ARCHIE J. DEUTSCHMAX, JR.,
4070
AND
HENRYW. KIRCHER
i-01. 83
with those used for the acetylation except that oiie equivalent of benzoyl chloride was used as the acylating agent. The product was crystallized in 157, yield as a brown solid, m.p. 95-102' from the ethanol-ethyl acetate solvent. On recrystallization from ethanol using decolorizing carbon, the pure product was obtained as rosettes of white needles, m.p. 110-111", [ o l I z 5 ~ 75" (62.54 in chloroform). Pedersen, et U Z . , ~ report ~ m.p. 110-112", [ C X ] ~ ~+75.3 D (chloroform); Zinner, et a1.,24 give 111-111.5', [ c Y ] ~ ~ f78" D (chloroform).
From the original mother liquor, there was obtained a second crop ( 7 % ) of a lower-melting material, m.p. 7882'. Further recrystallization from ethanol afforded white needles, m.p. 83-86', [ C Y ] ~ ~-D 20' ( c 1.1 in chloroform). Pedersen, et aZ.,*3 found 84-87', [ 0 1 ] 2 0 ~- 19.8" (chloroform). This isomer tended to be somewhat hygroscopic, especially in an impure state.
[CONTRIBUTIOX
BIOCHEMISTRY, USIVERSITY
+
FRO?d THE
DEPARrMENT
O F .iGRICULTURAL
Vinyl Ethers of Carbohydrates
.
A n d . Calcd. for C26H2207:acyl. no., 3.0. no., 3.03.
O F ARIZONA,
Found: acyl.
TUCSON, iIRIZ ]
I. Methy1 2-0-Viny l- a-D-glucopyranosid e
BY ARCHIEJ. DEUTSCHMAN, JR.,
AND
HENRYW. KIRCHER
RECEIVED MAY6, 1961 Crystalline methyl 2-O-vinyl-ol-~-glucopyranosidewas isolated as a product of the vinylation of methyl a-D-glucopyranoside with vinyl chloride or with acetylene. The structure of the compound was proved by methylation and hydrolysis t o and by hydrogenation and hydrolysis to 2-O-ethyl-~-glucose. methyl 3,4,6-tri-O-methyl-oc-~-glucoside
The preparation of vinyl ethers by the alkali- the same as that observed from the vinyl chloride catalyzed addition of alcohols to acetylene has reactions. received considerable study and is the basis for a The acetone-soluble portions of several reaction number of industrial processes. A review of the mixtures were redissolved in water and extracted field2 lists the preparation and properties of a large continuously with benzene to yield a fraction that number of vinyl ethers derived from primary, contained the substances of Rf 0.85 and 0.92. secondary and tertiary alcohols. Subsequent continuous extraction of the aqueous The preparation of vinyl ethers from polyfuiic- solution with ether yielded a fraction that contional alcohols and carbohydrates also has been tained the components of Xf0.68and 0.72. The reported.2-6 As a rule, the compounds were residual aqueous solution was evaporated to a poorly characterized and, where partial substitution sirup and extracted with chloroform. The chlorooccurred, the positions of the vinyl groups were not form extract evaporated to a sirup that crystallized established. 3-0-Viny1-1,2;5,G-di-O-isopropylideneupon standing a few days. Nucleation of the ether D-glucose, 3,5,6-tri-O-vinyl-l,2-0-isopropylidene-Dextract with these crystals caused a portion of i t glucose5 and methyl 2,3,4,6-tetra-O-vinyl-a-D-gluto crystallize. The material melted 122-126.5' coside3 are examples of the vinyl ethers of carbohy- after a single recrystallization from acetone, drates that have been prepared. acetonitrile or ether. Recrystallization of this This paper deals with the preparation, isolation material from acetone gave large prisms, m.p. and proof of structure of methyl 2-O-vinyl-a-~- 126-127.5', Rf0.68, [ a ] * j+136" ~ (water). glucopyranoside (11). The initial vinylations of The compound had all of the chemical charmethyl a-D-glucopyranoside (I) were done with acteristics that one would expect of a methyl monovinyl chloride2 because facilities for handling ace- 0-vinyl-a-D-glucopyranoside. It rapidly decolortylene under pressure were not available. Sub- ized bromine and permanganate solutions, it sequent reactions with acetylene confirmed the yielded acetaldehyde arid methyl a-D-glucopyranoresults that were observed with vinyl chloride. side upon mild acid hydrolysis, and i t was readily The reactions of I with vinyl chloride and sodium reduced with hydrogen. The vinyl derivative hydroxide or with acetylene and catalytic quanti- was methylated to a tri-0-methyl derivative (111) ties of potassium hydroxide led to water-soluble whose retention time on gas-liquid partition chroreaction mixtures. These were mixed with Dry matography was very similar to that of iiiethyl Ice to convert the hydroxides to the carbonates, 2,3,4,6-tetra-O-methyl-a-~-glucoside~ (Fig. 1). evaporated to dryness, and extracted with acetone The product of the methylation was hydrolyzed to yield a mixture of several vinylated products. with dilute acetic acid a t room temperature to a Paper partition chromatography ( d e iTzfm) showed methyl tri-0-methyl-a-D-glucopyranoside (117) (Fig. the presence of a t least four vinylated compounds, 1). two of lorn and two of high I+. The pattern of The four possible methyl tri-O-methyl-a&Dspots observed from the acetylene reactions was glucopyranosides were obtained from methylated (1) Presented a t the 139th meeting of the A.C.S.. St. Louis, Xfn , starch (2,3,6),' methylated dextran (2,3,4),' 3-0l l a r c h , 1961. benzyl-D-glucose (2,4,6)8and from %O-methyl-~(2) W. Reppe, e l al., Ann., 601, 81 (1956). glucose (3,4,6).9 The separation diagrams of the (3) RI. F. Shostakovskii, E. N. Prilezhaeva and L. 5'. Tsymbal, four methyl tri-O-methyl-a,P-D-glucopyranosides Doklady A k a d . Nairk S.S.S.R., 96, 99 (1954); C . A . , 4 9 , 5312 (195.5). (4) >F. I.Shostakovskii, E. N. Prliezhaeva and L. 5 '. Tsymbal, are shown in Fig. 2. Z h i i u . Obshch. Khim., 26, 739 (19%);
C . A , , SO, 14564 (1956). ( 5 ) B. I. Zfikhant'ev and V. L. Lapenko, Zhiiu. Obsliclz. Khiiiz., a7, 2~172,2840(1957); c. A , , 52, 8054, 8056 ( 1 g . m . (6) S. Kunichika and Y . Sakabibara, K o g y o K a g a k u Zassha. 6 0 , 701 (1957); C . A . , 63, 10009 (1959).
(7) H. W. Kircher, Aitol. Cizetiz., 32, 1103 (1960). (8) K . Freudenberg a n d E . Plankenhorn, A n n . . 636, 257 (1938). (9) R.L. Sundberg, C. M . hlccloskey, D. E . Rees and G . H . Coleman, J . A m . Chem. Soc., 67. 1080 (1945).
4071
METHYL2-O-VINYL-a-D-GLUCOPYR4NOSIDE
Oct. 5, 1961
I
I 0
I
I
I
I
I
IO
20
30
40
50
MINUTES.
Fig. 1.-Separation diagram showing (ZOO', 2 04 atrn. helium, 77 ml./min.) : A, methyl 2,3,4,6-tetra-O-methyl-aD-glucoside; B, methyl 0-vinyl-tri-0-methyl-a-D-glucoside; C, methyl tri-0-methyl-a-D-glucoside.
3,496
A
P
The methyl tri-0-methyl-a-D-glucopyranoside obtained from I1 corresponded in retention time with one of the peaks observed for methyl 3,4,6I I I 1 I I I 60 40 50 20 30 0 IO tri-O-methyl-a,P-D-glucoside on a number of different gas chromatographic columns. Methanolysis of the unknown product to the a,p-mixture of M I N U T € S, glycosides (IV and V) followed by gas-liquid parFig. 2.-Separation diagrams showing the methyl tri-0tition chromatography showed two peaks coinci- methyl-a,&D-glucopyranosides; 200°, 2.04 atrn. helium, dent in relative size and retention time with the 77 ml./min. two peaks shown by methyl 3,4,6-tri-O-methyl-o,~A D-glucoside. This indicated that the vinyl group had been in the two position. 2-0-Ethyl-~-glucosewas prepared from methyl 3,5,6-tri-0-benzyl-a,~-~-glucofuranoside by the pro-r cedure outlined for 2-O-methyl-~-glucose.lo It 0 10 20 30 40 50 so corresponded in both melting point and optical Y IN UTES. rotation with the 0-ethyl-D-glucose (VIII) obtained Fig. 3.-Separation diagram showing the products of by hydrogenation and hydrolysis of the crystalline methyl 0-vinyl-a-D-glucoside. The crystalline ma- methylation and dilute acid hydrolysis of the methyl monoterial obtained from the reaction of methyl a-D- 0-vinyl-a-D-glucopyranoside mixture (200°, 2.04 atm. glucopyranoside with vinyl chloride or acetylene helium, 77 ml./min.) : A, methyl 3,4,6-tri-#-methyl-a-~glucoside; B, methyl 2,3,4-tri-O-rnethyl-ar-~-g~ucoside; was therefore methyl 2-O-vinyl-a-~-glucopyranoC, methyl 2,3,6-tri-0-methy1-au-~-glucoside; D, methyl side (11). 2,4,6-tri-0-methyl-ar-~-glucoside.
OCH2CH3
,
.
HOCH,' b O H
The presence of the three other possible mono-0vinyl ethers of methyl a-D-glucopyranoside was shown by methylation of the ether extract that contained the components of Ri 0.68 and 0.72. After removal of the vinyl groups with dilute acetic acid, the resulting mixture of methyl tri-0-methyla-D-glucopyranosides was put through the gas (IO) F. Weygand and 0. Trauth, Chem. Ber.. 85, 57 (1952).
chromatograph. The separation diagram (Fig. 3) showed peaks for methyl 3,4,6-, 2,3,4-, 2,3,6and 2,4,6-tri-O-methyl-a-~-glucopyranoside. This indicated that the 2-, 6-, 4- and 3-0-vinyl ethers of methyl a-D-glucopyranoside were present in the ether extract. The sizes of the peaks in Fig. 3 are proportional to the amounts of each of these components in the mixture. Two convenient techniques are therefore available for the determination of the position of the vinyl ether groups on carbohydrates. The compounds can be catalytically hydrogenated to the 0ethyl derivatives that can be prepared by classical techniques. The vinyl derivatives can also be fully methylated without disturbing the position of the vinyl groups. Dilute acid hydrolysis removes the latter; the resulting partially methylated carbohydrates then can be separated and identified by gas-liquid partition chromatography. The vinyl ethers of methyl a-D-glucopyranoside were stable when stored in a desiccator over sodium hydroxide pellets. They were slowly hydrolyzed to acetaldehyde and methyl glucoside (over a period of months) when no precautions were taken to exclude atmospheric moisture and carbon dioxide.
4072
ARCHIE
J.
DEUTSCHMAN,
JR., AND
ExDerimental .~~ .~~...~ ~~~
Chromatography.-Paper chromatography was performed in the descending manner with the upper phase of butanol-ethanol-water 4: 1:5 (v./v.). The papers were dried in air and sprayed with 1% aqueous potassium permanganate. The vinylated products gave immediate yellow spots on a red background and methyl a-D-glucopyranoside gave a yellow spot after several minutes. The papers then were washed free of permanganate to prevent eventual yellowing of the background. Gas-liquid partition chromatography of the methylated sugars was performed as recently described.6.11 A 10-foot column, 20% butanediol succinate polyester on firebrick, was used in the Aerograph apparatus. Vinylation of Methyl a-D-Glucopyranoside (I) with Vinyl Chloride.-The reactor" was charged with I (48 g., 0.25 mole), sodium hydroxide (50 g., 1.25 moles), tetrahydrofuran (60 ml.) and water (20 n11.1. I t was cooled in a Dry Ice-bath, evacuated, and liquified vinyl chloride (70 g., 1.1 moles) was admitted. The reaction mixture was heated t o 130" and stirred for 10 hours. The pressure rose to and remained a t 31.6 atm. After cooling, the reactor was vented; the odor of acetylene in the exhaust gases was con6rnied by formation of cuprous acetylide. The tacky orange residue in the reactor was dissolved in water (600 ml.) and treated with excess Dry Ice. The aqueous solution was evaporated to dryness and t.he residue extracted with methanol to yield a dark sirup (55 g.) that contained the products, unreacted methyl glucoside, and some salts. The products (35.6 g.) were extracted from the mixture with acetone. Paper chromatography of the acetone extract showed five spots, I ( & 0.36) and spots of K I 0.68, 0.72, 0.85 and 0.92. The products were distilled in a Hickman molecular still i n vacuum, but no separation was obtained. Vinylations with Acetylene.-Compound 1 (50 g.), powdered potassium hydroxide (2 or 4 g.), and solvent (100 ml. of water-tetrahydrofuran mixtures) were placed in the reactor, I t was flushed with nitrogen and heated to 150'. The reactor was vented briefly and acetylene admitted a t 25.5 atm. pressure. After 12 hours the reactor was cooled, vented, and the contents were dissolved in water. The solutions were carbonated with Dry Ice, adjusted to 500 ml., and aliquots (1-4 nil.) were removed for vinyl ether determinations with iodine.18 The remaining solutions were worked up as described above. The results of the titrations are given in Table I ; the figurcs represent the average number of vinyl ether groups per molecule of methyl a-D-ghcopyranoside for the various runs. The occurreice of the highest substitution in 50:50 water-tetrahydrofuran illustrates the maximum effective solubility of the three components, sugar, alkali and acetylene, in this particular solvent. TABLE 1 AVERAGE DEGREEOF SUBSTITUTION 7 -
KOH, 100 Hz0 g.
2
4
0.71 0.95
Solvent composition (v./v , ml ) 80 Ha0, 50 Hz0, 20 H20. 20THF 50THF 80 T H F
0.72 1.24
1.00 1.50
0.67 1.37
100
TlIF
0.28 0.36
Isolation of Methyl 2-o-Vinyl-a-D-glucopyranoside (11).The acetone-soluble portions of several reaction mixtures (80 9.) were dissolved in water (500 ml.) and extracted continuously for 3 days with benzene. Evaporation of solvent from the extract left a sirup (23 g.) that contained only the components of R, 0.85 and 0.92. The aqueous solution was then extracted continuously for one daj7 with ether. Evaporation of solvent from this extract left a sirup (7.5 8 . ) that contained vinylated components of Rf 0.92, 0.85, 0.72 and 0.68. The residual aqueous solution was then extracted continuously with ether for a week to yield a third sirup (24 9.) that contained only the components of Rj 0.68 and 0.72. Evaporation of the aqueouz residue left a dark siruD (26 E.) comuosed mostlv of methvl glucoside. This was e?c
