Ecofriendly fast batch synthesis of dioxolanes, dithiolanes, and oxathiolanes without solvent under microwave irradiation

Article abstract of DOI:10.1021/op980043o

2,2-Dimethoxypropane and 3,3-dimethoxypentane react with 1,2-ethanediol, thio, and oxathio analogues to give the corresponding protected carbonyls in high yield under mild solvent-free conditions. These environmentally benign conditions under microwave irradiation are applied to a large-scale synthesis.

Full text of DOI:10.1021/op980043o

Organic Process Research & Development 1998, 2, 428−430
Ecofriendly Fast Batch Synthesis of Dioxolanes, Dithiolanes, and Oxathiolanes
without Solvent under Microwave Irradiation
†
‡
,†
Bertrand Perio, Marie-Joelle Dozias, and Jack Hamelin*
Synth e` se et Electrosynth e` se Organiques 3, CNRS et UniVersit e´ de Rennes 1, Campus de Beaulieu, 35042 Rennes, France
and Prolabo, 54 rue Roger Salengro, 94126 Fontenay sous bois, France
Abstract:
Scheme 1. Preparation of 2,2-dimethyl and
2,2-diethyl-1,3-dioxolanes, dithiolanes, and oxathiolanes
2
1
,2-Dimethoxypropane and 3,3-dimethoxypentane react with
,2-ethanediol, thio, and oxathio analogues to give the corre-
sponding protected carbonyls in high yield under mild solvent-
free conditions. These environmentally benign conditions under
microwave irradiation are applied to a large-scale synthesis.
Introduction
1
In a recent paper, we have reported various methods for
solvent-free protection of carbonyl groups under focused
microwave irradiation. The best procedure to prepare
dioxolanes was shown to be the exchange with 2,2-dimethyl-
1,3-dioxolane (DMD) over montmorillonite clay K10 under
microwave irradiation for 10-30 min in a Synthewave 402
apparatus.2 Although this is a two-step process (synthesis
of the dioxolane and then exchange), it gives better yields
without solvent as compared to the literature methods which
use benzene or toluene.
So, owing to the need for large quantities of DMD and
to its relatively high price, we decided to look for a less
expensive large-scale, solvent-free synthesis of this com-
pound and some related derivatives in order to check their
reactivity in exchange reactions.
This was achieved with DMD as a model on a 10 mmol
scale starting from acetone dimethyl ketal 1a and ethylene
glycol 2 (X ) Y ) O, 1 equiv) in the presence of 0.1 g of
montmorillonite clay K10 under microwave irradiation
during 30 min in a Synthewave 402 apparatus.5 The
temperature was monitored at 70 °C by continuous adjust-
ment of the emitted power between 0 and 150 W.
After filtration of K10, the workup is quite tedious,
because DMD 3a and methanol distilled together. This
problem was solved by extraction with chloroform, washing
with water, and then distillation through a glass helices-
packed column (bp 91-92 °C, conversion 96%, isolated
yield 75%).
The synthesis of DMD was previously described by
3
Dauben et al. according to the following procedure: acetone
and ethylene glycol in equimolecular amounts were added
with a catalytic amount of p-toluene sulfonic acid and
refluxed in benzene during 30 h in a modified Dean-Stark
separator. After workup and distillation through a glass
helices-packed column, the yield was 65%.
1
b is not commercially available, and we carried out the
Results and Discussion
synthesis from 3-pentanone (10 mmol) and methyl ortho-
formate (10 mmol) with clay K10 (0.1 g) under microwave
irradiation (15 min at 60 °C, 150 W). The conversion was
quantitative, and we got the resulting ketal 1b, which was
further reacted without purification with glycol 2 (X ) Y )
O) under the conditions described for DMD to give 2,2-
diethyl-1,3-dioxolane (3b, DED) in 88% yield after distil-
lation (bp 139 °C) (Scheme 1). These reactions were
extended on a 10 mmol scale to ethanedithiol and 2-hydroxy
ethanethiol for the preparation of the corresponding five-
membered rings.
According to our previous studies related to synthesis in
dry media under microwave irradiation,1,4 we tried to set up
an easier, cleaner, and faster procedure.
*
To whom correspondence should be addressed. Phone (33) 02 99 28 62
7
8, fax (33) 02 99 28 63 74, e-mail Jack.Hamelin@univ-rennes1.fr.
†
CNRS et Universit e´ de Rennes 1.
Prolabo.
‡
(
1) Perio, B.; Dozias, M. J.; Jacquault, P.; Hamelin, J. Tetrahedron Lett. 1997,
8, 7867 and references therein.
3
(
2) Commarnot, R.; Didenot, R.; Gardais, J. F. Fr. Demande, 2560529 (Cl.
B01J19/12), 06 Sept 1985, Appl. 84/3,496, 02 Mar 1984; Chem. Abstr.
1
986, 105, 17442e. Temperature measured by an IR captor: Prolabo, Fr.
Patent 62241D, 14669Fr, 23 Dec 1991.
(
(
3) Dauben, J.; L o¨ ken, B.; Ringold, H. J. J. Am. Chem. Soc. 1954, 76, 1359.
4) Jolivet-Fouchet, S.; Hamelin, J.; Texier-Boullet, F.; Toupet, L.; Jacquault,
P. Tetrahedron 1998, 54, 4561.
5) This apparatus operates with a power between 0 and 300 W, having quartz
reactors (8 cm high; 4, 2.5, or 1.5 cm diameter) fitted with a stirring device
and monitored either in power or in temperature.
(6) Patent ref 2. This apparatus operates with an adjustable power between 0
and 800 W and may be monitored either in power or in temperature. The
cylindrical quartz reactor (10 cm diameter) has a useful volume of 800
mL. The cover allows mechanical stirring, reflux, and, eventually addition
during the reaction.
(
4
28
•
Vol. 2, No. 6, 1998 / Organic Process Research & Development
10.1021/op980043o CCC: $15.00 © 1998 American Chemical Society and Royal Society of Chemistry
Published on Web 10/02/1998

Scheme 2. Two-step process for preparation of dioxolanes,
dithiolanes, and oxathiolanes
Table 1. Conditions and results for the synthesis of 3
temp,
°C
isolated
isolated
Figure 1. Photograph of Synthewave 1000 apparatus as it is
3
Ra
X
Y
weight, g yield, % literatureb
used.
a
b
c
d
e
f
Me
Et
Me
Et
Me
Et
O
O
S
S
O
O
O
O
S
S
S
S
70
80
70
80
70
80
154
231
240
269
203
252
75
88
90
83
86
86
3, 7, 8
8
9-11
To scale-up these syntheses, we used a Synthewave 1000
apparatus fitted with a 1-L quartz reactor, a mechanical
stirrer, and a glass helices-packed column (15 cm long, 1
cm diameter), as shown in Figure 1.
6
We worked on a 2-mol scale in a two-step process
according to Scheme 2 without any solvent.
a
When R ) Me, only the second step is realized, and irradiation lasts 30
min. When R ) Et, the two steps are carried out, 15 min for the first and 30
b
min for the second. Reactions are usually run in solution at a small scale and
During the first step, the resulting methyl formate was
continuously distilled so that, at the end of the process, we
got nearly pure ketal (NMR) 1b, R ) Et (1a is commercialy
available and was used directly in the second step). Then,
after addition of the substituted ethane 2, the irradiation was
continued during 30 min with continuous distillation of
methanol.
require 5-16 h to give equivalent or much lower yields, except for in ref 11,
where a quantitative yield is reported.
In fact, the 2-mol scale was easier than the 10-mmol scale,
owing to the possibility of continuous distillation under
irradiation in the Synthewave 1000 with a packed column,
which is not possible in the smaller Synthewave 402. It is
noteworthy that the conditions (time, temperature) were
exactly the same going from the 10-mmol scale to the 2-mol
scale.
Under these conditions, we got the various protected
carbonyls 3, together with 10% methanol, which was further
7
-14
removed by distillation to give pure 3a-f (see Table 1).
In summary, we have developed a new technique for the
synthesis of dioxolanes, dithiolanes, and oxathiolanes which
is fast, environmentally friendly, and easily scaled up.
(
(
(
7) Fife, T. H.; Hagopian, L. J. Org. Chem. 1966, 31, 1772.
8) Gelas, J.; Michaud, S. Bull. Soc. Chim. Fr. 1972, 6, 2445.
9) Shigeo, J.; Shigeo, T.; Tatsuo, O.; Masaya, O. Bull. Soc. Chim. Jpn. 1981,
4, 1434.
10) Keshinen, R.; Nikkil a¨ , A.; Pihlaja, K. J. Chem. Soc., Perkin Trans. 2 1973,
0, 1376.
5
(
(
1
Experimental Section
11) (a) Bernardi, F.; Distefano, G.; Modelli, A.; Pichopaolo, D.; Ricci, A. J.
Organomet. Chem. 1977, 28, 331. (b) Kim, J. K.; Pau, J. K.; Caserio, M.
C. J. Org. Chem. 1979, 44, 1544. (c) Fuhrer, H.; G u¨ nthard, H. H. HelV.
Chim. Acta 1962, 45, 2036.
In a typical experiment, we prepared 3b in the following
way: 3-pentanone (2 mol, 172.26 g), methyl orthoformate
(
12) Patney, H. K. Tetrahedron Lett. 1994, 35, 5717.
(14) Rakhmankulov, D. L.; Zorin, V. V.; Latypova, F. N.; Zlot-Skii, S. S. Ups.
Khim. 1983, 52, 619.
(13) Djerassi, C.; Gorman, M. J. Am. Chem. Soc. 1953, 75, 3704.
Vol. 2, No. 6, 1998 / Organic Process Research & Development
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429

(
2 mol, 212.24 g), and clay K10 (20 g, purchased from
filtered to remove K10 and distilled over a glass helices-
packed column to give 3b (bp 139 °C, 231 g, 88% yield).
The same procedure was applied for the syntheses of 3d
and 3f. In the cases of 3a,c,e, only the second step was
realized at an assigned temperature of 70 °C.
-1
Prolabo-France, d ) 300-370 g‚L , specific area ) 220-
2
placed in the 1-L quartz reactor of the Synthewave 1000
apparatus under mechanical stirring. The assigned temper-
ature of 60 °C was reached in 2 min and maintained during
2
-1
+
70 m ‚g , Na exchanged without further activation) were
13 min by continuous adjustment of the power between 0
Acknowledgment
and 150 W. During this time, the resulting methyl formate
was distilled. Then, ethylene glycol (2 mol, 124.14 g) was
added and irradiation started again in order to reach 80 °C
in 1 min. This temperature was maintained during 29 min.
During this time, methanol was distilled. The remaining
product, which still contained 10% methanol, was then
B.P. thanks Agence de l’Environnement et de la Maitrise
de l’Energie and Prolabo for a research fellowship.
Received for review May 14, 1998.
OP980043O
430
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Vol. 2, No. 6, 1998 / Organic Process Research & Development