Application of focused microwaves to the scale-up of solvent-free organic reactions

Article abstract of DOI:10.1021/op000031e

A series of typical solvent-free reactions have been safely and beneficially scaled-up to several hundred grams in a larger batch reactor (Synthewave 1000) with yields equivalent to those obtained under similar conditions (temperature, reaction time) in laboratory-scale experiments (Synthewave 402). They concern potassium acetate alkylation, regioselective phenacylation of 1,2,4-triazole, deethylation of 2-ethoxy-anisole, and typical examples in carbohydrate chemistry (peracetylation, glycosylation, saponification, halogenation, and epoxidation of D-glucopyranosides).

Full text of DOI:10.1021/op000031e

Organic Process Research & Development 2000, 4, 498−504
Application of Focused Microwaves to the Scale-Up of Solvent-Free Organic
Reactions
J. Cle´ophax,† M. Liagre,‡ A. Loupy,*,‡ and A. Petit‡
Institut de Chimie des Substances Naturelles, CNRS, aVenue de la terrasse, 91190 Gif-sur-YVette, France, and
Laboratoire des Re´actions Se´lectiVes sur Supports, CNRS UMR 8615, UniVersite´ Paris-Sud, baˆtiment 410,
91405 Orsay Cedex, France
Abstract:
rillonite,5 and the synthesis of 4-alkoxyquinazoline-2-car-
bonitriles and aryl thiocarbamates in different alcohols.6 In
these cases, the reactions could be safely and beneficially
scaled up to multigram levels with similar yields and
conditions (reaction time, temperature) from the Synthewave
402 (300 W) to the Synthewave 1000 (800 W).
In this report, we describe the systematic study of
significant organic reactions, performed either in the presence
or in the absence of solvent under microwaves, scaled up to
at least 100 g. To check the possible specific effect (non-
purely thermal) of microwaves, results obtained in the
Synthewave 402 apparatus are compared with those resulting
from conventional heating (4) under identical conditions
(amounts, time, temperature, etc.) and thus are not optimized
in this case.
A series of typical solvent-free reactions have been safely and
beneficially scaled-up to several hundred grams in a larger
batch reactor (Synthewave 1000) with yields equivalent to those
obtained under similar conditions (temperature, reaction time)
in laboratory-scale experiments (Synthewave 402). They concern
potassium acetate alkylation, regioselective phenacylation of
1,2,4-triazole, deethylation of 2-ethoxy-anisole, and typical
examples in carbohydrate chemistry (peracetylation, glycosy-
lation, saponification, halogenation, and epoxidation of
glucopyranosides).
D-
Introduction
Extensive improvements have been described in organic
synthesis, resulting from microwave (MW) irradiation by use
of either domestic ovens1 or, more recently, monomode
reactors.2 In the latter case, numerous reactions were
performed using the Synthewave 402 apparatus,3 with
noticeable success achieved by using a maximum of 30-40
g of reactants, a limit imposed by the reactor size.
Due to the evident industrial interest, we describe herein
the extension of the method to increased amounts of products
for typical solvent-free organic reactions using a convenient
larger apparatus recently developed by Prolabo: the Syn-
thewave 1000. This reactor was essentially designed for
scale-up with focused microwaves, fitted with a 1-L vessel,
a mechanical stirrer, and eventually a dropping funnel,
making it possible to perform reactions under controlled
atmospheres. The reactor operates with an adjustable power
between 40 and 800 W and may be monitored either in power
or in temperature, or both (Figure 1).
Results and Discussion
Alkylations. (a) Potassium Acetate Alkylation with n-
Bromooctane (Scheme 1). This reaction was first realized
under solid-liquid phase-transfer catalysis (PTC) without
any solvent using a multimode domestic oven.7 Yields were
quasi-quantitative (>95%) within 1 min on a 10-500 mmol
scale (i.e., from 3.21 to 160.5 g of total starting materials).
Scheme 1
The reaction was reconsidered with accurate control of
temperature, monitoring of the operations from 50 mmol
(Synthewave 402) to 2 mol (Synthewave 1000). The study
was completed by considering the medium effect in the
presence of solvent (either a polar one, DMF, or a nonpolar
one, 1,2-dichlorobenzene) or in its absence either under PTC
or in “dry media” conditions by impregnation of reactants
on basic alumina.8
The main results are given in Tables 1-3, with GC yields
in octyl acetate 1 (determined by use of a capillary column).
The profiles obtained upon raising the temperature are
presented in Figure 2, which also shows the evolution of
emitted power necessary to maintain a constant temperature.
Scale-up was realized without any problem under identical
conditions using the same time and temperature (5 min, 160
Some experiments were previously described that used
this reactor, including esterification of acetic acid with
n-propanol in “dry media”,4 the solvent-free synthesis of
dioxolanes, dithiolanes, and oxathiolanes on K10 montmo-
* To whom correspondence should be addressed. Fax: ++33 1 69 15 46 79.
E-mail: aloupy@icmo.u-psud.fr.
† Institut de Chimie des Substances Naturelles, CNRS.
‡ Universite´ Paris-Sud.
(1) Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; Laberge, L.;
Rousell, J. Tetrahedron Lett. 1986, 27, 279. Caddick, S. Tetrahedron 1995,
38, 10403.
(2) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.; Mathe,
D. Synthesis 1998, 1213.
(5) ) Perio, B.; Dozias, M. J.; Hamelin, J. Org. Process Res. DeV. 1998, 2,
428.
(3) Commarmot, R.; Didenot, R.; Gardais, J. F. (Prolabo). French Patent 84/
03496, 1986. Jacquault, P. (Prolabo). French Patent 549495 AJ, 1992.
(4) Poux, M.; Chemat, F.; Di Martino, J. L. Proceedings, 6th International
Conference MicrowaVe and High Frequency Heating, Fermo, Italy,
September 1997, pp 99-102.
(6) Besson, T.; Dozias, M. J.; Guillard, J.; Jacquault, P.; Legoy, M. D.; Rees,
C. W. Tetrahedron 1998, 54, 6475.
(7) Bram, G.; Loupy, A.; Majdoub, M. Synth. Commun. 1990, 20, 125.
(8) Bram, G.; Loupy, A.; Majdoub, M.; Gutierrez, E.; Ruiz-Hitzky, E.
Tetrahedron 1990, 46, 5167.
498
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Vol. 4, No. 6, 2000 / Organic Process Research & Development
10.1021/op000031e CCC: $19.00 © 2000 American Chemical Society and The Royal Society of Chemistry
Published on Web 10/03/2000

Figure 1. Photograph of Synthewave equipment. (a) Synthewave 402 (optimal power ) 300 W); (b) Synthewave 1000 (optimal
power ) 800 W).
Figure 2. Thermal behaviour for n-octylation of potassium acetate under solid-liquid PTC conditions and MW irradiation. (a)
S402; (b) S1000.
Table 1. Synthesis of 1 under solvent-free PTC conditions in
Table 2. Synthesis of 1 in the presence of DMF (5 min at
160 °C)
the presence of Aliquat 336 (5% mol); 5 min, Timposed
160 °C
)
amount of materials [g (mol)]
total yield
amount of 1
(g) (%)a
amount of materials [g (mol)]
activation
method
total final yield
CH3COOK nOctBr DMF
activation
method
Aliquat amount temp of 1
CH3COOK nOctBr
336
(g)
(°C) (%)b
MW, S402 4.9 (0.05) 9.7 (0.05) 9.4 (10 mL)
24
24
88
83
4, oil bath 4.9
9.7
9.4
MW, S402 4.9 (0.05) 9.7 (0.05) 1 (0.0025) 15.6 172 98
MW, S1000 4 (0.5)
96.5 (0.5) 94.4 (100 mL) 239.9 94
4, oil bath 4.9
MW, S1000 196 (2)
9.7
1
15.6 172 98
386 (2) 40.4 (0.1) 622.4 174 98 (96)a
a Yields evaluated by GC with internal standard.
a In parentheses, yield in isolated product after distillation. b Yields evaluated
by GC with internal standard (undecane).
Results are equivalent under solvent-free PTC (Table 1)
whatever the activation method and equipment and slightly
better than those obtained by use of supported reagents on
basic alumina. In this last case, the presence of 1,2-
dichlorobenzene allowed more efficient stirring without any
effect on the reactivity.
°C). Despite a quite large difference in the profiles obtained
upon raising the temperature (3.5 min was necessary to reach
the plateau value when using the Synthewave 1000 reactor,
versus only 2 min with the 402 one), yields were equivalent
in both situations.
Yields in ester remain very similar after extension of the
scale for the same reaction times at identical temperatures.
All of the reactions were repeated under traditional heating
(oil bath), and equivalent results were obtained, respectively
Vol. 4, No. 6, 2000 / Organic Process Research & Development
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499

Table 3. Synthesis of 1 with potassium acetate impregnated onto neutral alumina (1:5 w/w) with or without 1,2-dichlorobenzene
(DCB) (30 min at 160 °C)
amount of materials [g (mol)]
activation method
CH3COOK
nOctBr
alumina
DCB
total amount(g)
yield of 1 (%)a
MW, S402
4, oil bath
MW, S402
4, oil bath
MW, S1000
MW, S1000
4.9 (0.05)
4.9
14.5 (0.075)
14.5
24.5
24.5
12.25
12.25
122.5
122.5
43.9
43.9
28.5
28.5
219.5
285
48
50
53
49
54
50
2.45 (0.025)
2.45
7.25 (0.0375)
7.25
6.55 (5 mL)
6.55
24.5 (0.25)
24.5 (0.25)
72.5 (0.375)
72.5 (0.375)
65.5 (50 mL)
a Yields evaluated by GC with internal standard.
Figure 3. Thermal behaviour for the phenacylation of 1,2,4-triazole under MW irradiation. (a) S402; (b) S1000.
98, 83, and 50% for the three types of experiments (instead
of 98, 88, and 53% obtained under MW). No specific MW
effects are revealed under these conditions.
(b) Phenacylation of 1,2,4-Triazole. Selective alkylation
by substituted phenacyl halides at position 1 of 1,2,4-triazole
is an important goal, leading to the synthesis of biologically
active molecules such as fungicides (fluconazole, flutriafole,9
hexaconazole,10 epiconazole, etc.).
Table 4. Phenacylation of 1,2,4-triazole with
(2,4-dichloro)phenacyl chloride (20 min at 140 °C)
amount of materials [g (mmol)]
total
activation
method
amount yield of
N1/
b
triazole
R-X
(g) 2 (%)a N4/N1,4
MW, S402
0.414 (6)
0.414
1.12 (5)
1.12
1.534
1.534
92
35
89
100/0
36/27/37
100/0
∆, oil bath
MW, S1000 37.3 (540)
100.6 (450) 137.9
Under classical heating, direct alkylation gave a mixture
of 1- and 4-alkylated triazoles as well as quaternary salts
resulting from alkylations at both positions 1 and 4.11 We
have shown that MW-assisted benzylation11 and phenacy-
lation12 occurred selectively at position 1 without any base
and under solvent-free conditions (Scheme 2).
a Yields evaluated by GC with internal standard. b Measured by 1H NMR.
alkylation was obtained due to specific MW effects. Scale-
up gave the same results regardless of the amount of reactants
involved. The profiles obtained upon raising the temperature
are rather comparable, and the power involved remains quasi-
identical (from 15 to 60 W using Synthewave 402, and 40
W with Synthewave 1000) (Figure 3).
The reaction was extensively studied with (2,4-dichloro)-
phenacyl chloride (Table 4).
Scheme 2
(c) SelectiVe Deethylation of 2-Ethoxy-anisole. Alkyla-
tion-dealkylation is one of the most important protective-
deprotective processes of hydroxyl moieties of alcohols and
phenols. Dealkylation is generally performed under harsh
conditions, either acidic (i.e., AlCl3 or BX3)13 or basic,14
(9) Tsukuda, T.; Shiratori, Y.; Watanabe, M.; Ontsuka, H.; Hattori, K.; Shirai,
M.; Shimma, N. Bioorg. Med. Chem. Lett. 1998, 8, 1819.
(10) Worthington, P. A. Pestic. Sci. 1991, 31, 457.
(11) Abenhaim, D.; Diez-Barra, E.; De la Hoz, A.; Loupy, A.; Sanchez-Migallon,
A. Heterocycles 1994, 38, 793.
(12) Pe´rez, E.; Sotelo, E.; Loupy, A.; Mocelo, R.; Suarez, M.; Pe´rez, R.; Autie´,
M. Heterocycles 1996, 47, 539. Liagre, M. Ph.D. Thesis, Orsay, 28 January
2000.
Under microwave irradiation, both reactivity and selectiv-
ity were enhanced, and total regioselectivity in favour of N1-
(13) Burwell, R., Jr. Chem. ReV. 1954, 54, 615. Gerrard, W.; Lappert, M. F.
Chem. ReV. 1958, 58, 1081.
500
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Vol. 4, No. 6, 2000 / Organic Process Research & Development

Figure 4. Thermal behaviour for the deethylation of 2-ethoxy-anisole under MW irradiation. (a) S402; (b) S1000.
including dry media using KF/alumina.15
tion at high temperatures were needed.18 Because D-gluco-
sylation with 1-decanol in acidic medium is not convenient
(due to glucoside decomposition), a three-step microwave-
assisted solvent-free synthesis of decyl D-glucopyranoside
was established (peracetylation, glucosylation, and saponi-
fication).19 Rate enhancements and reduction of the reaction
time were observed in comparison to those observed with
conventional heating under the same conditions.
Selective dealkylation was recently described under MW
using PTC conditions induced by KOtBu as a base and
16
TDA-1 as a phase-transfer agent (Scheme 3).
Scheme 3
Peracetylation of D-Glucose. Peracetylation of D-glucose
with a slight excess (1.8 equiv per OH function) of acetic
anhydride catalyzed by zinc chloride (0.13 equiv) was
performed either under classical heating or under MW
activation in the Synthewave 402 equipment (11.1 mmol)
or Synthewave 1000 (200 mmol) (Scheme 4, Table 6).
The reaction was studied under MW using Synthewave
402 or 1000 reactors, depending on the amount of reactants
involved, and the results were compared with those obtained
by conventional heating (4) (Table 5).
Scheme 4
Table 5. Deethylation of 2-ethoxy-anisole in 20 min (KOtBu
(2 equiv), TDA-1 (10%))
amount of materials [g (mmol)]
total
activation temp ethoxy-
method (°C) anisole
amount yield of
KOtBu
TDA-1
(g)
3 (%)a
Table 6. Peracetylation of D-glucose at 125 °C within 6.5
min
MW, S402 120 0.76 (5)
1.12 (10) 0.324 (1) 2.206 90
1.12 0.324 2.206 50
82
4, oil bath 120 0.76
MW, S1000 140 37.24 (245) 54.98 (490) 15.9 (49) 108.12
amount of materials g (mmoles)
total
a Yields in isolated product.
activation
method
amount yield of
D-glucose
Ac2O
ZnCl2
(g)
4 (%)a
MW, S402
2 (11.1)
2
10.2 (100)
10.2
0.2 (1.47)
0.2
12.4
12.4
223.3
98b
83c
86b
A strong specific MW effect was evidenced as yields are
enhanced from 50 to 90% under MW after 20 min at 120
°C. Scale-up proved very satisfactory, requiring only a slight
modification of the temperature (140 instead of 120 °C) to
obtain a similar result (82-90%) (Figure 4).
4, oil bath
MW, S1000 36 (200) 183.8 (1800) 3.5 (26)
a Yields in isolated product. b R/â ) 1/1. c R/â ) 7/3.
Whatever the conditions, the yields were rather similar
with MW or classical heating and equivalent in scale-up.
Glucosylation of D-Glucose Pentaacetate with 1-Decanol.
It was previously shown that zinc chloride is a catalyst of
Examples in Carbohydrate Chemistry. (a) Glycosyla-
tion of Monosaccharides with a Three-Step Procedure. The
interest in alkyl- or aryl-glycosides is connected to their
physical properties (as liquid crystals and as nontoxic and
biodegradable surfactants).17 To obtain long-chain aliphatic
alcohols, previous butylation and subsequent transacetaliza-
(17) Ames, G. R. Chem ReV. 1960, 60, 541. Havlinova, B.; Kosik, M.; Kovak,
P.; Blazej, A. Tenside Deterg. 1978, 14, 72. Jones, R. F.; Camilleri, P.;
Kirby, A. J.; Okafo, G. N. J. Chem. Soc., Chem. Commun. 1994, 1311.
(18) Biermann, M.; Hill, K.; Wust, W.; Eskuchen, R.; Wollmann, J.; Buns, A.;
Hellmann G.; Ott, K. H.; Winkle, W.; Wollmann, K. European Patent 0
301 298, 1988. Ferrieres, V.; Bertho, J. N.; Plusquellec, D. Tetrahedron
Lett. 1995, 36, 2749. De Goede, A. T. J. W.; Van Deurzen, M. P. J.; Van
der Leij, I. G.; Van der Heijden, A. M.; Baas, J. M. A.; Van Rantwijk, F.;
Van Bekkum, H. J. Carbohydr. Chem. 1996, 14, 331.
(14) Brotherton, T. K.; Bunnett, J. F. Chem. Ind. (London) 1957, 80. Sainsbury,
M.; Dyle, S. F.; Moon, B. J. J. Chem. Soc. (C) 1970, 1797. Veriot, G.;
Collet, A. Acros Org. Acta 1995, 1, 40.
(15) Radhakrishna, A. S.; Prasad Rao, K. R. K.; Suri, S. K.; Sivaprakash, K.;
Singh, B. B. Synth. Commun. 1991, 21, 379.
(16) Oussaid, A.; Le Ngoc, T.; Loupy, A. Tetrahedron Lett. 1997, 38, 2451.
Vol. 4, No. 6, 2000 / Organic Process Research & Development
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501

Table 9. Chlorination of 7 in 10 min at 100 °C
amount of materials [g (mmol)]
activation method
7
CCl4
PPh3
KCl
pyridine
total amount (g)
yield of 8 (%)a
MW, S402
4, oil bath
MW, S1000
4, oil bath
0.39 (2)
0.39
20 (103)
20
1.23 (8)
1.23
63.4 (412)
63.4
0.79 (3)
0.79
40.5 (154.5)
40.5
1.49 (20)
1.49
74.6 (1030)
74.6
0.78 (0.8 mL)
0.78
39.1 (40 mL)
39.1
4.68
4.68
237.6
237.6
78
68
92
82
a Yields in isolated product.
Table 8. Saponification of decyl 2,3,4,6-tetra-O-acetyl-
r-D-glucopyranoside 5 in 2 min at 100 °C
choice for this reaction. Results are compared with those
obtained under similar conditions by classical heating or MW
activation (Scheme 5, Table 7).
amount of materials [g (mmol)]
activation
method
KOH/
alumina
total
yield of
Scheme 5
5
amount (g) 6 (%)a
MW, S402
1.09 (2.24)
1.09
2.91 (11.2)
2.91
145.5 (560)
4
4
200
96
<2
85
4, oil bath
MW, S1000 54.5 (112)
a Yields in isolated product (R anomer).
Table 7. ZnCl2-catalyzed glycosylation of 1-decanol with
peracetyl D-glucopyranoside 4 at 110 °C
diation. Chlorination using triphenylphosphine/carbon tetra-
chloride was realized in the presence of pyridine after addi-
tion of an excess of potassium chloride (Scheme 7, Table
amount of materials [g (mmol)]
reaction
total
activation time
amount yield of
method
(min)
4
1-decanol ZnCl2
(g) 5 (%)a
Scheme 7
MW, S402
4, oil bath
MW, S1000
3
3
4
1.95 (5) 1.19 (7.5) 0.68 (5)
1.95 1.19 0.68
97.5 (250) 59.4 (375) 34.1 (250) 191
3.82 74c
3.82
0b
72d
a Yields in isolated product. b After 5 h, yield is only 25%. c Yields of anomers
(%): R/â ) 64/10. d Yields of anomers (%): R/â ) 62/10.
9).
An important specific (non-purely thermal) MW effect
here is involved when one considers the 72-74% yield com-
pared to the absence of reaction under classical heating.
Scale-up under MW is fairly interesting, giving similar yields
under very close conditions (72-74% within 3 or 4 min).
Saponification of Decyl 2,3,4,6-Tetra-O-acetyl-R-D-glu-
copyranoside 5. Saponification was attempted with potassium
hydroxide impregnated on alumina (1:3 w/w) in dry condi-
tions (Scheme 6, Table 8).
Scale-up led in this case to improvements in yields as
well as by classical heating (4) and under MW activation.
The specific MW effect here is rather reduced, with only a
10% difference in yield in favour of the reaction with MW
activation.
(c) Epoxidation of a Protected Tosyl R-D-Glucopyranoside
9 (Scheme 8). By treatment of the 2-O-tosylate 9 under
Scheme 8
Scheme 6
microwave at 100 °C for 6 min in the presence of KOH/
alumina (1:3 w/w, 2 equiv), epoxide 10 was obtained in good
yield.21 Under classical heating (same conditions), the
required epoxide was obtained in only 25% yield (Table 10).
The effect of MW irradiation here is highly decisive
because with classical heating no reaction occurred after 2
min at 100 °C, whereas the yield was nearly quantitative
under MW. By extension of the reaction by a factor 50, scale-
up led to satisfactory results under the same conditions using
the Synthewave 1000 equipment (85% yield within 2 min).
(b) Chlorination of Methyl R-D-Glucopyranoside 7. It was
previously shown20 that halogenation could be performed
efficiently in highly concentrated solutions under MW irra-
Table 10. Epoxidation of 9 in 6 min at 100 °C
amounts of materials [g (mmol)]
total
activation
method
amount yield of
9
KOH/Al2O3
(g)
10 (%)a
MW, S402
4, oil bath
MW, S1000
1 (2.3)
1
20 (46)
2.1 (9.2)
2.1
41.2 (184)
3.1
3.1
61.2
99
25
95b
(19) Limousin, C.; Cle´ophax, J.; Petit, A.; Loupy, A.; Lukacs, G. J. Carbohydr.
Chem. 1997, 16, 327.
(20) Limousin, C.; Olesker, A.; Cle´ophax, J.; Petit, A.; Loupy, A.; Lukacs, G.
Carbohydr. Res. 1998, 312, 23.
a Yields in isolated product. b Reaction time ) 10 min.
502
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Vol. 4, No. 6, 2000 / Organic Process Research & Development

Figure 5. Thermal behaviour for epoxidation of 9 under MW irradiation. (a) S402; (b) S1000.
The profiles obtained upon raising the temperature were
recorded under MW with both the Synthewave 402 and the
Synthewave 1000 equipment (Figure 5). They are rather
comparable for 6 min using the Synthewave 402 equipment
(yield ) 99%) and 10 min with the Synthewave 1000 (yield
) 95%).
via an aqueous solution and subsequent removal of water
under reduced pressure. The dried powder was introduced
in the matras together with n-bromooctane and sometimes
1,2-dichlorobenzene (DCB) (Table 3). The reaction mixture
was then submitted to MW or immersed into a thermostated
oil bath at 160 °C for 30 min under stirring. Treatment and
analysis remain identical to those in the above cases.
Phenacylation of 1,2,4-Triazole. In the matras, 1,2,4-
triazole was added to the pure alkylating agent [(2,4-dichloro)
phenacyl chloride]. Under mechanical stirring, the mixture
was submitted to MW or immersed in a thermostated oil
bath (under the conditions indicated in Table 4). At the end
of the reaction, the mixture was dissolved in methanol and
analyzed by GC (capillary column CP Sil 19CB, 10 m,
temperature program from 160 (5 min) to 230 °C at 7 °C/
min gradient, pressure ) 50 kPa, internal standard )
phthalimide).
Conclusions
MW-enhanced synthetic organic chemistry is, at the
present time, experiencing considerable growth and has the
potential to greatly improve the image of chemistry and, in
particular, the chemical industry. In this paper we have shown
how it is possible to move from small-scale synthesis (grams)
to the multigram level (100-300 g). Furthermore, these MW
syntheses could be fairly applied under environmentally
benign solvent-free conditions, i.e., according to new rules
of so-called “green chemistry”.
Deethylation of 2-Ethoxy-anisole. In the matras adapted
to the MW reactor were introduced successively 2-ethoxy-
anisole, KOtBu, and TDA-1. After 5 min of mechanical
stirring, the mixture was either submitted to MW or
immersed into a thermostated oil bath (under the conditions
indicated in Table 5). After cooling to room temperature,
the mixture was treated with diluted sodium hydroxide
(0.5%) for 5 min with stirring to recover unreacted 2-ethoxy-
anisole. After concentration, the crude product was purified
by silica gel column chromatography (eluent ) pentane-
diethyl ether) to give pure 3.
Peracetylation of D-Glucose. In the matras, D-glucose,
acetic anhydride, and zinc chloride were introduced. This
mixture was either submitted to MW or immersed into a
thermostated oil bath under the conditions indicated in Table
6. After cooling to room temperature, the mixture was diluted
with methylene chloride. Powdered NaHCO3 (3 or 50 g) was
added, and the reaction mixture was stirred for 10 min and
then filtered on silica gel. After solvent removal, pure 4 was
obtained by precipitation in pentane.
Experimental Section
Alkylation of Potassium Acetate by n-Bromooctane.
(1) Under PTC Conditions or in DMF as a SolVent. In an
adapted microwave vessel (matras) were added successively
the potassium acetate, Aliquat 336 (methyl trioctylammonium
chloride), and n-bromooctane in relative amounts as indicated
in Table 1. The mixture was mechanically stirred and then
exposed to microwaves for 5 min (imposed temperature )
160 °C) or heated using a thermostated oil bath at 172 °C.
After the mixture was cooled to room temperature, organic
products were extracted with diethyl ether (50 mL or 1 L,
depending on scale). After filtration on a sintered glass, the
n-octyl acetate yield was measured by gas chromatography
(GC) using an internal standard (capillary column CP Sil
5CB, 25 m, isothermal 90 °C, pressure ) 70 kPa, standard
) undecane).
In the presence of DMF (Table 2), the order of introduc-
tion remained the same, and DMF was finally added.
Reaction, treatment, and evaluation of product were identical
to those in the previous case.
(2) On Basic Alumina. Potassium acetate was previously
impregnated onto basic alumina (1:5 w/w relative to support)
Glucosylation of D-Glucose Pentaacetate with 1-De-
canol. D-Glucose pentaacetate, 1-decanol, and zinc chloride
were introduced in the MW reactor under mechanical stirring.
This mixture was either exposed to MW or immersed into a
thermostated oil bath under the conditions indicated in Table
(21) Hladezuk, I.; Olesker, A.; Cle´ophax, J.; Lukacs, G. J. Carbohydr. Chem.
1998, 17, 869.
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503

7. After cooling to room temperature, the mixture was diluted
with methylene chloride. Powdered NaHCO3 (1 or 25 g) was
added, and reaction mixture was stirred for 10 min before
filtration over silica gel. The filtrate was evaporated to
dryness. Thin-layer chromatography (TLC) allowed the
detection of some amount of deacetylated compounds. To
peracetylate these compounds, acetic anhydride in pyridine
(3 mL/6 mL or 75 mL/150 mL) was added at 0 °C and
allowed to react for 3 h at room temperature. After
elimination of solvent and reactants by coevaporation with
toluene, the pure product 5 was isolated by silica gel column
chromatography (eluent ) ethyl acetate-heptane).
matras. CCl4 and pyridine were subsequently added. The
mixture was either introduced in the MW reactor or im-
mersed in a thermostated oil bath under the conditions
indicated in Table 9. After cooling to room temperature, the
heterogeneous mixture was diluted with methylene chloride/
ethyl acetate/ethanol (1:1:1) (20 mL or 1 L) and then filtered
on silica gel. The filtrate was evaporated to dryness and the
residue suspended in water. The aqueous phase (containing
the monohalide) was extracted twice with methylene chlo-
ride, concentrated, and purified by silica gel column chro-
matography (eluent ) ethyl acetate-heptane) to give pure
8.
Saponification of Glucoside 5. Glucoside 5 and impreg-
nated KOH on alumina (1:3 w/w) were introduced in the
MW reactor. Under mechanical stirring, this mixture was
either exposed to MW or immersed in a thermostated oil
bath under the conditions indicated in Table 8. After cooling
to room temperature, the mixture was diluted in methanol
and filtered through a silica gel bed. The filtrate was con-
centrated to dryness and purified by silica gel column chro-
matography (eluent ) ethyl acetate-ethanol) to give pure 6.
Chlorination of r-D-Methyl Glucopyranoside 7. Glu-
copyranoside 7, PPh3, and KCl were mixed in the MW
Epoxidation of Tosyl r-D-Glucopyranoside 9. Tosyl
R-D-glucopyranoside 9 was added to KOH impregnated on
alumina (1:3 w/w). Under mechanical stirring, the mixture
was either submitted to MW or immersed in a thermostated
oil bath under the conditions indicated in Table 10. After
cooling to ambient temperature, the mixture was diluted with
ethyl acetate and filtered on silica gel. Pure epoxide 10 was
obtained after solvent removal.
Received for review March 15, 2000.
OP000031E
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