Synthesis of New Diols Derived from Dianhydrohexitols Ethers under Microwave-Assisted Phase Transfer Catalysis

Article abstract of DOI:10.1016/S0040-4020(00)00539-1

Alkylation of mono-benzylated isosorbide and isomannide was performed under microwave assisted phase transfer catalysis (PTC). A small amount of solvent was necessary to provide good yields (90-96%) within 15 min. In order to minimize the competitive elimination, halide leaving group was changed to tosylate as competitive S(N)2-E2 processes were involved. After removal of benzyl moiety by hydrogenation, a series of new diols from dianhydrohexitols were thus prepared. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00539-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 5877±5883
Synthesis of New Diols Derived from Dianhydrohexitols Ethers
under Microwave-Assisted Phase Transfer Catalysis
*
Â
Saber Chatti, Michel Bortolussi and Andre Loupy
  à Â
Laboratoire des Reactions Selectives sur Supports, ICMO, UMR 8615, Bat. 410, Universite Paris-Sud, 91405 Orsay Cedex, France
Received 26 April 2000; accepted 9 June 2000
AbstractÐAlkylation of mono-benzylated isosorbide and isomannide was performed under microwave assisted phase transfer catalysis
(PTC). A small amount of solvent was necessary to provide good yields (90±96%) within 15 min. In order to minimize the competitive
elimination, halide leaving group was changed to tosylate as competitive SN2±E2 processes were involved. After removal of benzyl moiety
by hydrogenation, a series of new diols from dianhydrohexitols were thus prepared. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
order to be used further as starting monomers in polymer-
ization reactions and able to lead to non-symmetrical
compounds. The goal of these new molecules could be the
access to some biodegradable chiral macromolecules with
complexing properties.
Biomass constitutes a renewable source of natural products
used as unfailing starting materials for access to less
polluting new compounds able to substitute petroleum
derivatives. Among the important by-products of biomass
are the dianhydrohexitols obtained from sugar industry by
double dehydration of starch. These chiral compounds exist
as two main isomers according to the relative con®gurations
of their two hydroxyl functions1,2 (isosorbide A, isomannide
B, respectively, derived from d-glucose and d-mannose).
They could be prepared from isosorbide A or isomannide B
in a three-step procedure involving: (i) monobenzylation of
one of the hydroxyl functions, (ii) alkylation with a
difunctionalized alkylating agent, (iii) subsequent removal
of benzyl moiety by hydrogenation (see Scheme 1).
Selective mono-benzylations of A and B have been realized
according to a previous work.10 The so-obtained compounds
were submitted to alkylation with a,v-dihalides or dito-
sylates. As reported in a rather similar case, these reactions
were performed under microwave (MW)-assisted phase
transfer catalysis (PTC) using tetra-n-butylammonium
bromide (TBAB) as a phase transfer agent.11 To check the
possibility of intervention of speci®c MW effects (non-
purely thermal), the results obtained were compared with
conventional heating using a thermostated oil bath at the
same temperature and for similar reaction times. To this
purpose, a monomode microwave reactor (Synthewave
402 from Prolabo) was used, allowing an accurate control
of both temperature and emitted power, taking advantage
of a homogeneous electromagnetic ®eld (focused micro-
waves).
In spite of the interest of their structures and attractive
properties, very few publications concern their use in
macromolecular chemistry,3±9 possibly due to their weak
reactivity and selectivity problems resulting from the two
different hydroxyl functions. They consist essentially in
symmetrical polymers resulting from their reactions with
dihalides, diamino dihydrochlorides, dicarboxylic acid
dichlorides and diisocyanates.
Results and Discussion
As a model reaction, conditions were optimized with mono-
benzylated isosorbide and 1,8-dibromooctane (Table 1)
according to our previous paper11 dealing with the synthesis
of diethers from dianhydrohexitols. Besides the expected
ethers 1b, some amounts of alkene 3a were obtained
resulting from a dehydrobromination on the common inter-
mediate involved in SN2±E2 competitive processes (see
Scheme 2).
We describe thus herein the synthesis of new diols from
dianhydrohexitol moieties separated by ethers functions in
Keywords: dianhydrohexitols; microwaves; phase transfer catalysis (PTC);
O-alkylation.
* Corresponding author. Tel.: 133-1-69-15-7650; fax: 133-1-69-15-
4679; e-mail: aloupy@icmo.u-psud.fr
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00539-1

5878
S. Chatti et al. / Tetrahedron 56 (2000) 5877±5883
Scheme 1.
Scheme 2.
The most convenient conditions (yields ,70%) involve
the use of only 2% of catalyst in p-xylene for 5 min at
1408C or in toluene for 15 min at 1108C. Signi®cant
amounts (28±32%) of elimination by-products were
obtained. These conditions were then extended to various
aliphatic dibromides for both 1a and 1b with a change in
molar ratio of reactants using a slight de®cit of dibromide
(Table 2).
With the aim to enlarge the scope of the study, we have
examined the reaction with dialkyl chloride (in spite of
their lower reactivity), generally cheaper and easily
Table 1. Reaction of 1a (2 mmol) with 1,8-dibromooctane under MW in the presence of KOH and TBAB (relative amounts 1a:base:X±R±Xˆ2:3:1.5)
TBAB (%)
Solvent (0.25 mL)
Time (min)
Temperature (8C)
Yieldsa (%)
1a
2a
3a
1
1
2
5
p-Xylene
p-Xylene
p-Xylene
p-Xylene
5
30
5
140
140
140
140
30
10
0
47
23
20
28
28
70 (67)
72 (68)
70 (65)
5
2
2
2
Toluene
Toluene
5
15
110
110
5
0
66 (62)
68 (66)
28
32
a Yields were determined by 1H NMR and given in brackets for isolated products.

S. Chatti et al. / Tetrahedron 56 (2000) 5877±5883
5879
Table 2. Reaction of 1a or 1b (2 mmol) with Br±(CH2)n±Br under MW in
the presence of KOH and TBAB in toluene (0.25 mL) (relative amounts
1a:base:dibromide:TBABˆ2.5:2.5:1:0.02)
commercially available when compared to their bromide
equivalents. To enhance the possible complexing properties
of the target-molecule, dichlorides from di- and tri-ethylene
glycol were also used as alkylating agents (Table 3).
n
Time (min)
Yieldsa (%)
1a
2a
3a
1b
2b
3b
Cl±ꢀCH2CH2O†m±CH2CH2±Cl
m ˆ 1; 2
8
8
8
8
6
4
15
30
19
4
33
15
11
25
63
75
55
62
68
60
18
21
12
13
21
15
14
6
30
11
24
17
66
70
52
73
56
65
20
24
18
16
20
18
In order to improve the yields, reactions were performed in
the presence of NaBr. It is here expected to favor halogen
exchange from chloride to the more reactive bromide and to
regenerate TBAB by ion-pair exchange12 (Eqs. (1) and (2)).
15b
30b
15
15
a Yields were determined by 1H NMR.
R±Cl 1 n-Bu4N1; Br2 ! R±Br 1 n-Bu4N1; Cl2
ꢀ1†
b Reaction performed in re¯uxing cyclohexane (Tˆ808C).
n-Bu4N1; Cl2 1 Na1; Br2 O n-Bu4N1; Br2 1 Na1; Cl2
ꢀ2†
Table 3. Reaction of 1a or 1b (2 mmol) with Cl±R±Cl under MW in the
presence of KOH, NaBr and TBAB in toluene (0.25 mL) for 15 min (rela-
tive amounts 1a:base:dichloride:TBABˆ2.5:2.5:1:0.02)
In re¯uxing toluene or cyclohexane for 15 min, good yields
(60±74%) were obtained when the reaction was performed
with 20% mol TBAB in the presence of an excess of NaBr.11
When reactions were performed under classical heating
(thermostated oil bath at 110 or 808C) for 15 min, similar
yields were obtained (compared to microwave), revealing
thus the absence of any speci®c (non-purely thermal) effects
of the radiation under these conditions.
R
NaBr TBAB (%) Yieldsa (%)
1a 2a 3a 1b 2b 3b
(CH2)8
(CH2)8
(CH2)8
(CH2)8
(CH2)8
(CH2)8
CH2CH2OCH2CH2
CH2CH2OCH2CH2
(CH2CH2O)2CH2CH2
2
1
1
2
1
1
1
1
1
20
20
2
55 29 16 49 32 19
74 20 69 23
37 47 16 39 42 19
6
8
2b
71 27
64 35
2
1
69 28
64 33
3
3
2b
20b
20
2b
30 56 14 28 55 17
12 70 18 13 71 16
Finally, in order to minimize the competitive elimination
reaction leading to 3a and 3b, halide leaving group was
changed to tosylate as more prone to avoid elimination
and to favor nucleophilic substitution when a competition
between SN2 and E2 processes is involved13 (Scheme 3;
Table 4).
52 48
20 60 20 20 63 17
0
56 44
0
20
a Yields were determined by 1H NMR.
b Reaction performed in re¯uxing cyclohexane (Tˆ808C).
Scheme 3.
Yields were now considerably improved (up to 90±95%)
due to disappearance of elimination products and leading
also to a much more easy puri®cation of 2a and 2b.
Table 4. Reaction of 1a or 1b (2 mmol) with TsO±R±OTs under MW in
the presence of KOH and TBAB for 15 min (solventˆ0.25 mL) (relative
amounts 1:base:ditosylate:TBABˆ2.5:2.5:1:0.02)
R
Tˆ1108C (toluene)
Yieldsa,b MW (D)c
Tˆ808C
Due to high temperature level (1108C), the microwave
speci®c effect was not appreciable in toluene and results
remain identical with classical heating. When the tempera-
ture was lowered to 808C changing toluene for cyclohexane
(both non-polar solvents, i.e. transparent to microwave
exposure), an important speci®c microwave effect appeared.
In this case, good yields could be obtained only under
microwave. The speci®c microwave effect was demon-
strated when one considers the pro®les of raising in
temperature either under MW or D which were quasi-super-
posable whereas yields were clearly different (Fig. 1). Such
a speci®c MW increasing effect as the temperature is
decreased was described recently in the range 200±228C
(cyclohexane)
Yieldsa,b MW (D)c
2a
2b
2a
2b
(CH2)8
(CH2)6
(CH2)4
CH2CH2OCH2CH2
(CH2CH2O)2CH2CH2
95 (91)
95 (90)
91 (90)
92 (92)
90 (91)
84 (76)
84 (84)
92 (70)
90 (85)
91 (85)
96 (39)
96 (40)
96 (45)
91 (36)
90 (46)
95 (45)
92 (42)
91 (50)
89 (48)
92 (54)
a Yields for isolated products.
b Complement are monotosylates 4a or 4b.
c Results obtained by conventional heating (D) under the same conditions
are given in brackets.

5880
S. Chatti et al. / Tetrahedron 56 (2000) 5877±5883
Figure 1. Pro®les of raising in temperature and in emitted power for the reaction of monobenzylated isosorbide 1a and ditosylate (nˆ8) (®rst line in Table 4).
(rate enhancements from 1.05±21.6) during the transforma-
tion of 2- and 4-tert-butylphenols catalyzed by clays in
liquid phase.14
by modulation of emitted power. Mechanical stirring all
along the irradiation provided a good homogeneity (power
and temperature) and a data treatment, which was followed
by a computer. All reactions were performed in cylindrical
Pyrex open vessels. There is no need to use an upright
condenser as only small amounts of solvent are involved
and as the vessels walls remain at ambient temperature.
Continuous MW emission at power levels of 15±45 W
(5±15% of the optimal value) was suf®cient to keep
constant the reactions at 808C in cyclohexane and at
1108C in toluene.
In order to compare microwave irradiation with conven-
tional heating, the reactions were performed under similar
experimental conditions (weight of reactants, time and
temperature). When using a thermostated oil bath, the
temperature was measured inserted with a Quick digital
thermometer into the reaction mixture and the rate of the
temperature rise was adjusted to be similar to that measured
under microwave irradiation.
Finally, catalytic hydrogenation of benzylated ethers 2a and
2b in ethanol or ethyl acetate with 10% palladium charcoal
led, respectively, to ether diols 5a and 5b in excellent yields
(90±96% for isolated products).
Conclusion
Flash column chromatography was performed using 35±
70 mm silica gel (60) purchased from S.D.S. company. H
As a conclusion, various chiral alcohols linked by ether
bridges derived from isosorbide and isomannide were
synthesized under economic, easy-perform and mild condi-
tions. The use of a small amount of non-polar solvent
allowed the accurate control of temperature and could
lead to speci®c (non-purely thermal) effects of microwave.
1
and 13C NMR spectra were recorded at 200 and 51.32 MHz
and at 250 and 62.91 MHz (Bruker WP 200, WP 250,
respectively). Chemical shifts are given in ppm down®eld
from internal standard tetramethylsilane (dˆ0.00 ppm).
Melting points were measured on a Reichert apparatus
and are uncorrected. Optical rotation were determined
with a Perkin±Elmer 241 polarimeter.
Experimental
Reactants and equipment
General procedure for synthesis of the ditosylates
The different starting materials involved are purchased from
Aldrich or Acros, and were used without any puri®cation.
 Â
Only isosorbide and isomannide [gift from Societe
Á
Roquette-Freres (Lestrem, France)] were previously crystal-
lized from acetone.
The diols (100 mmol) were dissolved in dry pyridine
(200 mL) and cooled down to 08C. A slight excess of
p-toluenesulfonyl chloride (49.45 g, 230 mmol) was added
over a period of 30 min and the reaction mixture stirred at
08C for additional 3 h. It was poured into ice/H2O (1 L) and
3 M HCl (50 mL) to give a white solid, which was
recrystallized from absolute ethanol to give the ditosylates
in 80±90% yields. All spectroscopic analysis (1H and 13C
NMR) were in agreement with literature measurements.15±18
1,4-Bis-(toluene-4-sulfonyloxy)-butane (nˆ4): mp 708C
(lit.18 mp 67.5±69.58C); 1,6-bis-(toluene-4-sulfonyloxy)-
hexane (nˆ6): mp 718C (lit.17 mp 71±728C); 1,8-bis-
(toluene-4-sulfonyloxy)-octane (nˆ8): mp 738C (lit.16 mp
72.8±73.38C); bis-[2-(toluene-4-sulfonyloxy)-ethyl]ether
The microwave reactor was a monomode system (Synthe-
 Â
wave 402 from Societe Prolabo) with focused waves
operating at 2.45 GHz. The temperature was controlled all
along the reaction and evaluated by an infrared detector,
which indicated the surface temperature (the IR lecture
was calibrated by tuning the emissivity factor using a
thermocouple introduced into the reaction mixture).
Temperature was maintained constant at a choose value

S. Chatti et al. / Tetrahedron 56 (2000) 5877±5883
5881
(mˆ1): mp 788C (lit.15 mp 78.5±79.38C); 1,2-bis-[2-
(toluene-4-sulfonyloxy)-4-ethoxy]ethane (mˆ2): mp 818C
(lit.18 mp 81±828C).
69.77 (CH2, C-121C-13), 70.56 (C-1), 71.35 (C-6), 73.25
(C-7), 80.16 (C-4), 80.59 (C-5), 83.70 (C-2), 86.24 (C-3),
127.58 (C-11), 127.71 (C-10), 128.35 (C-9), 137.52 (C-8).
Anal. Calcd for C30H38O9: C, 66.42; H, 7.01; O, 26.56.
Found: C, 66.31; H, 7.00; O, 26.69.
General procedure for the synthesis of 2a and 2b
2a (mˆ2), isolated as a syrup; Rf 0.15 (pentane/EtOAc 1/1);
1H NMR (200 MHz, CDCl3): d 3.87 (m, 12H, 2 CH2, H-1a,
H-1b, H-6a, H-6b, H-11), 4.02 (m, 12H, 4 CH2, H-2, H-5,
H-9, H-10), 4.55 (m, 6H, H-3, H-7), 4.78 (dd, 2H,
J3,4ˆJ4,5ˆ5 Hz, H-3), 7.31 (m, 10H, H-8); 13C NMR
(50.32 MHz, CDCl3): d 69.84 (CH2, C-141C-13), 70.49
(CH2, C-12), 70.51 (C-1), 71.39 (C-6), 73.29 (C-7), 80.23
(C-4), 80.76 (C-5), 83.76 (C-2), 86.26 (C-3), 127.62 (C-11),
127.75 (C-10), 128.40 (C-9), 137.58 (C-8). Anal. Calcd for
C32H42O10: C, 65.52; H, 7.16; O, 27.32. Found: C, 65.41; H,
7.12; O, 27.47.
Synthesis of 2a and 2b were performed under microwave
irradiation or conventional heating. In a Pyrex cylindrical
open reactor adapted to the Synthewave reactor, 2 mmol
(0.5 g) of 1a or 1b were mixed with 1.6 mmol of alkyl
halide (or tosylate), 0.004 mmol (0.014 g) of TBAB,
2 mmol of powdered KOH (0.140 g) [containing about
15% of water] and 0.25 mL of solvent. The mixture was
then homogenized and submitted to microwave irradiation
under mechanical stirring. It was cooled down to room
temperature and diluted with 50 mL of methylene chloride.
The solution was ®ltered (KOH in excess, mineral salts).
The organic layer was concentrated under vacuum. Pure
products (2a and 2b) were isolated by liquid chromato-
graphy on silica gel with the adequate solvent system.
2b (nˆ8), isolated as a syrup; Rf 0.69 (pentane/EtOAc 1/1);
1H NMR (200 MHz, CDCl3): d 1.3 (m, 4 CH2, C-11 to
C-12), 1.6 (m, 2 CH2, C-10), 3.45 (m, 2H, H-6b), 3.70 (m,
6H, H-1a, H-1b, H-6a), 4.00 (m, 8H, H-2, H-5, H-9), 4.50
(m, 6H, H-3, H-7), 4.75 (d, 2H, J4,5ˆ9.6 Hz, H-4), 7.30 (m,
10H, H-8). 13C NMR (50.32 MHz, CDCl3): d 25.83 (CH2,
C-15), 29.69 (CH2, C-14), 30.90 (CH2, C-13), 70.99 (CH2,
C-12), 71.06 (C-1, C-6), 72.38 (C-7), 79.31 (C-5, C-2),
80.37 (C-4), 80.48 (C-3), 127.85 (C-11, C-10), 128.85
(C-9), 137.69 (C-8). Anal. Calcd for C34H46O8: C, 70.10;
H, 7.90; O, 22.00. Found: C, 70.60; H, 8.10; O, 22.80.
2a (nˆ8), isolated as a syrup; Rf 0.66 (pentane/EtOAc 1/1);
1H NMR (200 MHz, CDCl3): d 1.3 (m, 4 CH2, C-11 to
C-12), 1.6 (m, 2 CH2, C-10), 3.49 (m, 2H, H-6b), 3.61 (m,
4H, H-1b, H-6a), 3.96 (m, 10H, H-1a, H-2, H-5, H-9), 4.55
(m, 6H, H-3, H-7), 4.65 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz, H-4), 7.30
(m, 10H, H-8); 13C NMR (50.32 MHz, CDCl3): d 25.85
(CH2, C-15), 29.27 (CH2, C-14), 29.69 (CH2, C-13), 69.96
(CH2, C-12), 70.87 (C-1), 71.44 (C-6), 73.33 (C-7), 80.17
(C-4), 80.27 (C-5), 83.78 (C-2), 86.29 (C-3), 127.76 (C-11),
127.78 (C-10), 128.42 (C-9), 137.56 (C-8). Anal. Calcd for
C34H46O8: C, 70.10; H, 7.90; O, 22.00. Found: C, 69.53; H,
7.80; O, 22.63.
2b (nˆ6), isolated as a syrup; Rf 0.61 (pentane/EtOAc 1/1);
1H NMR (200 MHz, CDCl3): d 1.3 (m, 2 CH2, C-11), 1.6
(m, 2 CH2, C-10), 3.43 (m, 2H, H-6b), 3.71 (m, 6H, H-1a,
H-1b, H-6a), 4.03 (m, 8H, H-2, H-5, H-9), 4.54 (m, 6H, H-3,
H-7), 4.71 (d, 2H, J4,5ˆ9.6 Hz, H-4), 7.35 (m, 10H, H-8);
13C NMR (50.32 MHz, CDCl3): d 25.62 (CH2, C-14), 29.54
(CH2, C-13), 70.66 (CH2, C-12), 70.89 (C-1), 70.95 (C-6),
72.25 (C-7), 79.19 (C-5, C-2), 80.25 (C-4), 80.34 (C-3),
127.74 (C-11, C-10), 128.28 (C-9), 137.60 (C-8). Anal.
Calcd for C32H42O8: C, 69.31; H, 7.58; O, 23.10. Found:
C, 69.20; H, 7.53; O, 23.25.
2a (nˆ6), isolated as a syrup; Rf 0.56 (pentane/EtOAc 1/1);
1H NMR (200 MHz, CDCl3): d 1.3 (m, 2 CH2, C-11), 1.6
(m, 2 CH2, C-10), 3.49 (m, 2H, H-6b), 3.61 (m, 4H, H-1b,
H-6a), 3.98 (m, 10H, H-1a, H-2, H-5, H-9), 4.56 (m, 6H,
H-3, H-7), 4.65 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz, H-4), 7.32 (m,
10H, H-8); 13C NMR (50.32 MHz, CDCl3): d 25.65 (CH2,
C-14), 29.56 (CH2, C-13), 69.60 (CH2, C-12), 70.64 (C-1),
71.32 (C-6), 73.33 (C-7), 80.08 (C-4), 80.17 (C-5) 83.68
(C-2), 86.20 (C-3), 127.55 (C-11), 127.68 (C-10), 128.32
(C-9), 137.48 (C-8). Anal. Calcd for C32H42O8: C, 69.31; H,
7.58; O, 23.10. Found: C, 69.21; H, 7.64; O, 23.14.
2b (nˆ4), isolated as a syrup; Rf 0.36 (pentane/EtOAc 1/1);
1H NMR (250 MHz, CDCl3): d 1.6 (m, 2 CH2, C-10), 3.48
(m, 2H, H-6b), 3.70 (m, 4H, H-1a, H-1b, H-6a), 4.00 (m,
8H, H-2, H-5, H-9), 4.52 (m, 6H, H-3, H-7), 4.75 (d, 2H,
J4,5ˆ9.6 Hz, H-4), 7.34 (m, 10H, H-8); 13C NMR
(62.9 MHz, CDCl3): d 26.14 (CH2, C-13), 70.24 (CH2,
C-12), 70.89 (C-1, C-6), 72.20 (C-7), 79.14 (C-21C-5),
80.23 (C-3, C-4), 127.68 (C-11, C-10), 128.23 (C-9),
137.57 (C-8). Anal. Calcd for C30H38O8: C, 68.44; H,
7.22; O, 24.33. Found: C, 68.18; H, 7.20; O, 24.62.
2a (nˆ4), isolated as a syrup; Rf 0.52 (pentane/EtOAc 1/1);
1H NMR (250 MHz, CDCl3): d 1.6 (m, 2 CH2, C-10), 3.27
(m, 2H, H-6b), 3.45 (m, 4H, H-1b, H-6a), 3.99 (m, 10H,
H-1a, H-2, H-5, H-9), 4.37 (m, 6H, H-3, H-7), 4.45 (dd, 2H,
J3,4ˆJ4,5ˆ5 Hz, H-4), 7.13 (m, 10H, H-8); 13C NMR
(62.9 MHz, CDCl3): d 23.29 (CH2, C-13), 69.77 (CH2,
C-12), 70.35 (C-1), 71.42 (C-6), 73.32 (C-7), 80.24
(C-41C-5), 83.78 (C-2), 86.31 (C-3), 127.63 (C-11),
127.76 (C-10), 128.41 (C-9), 137.59 (C-8). Anal. Calcd
for C30H38O8: C, 68.44; H, 7.22; O, 24.33. Found: C,
68.36; H, 7.15; O, 24.49.
2b (mˆ1), isolated as a syrup; Rf 0.10 (pentane/EtOAc 3/8);
1H NMR (200 MHz, CDCl3): d 3.75 (m, 12H, 2 CH2, H-1a,
H-1b, H-6a, H-6b, H-10), 4.01 (m, 12H, 4 CH2, H-2, H-5,
H-9,), 4.52 (m, 6H, H-3, H-7), 4.70 (d, 2H, J4,5ˆ9.6 Hz,
H-4), 7.34 (m, 10H, H-8); 13C NMR (50.32 MHz, CDCl3):
d 69.87 (CH2, C-13), 70.65 (CH2 C-12), 71.04 (C-1, C-6),
72.36 (C-7), 79.27 (C-2, C-5) 80.40 (C-4), 80.86 (C-3),
127.82 (C-11, C-10), 128.37 (C-9), 137.70 (C-8). Anal.
Calcd for C30H38O9: C, 66.42; H, 7.01; O, 26.56. Found:
C, 65.51; H, 7.00; O, 27.49.
2a (mˆ1), isolated as a syrup; Rf 0.11 (pentane/EtOAc 1/1);
1H NMR (200 MHz, CDCl3): d 3.87 (m, 12H, 2 CH2, H-1a,
H-1b, H-6a, H-6b, H-10), 4.06 (m, 12H, 4 CH2, H-2, H-5,
H-9,), 4.56 (m, 6H, H-3, H-7), 4.77 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz,
H-4), 7.34 (m, 10H, H-8); 13C NMR (50.32 MHz, CDCl3): d

5882
S. Chatti et al. / Tetrahedron 56 (2000) 5877±5883
2b (mˆ2), isolated as a syrup; Rf 0.11 (pentane/EtOAc 3/8);
1H NMR (200 MHz, CDCl3): d 3.70 (m, 16H, 4 CH2, H-1a,
H-1b, H-6a, H-6b, H-10, H-11), 4.00 (m, 8H, 2 CH2, H-2,
H-5, H-9,), 4.51 (m, 6H, H-3, H-7), 4.69 (d, 2H,
J4,5ˆ9.6 Hz, H-4), 7.33 (m, 10H, H-8); 13C NMR
(50.32 MHz, CDCl3): d 69.80 (CH2, C-141C-13), 70.41
(CH2, C-12), 71.10 (C-1, C-6), 72.32 (C-7), 79.35 (C-2,
C-5) 80.49 (C-4), 80.81 (C-3), 127.76 (C-11, C-10),
128.40 (C-9), 137.85 (C-8). Anal. Calcd for C32H42O10:
C, 65.52; H, 7.16; O, 27.32. Found: C, 65.45; H, 7.10; O,
27.45.
70.62 (C-1), 75.74 (C-2), 76.28 (C-6), 80.02 (C-5), 80.66
(C-4), 88.12 (C-3). Anal. Calcd for C16H26O9: C, 53.03; H,
7.18; O, 39.78. Found: C, 52.90; H, 7.12; O, 39.98.
5a (mˆ2) [ethyl acetate]; Rf 0.26 (methanol/EtOAc 2/8); 1H
NMR (200 MHz, CDCl3): d 2.80 (m, 2H, OH), 3.85 (m,
22H, 6 CH2, H-1a, H-1b, H-2, H-6a, H-6b, H-7, H-8,
H-9), 4.25 (m, 2H, H-5), 4.45 (d, 2H, J3,4ˆ5 Hz, H-3),
4.70 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz, H-4); 13C NMR
(50.32 MHz, CDCl3): d 69.90 (CH2, C-9), 70.02 (CH2,
C-8), 70.49 (C-7), 70.69 (C-1), 75.78 (C-2), 76.38 (C-6),
80.06 (C-5), 80.71 (C-4), 88.19 (C-3). Anal. Calcd for
C18H30O10: C, 53.20; H, 7.40; O, 9.40. Found: C, 53.15;
H, 7.35; O, 39.50.
General procedure for the deprotection of 2a and 2b
To a solution of starting material 2a and 2b in absolute
ethanol or ethyl acetate (Cˆ0.2 mol L21) was added
palladium on charcoal (15%) and reaction was stirred
under hydrogen atmosphere. After 3 h, the starting
materials have disappeared. Filtration through celite, wash-
ing with adequate solvent and evaporation to dryness give a
syrup.
5b (nˆ8) [absolute ethanol]; Rf 0.55 (methanol/EtOAc 1/9);
1H NMR (250 MHz, CDCl3): d 1.3 (m, 4 CH2, C-9 to C-10),
1.60 (m, 2 CH2, C-8), 2.95 (m, 2H, OH), 3.47 (m, 2H, H-6b),
3.70 (m, 6H, H-1a, H-1b, H-6a), 4.00 (m, 6H, H-2, H-7),
4.27 (m, 2H, H-5), 4.55 (m, 4H, H-4ˆH-3); 13C NMR
(62.9 MHz, CDCl3): d 25.78 (CH2, C-10), 29.19 (CH2,
C-9), 29.64 (CH2, C-8), 71.02 (CH2, C-7), 71.34 (C-1),
72.15 (C-2), 74.94 (C-6), 80.00 (C-5), 80.58 (C-4), 81.77
(C-3). Anal. Calcd for C20H34O8: C, 59.70; H, 8.45; O,
31.85. Found: C, 59.45; H, 8.40; O, 32.15.
5a (nˆ8) [solvent for hydrogenation: absolute ethanol]; Rf
0.52 (methanol/EtOAc 1/9); 1H NMR (250 MHz, CDCl3): d
1.3 (m, 4 CH2, C-9 to C-10), 1.55 (m, 2 CH2, C-8), 2.8 (m,
2H, OH), 3.50 (m, 6H, H-1b, H-6a, H-6b), 3.97 (m, 8H, 2
CH2, H-1a, H-2, H-7), 4.25 (m, 2H, H-5), 4.45 (d, 2H,
J3,4ˆ5 Hz, H-3), 4.65 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz, H-4); 13C
NMR (62.9 MHz, CDCl3): d 25.77 (CH2, C-10), 29.17
(CH2, C-9), 29.62 (CH2, C-8), 69.94 (CH2, C-7), 70.90
(C-1), 75.77 (C-2), 76.49 (C-6), 80.01 (C-5), 80.23 (C-4),
88.26 (C-3). Anal. Calcd for C20H34O8: C, 59.70; H, 8.45; O,
31.85. Found: C, 59.30; H, 8.40; O, 32.30.
5b (nˆ6) [absolute ethanol]; Rf 0.50 (methanol/EtOAc 1/9);
[a]Dˆ1105 (c 0.05, CHCl3); 1H NMR (250 MHz, CDCl3):
d 1.35 (m, 2 CH2, C-9), 1.60 (m, 2 CH2, C-8), 3.00 (m, 2H,
OH), 3.47 (m, 2H, H-6b), 3.70 (m, 6H, H-1a, H-1b, H-6a),
4.00 (m, 6H, H-2, H-7), 4.27 (m, 2H, H-5), 4.55 (m, 4H,
H-4ˆH-3); 13C NMR (62.9 MHz, CDCl3): d 25.73 (CH2,
C-9), 29.62 (CH2, C-8), 70.94 (CH2, C-7), 71.37 (C-1),
72.16 (C-2), 75.04 (C-6), 80.03 (C-5), 80.62 (C-4), 81.80
(C-3). Anal. Calcd for C18H30O8: C, 57.75; H, 8.02; O,
34.22. Found: C, 57.65; H, 8.00; O, 34.35.
5a (nˆ6) [ethyl acetate]; Rf 0.47 (methanol/EtOAc 1/9);
[a]Dˆ11038 (c 0.02, CHCl3); 1H NMR (250 MHz,
CDCl3): d 1.3 (m, 2 CH2, C-9), 1.60 (m, 2 CH2, C-8), 2.8
(m, 2H, OH), 3.51 (m, 6H, H-1b, H-6a, H-6b), 3.95 (m, 8H,
2 CH2, H-1a, H-2, H-7), 4.25 (m, 2H, H-5), 4.45 (d, 2H,
J3,4ˆ5 Hz, H-3), 4.65 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz, H-4); 13C
NMR (62.9 MHz, CDCl3): d 25.61 (CH2, C-9), 29.49
(CH2, C-8), 69.87, (CH2, C-7), 70.72 (C-1), 75.71 (C-2),
76.41 (C-6), 79.94 (C-5), 80.17 (C-4), 88.17 (C-3). Anal.
Calcd for C18H30O8: C, 57.75; H, 8.02; O, 34.22. Found: C,
57.47; H, 8.06; O, 34.43.
5b (nˆ4) [absolute ethanol]; Rf 0.46 (methanol/EtOAc 1/9);
1H NMR (250 MHz, CDCl3): d 1.65 (m, 2 CH2, C-8), 3.00
(m, 2H, OH), 3.47 (m, 2H, H-6b), 3.70 (m, 6H, H-1a, H-1b,
H-6a), 4.00 (m, 6H, H-2, H-7), 4.27 (m, 2H, H-5), 4.55 (m,
4H, H-4ˆH-3); 13C NMR (62.9 MHz, CDCl3): d 26.26
(CH2, C-8), 70.49 (CH2, C-7), 71.32 (C-1), 72.14 (C-2),
74.87 (C-6), 80.00 (C-5), 80.54 (C-4), 81.77 (C-3). Anal.
Calcd for C16H26O8: C, 55.49; H, 7.51; O, 37.00. Found: C,
54.17; H, 7.57; O, 38.25.
5a (nˆ4) [ethyl acetate]; Rf 0.40 (methanol/EtOAc 1/9); 1H
NMR (250 MHz, CDCl3): d 1.60 (m, 2 CH2, C-8), 2.8 (m,
2H, OH), 3.50 (m, 6H, H-1b, H-6a, H-6b), 4.00 (m, 8H, 2
CH2, H-1a, H-2, H-7), 4.25 (m, 2H, H-5), 4.45 (d, 2H,
J3,4ˆ5 Hz, H-3), 4.65 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz, H-4); 13C
NMR (62.9 MHz, CDCl3): d 26.20 (CH2, C-8), 69.91,
(CH2, C-7), 70.38 (C-1), 75.72 (C-2), 76.43 (C-6), 79.96
(C-5), 80.18 (C-4), 88.19 (C-3). Anal. Calcd for C16H26O8:
C, 55.49; H, 7.51; O, 37.00. Found: C, 55.40; H, 7.42; O,
37.18.
5b (mˆ1) [ethyl acetate]; Rf10.25 (methanol/EtOAc 2/8);
[a]Dˆ185 (c 0.01, CHCl3); H NMR (200 MHz, CDCl3):
d 3.00 (m, 2H, OH), 3.87 (m, 18H,4 CH2, H-1a, H-1b, H-2,
H-6a, H-6b, H-7, H-8), 4.25 (m, 2H, H-5), 4.55 (m, 4H,
H-4ˆH-3); d 69.89 (CH2, C-8) 70.58 (CH2, C-7), 71.39
(C-1), 72.13 (C-2), 74.77 (C-6), 80.38 (C-5), 80.63 (C-4),
81.74 (C-3). Anal. Calcd for C16H26O9: C, 53.03; H, 7.18; O,
39.78. Found: C, 52.95; H, 7.15; O, 39.90.
5b (mˆ2) [ethyl acetate]; Rf 0.30 (methanol/EtOAc 2/8); 1H
NMR (200 MHz, CDCl3): d 3.05 (m, 2H, OH), 3.85 (m,
22H, 6CH2, H-1a, H-1b, H-2, H-6a, H-6b, H-7, H-8, H-9),
4.25 (m, 2H, H-5), 4.55 (m, 4H, H-4ˆH-3); 13C NMR
(50.32 MHz, CDCl3): d 69.93 (CH2, C-9), 70.42 (CH2,
C-8), 70.51 (CH2, C-7), 71.33 (C-1), 72.15 (C-2), 74.62
(C-6), 80.40 (C-5), 80.61 (C-4), 81.72 (C-3). Anal. Calcd
5a (mˆ1) [ethyl acetate]; Rf10.21 (methanol/EtOAc 2/8);
[a]Dˆ183 (c 0.07, CHCl3); H NMR (200 MHz, CDCl3):
d 2.8 (m, 2H, OH), 3.87 (m, 18H, 4 CH2, H-1a, H-1b, H-2,
H-6a, H-6b, H-7, H-8), 4.25 (m, 2H, H-5), 4.45 (d, 2H,
J3,4ˆ5 Hz, H-3), 4.70 (dd, 2H, J3,4ˆJ4,5ˆ5 Hz, H-4); 13C
NMR (50.32 MHz, CDCl3): d 69.84 (CH2, C-81C-7),

S. Chatti et al. / Tetrahedron 56 (2000) 5877±5883
5883
8. Stross, P.; Hemmer, R. Adv. Carbohydr. Chem. Biochem. 1991,
49, 93.
for C18H30O10: C, 53.20; H, 7.40; O, 39.40. Found: C, 52.53;
H, 7.27; O, 40.18.
9. Thiem, J.; Bachmann, F. Makromol. Chem. 1991, 192, 2163.
10. (a) Loupy, A.; Monteux, D. Tetrahedron Lett. 1996, 37, 7023.
(b) Abenhaim, D.; Loupy, A.; Munnier, L.; Tamion, R.; Marsais,
Acknowledgements
Â
F.; Queguiner, G. Carbohydr. Res. 1994, 261, 255.
 Â
Á
We are grateful to Societe Roquette-Freres (Lestrem,
France) for a kind gift of dianhydrohexitols, and to the
Higher Education Ministry of Tunisia for ®nancial support.
11. Chatti, S.; Bortolussi, M.; Loupy, A. Tetrahedron Lett. 2000,
41, 3367.
12. (a) Loupy, A.; Pardo, C. Synthetic Commun. 1988, 18, 1275.
(b) Yu®t, S. S.; Zinovyev, S. S. Tetrahedron 1999, 55, 6319.
(c) Cohen, S.; Zoran, A.; Sasson, Y. Tetrahedron Lett. 1998, 39,
9815.
References
13. (a) Beltrame, P.; Biale, G.; Lloyd, D. J.; Parker, A. J.; Ruane,
M.; Winstein, S. J. Am. Chem. Soc. 1972, 94, 2240. (b) Bartsch,
R. A.; Bunnett, J. F. J. Am. Chem. Soc. 1969, 91, 1376.
(c) Veeravagu, P.; Arnold, R. T.; Eigenmann, G. W. J. Am.
Chem. Soc. 1964, 86, 3072.
Á
È
1. Fleche, G.; Huchette, M. Starch/Starke 1986, 38, 26.
2. Jacquet, F.; Gaset, A.; Gorrichon, J. P. Inform. Chim. 1984, 246,
155.
Á
3. Majdoub, M.; Loupy, A.; Fleche, G. Eur. Polym. J. 1994, 30,
1431.
4. Bachmann, F.; Reimer, J.; Ruppenstein, M.; Thieme, J.
Macromol. Rapid. Commun. 1998, 19, 21.
Â
5. Cognet-Georjon, E.; Mechin, F.; Pascaut, J. P. Makromol.
Chem. Phys. 1995, 196, 3733.
6. Kricheldorf, H. R.; Sun, S. T. Makromol. Chem. Phys. 1997,
14. Hajek, M.; Radoiu, M. Second World Congress on Microwave
and Radio Frequency Processing, Orlando, USA, 2±6 April 2000.
Comm. MWB-CP2-02.
15. Martin, A. E.; Bulkowski, J. E. J. Org. Chem. 1982, 47, 2314.
16. Streitwieser, A. J. Am. Chem. Soc. 1955, 77, 195.
17. Pear, E. J. P.; Thrower, J.; Veitch J. Chem. Soc. 1958, 1322.
18. Curtis, W. D.; Laidler, D. A.; Stoddart, J. F.; Graham, H. J.
J. Chem. Soc., Perkin. Trans. 1 1977, 1756.
198, 2197.
7. Storbeck, R.; Rehahn, M.; Ballauff, M. Makromol. Chem. 1994,
194, 53.