Microwave-assisted protocols applied to the synthesis of 1′,2,3,3′,4,4′-Hexa-O-benzylsucrose

Article abstract of DOI:10.1080/00397911.2014.926555

The sucrose derivative 1′,2,3,3′,4,4′-hexa-O- benzylsucrose is a key intermediate for the chemoselective synthesis of various useful materials, such as macrocycles, crown ether analogs, and polymers. Several strategies for the synthesis of this compound were explored by applying microwave-assisted protocols, thus permitting significant reductions of time and energy compared to other routes. The outcomes of the different approaches were compared and the optimal one, in terms of yield and reproducibility, was found to be the initial protection at the positions 6 and 6′, with tert-butyldiphenylsilylchloride (TBDPSCl) in the presence of 4-(dimethylamino)pyridine (4-DMAP) and pyridine as a solvent, then perbenzylation of the remaining hydroxyl groups, followed by selective deprotection of the TBDPS groups to obtain the title compound.

Full text of DOI:10.1080/00397911.2014.926555

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Microwave-Assisted Protocols Applied to
the Synthesis of 1′,2,3,3′,4,4′-Hexa-O-
benzylsucrose
Cláudia D. Raposo a , Krasimira T. Petrova a & M. Teresa Barros a
a REQUIMTE, CQFB, Departamento de Química, Faculdade de
Ciências e Tecnologia , Universidade Nova de Lisboa , Quinta da
Torre , Caparica , Portugal
Accepted author version posted online: 24 Jun 2014.Published
online: 20 Aug 2014.
To cite this article: Cláudia D. Raposo , Krasimira T. Petrova & M. Teresa Barros (2014) Microwave-
Assisted Protocols Applied to the Synthesis of 1′,2,3,3′,4,4′-Hexa-O-benzylsucrose, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:20, 3027-3036, DOI: 10.1080/00397911.2014.926555
To link to this article: http://dx.doi.org/10.1080/00397911.2014.926555
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Synthetic Communications1, 44: 3027–3036, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2014.926555
MICROWAVE-ASSISTED PROTOCOLS APPLIED TO THE
SYNTHESIS OF 1’,2,3,3’,4,4’-HEXA-O-BENZYLSUCROSE
´
Claudia D. Raposo, Krasimira T. Petrova, and
M. Teresa Barros
´
ˆ
REQUIMTE, CQFB, Departamento de Quımica, Faculdade de Ciencias e
Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, Caparica,
Portugal
GRAPHICAL ABSTRACT
Abstract The sucrose derivative 10,2,3,30,4,40-hexa-O-benzylsucrose is a key intermediate
for the chemoselective synthesis of various useful materials, such as macrocycles, crown
ether analogs, and polymers. Several strategies for the synthesis of this compound were
explored by applying microwave-assisted protocols, thus permitting significant reductions
of time and energy compared to other routes. The outcomes of the different approaches
were compared and the optimal one, in terms of yield and reproducibility, was found to
be the initial protection at the positions 6 and 60, with tert-butyldiphenylsilylchloride
(TBDPSCl) in the presence of 4-(dimethylamino)pyridine (4-DMAP) and pyridine as a
solvent, then perbenzylation of the remaining hydroxyl groups, followed by selective depro-
tection of the TBDPS groups to obtain the title compound.
Keywords Carbohydrates; chemoselective synthesis; microwave chemistry; protection–
deprotection strategies; sucrose derivatives
INTRODUCTION
Sugars are an important resource for the development of new materials owing
to their low price.[1] Sucrose (1, Scheme 1) is a cheap bulk product and has great
potential for this purpose. The potential value of sucrose as a raw material has been
Received April 2, 2014.
Address correspondence to Krasimira T. Petrova, REQUIMTE, CQFB, Departamento de
´
Quımica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre,
2829-516 Caparica, Portugal. E-mail: k.petrova@fct.unl.pt
ˆ
3027

3028
C. D. RAPOSO, K. T. PETROVA, AND M. T. BARROS
recognized for many years and has been the subject of considerable research.[2]
Because sucrose has eight chemically active hydroxyl groups, regioselective derivati-
zation is important for the selective synthesis of sucrose-containing linear polymers.[3]
The methods used to produce and purify carbohydrate derivatives are often tedious
and complex,[4] making the synthesis of selectively protected sucrose derivatives
laborious. Clearly, there is a need for simpler procedures using faster and environ-
mentally friendlier heating methods, and these are provided by the use of microwave
(MW) techniques.[5] Microwave-enhanced synthesis has been extended to almost all
areas of chemistry.[6] Carbohydrate chemistry has suffered a certain delay in adopting
this technology, as documented by the limited number of applications.[7] It has been
applied to sucrose chemistry only in our laboratory,[5,8] because the general opinion
was that the method was hampered by the thermal instability of sucrose.[2]
We have been developing strategies to produce highly functional and biocom-
patible novel biomaterials in synthetically efficient ways from natural building
blocks.[8–10] For this, our approach has been to synthesize regioselectively structur-
ally well-defined bifunctional sucrose monomers for which the key intermediate
was 10,2,3,30,4,40-hexa-O-benzylsucrose 4. This compound has been first reported
by Jarosz et al.[4,11] and has found various applications for the synthesis of macro-
cycles, crown ether analogs, and polymers. To gain access to larger and affordable
quantities of this intermediate, we have explored the various methods described
in the literature for the synthesis of 4 under microwave irradiation and compared
their outcomes and applicability. The protocols presented in this work have allowed
significant reduction of time and energy compared with other routes[3,10] and have
potential for the automatization of tedious multistep syntheses of useful sucrose
derivatives. Another elegant method to obtain 4 was published by Yin et al., based
on a regioselective conversion of terminal benzyl ethers into silyl ethers using Co2(CO)8-
Et3SiH under 1 atm of CO.[12] This protocol was not tested under microwave irradiation
because of difficulties related to the use of CO.
RESULTS AND DISCUSSION
The key to successful synthesis under microwave irradiation is to use proper
equipment designed especially for chemical laboratories. Monomodal microwave
equipment has overcome the uncertainties associated with domestic and multimodal
microwave ovens, as it offers precise control of temperature and pressure, and
the software provides simplified process monitoring and control, which results in
accurate and reproducible reaction conditions. In many cases a simple transposition
of a reaction mixture from conventional conditions to a microwave reactor is not
possible. There are many factors to be taken into consideration, such as the dipole
moments of the components of the reaction mixture, their dielectric relaxation time,
the dielectric constant (or relative permittivity) e0, the dielectric loss e00 (complexed
permittivity), and tangent delta (d, loss tangent).[13] Sucrose is soluble in protic
solvents such as water, methanol, and ethanol and reasonably soluble in dipolar
aprotic solvents such as pyridine, dimethylformamide (DMF), and dimethyl-
sulfoxide (DMSO), which are suitable as nucleophilic substitution media. Both
pyridine and DMF have comparatively high boiling points (pyridine 115 ꢀC and
DMF 153 ꢀC) and a dipolarity suitable for the absorption of microwave radiation,

SYNTHESIS OF 10,2,3,30,4,40-HEXA-O-BENZYLSUCROSE
3029
which is why these solvents were used as reaction media for all experiments where the
substrate was sucrose. In these cases, room-temperature saturated solutions were
used, 1 g sucrose=15 mL pyridine or DMF. In the case of sucrose functionalization
the elimination of solvent is not recommended as this leads to significantly lower
yields because of overheating.
The energy transfer in a microwave-assisted reaction is incredibly rapid, and only
by programming temperature control could the decomposition of the substrates be
avoided and comparatively good yields of product obtained in short reaction times.
By this method, as the temperature reaches the set value, the power is reduced so that
the reaction mixture does not overshoot. It then stays at a lower level to maintain the
set temperature throughout the entire reaction. The maximum temperature that the
reaction mixtures were allowed to reach was chosen in every case according to the boil-
ing points and stabilities of the reagents and solvent. The maximum irradiation power
was set to 300 W for all the reactions in order to obtain comparable results, and the
reaction time was optimized with a view to the best yield. In some cases (for example,
the formation of compound 4 by method IV), an attempt to increase the yields by
increasing the reaction times lead to partial hydrolysis of the benzyl groups and the
formation of several side products; while at lower reaction times and=or lower
temperatures the conversion of the starting material was not complete.
Synthesis of 1’,2,3,3’,4,4’-Hexa-O-benzylsucrose 4 Under Microwave
Irradiation via Di-trityl Derivative, Method I
To access the primary hydroxyls of sucrose selectively, the first step was always
blocking of one, two, or all three primary positions of sucrose with bulky substitu-
ents. The groups most utilized for this purpose are triphenylmethyl- (trityl-, Tr) and
tert-butyldiphenylsilyl- (TBDPS) chlorides. The advantage of using TrCl over
TBDPSCl is that it is a relatively cheap reagent, but, on the other hand, it is ther-
mally unstable and not selective for mono-protection. tert-Butyldimethylsilyl
chloride (TBDMSCl) can also be used,[14] but as it is smaller than TBDPSCl,
it is less selective. This reagent is very useful for distinguishing between the 10 and
6,60-positions of sucrose.[15]
Methods to prepare 6,60-di-O-tritylsucrose 2 have been examined by Mach
et al.[16] It has been used as a starting compound in many synthetic sequences.
The optimized method to improve the yield up to 50% was to dissolve the sucrose
in pyridine at room temperature, and to the saturated homogeneous solution add
2.2 equiv of trityl chloride in one portion, followed by stirring at rt for 48 h. Trans-
position of this reaction to the microwave reactor allowed us to increase the yield of
crude product to 75% after only 5 min of irradiation (Scheme 1, Table 1). Although
the reaction proceeded smoothly and with good yield, we found it very difficult
to purify the resulting reaction mixture by conventional silica-gel chromatography.
The product 2 was always mixed with triphenylmethanol, as evidenced by
integration of the aromatic signals (7.00–8.00 ppm) of the proton NMR spectra.
We have also tried the reported improved procedure,[17] consisting of a series of
extractions and crystallization, but did not obtain pure compound. That is why
the yield reported is to be considered of crude product, which was not isolated in
pure form. We found this to be a great disadvantage of the method, as it was not

3030
C. D. RAPOSO, K. T. PETROVA, AND M. T. BARROS
Scheme 1. Preparation of 10,2,3,30,4,40-hexa-O-benzylsucrose 4 by method I. (i) TrCl, DMAP, pyridine,
90 ꢀC, 300 W, 5 min, 75% (crude); (ii) BnBr, NaH, DMF, 145 ꢀC, 300 W, 10 min, 72% (crude); and (iii)
I2, CH2Cl2=MeOH, 40 ꢀC, 300 W, 20 min, 59%.
possible to prove the rate of substitution by NMR spectroscopy and the compounds
mono-, di-, and tri-trityl sucroses can be distinguished only by thin-layer chromato-
graphy (TLC) using reliable reference samples.
The crude compound 2 was then benzylated using BnBr=NaH in DMF,
leading to compound 3 in 10 min (145 ꢀC, 300 W). Again 3 was isolated as a crude
product with 72% yield (see 1H NMR in the Supporting Information), which
was somewhat lower than that obtained under conventional conditions (84%),
probably because of the instability of the trityl group under microwave irradiation.
Table 1. Reaction conditions and experimental results under microwave heating compared with conven-
tional conditions
MW conditions,
reaction time, yield, ref.
Conventional conditions,
reaction time, yield, ref.
Method Compound
Reagents, solvents
TrCl, DMAP, Pyr
I
2
3
90 ꢀC, 300 W, 5 min,
75% (crude)
145 ꢀC, 300 W, 10 min,
72% (crude)
rt, 48 h, 50% (crude)[11]
rt, 5 h, 84% (crude)[11]
BnBr, NaH, DMF
4
5
6
4
7
8
I2, CH2Cl2= MeOH 40 ꢀC, 300 W, 20 min, 59%
reflux, 5 h, 58%[11]
60 ꢀC, 27 h, 78%[18]
II
TBDPSCl, Pyr
NaH, BnBr, DMF
TBAF, THF
90 ꢀC, 300 W, 5 min, 85%[5]
145 ꢀC, 300 W, 5 min, 50%[19] rt, 2 h, 32%
65 ꢀC, 300 W, 5 min, 7%[19]
90 ꢀC, 300 W, 10 min, 76%[5]
rt, 5 h, 65%
70 ꢀC, 2 h, 91%[22]
rt, 2 h, 0%
III
CBr4, PPh3, Pyr
BnBr, (NaH, KOH 145 ꢀC, 300 W, 15 min, 0%
or Ag2O), DMF
4
9
—
CCl4, PPh3, Pyr
—
70 ꢀC, 300 W, 10 min, 73%[5]
—
IV
70 ꢀC, 2 h, 65-75%[23]
rt, 12 h, 77%[11]
reflux (toluene), 2 h þ rt,
12 h, 72%[11]
10
11
BnBr, KOH, DMF 145 ꢀC, 300 W, 5 min, 14%
Bu4NþCH3COO-,
toluene
MeONa, MeOH
105 ꢀC, 300 W, 15 min, 59%
4
50 ꢀC, 300 W, 5 min, 32%
rt, 3 h, 82%[11]

SYNTHESIS OF 10,2,3,30,4,40-HEXA-O-BENZYLSUCROSE
3031
Selective detritylation with iodine in dichloromethane=methanol required
20 min under microwave irradiation (40 ꢀC, 300 W) to give 4 in a good yield (59%
or 32% overall from sucrose).
Synthesis of 1’,2,3,3’,4,4’-Hexa-O-benzylsucrose 4 Under Microwave
Irradiation via Di-TBDPS Derivative, Method II
The introduction of O-tert-butyldiphenylsilyl group is the first step in many
protection–deprotection sequences. When the silylation reaction of sucrose was
performed with 3 molar equiv of tert-butyldiphenylsilyl chloride,[18] the crystalline
6,60-di- and 6,l0,60-tri-O-tert-butyldiphenylsilyl sucroses in yields of 78% and
18.7%, respectively, were obtained. This reaction was complete in 5 min under
microwave irradiation (90 ꢀC, 300 W) using 2.2 equiv of TBDPSCl in dry pyridine,
to afford (85%) of 6,60-di-O-tert-butyldiphenylsilylsucrose 5 (Scheme 2, Table 1).[5]
The disilylated sucrose 5 was then perbenzylated using BnBr=NaH in DMF leading
to compound 6 in 5 min (50%, 150 ꢀC, 300 W). Chemoselective deprotection of
the silyl group, using TBAF in THF, led to 10,2,3,30,4,40-hexa-O-benzylsucrose 4
in a good 70% yield (30% overall from sucrose).[19]
All the intermediate compounds of this synthetic sequence have been readily
isolated in pure form and their structures have been proven by conventional spectro-
scopic methods. The advantage of the method is the possibility to perform the
reactions with the crude intermediate products, thus saving time and solvents. The
disadvantage was the significantly lowered yield of the benzylation step, due to the
relative instability of the tert-butyldiphenylsilyl protecting groups under the basic
reaction conditions, which led to the formation of 60-O-tert-butyldiphenylsilyl-
10,2,3,30,4,40,6-hepta-O-benzylsucrose (typically about 20%) and octabenzylated
sucrose (about 15%) as by-products for this step. A strategy to improve the yield
was to prepare the reaction mixture, perform the reaction, and do the workup as fast
as possible.
Scheme 2. Preparation of 10,2,3,30,4,40-hexa-O-benzylsucrose 4 by method II. (i) 2.2 eq TBDPSCl, DMAP,
pyridine, 90 ꢀC, 300 W, 5 min, 85%; (ii) BnBr=NaH, DMF, 145 ꢀC, 300 W, 5 min, 50%; (iii) TBAF, THF,
65 ꢀC, 300 W, 5 min, 70%.

3032
C. D. RAPOSO, K. T. PETROVA, AND M. T. BARROS
Scheme 3. (i) CBr4, PPh3, pyridine, 90 ꢀC, 300 W, 10 min, 76%; (ii) BnBr, (NaH, KOH, or Ag2O)
Bu4NþBrꢁ, DMF, rt, 2 h or 145 ꢀC, 300 W, 15 min, no product.
Synthesis of 1’,2,3,3’,4,4’-Hexa-O-benzylsucrose 4 Under Microwave
Irradiation via 6,6’-Dibromo-6,6’-dideoxysucrose, Method III
The compound 6,60-dibromo-6,60-dideoxysucrose 7 is another bifunctionalized
sucrose derivative, readily prepared under microwave irradiation and used as start-
ing material in various synthetic sequences.[5,20] Unfortunately, being a very good
leaving group, the dibromide proved very unstable under the basic benzylation con-
ditions and we were not able to obtain the product 8 (Scheme 3, Table 1).
Synthesis of 1’,2,3,3’,4,4’-Hexa-O-benzylsucrose 4 Under Microwave
Irradiation via 6,6’-Dichloro-6,6’-dideoxysucrose, Method IV
As the reaction sequence of method III was not successful, a starting
compound with a poorer leaving group, 6,60-dichloro-6,60-dideoxysucrose 9,[5,21]
Scheme 4. Preparation of 10,2,3,30,4,40-hexa-O-benzylsucrose 4 by method IV: (i) CCl4, PPh3, pyridine,
70 ꢀC, 300 W, 10 min, 73%; (ii) BnBr, KOH, Bu4NþBrꢁ, DMF, rt, 12 h, 77%; (iii) Bu4NþCH3COO-,
toluene, 105 ꢀC, 300 W, 15 min, 59%; and (iv) MeONa, MeOH, 50 ꢀC, 300 W, 5 min, 32%.

SYNTHESIS OF 10,2,3,30,4,40-HEXA-O-BENZYLSUCROSE
3033
was used (Scheme 4, Table 1). Perbenzylation of the remaining six hydroxyl groups
was performed using potassium hydroxide as a base.[11] The attempt to perform this
step under microwave irradiation (145 ꢀC, 300 W, 5 min) led to a yield of 10 only
14%, and we were not able to optimize it to a greater value. Thus it was performed
under conventional conditions, as previously described.[11] Subsequent reaction with
tetrabutyl-ammonium acetate afforded the corresponding 6,60-di-O-acetyl derivative
11 in 59% under microwave irradiation, which was followed by deacetylation to give
4. The last step also did not afford better yield under microwave irradiation: 32%
versus 82% at room temperature.
CONCLUSIONS
Four methods previously described in the literature for the synthesis of the key
intermediate 10,2,3,30,4,40-hexa-O-benzylsucrose 4 have been examined under micro-
wave irradiation. The most reliable method was the reaction sequence starting from
6,60-di-O-tert-butyldiphenylsilylsucrose 5 (method II). From 4, various bifunctional
derivatives such as esters and ethers substituted chemoselectively at 6 and 60-position
of sucrose could be obtained in good yields. The microwave-assisted protocols
described here resulted in significant reduction of time (from 2–48 h to 5–20 min)
and energy, and about a 50% reduction in the amount of solvents used, compared
with conventional methods.
EXPERIMENTAL
Reagents and solvents were purified before use.[24] Solvents used as reaction
media (pyridine, DMF, THF, toluene, CH3OH, and CH2Cl2) were freshly distilled.
The reactions under microwave irradiation were performed in open flasks equipped
with a temperature control sensor and under magnetic stirring using a monomodal
microwave reactor MicroSynth Labstation (MileStone, USA). This synthesizer has
a single-mode cavity with temperature and pressure control. In this way, temperature
runaway and explosion risks are avoided. The reaction conditions are expressed as
a function of the reaction temperature and not the magnetron power. NMR spectra
were recorded at 400 MHz in CDCl3 or DMSO-d6, with chemical shift values (d) in
ppm downfield from TMS (0 ppm) or the residual solvent peak of DMSO
(2.50 ppm). The signals were assigned with the aid of distortionless enhancement
polarization transfer (DEPT), correlation spectroscopy (COSY), and heteronuclear
multiple quantum correlation (HMQC) experiments. Optical rotations were
measured at 20 ꢀC on an AA-1000 polarimeter (0.5 dm cell) at 589 nm. The concen-
trations (c) are expressed in g=102 mL. Melting points were determined with a capil-
lary apparatus, and are uncorrected. Fourier transform infrared (FTIR) spectra were
recorded on Perkin-Elmer Spectrum BX apparatus in KBr dispersions (solids) or on
NaCl windows (liquids). Matrix-assisted laser desorption=ionization time-of-flight
(MALDI-TOF) spectra were recorded on an Ultraflex III TOF=TOF Bruker
equipped with laser type smartbeam and detecting system fast MCP-Gating. The
synthesized compounds were purified by flash column chromatography using Merck
silica gel 60 (230–400 mesh).

3034
C. D. RAPOSO, K. T. PETROVA, AND M. T. BARROS
6,6’-Di-O-triphenylmethylsucrose, 2[11]
Sucrose (1.00 g, 2.92 mmol) was dissolved in pyridine (15 mL). DMAP (4 mg,
0.03 mmol) and TrCl (1.84 g, 6.61 mmol) were added. The mixture was placed in
the microwave cavity and subjected to microwave irradiation of max 300 W at con-
stant temperature of 90 ꢀC for 5 min. The solvent was then evaporated at reduced
pressure and the residue was chromatographed using hexane–ethyl acetate (EtOAc),
1:2, and then EtOAc–acetone-H2O (10:10:1) to afford crude 2 as a white solid
20
(2.42 g, 75%), mp 98–100 ꢀC; lit.[11] mp 99–102 ꢀC. ½aꢂD þ 36:8 (c 1.1, CH3OH);
lit.[11] [a]D þ 38.7 (c 1.09, CH3OH). The compound was identical in all respects with
the substance previously described in the literature.[11]
1’,2,3,3’,4,4’-Hexa-O-benzyl-6,6’-di-O-triphenylmethylsucrose, 3[11]
Sodium hydride, NaH (60% suspension in oil, 94 mg, 2.34 mmol) was added
carefully at 0 ꢀC to a stirred solution of 2 (200 mg, 0.24 mmol) in DMF (5 mL). After
20 min, benzyl bromide (12 equiv., 501 mg, 2.93 mmol) was added dropwise over
15 min. The reaction mixture was placed in the microwave cavity and subjected to
microwave irradiation of max 300 W at constant temperature 145 ꢀC for 10 min.
TLC (EtOAc–acetone–H2O, 10:10:1) showed that the starting material had been
consumed. The mixture was poured into cold H2O (20 mL) and the product was
extracted with diethyl ether (4 ꢃ 15 mL). The combined organic layers were washed
with H2O (2 ꢃ 10 mL), dried over anhydrous Na2SO4, and concentrated. The residue
was chromatographed (hexane–EtOAc, 10:1, then 5:1) to give compound 3 as
20
a colorless solid. Yield 240 mg (72%), mp 97–100 ꢀC; no report in lit. ½aꢂD þ 17:6
(c 0.8, CHCl3); lit.[11] [a]D þ 20.6 (c 1.0, CHCl3). The compound was identical in
all respects with the substance previously described in the literature.[11]
1’,2,3,3’,4,4’-Hexa-O-benzylsucrose, 4[19]
Method I. 6,60-Di-O-trityl-10,2,3,30,4,40-hexa-O-benzylsucrose (3, 1.00 g,
0.73 mmol) was dissolved in dichloromethane–methanol (1:3, 20 mL) to which iodine
(185 mg, 0.73 mmol) was added; then the mixture was placed in the microwave
cavity and subjected to microwave irradiation of max 300 W at constant temperature
40 ꢀC for 20 min. A 10% aqueous solution of sodium thiosulfate was added until the
mixture became colorless (60 mL), and the product was extracted with diethyl ether
(4 ꢃ 30 mL). The combined organic extracts were washed with water and brine,
dried, and concentrated. Chromatography (hexane–EtOAc, 3:2) of the residue
20
afforded 4 as a colorless oil (380 mg, 59%), ½aꢂD þ 37:6 (c 0.9, CHCl3); lit.[16]
[a]D þ 40.8 (c 1.0, CHCl3). The compound was identical in all respects with the
substance previously described in the literature.[11,19]
1’,2,3,3’,4,4’-Hexa-O-benzyl-6,6’-dichloro-6,6’-dideoxysucrose, 10[11]
To a stirred solution of 6,60-dichloro-6,60-dideoxysucrose 9 (1.00 g, 2.63 mmol)
in DMF (15 mL) was added powdered KOH (1.33 g, 23.7 mmol), tetrabutylammo-
nium bromide (60 mg), and benzyl bromide (4.06 g, 2.82 mL, 23.7 mmol), and the

SYNTHESIS OF 10,2,3,30,4,40-HEXA-O-BENZYLSUCROSE
3035
mixture was placed in the microwave cavity and subjected to microwave irradiation
of max 300 W at constant temperature 145 ꢀC for 5 min. The mixture was then parti-
tioned between water (100 mL) and ether (100 mL); the organic phase was separated,
washed with water, dried, and concentrated; and the residue was chromatographed
20
(hexane–EtOAc, 7:1) to afford 10 as a colorless oil (340 mg, 14%), ½aꢂD þ 31:5 (c 0.9,
CHCl3); lit.[11] [a]D þ 32.0 (c 1.0, CHCl3). The compound was identical in all respects
with the substance previously described in the literature.[11]
6,6’-Di-O-acetyl-1’,2,3,3’,4,4’-hexa-O-benzylsucrose, 11[11]
Tetrabutylammonium acetate (3.25 g, 10.8 mmol) was added to a solution of 10
(500 mg, 0.54 mmol) in toluene (50 mL), and the mixture was placed in the micro-
wave cavity and subjected to microwave irradiation of max 300 W at constant tem-
perature 105 ꢀC for 15 min. After concentration, the residue was dissolved in CH2Cl2
(50 mL), the solution was washed with water (3 ꢃ 50 mL), and the aqueous phase was
extracted with CH2Cl2(2 ꢃ 25 mL). The organic phases were combined, dried, con-
centrated, and chromatographed (hexane–EtOAc, 3:1) to give 11 as a colorless oil
20
(310 mg, 59%). ½aꢂD þ 49:2 (c 1.0, CHCl3); lit.[11] [a]D þ 50.6 (c 1.0, CHCl3). The
compound was identical in all respects with the substance previously described in
the literature.[11]
1’,2,3,3’,4,4’-Hexa-O-benzylsucrose, 4[19]
Method IV. Compound 11 (500 mg, 0.52 mmol) was dissolved in methanol
(40 mL) containing catalytic amounts of sodium methoxide, and the mixture was
placed in the microwave cavity and subjected to irradiation of max 300 W at con-
stant temperature 50 ꢀC for 5 min. After concentration, the residue was chromato-
graphed (hexane–EtOAc, 1:1) to give colorless oil (0.15 g, 32%), which was
identical in all respect with the previously described substance 4 (see method I).
ACKNOWLEDGMENTS
The NMR spectra were obtained using spectrometers that are part of the National
ˆ
NMR Facility, supported by Fundac¸a˜o para a Ciencia e a Tecnologia (RECI=BBB-
´
BQB=0230=2012). MALDI-TOF spectra were acquired by the Laboratorio de
Analises=REQUIMTE at the Departamento de Quımica of Universidade Nova de
´
´
Lisboa.
FUNDING
ˆ
This work has been supported by Fundac¸a˜o para a Ciencia e a Tecnologia
through Grant No. PEst-C=EQB=LA0006=2013.
SUPPORTING INFORMATION
Supplemental data for this article can be accessed on the publisher’s website.

3036
C. D. RAPOSO, K. T. PETROVA, AND M. T. BARROS
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