NOTES
3 224
tory. The analyses reported were done by MicroTech Laboratories, Skokie, Illinois. ALLECANVBALIJS~ICS LAI~ORATORY HERCULES P O W D E R C O M P I N \ CUMRERIA n,\ ~ I A R Y L A N D
Synthesis of Acetobromo Sugars c:.SCHEURER A S D F.S M I T H " *
BY PAUL
RECEIVED F E B R U A R5Y, 1954
-2cetohalogen derivatives of sugars play an important role in synthetic carbohydrate chemistry and ease of preparation of these compounds is of considerable value. Formerly the classical procedure for preparing acetobromo sugars has involved treatment of the sugar acetate with a solution of hydrogen bromide in either glacial acetic acid or acetic anhydride. -j Acctyl bromide has also been used6 A simplified procedure for making acetobromoglucose has been described' in which the brominating agent (HBr) is generated in situ by adding water t o a mixture of bromine and red phosphorus in glacial acetic acid. TVe have been making use of a similar method except that no water was added to the brominating reagent (CH3COBr). The reaction may be applied to either the free sugars or their acetates. Thus acetobromo derivatives have been prepared from the following : L-arabinose, D-xylose, D-glucose, p-D-gltlCOSe pentaacetate and P-cellobiose octaacetate (see Table I ) .
VOl. 76
solution of sodium bicarbonate and dried (CaClZ). Removal of solvent in ZJUCUO gave a-acetobromo-D-glucose which was crystallized from ether. More material was obtained by adding petroleuin ether t o the ethereal mother liquors. (b) From the Sugar Acetates, e.g., P-D-Glucose Pentaacetate.-The acetate (216 g.) was added in portions with shaking t o the brominating reagent prepared from bromine (180 g.). After 2 hours at room temperature the reaction mixture was diluted with chloroform (300 ml.) and poured into a mixture of ice and water (800 ml.). The aacetobromo-n-glucose was isolated as in ( a ) .
Acknowledgment.-The authors thank Mr. E . F. Garner and Mr. G. H. HufTman for their help in carrying out these experiments. DEPARTMEST OF AGRICULTURAL BIOCHEMISTRY UNIVERSITY OF MINNESOTA ST. PAUL,MINSESOTA
Synthesis of Glycol Bis-(alkyl Sulfites) BY D. C. MORRISON RECEIVED JANUARY 29, 1954
Esters of sulfurous acid of various types are known, simple esters having been prepared long ago. Richter3 obtained diary1 sulfites while Carre and Libermann* prepared many mixed esters, including alkyl aryl sulfites. Some cyclic esters of glycols are known6 and also the cyclic ester of catechol.6 However, no mixed diesters of glycols have been reported. It was the purpose of this work to attempt to prepare mixed glycol bis-(alkyl sulfikes) of the type formula : R0430.0.(CH2)2.X.(CH2)2. 0 SO.OR where R is ethyl or 0-chloroethyl and TABLE I X is oxygen or sulfur. In addition diesters of Acetohromo deri vnti ve tetramethylene glycol were studied. Compound SI.I)., C. 1.1 2 1 (CIICId) ~ Ref. The compounds were employed in tumor chemoI.- Arabinose _99 137 f28-l' 8 D-Xylose CiX .?" .... .... 9 therapy tests in mice. Structures of this type o-Glucose C,(j 87-80 +lo.? 10 possess a formal analogy to the disulfonic esters of 84 88-8S +l98 10 j3-D-Glucose pentaacetate Timmis' who showed that the dimethanesulfonate 95-100 183 + !I4 11 8-Cellobiose octaacetate of tetramethylene glycol has activity in causing a This value is based on the yipld of methyl p-D-XylOpyranosine triacetate ( m . p . 112-113', [ e I z 4 D -60" (CHC13)) tumor regression. The glycol diesters were prepared by reaction of derived from the acetohroino cornpound. one mole of glycol in inert solvent medium with two Experimental moles of an ester chloride of sulfurous acid (alkyl Generation of the Brominating Reagent.-Bromine (180 9 . ) is added dropwise to suspension of red phosphorus (30 9.) chlorosulfites) in the presence of pyridine.8 The in glacial acetic acid (300 m l . ) with cooling. After the re- syntheses were successful with tetramethylene glyaction is complete the mixture is filtered (glass wool) and col, diethylene glycol, thiodiglycol and butyne diol, kept in the cold room if not required for immediate use. when reacted with ethyl or 0-chloroethyl chlorosulPreparation of Acetobromo Sugars. (a) From the Sugars, fites. The products, after appropriate purifica? . E . , n-Glucose.-The sugar (10 g . ) was added with shaking to the hromiriating rcagcnt (100 ml.), the temperature being tion, were high boiling oils of little or no odor. kept a t or below 40'. After 2 hours a t room temperature, Several of the bis-(ethyl sulfites) were distilled but the reaction mixture was diluted with chloroform (100 ml.) no attempt was made to distil the chloroethyl and poured with stirring into a mixture of ice and water (200 tnl.). The chloroform layer was separated and the aqueous esters. None of these substances is steam volalayer extracted with chloroform. The chloroform extracts tile and they did not appear to decompose during were combined, washed with water then with an aqueous short contact with boiling water. O
(1) T h e authors thank the du Pont Chemical Company for t h e award o f a Research Fellowship. (2) Paper S o . 3103, Scientific Journal Series, Minnesota Agricultural Experiment Station, University o f Slinnesota, St. Paul, Rlinn 13) A . Bodart. Monafsh., 23, 1 (1902). 14) E. Fischer and H. Fischer, Bpr,, 43, 2530 (1910). ( 5 ) C. S. Hudson and J. K. Dale, THISJOIJRSAL, 40, 004 (1918). (6) G. Chavanne, Comfit. v e n d . , 134, OR1 (1902). ( i )h l . Barczai-Martos and F . Kdrozy, Nature, 166, 369 (1950). (8) D. H . Brauns, THISJ O U R N A L , 46, 14% (1924). (9) J. K . Dale, ibid., 37, 2715 (1915). (10) E. Fischer, Bcr., 44, 1898 (1911). (11) E . Fischer and G. Zemplkn, ibid., 43, 2.736 ClOlO).
(1) T h e work described in this paper was aided by a grant to Prof. D. M. Greenberg from t h e National Cancer Institute, United States Public Health Service. (2) A. Kosenheim and W. Sarow, Bcr., 38, 1298 (1905). (3) h l . Richter, ibid., 49, 2339 (1916). (4) P. Carre and D. Libermann, Bull. soc. c h i m . , 53, 1060 (1033); C . A , , 28, 1658 (1934). (5) R Majima a n d H. Simanuki, Proc. I m 9 . Acod. ( T o k v o ) , 2, 54.1 (1926); C. A , . 21, 1796 (1927). (6) R. Anschutz and W. Posth, Be*., 2'7. 2751 (1894). (7) G. M.Timmis, "Ann. Rpts. Brit. Empire Cancer Camp.," No. 27, p. 43. :.5) W. Gerrnril, J . C h e m .Soc., 09 f 1039).
