Organic Syntheses, CV 8, 363
[Glucopyranoside, methyl 6-bromo-6-deoxy-, 4-benzoate, α-D-]
Submitted by S. Hanessian
1
Checked by Janice Cammack and James D. White.
1. Procedure
To a suspension containing
20.5 g (72.61 mmol) of methyl 4,6-O-benzylidene-α-D-glucopyranoside (Note
1) in
1 L of carbon tetrachloride and
60 mL of 1,1,2,2-tetrachloroethane (Note
2) are added
15 g (84.27 mmol) of N-bromosuccinimide and
8 g (31.13 mmol) of barium carbonate (Note
3). The resulting suspension is heated at the reflux temperature of the mixture with mechanical stirring for a 2.5-hr period and filtered while hot. During the initial period of heating, a reddish orange color develops but fades before termination of the reaction. The yellowish gummy residue in the flask is washed with two
100-mL portions of hot carbon tetrachloride and the filtrate and washings are evaporated under reduced pressure to give a pale-yellow oil that is dissolved in
500 mL of ether. The solution is washed with three 60-mL portions of water, then dried over anhydrous
sodium sulfate. Evaporation affords a pale-yellow oil that crystallizes (Note
4) on trituration with cold
ether to yield
12.1 g of white crystals, mp
120–123°C. A second crop of
1.72 g is obtained from the mother liquors (Note
5). Recrystallization of 1 g of product by dissolution in a minimum volume of
acetone and addition of
ether, then
pentane gives
0.9 g of white crystals, mp
131–132°C;
[α]D + 118° (CHCl
3,
c 1).
2. Notes
1. The preparation of
methyl 4,6-O-benzylidene-α-D-glucopyranoside follows essentially the procedure reported.
2 A mixture of
60 g (0.31 mol) of methyl α-D-glucopyranoside,
45 g of freshly fused and powdered zinc chloride, and
150 mL of benzaldehyde ("practical" grade) is stirred at room temperature for a period of 48 hr. The resulting pale-yellow, cloudy reaction mixture is poured slowly, with stirring, into 1.25 L of cold water, stirred for an additional 10 min, and refrigerated overnight.
Hexane (75 mL) is added and the resulting mixture is stirred for 0.5 hr to aid in removing excess
benzaldehyde. The product is separated on a
Büchner funnel, washed twice with 100 mL of cold water, and dried under vacuum at room temperature overnight. Recrystallization from
chloroform–ether affords
55 g (
63% yield) of analytically pure material, mp
164–165°C.
4. Crystallization did not occur if traces of
tetrachloroethane were present. The checkers found it necessary to evaporate at

0.05 mm in a warm
water bath for ca. 2 hr to remove residual solvent.
5. Evaporation of the mother liquors and flash-column chromatography (
350 mL of silica gel; column height 28 cm; eluant
70% ethyl acetate–hexanes, fraction size, 30 mL), given additional (
1.87 g) product that was eluted with fractions 25–36; total yield
15.69 g, (Silica gel, Kieselgel 60; E. Merck AG, Darmstadt, Germany.)
3. Discussion
Halogeno sugar derivatives are versatile intermediates for the preparation of aminodeoxy, deoxy, thio, and related analogs.
3 These transformations are easily achieved in the case of primary halides, which in turn can be prepared by a variety of methods. A number of 6-deoxy and 6-amino-6-deoxy hexoses are components of antibiotics and related natural products.
4,5 Benzylidene acetals of the 1,3-dioxane or 1,3-dioxolane type undergo a ring-opening reaction in the presence of
N-bromosuccinimide to give the corresponding
O-benzoylated bromohydrins.
6 This transformation has been known for a number of years in the carbohydrate series (Hanessian–Hullar reaction),
7 and has been used extensively in synthetic work. In the case of 4,6-
O-benzylidene acetals, the products are the 6-bromo-6-deoxy-4-benzoates. Internal acetals of the 1,3-dioxolane type often undergo ring opening to give the two possible regioisomeric bromo benzoates. The reaction is compatible with a variety of functional and protecting groups (ester, ether, amide, halide, epoxide, etc.). It is also applicable to substrates containing free hydroxyl groups such as the example given above. A unique feature, which arises as a consequence of the nature of the ring opening, is seen in the case of
methyl 4,6-O-benzylidene-α-D-galactopyranoside and its derivatives. In this series the benzoate group is found at the C-4 position which has an axial orientation. Hence one achieves halogenation at the primary position as well as an indirect benzoylation of an axial hydroxyl group in the parent sugar. Other applications have been found in amino sugars and nucleosides. Table I illustrates a selection of such ring-opening reactions. The reaction has also been applied with disaccharide acetals.
6,8
TABLE I
REACTION OF O-BENZYLIDENE ACETALS WITH N-BROMOSUCCINIMIDE
|
Starting Acetal |
Product(s) |
Reference |
|
|
|
5 |
|
|
5 |
|
|
5 |
|
|
5 |
|
|
5 |
|
|
5 |
|
|
9 |
|
|
10 |
|
|
11 |
|
|
5 |
|
|
12 |
|
Acknowledgments
The authors thanks Mrs. Ani Glamyan for valuable technical assistance.
13
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved