planar fructofuranose ring and therefore 1', 6' - O-methylati on should occur in the fructose moiety whereas in the glucopyranose ring, acetyl migration was to be expected, either of the type G2-*C6 or Ci|.-*C6 both having been reported in structurally analogous gluco pyranose compounds (61, 62, 67, 68), A third reason for the methylation was that i f offered an excellent opportunity to prepare a new tri-O-methyl sucrose and, i f the above predictions held, the previously unknown 1, 6-di-O-methyl-D-fructose. The progress of the methylation was followed by deacetylating a portion of the product after each treatment with the reagents and analysing by means of paper chromatography. When 26 the paper chromatograms were developed with butanol-ethanol-water (5:l:u) (69) and sprayed with p-anisidine hydrochloride reagent (70), sucrose and i t s methyl eethers showed as bfight yellow, U.Vt fluorescent spots. The course of the methylation reaction is shown i n TABLE II. TABLE II Progress of methylation of Penta-O-acetyl Sucrose as followed by  Paper Chromatography No. of Sucrose, Mono-O-methyl Bi-rO-methyl Tri-O-methyl Methylations R* 0.0k Sucrose, Sucrose, Sucrose, ' Rr 0.08 Rf 0.20 Rf O.4O 1 distinct distinct 2 faint very distinct distinct 3 - distinct distinct faint $ - faint distinct After j> treatments with the reagents, the product f I17 obtained was a colorless, viscous glass,L^JD =+57.7° (c> 3.72 i n chloroform) which showed approximately the methoxyl and acetyl content of a tri-O-methyl-penta-O-acetyl sucrose. It was interesting to note that the rotation was in reasonable agreement with that reported by Percival for his 1*, 6, 6 1 -tri-O-methyl-penta-Q-acetyl sucrose (20). Despite repeated attempts over a period of six months, the product could not be induced to crystallize and no convenient chromatographic procedure could be found for further 27 purifying the high molecular weight, hydrophobifce compound. The methylated pentaacetate was therefore de- acetylated in 90% aqueous methanol with Dowex I anion exchange resin to give a quantitative yield of a colorless, viscous sirup which was indicated by paper chromatography to be a mixture con taining approximately 7$% tri-O-methyl sucrose, 25$ di-O-methyl sucrose and a trace of mono-O-methyl sucrose. The mixture of sucrose-O-methyl ethers was separated by partition chromatography on a column of powdered cellulose using butanol-water as developer. The appropriate fractions were combined and evaporated to give 193 mg. of a di-O-methyl sucrose as a colorless, viscous glass and 472 mg. of a tri-O-methyl sucrose as a colorless viscous sirup. The latter r .-[24 compound, L JD =467.6° (c • 1.74 in water), on analysis showed the correct methoxyl content for a tri-O-methyl sucrose. From the known preferred conformation of the sucrose molecule (66) i t was predicted that methylation and deacetylation of penta-O-acetyl sucrose should give either 1', 2, 6' -, or 1', k, 6', - but not 1», 3, 6'- or 1«, 6, 6'- tri-O- methyl sucrose. Confirmation of the prediction was provided by periodate oxidation of the tri-O-methyl compound. Whereas sucrose or 1', 6, 6 1- tri-O-methyl sucrose should consume 3 moles of periodate with a production of 1 mole of formic acid, 1', 2, 6'- or 28 1", ii, 6'- tri-O-methyl sucrose should consume only 2 moles of periodate with no formic acid production and the 1 3 , 6 1 tri-O- methyl sucrose should consume only one mole of periodate with no formic acid* A periodate oxidation was carried out on sucrose and after 2ii hours, 3*1 moles of periodate were consumed with the formation of 0*6l moles of formic acid* These results are in good agreement with those of Fleury and Courtois (71)* The tri-O-methyl sucrose, on the other hand consumed after 2k hours only 1*8 moles of periodate with the formation of no formic acid. These results indicate a l ' , 2, 61, - or l 1 , k, 61 - structure for the tri-O- methyl sucrose* A sample of the sirupy tri-O-methyl sucrose was hydrolysed in aqueous acetic acid and the product separated on a cellulose column into two paper chromatographically homogeneous fractions which analysed correctly for a mono-O-methyl and a di-O- methyl hexose derivative. The sirupy mono-O-raethyl hexose was identified as ii-O^methyl-D-glucose (III) by the following evidence: The specific rotation, L J D «=+ 61.2° (c» l.i+28 in water, equilibrium value), was in good agreement with previously reported values (72, 73)* Paper chromatography revealed a single spot of hue and Rf value identical to that obtained with an authentic sample of ii-O-methyl-29 D-glucose. The sirup did not crystallize on nucleation with 2- , 3 - , or 6- O-methyl-D-glucose. On treatment with phenylhydrazine and acetic acid the sugar yielded a crystalline osazone which melted correctly for U-Cwaethyl-D-glue osazone and showed no de pression in melting point on admixture with an authentic sample. GHO 1 H - 1 G - OH HO - | C - H • H - 1 C - OGH. 1 H - C - OH 1 CH2OH l3 The structure of the liquid di-O-methyl hexose was established as that of the previously unreported 1, 6-di-O- raethyl-D-fructose (IV) by the following evidencet substitution on the 6-position was indicatedeby the positive specific rotation, r ' i 2 k L^JD =+ 17,U° (c » 1.8U3 in water, equilibrium value). (All known 6-0-methyl fructose,and therefore fructofuranose deriva tives show a positive rotation (74) whereas fructose derivatives with a free 6-position show high negative rotations (74)). The Seed crystals of 2-0-methyl-D-glucose were supplied by Dr. M.L. Wolfrom of Ohio State University, and seed crystals of 6-0-methyl- D-glucose were supplied by Dr. Tore Timell, of McGill University. The author is appreciative of this courtesy. 30 sugar on treatment with phenylhydrazine and acetic acid i n the usual manner failed to form an osazone. Paper chromatography (butanol-ethanol-water (5:1«U)) revealed a single spot of high Revalue (0.57) the color of which was characteristic of a ketose (70). (The value found for 3 , hf-di-O-methyl-D-fructose was 0 . 5 l ) . ' A periodate oxidation of the sugar derivative revealed after 58 hours, a consumption of 3.2 moles of periodate, and the production of 1.71 moles of formic acid and no formaldehyde. These results are in harmony with the predicted behavior of 1, 6-di-G- methyl-D-fructose toward periodate oxidation. I 2 3 C - 0 IV I HO - C - H I H - G - OH I H - C - OH I CH2OGH3 The foregoing evidence conclusively established the structure of the parent sucrose derivative as l 1 , h, 6 ' - t r i - 0 - methyl sucrose (V). Acetyl migration from to C5 had occurred during the synthesis as predicted above. V In the second phase of this research a new penta- O-methyl sucrose was prepared and i t s structure established as outlined in FIGUSE II. The difficulties encountered in attempts to pre pare tri-O-trityl sucrose by direct tritylation of sucrose have already been discussed. A convenient route to tri-O-trityl sucrose was found in the deacetylation of tri-O-trityl-penta-O-acetyl sucrose. The latter was prepared i n pure crystalline form and deacetylated with sodium methoxide. The product obtained was a colorless glass, T 122 If*J D • +1U.7 Cc = 3.3 in chloroform), which was so viscous that i t could be pulverized to a fine, white powder. The substance showed on analysis a t r i t y l content which corresponded approximately to that calculated for a tetrahydrate of tri-O-trityl sucrose. It reduced Fehling's solution only after acid hydrolysis. Aee- tylation gave back tri-0-trityl-penta-O-acetyl sucrose i n good yield. An attempt to detritylate a sample of the product by cat alytic hydrogenolysis was unsuccessful. Catalyst poisoning as encountered in the tri-O-trityl-penta-O-acetyl sucrose study halted 32 FIGURE II Sucrose 1 Tri-O-1rityl-penta-O-acetyl sucrose T r i - O - t r i t y l sucrose Tri-0-trityl-penta-O-methyl sucrose Penta-O-methyl sucrose f — : — 2,3, k - tri-O-methyl- D-glucose r \ 3, h - di-O-methyl- D-fructose / 33 the reaction at an intermediate stage. Thus only a trace of sucrose was detected by paper chromatography of the reaction mixture. ; Methylation of t r i - O - t r i t y l sucrose was undertaken for two principal reasons. A characterized, p a r t i a l l y substituted sucrose derivative was desired which would be stable to a l k a l i and hence suitable for future vinylation studies using the Reppe method; a penta-O-methyl sucrose possessing free primary hydroxyl groups should serve admirably for this purpose. Furthermore a t r i - 0-vinyl-penta-G-methyl sucrose would be d i s t i l l a b l e and therefore easily purified. The second objective was to establish unequivo ca l l y the structure of the t r i - 0 - t r i t y l sucrose and therefore also the tri-0-1rity1-penta-0 -acetyl sucrose. Because of the in s o l u b i l i t y of the derivative i n water the Purdie method of methylation rather than that of Haworth was employed. The course of the methylation of t r i - O - t r i t y l sucrose was followed by detritylating and bydrolysing a sample after each methylation with aqueous acetic acid and chromato- graphing the hydrolysate on paper. The reaction was found to proceed very slowly and eleven treatments with the reagents were necessary to achieve a satisfactory degree of methylation. The f i n a l product was a colorless glass, L"\J D * + 32 ,h° (c • 6.1ii i n chloroform) which showed on analysis a t r i t y l and methoxyl content approximating that of a tri-0-trityl-penta-O-methyl sucrose. 3k Paper chromatography of a p a r t i a l l y hydrolysed sample showed a number of spots which were tentatively identified as due to penta-Cwnethyl sucrose, tetra-O-methyl sucrose, tri-O-methyl-D-glucose, di-O-methyl- 0 - fructose and mono-O-methyl-D-fruetose (the latte r spot was somewhat elongated and probably represented a mixture of 3- and ii-O-methyl- D-fructose). The. problem of effecting a detritylation of the methylated t r i - O - t r i t y l sucrose had now to be solved. The previous experiences with catalytic hydrogenation did not recommend this method. A graded hydrolysis seemed to offer more promise. Here a d i f f i c u l t y arose i n the question of how to determine the optimum conditions for obtaining i n good y i e l d the desired penta-O-methyl sucrose. The arbitrary assumption could be made that t r i - O - t r i t y l - penta-O-methyl sucrose and tri - 0-trityl-penta-O-acetyl sucrose hydrolyse and detritylate at about the same rates. However, such an assumption did not seem to be j u s t i f i e d i n view of the results of_preliminary experiments. A more precise method was f i n a l l y devised. The specific rotation of the methylated t r i - O - t r i t y l sucrose i n g l a c i a l acetic acid was known to be about +50°, and i f the assumption was made that the specific rotation of the penta-O- methyl sucrose was about +65° (this seemed a reasonable assumption since sucrose, tri-O-methyl sucrose, and octa-O-methyl sucrose a l l show specific rotations of about this value), then a d e t r i t y l  ation reaction should cause a decrease i n specific rotation from 35 +50° to about +18° when a correction was made for the loss in mole cular weight accompanying detritylation* On the other hand, complete hydrolysis to D-glucose and D-fructose fragments should cause a decrease in rotation to about 0°* A sample of the methylated tri-O-trityl sucrose was dissolved i n 98$ aqueous acetic acid (initial rotation + U8.8°) and heated on the steam bath and the specific rotation rapidly decreased: after ten minutes, +35°} after 20 minutes, 28*2°; after 30 minutes, 24.2°j affcer 1+0 minutes, +22*0; and after 50 minutes, +19.8°. The rate of decrease of the optical rotation had begun to level off as predicted so the reaction was stopped at this point and the reaction mixture was then evaporated to yield a partly crystalline (tritanol) sirupy residue from which the detritylated products were extracted with water* The next problem was to isolate the desired penta- O-methyl sucrose from the mixture* If the reducing sugars could be removed, then the separation of the methyl sucroses could be easily achieved by chromatography* In a f i r s t attempt, a quantity of the detritylation product was dissolved in water and heated on the steam bath in the presence of excess barium hydroxide (75)* The colorless mixture rapidly discolored to a dark brown. After 2 hours heating the mixture was filtered, the pale-yellow filtrate deionized by exchange resins and the eluate evaporated to give a colorless sirupy residue. A paper chrcmatogram (butanol-ethanol-3 6 water ($iltk) developer) showed two spots which appeared to ro of present penta- and tetra-O-methyl sucrose. ' Separation^the supposed penta-O-methyl sucrose on a cellulose column gave a sirupy product, r~] 2 3 L * J D = * 6 U . 1 ° (c= 1 . 1 in water). However, when a sample, 6 8 mg., of this product was hydrolysed and the hydrolysis products separated by chromatography only 2 0 mg. of what was believed to be 3, U-di-O- methyl-D-fructose was obtained, whereas UO mg. of what was believed to be 2,3,ii-tri-0-methyl-D-glucose was obtahed. The results strongly indicated that the supposed penta-£-methyl sucrose was actually a mixture containing some 30$ 2 , 3, li-tri-O-methyl-D-glucose. The latter was probably i n the form of 2 , 3, k-trir-O-methyl-D-glucosan < l-S / V^l - 6 ) > which i s known to be stable to alkali ( 7 6 ) . This method of isolating the penta-O-methyl sucrose was clearly of l i t t l e value. A convenient means of isolating the desired penta-O-methyl sucrose was found i n partition chromatography with methyl ethyl ketone-water azeotrqpe (77). This very useful devel oper not only gives clean separations of sugars and their derivatives of relatively low Rf values but also gives excellent separations of the higher methylated sugars. This feature makes the solvent an invaluable complement to the more c cmmonly used developers, for example, butanol-water, which give poor separations of the highly methylated sugars. A sample of the detritylation product was f i r s t 37 subjected to a preliminary purification by chromatography with butanol-water to remove the sugars of low methoxyl content, i.e., di-O-methyl-D-fructose, mono-O-methyl-D-fructose and traces of free sugars. This step was necessary as such substances would require up to a week »s washing to be completely removed from a methyl ethyl ketone-water column of cellulose. After the pre liminary separation the product, presumably now largely a mixture of penta-O-methyl sucrose and tri-O-me thyl-D-glue ose, was chromato- graphed twice on a cellulose column using methyl ethyl ketone- water. The appropriate fractions yielded a colorless viscous sirup, r 1 23 J D = + 6U.3 (c= I.I4.6 i n water), which showed the methoxyl content calculated for a penta-p^methyl sucrose and reduced Fehling's solution only after acid hydrolysis. A sample of the penta-O-methyl sucrose was subjected to acid hydrolysis and the product separated on a cellu lose column into two paper chromatographically pure fractions which analysed correctly for a tri-O-methyl hexose and a di-O-methyl hexose. The sirupy tri-O-methyl hexose was identified as the known 2, 3, U-tri-O-methyl-D-glucose (VI) by the following r 7 2 k evidence: The specific rotation[f^J D = + 70.6 (c» 3.26, equili brium value in water), was in good agreement with previously reported values (76, 7.78). Paper chromatography using several 38 solvents gave a spot of hue and Rf value identical to that shown by an authentic sample of 2, 3 , U-tri-O-methyl-D-glucose. Treat ment of the sugar with aniline gave in good yield a crystalline product melting at 127-8°C wiich showed no depression on admixture with an. authentic sample of 2 , 3 , U-tri-O-methyl-D-glucose anilide. CHO I H - C- OCHo VI | J CH3 0 - C- H I H - C-OCHo I H - C-OH I GHgOH The sirupy di-O-methyl hexose was identified as the known 3* U-di-O-methyl-D-fructose (VII) by the following r i2k evidence: The specific rotation,^ JD = - 58.5° (c« 2.0 i n water, equilibrium value), was i n good agreement with previously reported values (79, 80). Paper chromatography using butanol-ethanol-water (5:1:4) revealed a single spot of the characteristic color of a ketose and an Rf value in agreement with the recorded value (69 )• Periodate oxidation of the sugar derivative showed, after £8 hours, a consumption of 1.8 moles of periodate, and a production of 1.53 moles of formaldehyde. Although the theoretical behavior of 3 ,4- di-O-methyl-D-fructose toward periodate calls for values of 2 and The sample of 2, 3 , 4-tri-O-methyl-D-glucose anilide was supplied by Dr. G.G.S. Dutton of this University to whom the author i s indebted. 39 2 moles respectively, this sugar has been reported to give low yields of formaldehyde of the order of 1.5 moles (81). VII GHo0H < 2 G s 0 I CH3O - C - H H - C - OGH- I H - C - OH I CHgOH This evidence clearly established the structure of the parent sucrose derivative as the new 2, 3, 3'» 4, 4 1 -penta- O-methyl sucrose (VTII). VIII The structures of tri-O-trityl sucrose (IX) and tri-O-trityl-penta-O-acetyl sucrose (X) could now be designated. X H OAc OAc H Attempts to vinylate the penta-Q-acetyl sucrose by the method of Adelman (U?) were begun shortly after the isolation of this compound was achieved* A major obstacle was evident from the beginning* Adelman in his studies used a series of low molecular weight, relatively stable alcohols which gave easily distillable products. Thus the isolation and purification of the desired vinyl ethers presented no special problems. In this research, however, the la starting material was a non-volatile compound unstable toward both acids and bases* The desired product also possessed the same limitations and i n addition a tendency toward polymer formation* The isolation process involved working up a residue, not a dis t i l l a t e . Furthermore, in view of well-known tendency of carbohy drates to form non-crystaliizable sirups, fractional crystallization could not be depended upon as a means of isolating the desired product should the residues prove to be complex mixtures* In a series of runs, with minor variations i n temperature, reaction time and quantities of reagents, the penta- O-acetyl sucrose was treated with vinyl acetate according to Adelman's general method* The reaction mixtures were worked up by washing with cold aqueous sodium carbonate, followed by drying and evaporation of excess vinyl acetate* The composition of the residues varied considerably but i n general, three products were obtained: a non-crystallizable colorless sirup, a crystalline product, and unchanged penta-O-acetyl sucrose. The sirupy material was identified as a partially vinylated penta-O-acetyl sucrose. Thus the substance decolorized bromine and on hydrogenation gave a sirupy product which analysed approximately as a mono-0-ethyl-penta-O-acetyl sucrose. Also the partially vinylated product slowly polymerized spontaneously to form a coiorless, insoluble film. The crystalline compound appeared to be a mole-42 cular complex of mercuric acetate and vinyl acetate. The specific rotation was zero. Analyses for mercury and acetyl were variable as was the melting point (90-110°G). In view of these results, further work on the penta-O-acetyl sucrose was postponed and i t was decided to study the vinylation of a model compound which did not possess the limit ations and complexities of the disaccharide derivative. Di-O-acetone- D-galactose (1: 2 -3 : 4-di-O-isopropylidene-D-galactose) (XI) was chosen for this purpose since the compound contained a free primary hydroxyl, could be distilled without decomposition and could be easily prepared from readily available starting materials. XI The transformations involved in the vinylation study of di-O-acetone-D-galactose are outlined i n FIGURE III. In a preliminary run, a 13.0 g. sample of di-O- acetone-D-galactose was treated with vinyl acetate according to Adelman's method for a period of 3 hours at -23>°C. The reaction h3 FIGURE III 6-O^othyl-di-O-acetone-D-galact ose 6-Oj-ethyl-B-galactose mixture was then washed with sodium carbonate solution, dried with anhydrous sodium carbonate and the solvent evaporated to yield a viscous, colorless sirup• The sirup was distilled under high vacuum to yield 3«f> g. of a colorless distillate which con tained a considerable quantity of unchanged di-O-acetone-D-galactose. Redistillation from both sodium hydroxide and sodium failed to give a homogeneous product. A sample was then hydrogenated catalyti- cally and the product hydrolysed. Chromatographic studies on the hydrolysate showed at least four substances to be present: D- galactose, 6-0-ethyl-D-galactose, and two unidentified products of R^  values similar to that of the mono-0-ethyl derivative. The 6-0-ethyl-D-galactose was easily recognized by i t s brown non- fluorescent spot (a feature seemingly characteristic of terminally substituted aldohexoses, e.g. 6-0-methyl-D-glueose and 6-O-methyl- D-galactose) whereas the unknown compounds gave yellow-brown fluore scent spots. The unknown compounds could conceivably be 3- and li-O-isopropyl-D-galactose derivatives which could arise from ring opening of di-O-acetone-D-galactose during hydrogenation. A second vinylation was carried out on di-O-acetone- D-galactose and the distilled product was hydrogenated directly and then hydrolysed. D-galactose was removed from the sirupy product by a preliminary purification on a cellulose column using butanol- water. The semi-purified product was then chromatographed twice on a column using methyl ethyl ketone-water as developer. A final 1+5 purification was achieved by preparative paper chromatography using the same solvent, ELution of the appropriate zones with water gave a 0,7$ yield of sirupy product which was shown to be 6-0-ethyl-D-galactose (SSII) by comparison of i t s specific rotation and paper chromatographic behavior with an authentic sample pre pared by direct ethylation of di-O-acetone-D-galactose• GHO I x n H - C - OH I HO - C - H I HO - C - H I H - C - OH I C^OCHgCEj During the work with acetylated derivatives, some experiments were carried out to determine the effect of a strongly basic anion exchange resin on such compounds* Acidic resins have often been used as catalysts for hydrolysis and other reactions (82, 83, 8 u , 85, 86, 87, 88) i n carbohydrate chemistry; i t was reasoned that a basic resin might well cause deactylation. A solution of octa-0-acetyl sucrose i n methanol was run onto a column of Dowex I strongly basic resin* After standing 2l+ hours at room temperature the c olumn was washed with aqueous methanol and the eluate evaporated* Pure, crystalline U6 sucrose was obtained in 92% yield and identified by melting point, specific rotation, paper chromatography and the Raybin test (09)• Other acetates of non-reducing carbohydrate derivatives were also tested and found to give the corresponding deacetylated products in yields up to 99%* An interesting observation was made when a solution of octa-O-acetyl sucrose was passed rapidly through a column of Dowex I * The eluate yielded on evaporation a sirupy product which did not crystallize on nucleation with either sucrose or octa-O-acetyl sucrose. It gave however, crystalline sucrose on further treatment with the resin. It would appear that the original product was a partially deacetylated sucrose derivative. The results of this research have shown that vinylation in the carbohydrate fie l d by means of the Adelman reaction i s not likely to prove of much value. As an exception however, one possible application should be noted. At present there is mo reliable method for determining the precise structure of a partially acylated carbohydrate derivative (e.g. our penta- O-acetyl sucrose). The usual method of determining the location of free hydroxyl groups i s by methylation and identification of the products. However, even under the mildest conditions of methylation acyl migration and even deacetylation have been shown to occur. The Adelman reaction on the other hand, offers a means of alkylation under conditions (slightly acid and low temperature) kl i n which acyl migration i s not likely to occur. The supposed 2, 3> 31* kt k '-penta-O-acetyl sucrose can serve as an illustration. This compound would be subjected to an Adelman vinylation and the product would then be hydrogenated, deacetylated and hydrolysed. Detection by chromatography of 6-0-ethyl-D-glucose and I , 6-di- O-ethyl-D-fructose even in low yields would establish the struct ure of the original disaccharide derivative. At this stage, i t would appear that the most profitable approach to a tri-O-vinyl sucrose would be through the 2» 3, 3', kf k'-penta-O-methyl derivative. This compound should be capable of withstanding the harsh reaction conditions of a Reppe vinylation and the completely, vinylated product could be readily isolated and purified by distillation. Moreover, i f such a product showed desirable properties on polymerization, commercial adapt ation should be relatively straightforward. Sucrose could be partially methylated directly and a suitable starting material isolated by distillation. i U8 EXPERIMENTAL A. Materials Silver Oxide Silver oxide catalyst for the methylations was prepared according to a standard procedure (90). As the freshly- prepared material did not seem to differ appreciably in activity as compared to the commercial product, both commercial and prepared samples were used. Palladiged charcoal catalyst Palladized charcoal catalyst used for detrityl- ations and hydrogenations was prepared after the method of Hartung (91). Trityl chloride (Triphenylmethyl chloride) Commercial samples of t r i t y l chloride were found to be contaminated with considerable quantities of tritanol and other substances. The t r i t y l chloride used in the tritylation reactions was freshly prepared according to the method of Bachmann (92). Platinum oxide catalyst The platinum oxide catalyst used in the hydro- genolyses and hydrogenations was the commercial product as supplied by Brickman and Company, Montreal; A k9 Solvents and reagents Solvents and reagents were purified by standard procedures; special purification methods are noted in the text. B. Analytical Methods Trityl Trityl determinations were carried out according to the method of Helferioh and Koester (93)• Acetyl Acetyl determinations were carried out as des cribed by Glark (9k)• Alkoxyl Alkcxyl (methoxyl and ethoxyl) determinations were carried out according to the method of Viebock and Schwappach as described by Clark (9k)• Carbon and hydrogen A l l carbon and hydrogen analyses were done by W. Manser, Zurich, Switzerland. Periodate oxidations The procedures described by several authors (73, 95, 96, 97) were adapted and combined so that a single 20 mg. sample revealed the consumption of periodate, the production of formic acid and the formation of formaldehyde. A 20 mg. sample was dissolved in 20 ml. of 0.02 M sodium metaperiodate solution and let stand at room temperature in the dark. At suitable intervals 2 ml. aliquots were removed 50 and titrated with 0.01 N sodium hydroxide using methyl red indicator to determine the amount of formic acid produced. To the neutral ized solution was then added 0.5 g« sodium bicarbonate, 0.25 g. potassium iodide and 2 ml. of 0.05 N sodium arsenite solution, and after standing 15 minutes, the solution was titrated with 0.05 N iodine solution in the presence of starch indicator to reveal the consumption of periodate ion. A 5 ml. aliquot of the oxidation solution was treated with 2.5 ml. N hydrochloric acid, 20 ml. 0.05 N sodium arsenite, 1 g. of solid sodium acetate and 2 ml. of an 8$ solution of dimedone in ethanol, and after standing 2k hours at 0°C, the precipitate was recovered, dried and weighed to determine the amount of formaldehyde formed i n the oxidation. C. Tri-0-trityl-penta-O-acetyl Sucrose • Preparation at an elevated temperature Into a 1 l i t e r flask equipped with au mechanical stirrer and a reflux condenser was introduced 300 ml. of anhydrous pyridine, 17.1 g. (0.05 mole) of powdered sucrose and 50 g. (0.15 mole) of t r i t y l chloride. The latter dissolved readily to give a pale-yellow solution. The reaction mixture was then heated to about 65°C and maintained at this temperature with constant stirring for 2k hours. After this period, a l l of the sucrose had dissolved. The now dark-red solution was cooled to 35°C and 50 ml. acetic anhydride was added which caused an immediate rise in temperature to U0°C. After standing 7 hours, the solution was 51 poured i n a fine stream into ice water which caused the precipit ation of a brown, viscous sirup. The product was recovered by decantation and crystallized from tetra hydrofuran-methanol. The crude product weighed 31.6 g., a yield of k9%* The mother liquors were found to be strongly reducing toward Fehling's solution and could not be induced to yield any additional cry stalline product* The yields obtained by this method varied con siderably, from 10 to k9% and the crude products were of low purity, usually giving on recrystalllzation only about a 6$% yield of the pure tri-O-trityl-penta-O-acetyl sucrose. Preparation at room temperature Into a 250 ml. flask was introduced 5»0 g. of powdered suOfcose, 14.3 g» of t r i t y l chloride and 100 ml. of anhydrous pyridine. The flask was tightly stoppered allowed to stand with occasional shaking for ij.8 hours at room temperature. Acetic anhydride ( 20 ml.) was then added and the colorless solution was stored overnight i n the refrigerator* During this interval, colorless crystals were deposited from the solution. This product was removed by filtration and dried in 117 vacuo. The dried material weighed 6.7 g. and melted at 175-T?°C. — " — — y\ It was very hygroscopic, showed an acid reaction to pH paper and a positive test for chloride ion and gave tritanol (m.p. 161 l60-i°C) on hydrolysis. The reported melting point of tritanol-52 pyridLnium hydrochloride is 172-174° C (50, 51). ^ The filtrate was poured with stirring into 1500 ml* of ice-water causing the precipitation of a colorless, amorphous solid which was recovered by filtration and washed thoroughly with water* Precipitation in water at 10°C gave a sticky mass which could not be filtered or washed efficiently* The solid product was dried in vacuo over phosphorus pentoxide and then crystallized from chloroform-methanol to give 8*5 g. (U5% yield) of colorless tri-0-trityl-penta-O-acetyl sucrose of high purity judging by the melting point and color* Again the mother liquors were strongly reducing toward Fehling's solution* On recrystallization to a constant melting point, the pure tri-0-1rityl-penta-0-acetyl sucrose which formed in colorless hexagonal crystals melted at 235-236°C. (corr* );[°^ ]J= + 68*9° (c « 2.U5 i n chloroform)* Analysis': calc. for 079^016: G, 74*2^5 H, 5.81$. Found: C, 73.7$ H, £ . 9 $ . The compound was soluble in chloroform, ether, tetrahydrofuran, ethyl acetate, insoluble in water, methanol, ethanol, petroleum ether and reduced Fehling's solution only after acid hydrolysis. The compound gave a negative Raybin test ( 8 9 ) . D* Tri-O-trityl sucrose  Direct tritylation of sucrose Into a 1 l i t e r flask equipped with a reflux 53 condenser and a mechanical s t i r r e r was introduced 500 ml. of anhydrous pyridine, 3U.2 g. (0.1 mole) of sucrose, 50 g. of Drierite and 85 g. ( 0.3 mole) of t r i t y l chloride. The solution was heated to 80°C, Maintained at this temperature for 3 hours and then allowed to cool to room temperature. The now dark-red colored reaction mixture was f i l t e r e d free of solids and poured i n a fine stream into ice water with s t i r r i n g . The brown amor phous precipitate was purified by several precipitations from methanol with water. During several unsuccessful attempts to crystallize the product from a variety of solvents, approximately 25 g. of t r i t a n o l (m.p. 159-61°) was isolated from the mixture. Also, from ethyl acetate and petroleum ether, 0.25 g« of colorless needle-like crystals were obtained which melted sharply at 146-7°C and gave a positive reaction with Fehling's solution only after acid hydrolysis. T r i t y l analysis: found, 57«2$s calculated for d i - 0 - t r i t y l sucrose , 58.8$. The semi-purified t r i - 0 - t r i t y l sucrose was a colorless glass with a variable softening point around 125 to 130°C. Analysis: calc. for C^aB ^ O n : t r i t y l , 68.3$. Founds 55.7$• The substance showed a slight reducing action toward Fehling's solution before and a strong reducing action after acid hydrolysis. Deacetylation of tri - 0-trityl-penta-O-acetyl sucrose To a solution of 10.0 g. of pure t r i - O - t r i t y l -Sk penta-O-acetyl sucrose in 25 ml. of anhydrous tetrahydrofuran was added 100 ml. anhydrous methanol and 5 ml. of 0.1 N sodium raeth- oxide solution. The solution was heated to reflux for 10 minutes, cooled to room temperature and let stand overnight. The solution was then evaporated to dryness under reduced pressure and the residue was taken up in ethyl acetate and washed with water. Evaporation of the organic layer yielded a colorless glass which was dried for 10 days in vacuo over phosphoruss pentoxide. The dried product weighed 8.6 g. (yield 103$, calculated for anhydrous tri-O-trityl sucrose). The product was a colorless glass of such high viscosity that i t could be pulverized to a fine, white pqwder. It showed a softening point of about 125-30°C and was soluble i n methanol, ethanol, ethyl acetate, insoluble in water and petroleum r - I 22 ether. Specific rotation j L* J D - + l4«7° (c= 3.3 in chloroform). Analysis: calc. for C^H^O-^s t r i t y l , 68,3$ (tetrahydrate, 63.9$; pentahydrate, 63.0$)j mol. wt., IO69. Found: t r i t y l , 63.6, 6 3 . 5 $ . , mol. wt., 950 (East method). The substance reduced Fehling's solution only after acid hydrolysis. After standing for more than a year, samples i n various solvents failed to crystallize. Acetylation of tri-O-trityl sucrose. Tri-O-trityl sucrose, 71 mg., was dissolved i n a mixture of 2 ml. pyridine, and 1 ml. acetic anhydride and let 55 stand for 2k hours. The solution was then diluted with 50 ml. of water and the resulting amorphous precipitate vjas recovered by filtration, washed with water and dried. Crystallization; from chloroform and methanol yielded 66.2 mg. (7Q% yield) of colorless, hexagonal crystals melting correctly at 233-U°C and showing no depression in melting point on admixture with an authentic specimen of tri-O-trityl-penta-Oj-acetyl sucrose. Attempted catalytic detritylation of tri-O-trityl sucrose Tri-Oj-trityl sucrose, 0.500 g. was dissolved i n 25 ml. of ethyl acetate and shaken under 3 atmospheres pressure of hydrogen with 0.25 g. of palladized charcoal catalyst for 2k hours. The catalyst was then removed by filtration and the filtrate evaporated to yield a pale-yellow sirup. Even after nucleation, neither sucrose nor tritane could be induced to crystallize from the sirup. A paper chromatogram developed with butanol-ethanol-water ( 5 s l : U ) and sprayed with p-anisidine hydrochloride reagent (70) showed that only a trace of sucrose was present as evidenced by a faint yellow, fluorescent, spot of % 0 . 0 3 . E. Penta-O-acetyl Sucrose Catalytic hydrogenation of tri-O-trityl-penta-O-acetyl sucrose Tri-O-triiyl-penta-0-acetyl sucrose, 10.0 g., melting at 229-32°C, was dissolved with warming in 200 ml. of 56 glacial acetic acid* Two g. of Adams platinum oxide catalyst was added and the mixture was shaken under h atmospheres pressure of hydrogen for 36 hours at 50°C. After recovery of the catalyst by filtration, the filtrate was evaporated under reduced pressure to yield a colorless sirup which was extracted with 600 ml. of hot petroleum ether (b.p. 100-120°C). The residue, a colorless sirup (2.02 g.) which could not be induced to crystallize, reduced Fehling's solution r 122 only after acid hydrolysis;L^JD =+53.3° (c= 15.08 in chloroform). Analysis: calc. for di-0-trityl-penta-&-acety 1 sucrose: acetyl, 20.8$. Found: acetyl; 21.9$. Acetylation of 2^ 0 mg. of the sirup using acetic anhydride i n pyridine gave a sirupy product which yielded 87 mg. of colorless crystalline material melting at 100-120°• Analysis: calc. for di-0-trityl-hexa-0-acetyl sucrose: acetyl, 23.9$. Found: acetyl, 23.7$. Nucleation of the sirupy residue with octa-O-acetyl sucrose did not induce crystallization. The petroleum ether extract was evaporated to dryness and the sirupy residue fractionally crystallized from methanol. Tricyclohexylmethane, 1.8 g. , melting correctly at 57.5 - 58.0°C (55, 56) was obtained. Analysis: calc. for C^H^ t G, 86.9$; H, 13.1$. Found: C, 86.3$; H, 13.0$. Also O.98 g. of a crystalline material was obtained which formed i n colorless, hexagonal crystals, m.p. 218-19° C , ] * ] ^ 0 ( c . £^3 i n chloroform), which was believed to be partially saturated starting 57 material. Analysis: calc. for G70H02O16S G> 73.1$; H, 7.15$. Found: C, 72Mi H, 7.11$. Another sample of tri-O-tritylppenta-Oj-acetyl sucrose when hydrogenated under similar conditions using (oaUadized charcoal as catalyst, was also found to be partially detritylated yielding a glass of t r i t y l content approximating that of a mono-O- trityl-penta-O-acetyl sucrose. Analysis: calc. for mono-trityl- penta-O-acelyl sucrose: t r i t y l , 30.6$. Found: t r i t y l , 26.8$. However, hydrogenation of the aromatic rings did not take place with the palladium catalyst j thus triphenyl-methane and some un- reacted tri-0j-trityl-penta~O-acetyl sucrose were recovered from the reaction mixtures but no tricyclohexylraethane or "reduced" tri-0- trityl-penta-O-acetyl sucrose. A 5*0 g. sample of tri-O-trityl-penta-O-acetyl sucrose, m.p. 231-2°C, which had been purified by repeated re- crystallization alternately from tetrahydrofuran-methanol and tetrahydrofuran-petroleum ether (b.p. 30-60°C) was dissolved on warming i n 100 ml. of glacial acetic acid and shaken under 4 atmospheres pressure of hydrogen in the presence of 0.5 g. of platinum oxide catalyst at 50°C. After 34 hours the theoretical uptake of hydrogen had occurred and a colorless, crystalline material had deposited from solution. The crystalline material, tricyclohexylmethane, m.p. 57.5 - 58.0°C, weight 2.55 g. (83$ yield), was filtered off. The filtrate was evaporated to dryness 58 and the residue crystallized from chloroform-petroleum ether (b.p. 3C~60°C) to give 0.60 g. (27$ yield) of colorless, needle like crystals. This product was recrystallized to a constant r 1 2 2 melting point j m.p. 155*-156° C ; l* J D =+22.0 (c= 3.1 in chloroform). Analysis: calc. for ^Z^yZ^lS9 2H2O: acetyl, 36.6$. Found: acetyl, 36.6$, 36.6$. The compound was soluble i n methanol, acetone, chloroform, insoluble in water, petroleum ether and reduced Fehling's solution only after acid hydrolysis. In subsequent hydrogenations using platinum oxide as catalyst, yields of 20, 38, 16 and 23$ of the pentaacetate were obtained. A highly purified sample of tri-O-trityl-penta- 0-acetyl sucrose, 0 .50g. , in 50 ml. glacial acetic acid was shaken over 0.25 g. of palladized charcoal catalyst under 3 atmospheres pressure of hydrogen at 50°G for 6I4. hours. The reaction mixture was worked up i n the above manner to yield kk mg. (20$ yield) of crystalline penta-O-acetyl sucrose. A sample of crude penta-O-acetyl sucrose when repeatedly recrystallized from chloroform-petroleum ether (b.p. 30-60°G) exhibited the following progression in melting point: 138-U3°j 154-54.5°; 155-55.5°; 155-155.5°; 152-53°; and 155-56°; 152-3° and 155-56°. Another sample when recrystallized from chloroform -petroleum ether acidified with a trace of glacial acetic acid did not show the double melting point. 59 graded hydrolysis of tri-0-trityl-penta-O-acetyl sucrose Tri-O-trityl-perrta-O-acetyl sucrose, 2.0 g., was dissolved on warming in 50 ml. of glacial acetic acid, the solution was heated to reflux temperature and 1 ml. of water was introduced. After refluxing for 30 minutes the solution was cooled, the solvent evaporated and the partially crystalline residue dried in vacuo. Recrystallization from chloroform-petroleum ether acid ifi e d with acetic acid yielded 50U mg. (58$ yield) of crystalline penta-O-acetyl sucrose. Reworking of the mother liquors, which showed reducing activity toward Fehling's solution yielded t r i - tanol. The yields of penta-O-acetyl sucrose obtained in subsequent runs varied, between U3 and 60$. The effect of time of hydrolysis on the yield of penta-O-acetyl sucrose was as follows: 15 minutes, 23-31$j 30 minutes, 43-60$; 60 minutes, 35$J 120 minutes, 0$. Variation of the amount of water did not greatly influence the yields 0.25 ml. water, 23$j 1.0 ml. water, 31$; 2.0 ml. water 26$ (reaction time, 15 minutes). Acetylation of penta-O-acetyl sucrose Penta-O-acetyl sucrose, 100 mg., was dissolved in a mixture of 2 ml. pyridine and 1 ml. acetic anhydride and let stand at room temperature overnight. The colorless solution was then diluted with 50 ml. of waterj seeded with octa-O-acetyl sucrose 60 and let stand i n the refrigerator. After several hours, colorless, needle-like crystals had formed which were recovered by filtration, washed with water and dried in vacuo; weight 75 nig. (yield 6$%); m.p. 83-87°• After recrystallization from ether-petroleum ether (b.p. 30-60°G), the product melted at 86-88°C and showed no depression in melting point on admixture with an authentic specimen of octa-O-acetyl sucrose. F. Methylation of penta-O-acetyl sucrose Penta-O-acetyl sucrose, 1.579 g«, was dissolved in 25 ml. of dry acetone and 15 ml. freshly distilled methyl iodide, 5 g» freshly prepared silver oxide and 2 g. Drierite were added. After 15 hours refluxing, the reaction mixture was filtered, the solids washed with acetone and the combined filtrate and washings evaporated to yield a viscous, colorless sirup, weight 1.527g» A few milligrams of the sirup was dissolved in aqueous methanol and heated with Dowexl strongly basic ion exchange resin on the steam bath for 2 hours. A-paper chromatogram was then run of the deacetylated product using butanol-ethanol-water (5xl:U) as developer. On treating the developed chromatogram with the p-anisidine hydrochloride spray reagent, two bright yellow, U.V. fluorescent spots appeared: Rf O.OU, distinct, for sucrose, and R» 0.08, distinct for mono-O-methyl sucrose. 61 The main product was remethylated using 25 ml. of acetone, 25 ml. of methyl iodide, 5 g» of silver oxide and 2 g. of Drierite and a reflux time of 20 hours. A chromatogram c£ a deacetylated sample showed a faint spot for sucrose and a dis tinct spot for a mono-Q-methyl sucrose. A thirdmethylation using 50 ml. methyl iodide, 10 g. silve r oxide and 3 g» Drierite (no acetone was necessary to effect solution of the p a r t i a l l y methylated sirup) was run for 21+ hours. Chromatographic analysis showed a distinct spot, R^ 0.08, for mono-Q-methyl sucrose, a distinct spot, R^ 0.20, for di-0- methyl sucrose, and a faint spot, Rf 0.1+0, for tri-O-methyl sucrose. A fourth methylation using 1+0 ml. methyl iodide, 10 g. silver oxide and 3 g. Drierite was run for U8 hours. After working up the reaction mixture as described above, a colorless, viscous sirup was obtained which was analysed for methoxyl content^ found ll+.l+$, calculated for tri-0-methyl-penta-0-acetyl sucrose, 15.1%. A f i f t h methylation using 1+0 ml. methyl iodide, 5 g. s i l v e r oxide and 2 g. Drierite was run for 21+ hours. A chrom atogram on a deacetylated sample of the product showed a very distinct spot, R^ 0#J+0 for tri-0-methyl sucrose and a faint spot for di-0-methyl sucrose. The methylated penta-0-acetyl sucrose, weight 1*55 g», was a colorless, viscous glass;JotJj? s+£jtfo (Csi 3.72 62 in chloroform). Analysis: Calc. for tri-0-metbyl-penta-O-acetyl sucrose, p25H38°i6* raethoxyl, 15.7$; acetyl, 36.2$. Found: methoxyl, 15.5$, l5»8$j acetyl, 36.2$, 36.0$. After six months the product has not crystallized. . G. Tri-O-methyl sucrose Deacetylation of methylated penta-O-acetyl sucrose The methylated penta-O-acetyl sucrose, 1.30 g., was dissolved in 5 ml. methanol and run onto a 20 x 1.8 cm. column of UO-80 mesh Dowex I ion exchange resin. The solution was washed in with an additional 7 ml. of methanol. After standing 2b, hours at room temperature, the column was eluted with 90$ aqueous methanol. Fractions of 200 ml., were collected and evaporated to dryness. Fraction #1 yielded 776 mg., fraction#2 yielded 51 mg., and fraction #3 yielded 8 mg., of a colorless, viscous sirup (a total of 835 mg., 99$ yield). Paper chromatography revealed that the product was a mixture containing 75$ tri-0-methyl sucrose, 25$ di-0-methyl sucrose and 1$ mono-0-methyl sucrose. Chromatographic purification of the tri-O-methyl sucrose Approximately 650 mg. of the tri-O- and di-0- methyl sucrose mixture was dissolved in 2 ml. of butanol-water and run onto a 30 x 2.6 cm. column of cellulose which was then (5 developed with the same solvent while Afractions were collected at one hour intervals. The fractions were qualitatively analysed by 63 spotting on paper and treating the paper with the p-anisidine hydrochloride reagents• The appropriate fractions were then combined and evaporated under reduced pressure to dryness. The di-Q-methyl sucrose fractions^yielded 193 mg. of a colorless glass • The tri-O-methyl sucrose fractions.yielded 1*72 mg. of r i2k a colorless, viscous sirup; 1 * * J D =+67.6° (c= 1 . 7 1 + i n water). Analysis: calc. for tri-O-methyl sucrose, 0^^280^: methoxyl, 2h*2%. Found: methoxyl, 2k»9%, 2kS%» Periodate oxidation of tri-O-methyl sucrose A sample of 19.2 mg. (0.Q5 m i l l i mole) of tyxe tri-O-methyl sucrose was oxidized with 10 ml. of 0.02 M sodium metaperiodabe.solution. The results are indicated i n TABLE III. TABLE III Periodate Oxidation of Tri-0-methyl sucrose  Reaction time Periodate consumed Formic acid 3 hours 1.7 moles 0.025 moles 6 hours 1.8 moles 0.025 moles 2k hours 1.8 moles 0.025 moles For comparison, a sample of sucrose, (166.27 mg.) was also oxidized with sodium meta-periodate (100 ml. 0.02M) under the same conditions. The results are listed i n TABLE IV. Sk TABLE.IV  Periodate Oxidation of Sucrose Reaction time Periodate consumed Formic acid 1 hour 2#3 moles 0,26 moles 3 hours 2*7 moles 0»3I> moles 6 hours 2.9 moles O.I4.7 moles 2k hours' 3»1 moles 0.6l moles Hydrolysis of tri-O-methyl sucrose Tri-O-methyl sucrose, about 358 mg., was dissolved i n 10 ml. of 1% aqueous acetic acid and heated to reflux temperature. In order to follow the progress of the hydrolysis conveniently, 5 g» of sucrose, which should hydrojyse at approx imately the same rate as a partially methylated sucrose,, was -treated sifajilJarTy-i'.od in 100 ml. of 1% aqueous acetic acid and the optical rotation was measured at one hour intervals. The change in specific rotation with time is shown in TABLE V. TABLE V • Hydrolysis of Sucrose Reaction time (hours) Specific rotation a +66.5 t -16.2 2 -17.7e 3 -18.7° k -18.8° constant value 65 After 5 hours, the hydrolysis of the tri-&-methyl sucrose was stopped, the hydrolysate filtered through Celite and evaporated to dryness under reduced pressure. A colorless sirup was obtained which was dried i n vacuo to a constant weight of 3U2 mg. Chromatographic separation of the tri-O-methyl sucrose hydrolysis products The entire hydrolysis product of tri-O-methyl sucrose was dissolved in 2 ml. of the butanol-water solvent and run onto a 30 x 2.6 cm. cellulose column which was then developed (to ml.) with the same solvent while fractions were collected at 30 minute intervals. The location of the sugars within the series of frac tions was determined by spotting on paper and spraying with the p-anisidine hydrochloride reagent. Fractions 15 - 19, which contained a di-0-methyl hexose were combined and evaporated. The sirupy residue was then taken up i n water and filtered through Celite to remove colloidal particles of cellulose coming from the column and the f i l t r a t e -was evaporated. After drying to constant weight in vacuo over phosphorus^ pentoxide the colorless, sirupy residue weighed 161 mg. Fractions 31 - 39, which contained a mono-0- methyl hexose, were combined and evaporated to .yield a colorless 66 sirup which was then taken up i n water, filtered through Celite and the filtrate again evaporated. After drying i n vacuo over phosphoruss pentoxide, the residue, a colorless sirup.weighed I48 mg. H. 4-O-methyl-D-glucose The sirupy mono-O-methyl hexose isolated from the hydrolysis product of tri-O-methyl sucrose showedL JD «=46l.2° (c= 1.U28 in water, equilibrium value). Analysis: calc. for mono-O-methyl hexosej CyH^O^j methoxyl, 16.0$. Found: methoxyl, 15.5, l5»9#. Crystallization was not induced by nucleation with 2- 0j-methyl-D-glucose, 3-0j-methyl-D-glucose or 6-0j-raethyl-D-glucose. Paper chromatograms using the developers butanol- ethanol-water (5:1:4), and methyl ethyl ketone-water were run on the mono-O-methyl sugar along with authentic specimens of 2-, 3-, k- and 6-O-methy 1 -D-glucose. The % value and color of the spot (p-anisidine hydrochloride spray reagent) for the mono-O-methyl hexose was found to be identical with that given by 4-0-methyl- D-glucose. The 2- and 6-0-methyl-D-glucose gave brown spots which did not fluoresce under U.V. light whereas the 3- and 4-0-methyl- D-glucose gave yellow-brown, fluorescent spots. The values of 3- and 4-O-methyl-D-glucose differ considerably, the 3- isomer having the higher value. 67 The mono-O-methyl hexose, 27 mg., was heated for 1 hour on the steam bath in a mixture containing 0,35 ml. of freshly distilled phenylhydragine (b.p. l l 5°C/ 0 . 3 mm), 0.30 ml. glacial acetic acid and 2.5 ml. water. The resulting yellow solution was diluted with 5 ml. of water and let stand at room temperature. A yellow crystalline precipitate formed which was recovered on a Pregl f i l t e r , washed with water and dried: weight of precipitate, 21 mg., yield h0%, Recrystallization twice from aqueous acetone gave 10 mg. of fine, yeilow, needle-like crystals which melted at l56-8°C and showed no depression in melting point on admixture with an authentic sample of 4-0-methyl-D-glucose• I. 1, 6-di4Q-methyl-D-fructose The liquid di-O-methyl hexose obtained from the hydrolysis of the tri-O-methyl sucrose showed a positive rotation DO D =+17.4° (c= 1.842 in water, equilibrium value). Analysis: calc. for di-O-methyl hexose, CQH-^O^: methoxyl, 29.8$. Found: methoxyl, 29.8, 29.3$. A paper chromatogram developed with butanol- ethanol-water (5:1:4) gave a single bright yellow, U.V. fluorescent spot of Rf 0.57 ( R J Q * 0.69) (3, 4 di-O-methyl-D-fructose has a considerably lower Revalue: 0.51, Hjg 0 .61) . * % Q represents travel on the chromatogram relative to tetra -0- raethyl-D- glucose • "" 68 A sample of the di-O-methyl-D-fructose, 22 mg., was oxidized with 0.02 M sodium metaperiodate. The results are shown i n TABLE VI. TABLE VI Periodate oxidation of 1,6-di-O-methyl-iP-fructose  Time Consumption Formic acid Formaldehyde k hours 3*1 moles 1.26 moles 2k hours 3.2 moles 1.58 moles 0 moles 58 hours 3.2 moles 1.71 moles A 35 mg. sample of the di-0-methyl hexose was heated with a mixture of 3.5 ml. of phenyliiydraisine, 0.3 ml. of glacial acetic acid and 5 ml. of water for one hour on the steam bath. A dark-red o i l precipitated on cooling which partially crystallized. Repeated recrystallization from acetone/water gave an impure reddish-yellow crystalline product, 10 mg., which melted with decomposition at about 170-5°C. 69 J , Methylation of tri-O-trityl sucrose Tri-O-trityl sucrose, 8.6 g., was dissolved in 50 ml. of methyl iodide and 10 g. of silver oxide and 15 g. of Drierite were added. The mixture was refluxed for 2k hours, then cooled and filtered through a sintered, glass funnel. The solids were washed with 50 ml. of chloroform and the combined filtrate and washings evaporated to yield a colorless glass. The dried product was remethylated using 25 ml. methyl iodide, 10 g. silver oxide and 10 g. Drierite for a reflux time of 2k hours. The reaction mixture was worked up as before to give a colorless glass. A sample of the product was hydrolysed and detritylated by heating for 3 hours on the steam bath in aqueous acetic acid and the hydrolysate was then chromatographed on paper using butanol-ethanol-water (5«1»4). The chromatogram indicated the hydrolysate to be a complex mixture containing D-fructose, mono-O-methyl-D-fructose, di-O-methyl-D-fructose, di-O-methyl-D-glucose and tri-O-methyl-D-glucose. The product was subjected to a third methylation using 25 ml. methyl iodide, 10 g. silver oxide and 5 g« Drierite for a reflux time of 2k hours. The reaction mixture was worked a3 before to yield a colorless glass. A sample was again hydrolysed and detritylated with aqueous acetic acid and a paper chromatogram run on the hydrolysate. A very faint yellow spot, Rf 0.13, was 70 obtained for D-fructose; a very distinct yellow spot, Rf 0.28, for mono-O-methyl-D-frue to se; a distinct yellow spot, R^  0.51, for di-O-methyl-D-fructose and probably di-O-methyl-D-glucose; and a distinct red-brown spot, Rj. 0.74 for tri-O-methyl-D-glucose. The product was methylated a fourth time using 2f> ml. methyl iodide and 5 g. silver oxide for a reflux time of 2b, hours. After working up the mixture, paper chromatographic analysis was carried out as before. The chromatogram was similar to the previous one except that the D-fructose spot was less distinct while the tri-O-methyl-D-glueose spot was more pronounced. The product was methylated a f i f t h time using b,0 ml. methyl iodide and $ g. of silver oxide with mechanical stirring. In this run the silver oxide catalyst was added i n portions during the methylation. After iif> hours, the reaction mixture was worked up as before. A sample of the product was again hydrolysed and chromatographed. This paper chromatogram showed, a very distinct red-brown spot for tri-O-methyl-D-glue ose, a very distinct yellow spot for di-O-methy 1-D-fructosej and a distinct yellow spot for mono-O-methyl-D-fruetose. The product was methylated a sixth time using 25 ml. methyl iodide and 3 g» silver oxide for a reflux time of b-8 hours with mechanical stirring. A paper chromatogram run on a hydrolysate showed distincts spots for tri^O-methyl-D-71 glucose and di-O-methyl-D-f ructose and a faint spot fSr mono-O- methyl-D-fructose• The product was methylated a seventh time using 2$ ml. methyl iodide, $ g. silver oxide and 2 g. Drierite for a reflux time of 1 6 hours with mechanical stirring. The reaction mixture was worked up as bef oreto yield a colorless glass which was pulverized to a fine, white, amorphous powder and dried in  vacuo over phosphoruss pentoxide to a constant weight of 8.61; g. Analysis: calc. for tri-0-trityl-penta-O-methyl sucrose: meth oxyl, 13 . 6 $ . Found: methoxyl, U . 6 , 11 . 8 $ . The product was remethylated an eighth time using $0 ml. methyl iodide, 10 g. silver oxide and 3 g« Drierite with a reflux time of 4 8 hours. The reaction mixture was worked up as before and the product was dried in vacuo. Found: methoxyl, 12 . 6 $ , A ninth methylation was carried out using $0 ml. methyl iodide, 10 g, silver oxide and 3 g« Drierite with a reflux time of 4 8 hours. The reaction mixture was worked up as before and a dried sample analysed. Found: methoxyl, 13»0$. Chromatographic analyses of a hydrolysed sample showed distinct spots for tri-O-methyl-D-glucose and di-O-methyl-D-fructose and a faint spot for mono-O-methyl-D-f ructose • The product was remethylated a tenth time using 40 ml. methyl iodide, 5 g, silver oxide and 2 g. Drierite with a 72 reflux time of 48 hours. Chromatographic analysis of a hydrolysed sample showed distinct spots for tri-O-methyl-D-glucose and di-O- methyl-D-fructose and a very faint spot for mono-O-raethyl-D-fructose. An eleventh and la s t methylation was carried out using kO ml. methyl iodide, 10 g. si l v e r oxide and 3 g. Drierite with a reflux time of 72 hours. The reaction mixture was worked up as before to y i e l d a colorless glass which was pulverized to a fine, white powder and dried i n vacuo over phosphoruas pentoxide r i 1 7 at 55°C;L°*JD «+ 32.4° (c = 6.14 i n chloroform)... Analysis: calc. for tri-O-trityl-penta-O-methyl sucrose, C H„,0__: t r i t y l , ~~ — 74 64.1$; methoxyl, 13.6$. Found: t r i t y l , 63.9, 64.4$; methoxyl, 13.3, 13.4$. K. Penta-O-methyl sucrose Graded hydrolysis of methylated t r i - O - t r i t y l sucrose 1. Methylated t r i - O - t r i t y l sucrose, 1.00 g., was dissolved i n 2f> ml. glacial acetic acid and the solution heated to reflux. One ml. water was then added and the refluxing con tinued for 30 minutes. The solution was then cooled, the solvent evaporated under reduced pressure and the partly crystalline residue dried i n vacuo. Extraction of the residue with four 10 ml. portions of water i n the cold yielded a cloudy extract which was c l a r i f i e d by f i l t r a t i o n through Celite and evaporated to y i e l d a colorless sirup, 368 mg^lK-D^ =+28.3 (c = 7.36 i n ethanol). 73 The product was studied by paper chromatography using butanol-ethanol-water (5:1:U) as solvent and the p-anisidine hydrochloride spray reagent. To detect ketose derivatives, the developed and sprayed chromatograms were heated only 1.5 minutes instead of the usual 10 minutes. This treatment caused a pre ferential development of fructose derivatives ( including sucrose). A chromatogram developed in the usual manner showed five spots: (i) red-brown spot, very distinct, Rf 0.71, RQIQ 0.85, probably represents 2,3,4-tri-O-methyl-D-glucose, reported value ( 6 9 ) R^ 0.85; ( i i ) bright yellow U . V . fluorescent spot, very dis tinct, R£ 0.51, JtfQ 0.61, probably represents 3,4-di-O-methyl-D- fructose, reported value (69) R ^ Q 0 . 6 l ; ( i i i ) bright yellow, U . V . fluorescent spot, faint, Rf 0 . 2 9 , % Q 0.35, somewhat elongated, probably represents mixture of 3- and U-mono-0-methyl-D-fructose, no reported values available; (iv) bright yellow, U . V . fluorescent spot, very distinct, partially obscured by the tri-O-methyl-D-glucose spot, Rj» and R^, approximately 0.77 and 0 .93, probably represents penta- O-methyl sucrose; (v) bright yellow, U . V . fluorescent, R£ 0 . 6 l , R J Q . 0.73j faint, probably represents tetra-O-methyl sucrose. A developed and sprayed chromatogram was heated for only 2&£§. minutes: 74 one very distinct, bright yellow, U.V. fluorescent spot appeared, Rj» 0 . 7 5 , R«JIQ 0.91, which probably represents penta-O-methyl sucrose. Since no other fructose derivative spots showed up on the chrom atogram, e.g., tetra-O-methy 1 sucrose and di-O-methyl-D-fructose, i t seemed reasonable to assume that the penta-O-methyl sucrose was in high concentration. 2. Methylated tri-O-trityl sucrose, 1 . 7 5 9 g«, was dissolved i n 2h ml.of glacial acetic acid and 1 ml. of water added and the solution was allowed to stand at room temperature. The specific rotation was determined at intervals: i n i t i a l , + J i 8 . 0 ° j 3 hours, 4 ^ 6 . 0 ° j 6 hours, +U4.O0; 2k hours, + 3 7 . 2 ° j 4 5 hours, +30.3° 7 3 hours, + 2 9 . 0 ° ; 96 hours, +27.7°. The solvent was evapor ated and the partly crystalline residue dried i n vacuo over sodium hydroxide. The dried residue was extracted with seven 15 ml. portions of water i n the cold to give a cloudy extract which was clarified by filtration through Celite and evaporated to yield 3 1 2 mg. (yield of detritylated sugars, k7%) of colorless sirupj L»* J D « + 5 8 ° (c= 2 . 3 0 in water). A chromatogram run on this product indicated the presence of a considerable quantity, of tri-O- methyl-D-glucose and di-O-methyl-D-fructose. The product was then worked up as will be described below to yield partially methylated sucrose. 3 . Methylated tri-O-trityl sucrose, 2 . 2 8 g., was 75 dissolved in $0 ml. glacial acetic acid and 1 ml. of water added; i n i t i a l rotation, +48.8°. The solution was then heated on the steam bath for 5 minutes then cooled rapidly- to room temperature; 1/* -» D=+38°. The solution was again heated for 5 minutes and then cooled; £c3*),s+3£0» solution was heated a third time for 10 minutes duration;(f^J D=+28.2°. After a fourth heating for 10. minutes duration,[*ll)=+2U.20. After a f i f t h heating of 10 minutes, D = + 22.0°. After a final heating of 10 minutes, J^ c'J DB+19.8°. The reaction mixture was then evaporated and the partly crystalline residue dried in vacuo over sodium hydroxide. The residue was extracted with 20 ml. portions of water i n the cold; the progress of the extraction was followed by measuring the optical rotation of the extracts. After 6 treatments, the extraction process appeared to be complete, and the combined extracts were evaporated and the residue dried in vacuo, weight 700 mg. (yield of detritylated sugars, 82$). As described below, penta-0-methyl sucrose was obtained from this product by chromatographic separation. Isolation of penta-P-methyl sucrose K, 2, was dissolved in 15 ml. of water, one g. of hydrated barium hydroxide was added, and the mixture was heated on the steam bath for 2 hours, The mixture rapidly discolored during the degrad ation to finally yield a dark-brown paste. The mixture was cooled, solid carbon dioxide was added and the solids were recovered on a The sirupy mixture obtained as described under 76 f i l t e r and washed with water. The combined pale-yellow filtrate and washings were passed through a 20 x 1.8 cm. column of Dowex I anion exchange resin and a similar column of Amberlite IR-G-50 cation exchange resin in that order followed by 35 0 ml. of wash water. The eluate was evaporated and the sirupy residue dried in vacuo, weight 172 mg. A paper chromatogram run on this product showed a very distinct spot for penta-O-raethyl sucrose, a distinct spot for tetra-0-methyl sucrose and a faint spot for tri-O-methyl sucrose. The product was chromatographed on a 30 x 2.6 cm. column of cellulose using butanol-water as developer. The appropriate fractions were combined and evaporated to yield U l mg. of tetra-0-methyl sucrose and 87 mg. of penta-O-methyl sucrose. The latter showed the specific rotation,!* J n *+64.1° (c= 1.1 in water). Analysis: calc. for penta-O-methyl sucrose, ^2.7^32^11' methoxyl, 37»6%. Found: methoxyl, 37.2, 37,5$. A 68 rag. sample of the product was dissolved i n 10 ml. of 1% aqueous acetic acid and refluxed for 6 hours. The hydrolysate was evaporated and the sirupy residue chromatographed on a cellulose column using butanol-water as developer. The di-0-methyl hexose on evaporation yielded only 20 mg. of a color less J&qu&d, whereas the tri-O-methyl hexose fractions yielded h0 mg. of colorless sirup. It i s suspected that during the hexose 7 7 degradation with barium hydroxide, some 2,3,li-tri-0-methyl-D- glucosan«£ 1 - 5^/5^ 1 - 6 ^ was formed which subsequently contaminated the penta-O-methyl sucrose fraction. Chromatography appeared to offer the only means of isolating a pure sample of penta-O-methyl suctfose from the complex mixture obtained by the graded hydrolysis of the methylated tri-O-trityl sucrose. The major obstacle was to effect a separ ation of the desired product from the tri-O-methyl-D-glucose. The values, 0 . 7 5 and 0.71 respectively, were so close a clean separation could not be expected using butanol-water. However, the methyl ethyl ketone-water azeotrope as developer was found to give better results. Paper chromatogfams revealed the values of the penta- O-methyl sucrose and the tri-O-methyl-D-glucose to be 0 . 6 0 and 0 . 5 2 using this solvent. The sirupy mixture ( 7 0 0 mg.) obtained as described under K, 3 , was dissolved i n 2 ml. methyl ethyl ketone-water and run onto a 5 0 x 2 . 6 cm. column of cellulose and the chromatogram was developed with that solvent. Fractions of approximately 1 0 ml. volume were collected over 5 minute intervals. The highly diluted fractions were carefully examined byi (i) the usual spotting technique; ( i i ) by measuring the optical rotations and ( i i i ) by paper chromatography. The bulk of the desired product was found to be concentrated i n h fructions which were combined and evaporated 78 to yield 228 mg, of a colorless sirup. This product was rechromato- graphed and the fractions examined as described above. The bulk of the desired product was found to be contained in 3 fractions and to be free of the tri-O-methyl-D-glucose• The combined fractions were evaporated and the residue taken up i n ethanol and filtered through Celite to remove colloidal particles of cellulose. The clear filtrate was evaporated and the residue dried in vacuo to a constant weight, 1J>3 mg. (ld% yield). The pure penta-O-methyl sucrose was a colorless, calc. for penta-O-methyl sucrose, ^ y ^ ^ ^ l l ' ms^aaxy^» 37»6$. Found: methoxyl, 37«7, 37.2$. The product reduced Fehling»s solution only after acid hydrolysis. dissolved in 10 ml. of 0,05 N sulfuric acid and heated under reflux on the steam bath for 2 hours. Barium carbonate, 500 mg,, was then added and the mixture was stirred until neutral to pH paper. The mixture was then filtered, the solids were washed with water and the combined filtrate and washings were evaporated to dryness • The residue was extracted with acetone, and the extract was filtered through Celite and evaporated to yield a viscous sirup. Hydrolysis of penta-O-methyl sucrose The sirupy penta-O-methyl sucrose, lU6 mg,, was 79 The sirupy hydrolysate was chromatographed on the methyl ethyl ketone-water column to yield on evaporation of the appropriate fractions, 70 mg. of a tri-O-methyl hexose and 55 mg. of a di-O-methyl hexose. L . 2,3,4-Tid-O-methyl-D-glucose The tri-O-methyl hexose was a colorless, viscous sirup i L J D =+70.6° (c= 3»26 in water, equilibrium value). Analysis: calc. for tri-O-methyl hexose, G^E^QO^Z methoxyl, 41.8$. Found: methoxyl, 4 l . l , 41*5$. Paper chromatography of the compound revealed a single spot of color and R^  value identical to that obtained with authentic 2,3,4-tri-O-methyl-D-glucose using both butanol- ethanol-water (5:1:4) and methyl ethyl ketone-waterj red-brown spots (p-anisidine hydrochloride spray) were obtained of Rf values 0.71 and 0.52 respectively. A 36 mg. sample of the tri-O-methyl sugar was heated on the steam bath under reflux with 70 mg. of freshly distilled aniline and 2 ml. of absolute ethanol for 6 hours. The volatile constituents were then removed in vacuo at 60°C to yield 48 mg. of a viscous, yellow sirup. On seeding with authentic 2,3,4-tri-O-methyl-D-glucose anilide, the product cry stallized in fine, colorless needles. After three recrystallizations 80 from ether-petroleum ether the derivative melted sharply at 127-8°C and showed no depression on admixture with the authentic sample. _M. 3«U-Di-O-methyl-D-fructose The di-O-methyl hexose was a colorless, viscous liquid, L JD =-58.5° (c<= 2.0 in water, equilibrium value). Analysis: calc. for di-O-methyl hexose, 0(^3.6^6* methoxyl, 29.8$ Found: methoxyl, 29.5, 29.6$. A paper chromatogram of the compound using butanol-ethanol-water (5:1:U) and the p-anisidine hydrochloride spray reagent showed a single, bright yellow, U.V. fluorescent spot of R„ value 0.£L and R 0.61.. f TG A 20.8 mg. sample was oxidized with 20 ml. of 0.02M sodium metaperiodate at room temperature. The rate of consumption of periodate was as follows: after 6 hours, 1.5 moles; 2U hours, 1.7 moles; and 48 hours, 1.8 moles. After 48 hours 1.53 moles of formaldehyde were produced, as determined by the formation of the dimedone complex which melted sharply at 186-8°C. 81 N. Attempted vinylation of penta-O-acetyl sucrose Penta-O-acetyl sucrose, 225 mg., was dissolved in 15 ml. of chloroform and 25 ml. of vinyl acetate (freshly distilled, b.p. 71-72°C) was added and the solution cooled to -25°C. One g. of mercuric acetate and one drop of concentrated sulfuric acid were added and the mixture stirred mechanically for 3 hours. The reaction mixture was then washed free of acid with 1% sodium carbonate, washed with water, dried with sodium sulfate andevaporated under reduced pressure to yield 192 mg. of a color less sirupy residuej soluble in methanol and chloroform; insol uble in water and petroleum ether. The residue did not reduce Fehling's solution, yielded a dark-colored, insoluble residue on treatment with acid, and showed unsaturation toward bromine i n carbon tetrachloride. On repeated attempts at crystallization, the substance gradually was transformed into an insoluble, hard, colorless film. Another run, in which 167 mg.of penta-O-acetyl sucrose was treated with vinyl acetate at -30°C for 6 hours, was halted by the addition of 10 ml. of pyridine. The mixture was washed with water, then evaporated to yield a colorless sirup, 208 mg., which on drying in vacuo partially crystallized i n needle like crystals. Ethanol readily dissolved the sirup but not the crystalline material (m.p. 107-8°C). The ethanol extract was 82 hydrogenated over palladized charcoal to yield a colorless sirup which was purified by chromatography on alumina using chloro form as solvent and developer. The eluate (under the conditions of the purification, penta-O-acetyl sucrose would be retained on the column) on evaporation gave 72 mg. of a colorless sirup. Analysis: calc. for a mono-O-ethyl-penta-O-acetyl sucrose, G27H42°l6s ethcxyl, 6.7$; acetyl, 34.5$. Found: ethoxyl, 5.0$: acetyl, 32.3$. This experiment and similar ones indicated that vinylation was not proceeding to any appreciable extent. In one experiment, unreacted penta-O-acetyl sucrose was recovered i n 37$ yield. Penta-O-acetyl sucrose, 107 mg., dissolved in 10 ml. ethyl acetate and 20 ml. vinyl acetate, was treated at -30°G with mercuric acetate and sulfuric acid for 6 hours. The reaction mixture was then treated with 10 ml. pyridine, washed with water, dried, and evaporated to yield a partially cry stalline residue. This product was purified by chromatography on alumina and recrystallized from chloroform-petroleum ether to r -1 23 yield 46 mg. of colorless crystals: m.p. 107-8°C;L ** J D =0.00° (c= 4*7 in chloroform); soluble i n chloroform, ethyl acetate, ether, insoluble in water, methanol, petroleum ether. Found: acetyl, 38.1, 39.7$; mercury, 42.9, 43.2$. This crystalline product was also obtained when only vinyl acetate, mercuric sulfate and sul furic acid were brought together. The substance was unstable, 83 on standing a gradual decomposition took place to yield dark- colored insoluble product. The melting point was variable ranging from 90 to 110° C. It was probable that the substance was a com plex of vinyl acetate and mercuric acetate. 0 . Preparation of 1:2-3:4-di-0-isopropylidene-D-galactose Di-O-acetone-D-galactose was prepared according to the method of Van Gruneriberg, Bredt and Freudenberg (98). Anhydrous -D-galactose, m.p. l60-3°C, D=+130° (after 3 minutes) -*+80°(constant at 5 hours) (c= 9112 in water), 100 g., was suspended i n 2 liters of anhydrous acetone and 120 g. of zinc chloride and a mixture of 20 g. of phosphorus pentoxide and hO g. of phosphoric acid added. The mixture was shaken mechanically for U8 hours at room temperature. A con siderable quantity of the sugar did not dissolve. The solution was poured with vigorous stirring into a solution of 200 g. sodium carbonate in 500 ml. of water. After standing several hours the mixture was filtered, the solids washed with acetone, and the combined filtrate and washings evaporated under reduced pressure until most of the acetone was driven off. The aqueous solution was then extracted with three 150 ml. portions of ether and the combined ether extracts evaporated. Distillation of the sirupy residue yielded i+9«6 g. (34$ yield) of a colorless, viscous 84 sirup; L°^JB = -55«0° (c= 6.656 in chloroform). A chromatogram using butanol-ethanol-water (5:1:4) and the p-anisidine hydrochl oride reagent showed a single^yellow spot, R^  0 . 8 8 . P. 6-0-Ethyl-1s2-3;U-di-0-isopropylidene-D-galactose To 5»037 g« of di-O-acetone-D-galactose, i n a 500 ml. flask equipped with a stirrer, reflux condenser and dropping funnel, was added 10 ml. of acetone and 10 g. sodium hydroxide dissolved in 25 ml. of water. The mixture was heated to 55°G and with vigorous stirring 13 ml. of diethyl sulfate was added dropwise over a period of 45 minutes. The temperature of the mixture was then raised to 85°C and maintained for 1 hour. The reaction mixture was cooled to room temperature and extracted with three 20 ml. portions of chloroform. The combined extracts were dried with anhydrous sodium carbonate, evaporated and the residual sirup distilled under high vacuum from sodium carbon ate. A colorless, mobile sirup was obtained; weight 3»677 g» (yield 66$(). A sample of the product was hydrolysed i n boiling 70$ aqueous acetic acid and the hydrolysate chromatographed using butanol-ethanol-water (5:1 :4) as developer and the p-anisidine hydrochloride spray reagent. A distinct, brown, non-fluorescent spot, Rf 0.40, appeared for 6-0-ethyl-D-gipactose plus a faint, yellow-brown, U.V. fluorescent spot, Rf 0.11 for D-galactose. The isirupj t was redistilled under high vacuum 85 from sodium hydroxide to give 2,631; g. of a colorless, mobile r i 2 7 sirup, b.p. 101-103°C/0.2 mm.,[«<JD - -57.6° (c= U.895 i n ethanol). After standing 5 months the product failed to crystallize. Q. 6-Q-Ethyl-D-galactose A 783 mg. sample of 6-0-ethyl-di-O-acetone-D- galactose was dissolved i n 10 ml. of 80$ aqueous acetic acid and heated on the steam bath under reflux for 15 hours. The solution was then cooled and evaporated to dryness and the residue was refluxed in 10 ml. water for 5 hours i n order to reverse any acetate formation. On evaporation, a viscous, colorless sirup was obtained which failed to crystallize on standing 3 months. A chromatogram showed the presence of a trace of D-galactose in the product. The product was purified by chromatography on a cellulose column using butanol-water as developer. The approp riate fractions yielded on evaporation a colorless sirup which on drying to constant weight formed a hard glass, weight 358 mg., r n 2 * \d. J D =s+7U.2° (c= 6.0 i n water, equilibrium value). Analysis: calc. for mono-0-ethyl hexose, C8H15O6* ethoxyl, 21.6$. Found: ethoxyl, 21.7, 21.5$. A paper chromatogram using butanol-ethanol- water (5:1:U) and the p-anisidine hydrochloride spray reagent revealed a single, brown, non-fluorescent spot of Rf O.UO. 86 R. Vinylation of 1:2-3:u-di-0-isopropylidene-D-galactose A solution of 13.0 g. (0.05)mole) of di-Q-acetone- D-galactose in 9 6 ml. (l mole) of vinyl acetate was mechanically stirred and cooled to -25°C and mercuric acetate, 0.5 g., and 2 drops of concentrated sulfuric acid were added. The mercuric acetate dissolved within a few minutes to give a slightly milky solution. After 3 hours, the reaction mixture was transferred to a separatory funnel and washed rapidly with three 25 ml. portions of a cold saturated solution of sodium carbonate. The organic layer was dried with anhydrous sodium carbonate and immediately evaporated under reduced pressure ajt a temperature less than U5°C to yield a colorless, mobile sirup, which was then distilled under high vacuum from sodium carbonate. At a bath temperature of 210°C, a colorless product began to come over (b.p. about 135°C/0.3 mm.). After about 5 ml. distillate had been collected, the s t i l l head temperature dropped rapidly. The holdup was a dark-colored, non- mobile substance which was discarded. The distillate, weight 3 . 4 9 g«, was a colorless sirup having a mobility intermediate between that of di-O-acetone- D-galactose (like liquid honey) and 6-O-ethyl-di-O-acetone-D- galactose (like glycerol). It decolprized bromine in carbon tetrachloride readily with the formation of a pale-yellow pre cipitate. Di-O-acetone-D-galactose also was found to decolorize 87 bromine i n carbon tetrachloride with the formation of a precipitate but at a considerably slower rate* A 637 mg*, sample of the distillate was dissolved in $0 ml. of absolute methanol and shaken under 2 atmospheres pressure of hydrogen in the presence of palladized charcoal catalyst for 5 hours. The colorless sirup, obtained.after filtration and evaporation of the solvent was dissolved in 25 ml. of N sulfuric acid and heated on the steam bath for 16 hours* The hydrolysate was deioniaed by passage through a column of Amberlite IR-UB and evaporated to yield a colorless sirup. A chromatogram using butanol- ethanol-water (5.1.U) and the p-anisidine hydrochloride spray reagent showed (i) a very distinct, yellow-brown, U.V. fluorescent, spot, 0.10 for D-galactose, and ( i i ) an elongated, diffuse, yellow-red-brown spot, R^, O.38 (approximately). T1B latter re presented a mixture. The remainder of the distillate was redistilled from sodium hydroxide to yield 0.5U g. of a colorless, fairly mobile sirup boiling at 130°C/0.3 mm. This product was hydrogen ated in dry ether in the presence of 100 mg. of platinum oxide catalyst for 2k hours. The product obtained after filtration and evaporation of the solvent was redistilled from sodium carbonate, then from sodium hydroxide, and finally from sodium to. yield 68. mg. of a colorless, fairly mobile sirup boiling at 90°C at 0*3 mm. This product was hydrolysed with boiling 0.1 N sulfuric 88 acid for 19 hours, neutralized with barium carbonate, filtered and evaporated* The residue was taken up i n methanol, filtered and evaporated to give a colorless sirup. On a chromatogram run for UO hours using methyl ethyl ketone-water and the p-anisidine hydrochloride spray reagent, four spots were observed (i) a brown, non-fluorescent spot identic&ldin color and Rf value with 6-0- ethyl-D-galactose, (i i ) a yellow, U.V. fluorescent spot travelling slightly ahead of the 6-0-ethyl-D-galactose ( i i i ) a yellow, U.V. fluorescent spot travelling slightly behind 6-0-ethyl-D-galactose, and (iv) a brown-yellow, U.V. fluorescent spot corresponding to D-galactose. In a second run, 10 g. of di-O-acetone-D-galactose was treated with vinyl acetate, mercuric acetate and sulfuric acid at -25°G as described above. After a reaction time of 2 hours, the solution was washed with cold aqueous sodium carbonate, dried, evaporated and the colorless residue distilled. A fraction boil ing at ll4 - l l 6°C at 0.3 mm. was obtained. After a redistillation from sodium hydroxide, the colorless, sirupy product was dissolved in 25 ml. anhydrous ether and shaken under 2 atmospheres pressure of hydrogen over 100 mg. platinum oxide catalyst for 6 hours at room temperature. Filtration and evaporation of. the solvent yielded a clear sirup. The sirup was dissolved i n $0% aqueous ethanol, the solution adjusted to 0.1 N with concentrated sulfuric acid and heated on the steam bath under reflux for 3U hours. The 09 hydrolysate was neutralized with barium carbonate, filtered and evaporated to yield a colorless sirup. A chromatogram developed with methyl ethyl ketone-water revealed four spots : (i) a yellow, fluorescent spot for D-galactose, ( i i ) a brown spot which corres ponded with 6-O-ethyl-D-galactose, and ( i i i ) (iv) two yellow, fluorescent spots of unknown identity in the neighbourhood of 6-0-ethyl-D-galactose• A preliminary purification was carried out on a 30 x 2.6 cm. cellulose colunjn using butanol-water* The fractions containing ( i i ) ( i i i ) and (iv) were combined and evaporated to yield 311 mg. of colorless, viscous sirup. A second purification was carried out one a £0 x 2.8 cm. cellulose column using methyl ethyj. ketone-water and collecting 10 minute fractions of about 20 ml. volume. To obtain the 6-Q-ethyl-D-galactose, the appropr iate fractions were combined and evaporated to yield 88.2 mg. of colorless sirup. Final purification was achieved by chrcmato- graphing 1+0 mg. of the sirup on paper (spots of about 2 mg. of sirup) and developing with methyl ethyl ketone-water. Extraction of the appropriate zones of the paper with cold water yielded 28.5 mg. of the desired product (0.7$ yield). Drying to constant weight gave the 6-B-ethyl- D-galactose as a colorless, hard glass, j ^ J D^ «+ 76.5° (c» 1.1+ in water). Analysis: calc. for a mono-0-ethyl hexose, CglLggk. 90 ethoxyl, 21.6$. Found;: ethoxyl, 21.4, 21.0$. The substance was chromatographed using butanol-ethanol-water (5:1:U) and methyl ethyl ketone-water: the spots obtained were found to be identical in color and value with authentic 6-0-ethyl-D-galactose. S. Deacetylation experiments with anion exchange resin Dowex I anion exchange resin was air-dried, pulverized and sieved and 25 g. of the 4O-8O mesh fraction was placed in a glass tube of 1.8 cm. I.D. closed at one end with a constriction and glass wool plug. The length of the resin column was 23.3> cm. after welting and the liquid capacity was 25 ml. The column was treated with 10$ aqueous sodium hydroxide, washed free of base with water and then washed with successive 50 ml. portions of 20, 40, 60, 80 and 90$ aqueous methanol and was then ready for use. The same column was used throughout and was re,- generated after each experiment by washing out with the aqueous solutions applied i n the reverse order followed by their reapplic- ation in the original order. Direct application of 90$ aqueous methanol to the water-wet column caused the formation of air bubbles in the column. In a typical deacetylation experiment 5 ml. of a 90$ aqueous methanol solution containing 0.5000 g. of sucrose octaacetate (m.p. 98.5-89.0°C, f r f l 2 l L JD «+ 59.5° (c=» 0.79 in chloroform)) 91 (32) was run into the prepared column and washed i n with 10 ml« of the solvent. The loaded column was allowed to stand for 21+ hours and was then eluted with 90% aqueous methanol; successive 200 ml. fractions of the eluate was separately collected and evaporated to dryness. The yield of colorless, sirupy residue recovered from each fraction is shown in TABLE VIII. The dried residues were dissolved i n water and combined and the aqueous solution was filtered and evaporated to a colorless sirup and seeded with sucrose. After 2 days the completely crystalline product (25U mg.) was pulverized, washed with 5 ml. of methanol and dried in vacuo. The dried sugar (232 mg., 92% yield) melted at 181+-69, {. * J D =+65 «5° (c= 1.661+ i n water) and had the crystal form and taste of pure sucrose. A paper chromatogram of the sirup developed with butanol-ethanol-water (1+:1 .1:1:9) showed a well- defined spot, R^O.15, which corresponded to sucrose (99); the Raybin test (89) was positive. (TABLE Virc) were treated by the above procedure and the corres ponding deacetylated compounds were quantitatively recovered in fractions were required, for complete recovery of sucrose (TABLE VIII). In a preliminary experiment a solution of 1.000 g. of sucrose octaacetate in 50 ml. of 90$ aqueous methanol was passed through the column at a flow rate of one ml. per minute and the column was then washed out with a further 50 ml. of the 19 The acetates of the monosaccharide derivatives the first two or three 200 ml. fractions of eluate, whereas eight 92 solvent at the same rate. Evaporation of the eluate yielded 0,93 g. of a colorless sirup, which did not crystallize on seeding with sucrose octaacetate and sucrose and showed no spot for sucrose when chromatographed on paper. When this sirupy product was again run through the column, the eluate yielded crystalline sucrose. TABLE VII Deacetylation of Sugar Acetates on a Column of Anion Exchange Resin Sugar Acetate Deacetylated Product Yield Mixed Reported % m.p.°C. m.p.°C. m.p.°C. Sucrose octaacetate D-Mannitol hexaacetate 92 95 ldU-186 16U-166 16V166 185-188 (100) 187 (lU) 166 (101) Cyclohexyl-p-D-gluco- pyranoside tetraacetate 97 13ii-135 13l*-135 133-135 (102) Methyl-U-O-methyl -D-glucopyranoside triacetate 99 100-101 100-101 101- 102 (73) 102- 103 (103) With authentic specimens of the non-acetylated sugar derivatives. fr The melting point of even very pure sucrose i s reported to vary with the medium used for purification; a mixed melting point was therefore not definitive (101). 93 TABLE VIII ELution of Deacetylated, Compounds from the Resin Column Fraction Weight of Saccharide Recovered (mg«) Number* Sucrose D-Mannitol C.G.*W M.M.G.*** 1 k 29 124 157 2 22 68 0 0 3 57 10 « k 73 0 - 5 58 - 6 34 - 7 18 - 8 8 Total yield:: ^ 107 12IT 1 5 7 Weight of washed and dried crys talline residue;: 23_2 102 118 155 Theoretical yield:253 105 122 156 Successive 200 ml. portions of the eluate. Cyclohexyl- /5 -D-glucopyranoside. Methyl-4-0-methyl- /3 -D-glucopyranoside • 9k CLAIMS TO ORIGINAL RESEARCH 1. Four new derivatives of sucrose have been pre pared and their structures established. These compounds are: l',4,6'-tri-O-methyl sucrose, 1', 6,6'-tri-O-trityl sucrose, 2,3,3',U,U'-penta-O-acetyl sucrose and 2,3,3',4,U'-penta-O-methyl sucrose. 2. A new di-O-methyl-D-fructose derivative has been prepared and characteristized as 1, 6-di-0-methy1-D-fructose. 3. The direct t r i t y l a t i o n of sucrose was reexamined and shown to lead to a mixture of t r i t y l a t e d sucrose derivative* and reducing sugars. 4* The selective detritylation of sucrose derivatives was accomplished by catalytic hydrogenation and by graded hydrolysis. 5« The course of the Purdie methylation of sucrose derivatives was studied by means of chromatography. Acetyl migra t i o n from CU to C6 i n the glucose moiety of sucrose has been shown to occur under the methylation conditions. 6. The Adelman vinylation procedure was applied to selectively substituted sucrose and D-galactose derivatives and the usefulness of this reaction i n the carbohydrate f i e l d was assessed. 7. A new compound, 6-O-ethyl-D-galactose has been synthesised for the f i r s t time by two different routes which establish the structure. 95 8, The deacetylation of the acetate derivatives of several carbohydrates by passage through columns of basic ion exchange resin was developed as a rapid and convenient laboratory method particularly applicable to acid-sensitive compounds. 96 BIBLIOGRAPHY 1. von Lippmann, E.O., "Geschichte des Zuckers", 2nd Edn., Berlin (1929), p. 76. 2. loc. c i t . , p. 83. 3. loc. dt., P« 113. 4. loc. cit., P« 219. 5. loc. cit., P> 238 f f . 6. loc. cit., P. 105. 7. loc. cit., P» U25. 8. Quoted by Beguin, C, Pharm. Acta Helv., 1, 90 (1926). 9. Long, L., Jr., "Sugar and sugar By-products i n the Plastics Industry", Sugar Research Foundation, Inc., New York, 1949, p. 1. 10. 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