1, D DICHLORIDE
May, 1940
[CONTRIBUTION FROM
THE
aldehydo-GALACTOSE PENTAACETATE
OF
1149
CHEMICAL LABORATORY OF THEOHIO STATE UNIVERSITY ]
The Action of Phosphorus Pentachloride upon aldehyde-Galactose Pentaacetate. The 1,l-Dichloride of aldehyde-Galactose Pentaacetate BY M. L. WOLFROM AND D. I. WEISBLAT The action of phosphorus pentachloride upon aldehydes to produce the 1,l-dichlorides1 is a well-known reaction. We were interested in its extension to an aldehydo-sugar acetate and were successful in obtaining a crystalline product in the galactose structure. The product, 1,l-dichloro-aldehydo-d-galactose pentaacetate (IV) is the first substance of this type in the sugar series. It is a very stable substance and reduces Fehling It does solution not reduce onlyneutral on prolonged copper boiling. acetate [Hsolution on boiling. We have found that the
that it contains one reactive chlorine extremely readily replaceable by an alkoxy1 group. On recrystallization from ethanol, I yields the substance 11, designated di- (l-chloro-aldehydo-d-galactose pentaacetate) ethyl phosphate. I1 exhibits the predicted molecular weight and on acetylation with acetic anhydride and zinc chloride, yields aldehydo-galactoseheptaacetate. The
i : Hy-cl I c1
pc16
(CH0Ac)r ___
(CHOAC)~
I
reduction of neutral copper acetate solution CHzOAc CH~OAC is a general property of aldehydo-sugar aceIV tates and also of the very reactive acetyl c1 chloride carbonyl addition compound of L--t HC---P--O-&H nldehydo-galactose pentaacetate.2 The beI havior of a number of significant sugar strucI Ag2CO8 (CHOAC)~ C1 ( CHOAC)4 _ _ _ _ ~ I I tures toward this reagent is tabulated in HOH CH~OAC I CH~OAC Table I. We believe that this lack of reduction toward neutral copper acetate confirms c1 0 c1 our assigned structure for substance IV. l II I HC-0-P-0-CH If the reaction of phosphorus pentachloride HC(0Ac)z I ACZO I I I with aldehydo-galactose pentaacetate is car- (CHOAch t (CHOAC)~ OR (CHOAC)~ ried out in ether solution, an insoluble reac- CH20Ac I ZnClz I I
1"""
tion product separates which is assigned structure I. This may be considered as a carbonyl addition compound of phosphorus pentachloride with two moles of the aldehyde in which two of the chlorine atoms attached to phosphorus have been hydrolyzed. c1
c1 c 1
c1
2 H C 4
1 I + PClj +HC--O--IJ--O-CH
I
I
R
R
C1
I
I
R c1
I
HOH +
I1
H-C-0-P-0-CH I I R C1
I I
R
The structure of substance I, designated di(I -chloro-aldehydo-d-galactose pentaacetate) chlorophosphate, is made probable by its analysis, its
CHzOAc 11, R = Et 111, R = Me
CH~OAC
compound 111, analogous to I1 but containing a methoxyl group, also was synthesized. I t is probable that the substance I represents a general structure for the initial reaction stages of aldehydes with phosphorus pentachloride. In the cyclic sugar structures, Freudenberg and Braun3 have reported a crystalline reaction product of 2,3,6-trimethylglucose with phosphorus pentachloride which on analysis proved to be (C6H803(0CH3)&PCl3. Helferich and du Mont4 have obtained a crystalline tri-(P-d-glucopyranose tetraacetate)-&phosphate by the reaction of phosphorus oxychloride with @-&glucose1,2,3,4-tetraacetate.
Experimental
hydrolysis with water and silver carbonate to aldehydo-galactose pentaacetate and by the fact
Di-( 1-chloro-aldehyde-d-galactose pentaacetate) Chlorophosphate (I).-aldekydo-&Galactose pentaacetate6 (10 g.,
(1) C. Friedel (A. Wurtz). Conrpt. rend., 46, 1015 (1857); A. Wurtz and C. Frapolli, ibid., 47, 418 (1858); A. Geuther, Ann., 106, 321 (1858). (2) M.L. Wolfrom, THIS JOURNAL, 67, 2198 (1985).
(3) K.Freudenberg and E. Braun, Ann., 480, 303 (1928). (4) B. Helferich and H. du Mont, 2. phrriol. Chem., 181, 800 (1929). (5) M.L. Wolfrom, Tats JOURNAL, 64, 2464 (1980).
1150
M. L. WOLFROM AND D. I. WEISBLAT
Vol. 62
TABLE I &GALACTOSE DERIVATIVES BY COPPER ACETATE^
purity. No conditions could be found for converting compound I into the dichloride (IV). Ana2. Calcd. for C32H12023C18P: C1, 11.41; P, 3.32; saponification value (15 equivalents), 16.1 cc. 0.1 N Time at Reducb. p.. sec.b tion Substance NaOH per 100 mg. Found: C1, 11.3; P, 3.34; saponifica&Galactose 0 tion value (Kunz and Hudson procedure'), 16.0 cc. 120 p-d-Galactopyranose pentaacetate Hydrolysis of Di-( 1-chloro-aldehyde-d-galactose penta120 a-d-Galactopyranose pentaacetate acetate) Chlorophosphate (I) to aldehyde-&Galactose aldehydo-&Galactose pentaacetate 15 Pentaacetate.-I (2 g.) was suspended in 100 cc. of toluene aldehydo-&Galactose isopropyl and 4 g. of freshly prepared silver carbonate and 0.5 cc. of hemiacetal 45 water added. The mixture was refluxed for twenty-one &Galactose heptaacetate 50 hours with vigorous mechanical stining. The silver salts 1-Chloro-d-galactose hexaacetate 60 were then removed by filtration and crystalline material 1-Methoxy-d-galactose hexawas obtained by solvent removal under reduced pressure. acetate 90 The crystalline material was recrystallized from absolute 1- Chloro- 1- ethoxy - d - galactose ethanol and 0.3 g. of pure aldehyde-d-galactose pentaacepentaacetate 30 tate ethyl hemiacetal was obtained which was identified d-Galactopyranose tetraacetate 90 by melting point (133-135'), mixed melting point and 1,l-Dichloro-aldehyde-d-galactose optical behavior in chloroform solution.' 120 pentaacetate' Di-( 1-chloro-uldehydo-d-galactose pentaacetate) Ethyl Di- (1-chloro-uldehydo-d-galactose Phosphate (II).-When di-( 1-chloro-aldehydo-d-galactose 120 pentaacetate) chlorophosphate' pentaacetate) chlorophosphate (I) was recrystallized from One mole equivalent of 0.05 g. d-galactose in 5 CC. of 75 parts of boiling absolute ethanol, hydrogen chloride saturated aqueous cupric acetate solution. * In the case was evolved and on cooling, filtering, and concentrating of a positive reduction, the time of boiling recorded is that the mother liquors, a practically quantitative yield of the a t which visible reduction was initiated. &Galactose di-( 1-chloro-aldehyde-d-galactose pentaacetate) ethyl phosgave a visible reduction before the boiling point was phate (11) was obtained; m. p. 156-158", spec. rot. -24' attained. No reduction also on addition of ethanol. (21"; C, 1.3; CHCls). The product was similar to substance I in solubility 1 mol) and powdered phosphorus pentachloride (5 g., 0.9 and behavior toward copper acetate, Fehling solution and mol) were suspended in 200 cc. of anhydrous ether and re- the Schiff reagent. fluxed for twelve hours in an all-glass apparatus equipped Anal. Calcd. for C ~ ~ H U O Z ~ ( O C ~ HC1, ~)C 7.53; ~ ~ PP, : with a drying tube. The product began to separate from 3.29; OCzHs, 4.79; saponification value (15 equivalents), the reaction mixture within the f i s t hour of reflux. At 15.9 cc. of 0.1 N NaOH per 100 mg.; mol. wt., 941.6. the end of this period of refluxing an equal volume of pe- Found: C1, 7.60; P, 3.30; OCzHs, 5.0; saponification troleum ether (b. p. 65-110') was added and the mixture value,' 15.9 cc.; mol. wt. (Rast), 950. kept overnight a t icebox temperature, The product was Conversion of Di-( 1-chloro-aldehydo-d-galactosepentaremoved by filtration and washed three t o four times with acetate) Ethyl Phosphate (11) to aldehydo-&Galactose ether-petroleum ether (1:l); yield 4.5-6 g., m. p. 145- Heptaacetate.-11 (1 9.) was dissolved in a solution of 0.3 155 ', The product was immediately recrystallized from g. of freshly fused zinc chloride in 10 cc. of acetic anhydride about 80 parts of hot ethyl acetate; yield 3.5 g., m. p. 190' and the solution heated for one hour at 98". The black (dec.), spec. rot. -20' (26'; c, 2.2; CHCl3).' solution was poured on a mixture of sodium bicarbonate The substance was very soluble in chloroform, moder- and crushed ice. This mixture was extracted with chloroately so in acetone and practically insoluble in ether, form and the extract washed with an aqueous solution of petroleum ether and cold water. It showed no reduction sodium bicarbonate and finally with water. The dark toward copper acetate (see Table I) but slowly reduced sirup obtained on solvent removal of the dried (decolorizboiling Fehling solution. It gave a positive Schiff test ing charcoal) extract was dissolved in benzene and pevery slowly on standing. The material is very unstable troleum ether added to incipient opalescence. After unless of maximum purity, in which condition a sample in a standing overnight a t icebox temperature the supernatant desiccator over soda lime has shown no decomposition liquid was removed by decantation and the separated over a period of one year. sirup was crystallized from 500/, ethanol; yield 0.32 g., The substance was also formed by shaking the reaction m. p. 95". Pure material was obtained on recrystallizamixture at room temperature over a period of several days. tion from ethanol and from methanol; yield 0.10 g., m. p. No appreciable difference was noted on starting with the 100-102° (mixed m. p. unchanged), spec. rot. +lo" aldehydrol form of aldehydo-d-galactosepentaacetate. (20'; c, 2, abs. EtOH). Micheel and co-workers9 report By working up the mother liquor material from the ethyl for aldehydo-d-galactoseheptaacetate m. p. 103', spec. rot. acetate recrystallizations by means of alcohol-water, a + l o " (EtOH). very small amount of 1,l-dichloro-aldehydo-d-galactose Di-( 1-chloro-aldehydo-d-galactosePentaacetate) Methyl pentaacetate (see below) could be obtained in very high Phosphate (III).-This substance was prepared according REDUCTION OF
+-
+ + ++
+ ++
(6) All spedfic rotations are recorded to the D-line of sodium light: 2 6 O is the temperature; cis the concentration in grams per 100 CC. of
solution.
(7) A. Kunz and C.S.Hudson, THISJOURNAL, 48, 1982 (1926). (8) M. L. Wolfrom, ibid., 68, 2276 (1931). (8) F. Micheel, H. Ruhkopf and F. Suckfilll, k., 0,1625 (183s).
May, 1940
CRYSTALLINE PHENYLURETHANS OF SUGAR GLYCOSIDES
t o the procedure described for the corresponding ethyl compound (11) except that 150 parts of methanol was used in place of the ethanol. A good yield was obtained; m. p. 187-188" (dec.), spec. rot. -19" (30"; t, 4.2; CHCII). The substance crystallized in rod-shaped prisms and showed solubilities and behavior similar to 11. Anal. Calcd. for C82H11028(OCH8)C12P:OCHs, 3.35. Found: OCH,, 3.97. 1,l-Dichloro-aldehydtydo-d-galactose Pentaacetate (IV).-aldehyde-&Galactose pentaacetate (10 g., 1 mol) was dissolved in 100 cc. of pure benzene, 15 g. of Drierite (anhydrous calcium sulfate) added and the whole refluxed in a n all-glass apparatus equipped with a drying tube. Powdered phosphorus pentachloride (6.8 g., 1.3 mol) was introduced quickly and the reflux maintained for twelve hours, whereupon the pale yellow solution was filtered and the filtrate washed with ice water and with a n aqueous solution of sodium bicarbonate until halogen free (eight to twelve washings). Solvent removal from the dried (decolorizing charcoal) solution left 3 to 5 g. of a pale yellow sirup. This sirup was dissolved in the minimum quantity of hot ethanol and was crystallized on the addition of an equal volume of water. Pure material was obtained on further recrystallization from 80% ethanol; yield 0.8-1.6 g. of m. p. 148-150"; spec. rot. +1l0 (20'; t, 3.2; CHC18). The substance was soluble in the common solvents except petroleum ether and cold water. It showed no reduction toward copper acetate (see Table I) and reduced Fehling solution only on long boiling. It gave a positive Schiff test very slowly on standing. It was found that a reflux period less than specified above (twelve hours) yielded compound I while a longer period yielded only sirups which could not be crystallized and which readily decomposed.
[CONTRIBUTION FROM THE CHEMICAL
1151
Anal. Calcd. for C~H,06(CHIIC0)6Cl~: C, 43.2; H, 4.98; C1, 15.9. Found: C, 43.3; H, 5.07; C1, 15.6.
We are indebted to Mr. John Walker (W. P. A. Project 18062) for assistance rendered in the analytical determinations. We also acknowledge the general assistance of Mr. Irving Auerbach (N. Y. A. Project 0. S. U. 167).
Summary 1. The action of phosphorus pentachloride upon aldehydo-&galactose pentaacetate in dry benzene produces a crystalline substance (IV) which is shown to be 1,l-dichloro-aldehydo-dgalactose pentaacetate. 2. The action of phosphorus pentachloride upon aldehydo-d-galactose pentaacetate in ether leads to the isolation of a crystalline substance (I) designated di-(1-chloro-aldehydo-d-galactose pentaacetate) chlorophosphate. 3. From I is obtained di-(l-chloro-aldehydo-dgalactose pentaacetate) ethyl (and methyl) phosphate, 11, and 111. 4. The structure assigned to I is made probable by its hydrolysis to aldehydo-d-galactosepentaacetate and by its reaction with ethanol to form 11, from which aldehydo-d-galactose heptaacetate is obtained on acetylation. COLUMBUS, OHIO
LABORATORY OF THEOHIO STATE
RECEIVED MARCH 2, 1940
UNIVERSITY]
Crystalline Phenylurethms (Carbanilates) of Sugar Glycosides BY M. L. WOLFROM AND D. E. PLETCHER
A well-established procedure in organic chemis-
try is the characterization of carbinols as N-aryl urethans prepared by the reaction of N-aryl isocyanates with the carbinol. Maquenne and Goodwin' investigated the extension of this reaction, using phenyl isocyanate, to a number of unsubstituted sugars but obtained only amorphous powders. Jolles and Botrini12 likewise employing phenyl isocyanate, obtained as amorphous powders the phenylurethans or carbanilates of several naturally occurring glycosides. Crystalline fully substituted carbanilates of some of the sugar alcohols have been reported.'#* (1) L. Maquenne and W. Goodwin, Bull. soc. chim., 131 81, 430 (1904). (2) E. Jolles and M.Botrini, Gas% chim. ifal., 66, 1217 (1985).
(8) H. Tcsclmu, Ber., 18, 968 (1886).
We have now been successful in obtaining in crystalline form the carbanilates of four of the methyl glycosides of the sugars, in which derivatives all of the free hydroxyls have been brought into reaction. These substances melt with decomposition a t high temperatures and exhibit correspondingly low solubilities. Under certain conditions they show a pronounced tendency to separate as gels and are in general rather difficult to manipulate. These polyurethans or polycarbanilates were not sficiently soluble in chloroform for satisfactory polarizations. Rotations are recorded in acetone solution for all except /3-methyl-d-glucoside tetracarbanilate, for which pyridine was found to be the only suitable polarization sol-
