Acylation and Related Reactions under Microwaves
J . Org. Chem., Vol. 66, No. 2, 2001 425
Typ ica l P r oced u r e for th e CMWI Mod e: Ben zen e-
su lfon yla tion of m -Xylen e (2b) (Ta ble 2, En tr y 2). m-
Xylene (2b) (2.12 g, 20 mmol)), benzenesulfonyl chloride (12)
(1.77 g, 10 mmol), and iron(III) chloride (80 mg, 0.5 mmol) were
introduced together in the quartz reactor of the MW apparatus
fitted with a refluxing condenser (dry ice/acetone) and a
calcium chloride tube. The reaction mixture, mechanically
stirred (Teflon paddle), was irradiated under an incident power
of 300 W for 50 s. At the end of irradiation, a maximum
temperature of 166 °C was indicated by the IR pyrometer.
After the reaction mixture was cooled, the conversion rate was
determined by analyzing an aliquot of the reaction mixture
by GC, using tetradecane as an internal standard: 99%. The
reaction mixture was quenched with 20 mL of a saturated
sodium carbonate aqueous solution. The aqueous layer was
extracted with 3 × 10 mL of dichloromethane. After drying
and concentration under reduced pressure of the organic
phase, the crude product (white solid) was analyzed by GC
(125 °C to 300 °C; 20 °C/min; 2 peaks, tR ) 6.89 and 7.16 min,
1:99) and identified as a mixture of (2,6-dimethylphenyl)
phenyl sulfone (25b2) and (2,4-dimethylphenyl) phenyl sulfone
(25b1) by comparison with pure samples.14 Mass obtained: 2.34
g (95% yield from 12). A crystallization from methanol gave
25b1 [4212-74-2]: mp 87 °C (lit.14 mp 87 °C).
Typ ica l P r oced u r e for th e MWIC Mod e: Ben zen esu lfo-
n yla tion of Eth ylben zen e (4) (Ta ble 2, En tr y 5). Ethyl-
benzene (4) (2.12 g, 20 mmol), benzenesulfonyl chloride (12)
(1.77 g, 10 mmol), and iron(III) chloride (80 mg, 0.5 mmol) were
placed in the reactor. Under stirring, the mixture was irradi-
ated for 4 min with a maximum temperature controlled to 135
°C. After treatment similar to that used before, the crude
product (white solid) was analyzed by GC (125 °C to 300 °C;
20 °C/min; 3 peaks, tR ) 8.03, 8.21 and 8.51 min, 20/8/72) and
identified as a mixture of isomers of the (ethylphenyl) phenyl
sulfone (27).15 Mass obtained: 2.32 g (94% yield from 12).
that FeCl3 is a catalyst able to give a convenient sulfo-
nylation of toluene in a short reaction time, a search of
optimal MW irradiation conditions were undertaken with
benzene and various of its derivatives. Three different
MW irradiations were undertaken: CMWI or MWIC,
with the more reactive and/or nonvolatile reagents, and
SMWI, with the less reactive and/or low boiling ones.
Yields were good and reaction times often very short
(CMWI).
Under solvent-free conditions, an excess of aromatic
is necessary to achieve a homogeneous medium, but this
excess must be limited to allow MW-absorbent species,
in proportionately small amounts, to induce a fast enough
temperature rise. Effectively, the study of the interaction
between a MW radiation and chemical species involved
in the reaction showed that the most absorbent species
is the reaction product, the aryl sulfone, and especially
its FeCl3 complex. However, the MW absorbed energy is
completely converted into thermal energy. Indeed, non-
thermal activation was not observed. A noticeable in-
crease in rate of sulfonylation of chlorobenzene was
observed under MWs relative to thermal heating. This
activation is not due to a nonthermal effect, but to a
specific effect of MW heating, resulting in the superheat-
ing of liquid chlorobenzene that, without stirring, delays
its boiling (NLBP). These observations are in agreement
with our previous results relating to the FC acylation5b,c
and recent publications concerning the kinetics of organic
reactions under MWs in homogeneous media.10
Among the technological aspects are the following: (1)
recent progress in the design of MW apparatus, in
particular the control of reaction mixture temperature,
has allowed open reactors to be used, thereby avoiding
thermal degradation of products; and (2) owing to the
different modes of irradiation, MW heating can be
adapted to each reaction according to the reactivity and
bp of the starting compound.
Microwave heating is no longer a laboratory curiosity
of questionable use; its broad potential has already been
clearly demonstrated, sometimes in solvent-free condi-
tions,11 an aspect of particular importance for reactions
on a scaled-up industrial process. We are exploring this.
Typ ica l P r oced u r e for th e SMWI Mod e: Ben zen esu lfo-
n yla tion of Ben zen e (6) (Ta ble 3, En tr y 2). Benzene (6)
(2.12 g, 20 mmol), benzenesulfonyl chloride (12) (1.77 g, 10
mmol), and iron(III) chloride (80 mg, 0.5 mmol) were put into
the reactor, and the mixture was stirred. A MW irradiation of
300 W applied power was programmed using the computer
according to a sequential process of irradiation in which the
sample was exposed to MWs for periods of 15 s separated by
periods of 45 s. This sequence was repeated six times. At the
end of the irradiation, a maximum temperature of 160 °C was
indicated by the IR pyrometer. The same workup as before
gave a crude product (white solid) identified as the diphenyl
sulfone (30) [127-63-9] by comparison with a pure sample.16,17
Mass obtained: 1.92 g (88% yield from 12): mp (from etha-
nol): 123 °C [lit.16 mp 122-123 °C].
Exp er im en ta l Section
Gen er a l Meth od s. All starting materials, including metal-
lic salts, with the exception of bismuth(III) and iron(III)
trifluoromethanesulfonates, were commercially available (from
Aldrich). Bismuth(III) trifluoromethanesulfonate was prepared
as previously described from triphenylbismuth and triflic
acid.12,13 The experimental procedure of MW heating using a
monomode MW oven, equipped with an IR pyrometer, have
been previously described.5b,c The diaryl sulfones being solid
products, the use of an excess of the starting aromatic
compound permitted the retention of a homogeneous liquid
medium during the reaction.
Ack n ow led gm en t. Support of this work by the
Centre National de la Recherche Scientifique and
Rhodia Organique Fine is gratefully acknowledged. We
thank Professor M. Onyszchuk (McGill University) for
his assistance in the preparation of the manuscript. We
thank also Dr. C. Le Roux (Paul-Sabatier University)
for a gift of iron(III) triflate.
Su p p or t in g In for m a t ion Ava ila b le: Gas chromato-
1
graphic, GC-MS, and H NMR analyses of sulfones 19-37; T
(10) Recent articles concerning the question of nonthermal effects
of MWs on the rates of organic reactions: (a) Gedye, R. N.; Wei, J . B.
Can. J . Chem. 1998, 76, 525; (b) Gedye, R. N. Ceram. Trans. 1997, 80,
165.
and P (MW incident power) ) f(MW irradiation time) curves
for each irradiation mode (Figures SI.1-3). This material is
(11) Recent reviews: (a) Loupy, A.; Petit, A.; Hamelin, J .; Texier-
Boulet, F.; J acquault, P.; Mathe´, D. Synthesis 1998, 1213. (b) Loupy,
A. In Top. Curr. Chem. 1999, 206 (Modern Solvents in Organic
Synthesis; Knochel, P.; Ed.), 153. (c) Loupy, A.; Haudrechy, A. In
Me´thodes et techniques de la chimie organique; Presses Universi-
taires: Grenoble, France, 1999; Chapter 6, pp 239-277. (d) Varma,
R. S. Green Chem. 1999, 43 and references therein.
(12) Labrouille`re, M.; Le Roux, C.; Gaspard, H.; Laporterie, A.;
Dubac, J .; Desmurs, J . R. Tetrahedron Lett. 1999, 40, 285.
(13) Loue¨r, M.; Le Roux, C.; Dubac, J . Chem. Mater. 1997, 9, 3012.
J O0010173
(14) Truce, W. E.; Ray, W. J . J . Am. Chem. Soc. 1959, 81, 481.
(15) (a) Horner, L.; Subramaniam, P. V. Liebigs Ann. 1968, 714, 91.
(b) Drozd, V. N.; Nikonova, L. A. Zh. Org. Khim. 1969, 5, 1453.
(16) Henze, H. R.; Artman, N. E. J . Org. Chem. 1957, 22, 1410.
(17) Huismann, J . (General Aniline & Film Corp.) US Patent
2,224,964, Dec 17, 1940; Chem. Abstr. 1941, 35, 21589.