Org. Synth. 2000, 77, 91
DOI: 10.15227/orgsyn.077.0091
O4,O5-ISOPROPYLIDENE-1,2:3,6-DIANHYDRO-D-GLUCITOL FROM ISOSORBIDE
Submitted by S. Ejjiyar
1
, C. Saluzzo
2
, and R. Amouroux
2
.
Checked by Yuji Koga, Katsuya Uchiyama, and Koichi Narasaka.
1. Procedure
O4,O5-Isopropylidene-3,6-anhydro-1-deoxy-1-iodo-D-glucitol
(1)
. A
1-L, two-necked, round-bottomed flask equipped with a reflux condenser connected to a mineral oil bubbler, a 100-mL, pressure-equalizing, dropping funnel capped with a rubber septum through which is inserted a
nitrogen-inlet needle, and a
magnetic stirring bar is charged with
anhydrous sodium iodide (30.0 g, 0.200 mol)
(Note 1),
isosorbide (14.6 g, 0.100 mol)
(Note 2),
dry acetone (15 mL, 0.200 mol)
(Note 3), and
dry acetonitrile (350 mL)
(Note 3). To this stirred mixture is added dropwise, at room temperature, through the dropping funnel, freshly
distilled chlorotrimethylsilane (25.5 mL, 0.200 mol)
(Note 4). After the addition is complete, the dropping funnel is rinsed with
10 mL of dry acetonitrile
. The reaction mixture is stirred for 12 hr, with protection from light, at room temperature. To the resulting orange-brown mixture,
ether (200 mL) and
aqueous saturated sodium carbonate (60 mL) are added, and then the whole mixture is transferred to a
1-L separatory funnel and 100 mL of water is added. The aqueous phase is separated and extracted with two
100-mL portions of ether
. The combined organic layers are washed successively with
40 mL of an aqueous saturated sodium thiosulfate
solution,
50 mL of an aqueous saturated sodium chloride
solution, dried over
anhydrous sodium sulfate
, and filtered. The solvent is removed with a
rotary evaporator at 35°C. The resulting pale yellow oil solidifies on standing to afford
31.0 g (
99%) of crude product
1
as a pale yellow solid
(Note 5), which was used in the next step without further purification.
O4,O5-Isopropylidene-1,2:3,6-dianhydro-D-glucitol
(2)
. An
oven-dried, 500-mL, two-necked, round-bottomed flask is equipped with a magnetic stirring bar, a 250-mL, pressure-equalizing, dropping funnel, and a rubber septum with a needle connected to a dry nitrogen source. The nitrogen-flushed apparatus is charged with
100 mL of dry tetrahydrofuran
(Note 6) and
2.8 g (0.117 mol) of sodium hydride
(Note 7). The stirred suspension is cooled in an
ice-water bath and a solution of
31 g (0.099 mol) of the crude iodo alcohol
1
in
150 mL of dry tetrahydrofuran
is added dropwise through the dropping funnel during 1 hr. After the addition is complete, the dropping funnel is rinsed with
10 mL of tetrahydrofuran
. After the mixture is stirred for 5 hr at room temperature, it is concentrated to a volume of about 100 mL under reduced pressure; then
150 mL of diethyl ether
is added. The solution is recooled to 0°C and carefully quenched with
30 mL of an aqueous saturated solution of ammonium chloride
. The whole mixture is poured into a
500-mL separatory funnel. After separation of the aqueous layer, the organic layer is washed twice with
20 mL of an aqueous saturated solution of sodium chloride
. The combined aqueous layers, after addition of 50 mL of water, are extracted with two
50-mL portions of dichloromethane
. The combined organic layers are dried over
sodium sulfate
, filtered and concentrated under reduced pressure to afford
16.6 g of a light beige solid. Recrystallization from
hexane (180 mL) gives
13.3 g of pure epoxide
2
as white needles (mp
77°C)
(Note 8). The overall yield from
isosorbide is
72%.
2. Notes
1.
Sodium iodide was obtained from Acros Organics, a Fisher Scientific Company
, and dried in a "drying pistol" under vacuum at 113°C in the presence of
phosphorus pentoxide (P2O5).
2.
Isosorbide (dianhydro-D-glucitol) was purchased from Fluka Chemical Corporation
and was used without further purification. The checkers purchased
isosorbide from Tokyo Chemical Industry Corporation
.
3.
Acetone (Purex analytical grade) and acetonitrile (HPLC grade) were purchased from SDS Company
and used as received. The checkers purchased
anhydrous acetone and acetonitrile from Kokusan Chemical Works
and used them as received.
4.
Chlorotrimethylsilane was obtained from Aldrich Chemical Company, Inc.
, and distilled from
magnesium prior to use.
5.
Physical properties and spectral data for
1
purified by recrystallization from
petroleum ether
(bp
40-60°C) are as follows: mp
72°C;
[α]
D
22 −66.6 (CH
2Cl
2,
c 1.0); IR (CH
2Cl
2) cm
−1: 3600, 3500, 2940, 2860, 1430, 1380, 1280, 1220, 1170, 1100, 1070, 1040, 980, 930, 900, 860, 840
;
1H NMR (CDCl
3, 200 MHz) δ: 1.32 (s, 3 H), 1.48 (s, 3 H), 3.02 (d, 1 H, J = 4.9, OH), 3.4-3.6 (m, 4 H), 3.95 (dddd, 1 H, J = 5.2, 5.2, 5.2, 4.9), 4.17 (d, 1 H, J = 10.8), 4.72 (dd, 1 H, J = 6.2, 3.6), 4.82 (dd, 1 H, J = 6.2, 3.6)
;
13C NMR (CDCl
3, 50 MHz) δ: 9.4, 24.5, 25.9, 69.1, 72.5, 80.0, 81.2, 84.7, 112.4
; MS (EI) m/e (rel. intensity): 299 (M −15, 17), 187 (M −127, 3), 171 (15), 144 (30), 127 (3), 86 (26), 69 (59), 59 (51), 57 (51), 55 (23), 44 (24), 43 (100)
. Anal. Calcd for C
9H
15IO
4: C, 34.41; H, 4.81; I, 40.40. Found: C, 34.55; H, 4.80; I, 40.27.
6.
Tetrahydrofuran was predried over
potassium hydroxide
, then dried by distillation from
sodium/benzophenone ketyl
under
nitrogen. The checkers purchased anhydrous
tetrahydrofuran from Kanto Chemical Corporation
and used it as received.
7.
Sodium hydride was purchased from Aldrich Chemical Company, Inc.
, and used as received.
8.
Physical properties and spectral data for
2
are as follows: white solid (mp:
77°C);
[α]
D
26 −80.5 (CH
3OH,
c 0.502); IR (CH
2Cl
2) cm
−1: 3050, 2960, 2900, 2840, 1600, 1430, 1350, 1200, 1150, 1080, 1060, 1040, 1010, 970, 910, 880, 850
;
1H NMR (CDCl
3, 200 MHz) δ: 1.34 (s, 3 H), 1.53 (s, 3 H), 2.66 (dd, 1 H, J = 4.8, 2.7), 2.91 (dd, 1 H, J = 4.8, 4.4), 3.03 (dd, 1 H, J = 6.9, 3.7), 3.29 (ddd, 1 H, J = 6.9, 4.4, 2.7), 3.52 (dd, 1 H, J = 10.8, 3.6), 4.10 (d, 1 H, J = 10.8), 4.70 (dd, 1 H, J = 6.1, 3.7), 4.80 (dd, 1 H, J = 6.1, 3.6)
;
13C NMR (CDCl
3, 50 MHz) δ: 24.8, 26.0, 43.8, 50.0, 73.2, 81.2, 81.4, 84.6, 112.7
; MS (EI) m/e (rel. intensity): 186 (M
+., 0), 171 (M-15, 89), 149 (5), 111 (33), 69 (55), 68 (12), 59 (29), 57 (44), 55 (48), 43 (100), 41 (52), 39 (22), 29 (34)
. Anal. Calcd for C
9H
14O
4: C, 58.05; H, 7.58. Found: C, 57.83; H, 7.36.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
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3. Discussion
Isosorbide and isomannide are important by-products of the starch industry, arising from dehydration of
D-sorbitol
and
D-mannitol
. These commercial starting materials provide an easy and inexpensive access to optically pure functionalized tetrahydrofurans like O4,O5-isopropylidene-1-iodo-3,6-anhydro-1-deoxy-D-glucitol and O4,O5-isopropylidene-1-iodo-3,6-anhydro-1-deoxy-D-mannitol. This procedure describes a preparation of the former compound and the epoxide derived therefrom.
Ring opening of tetrahydrofuranic alcohols
3,4 was previously described using
iodotrimethylsilane
in
acetone, leading to iodo diols protected as their acetonide derivatives
5. When
isosorbide is treated with two equivalents of
iodotrimethylsilane (TMSCl/NaI) in
acetonitrile, in the presence of two equivalents of
acetone, only one of the two rings was cleaved. Although two different products may be expected from the scission of one of the two heterocycles of
isosorbide, the reaction turned out to be regioselective. In fact the reaction is controlled by the acetonide formation, which requires that the two oxygen atoms be in a cis relationship. A plausible mechanism for the ring opening of
isosorbide is illustrated below.
Basic treatment (NaH, THF) of the iodo alcohol from isosorbide gives the corresponding epoxide. This epoxide presents two advantages: first, it is more stable than the iodo alcohol on storage, and secondly, it offers a great potential for transformations.
Similar chemistry has been used to convert isomannide
3 into iodoalcohol
4 and epoxide
5.
3
To the submitters' knowledge,
O4,O5-isopropylidene-1-iodo-3,6-anhydro-1-deoxy-D-glucitol and
O4,O5-isopropylidene-1,2:3,6-dianhydro-D-glucitol have not been prepared before. However, the corresponding isomannide derivatives have been obtained in five steps from
mannitol in low overall yield by Foster and Overend in 1951.
6,7 The present method is a simple, rapid and inexpensive route to multigram amounts of these tetrahydrofuran derivatives in reasonable yields.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Isosorbide:
Glucitol, 1,4:3,6-dianhydro- (8);
D-Glucitol, 1,4:3,6-dianhydro-, (9); (652-67-5)
Sodium iodide (8,9); (7681-82-5)
Acetonitrile: (8,9); (75-05-8)
Chlorotrimethylsilane:
Silane, chlorotrimethyl- (8,9); (75-77-4)
Sodium thiosulfate:
Thiosulfuric acid, disodium salt (8,9); (7772-98-7)
Sodium hydride (8,9); (7646-69-7)
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