34
J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
Thermolysis Improvements in Retro-Diels–Alder Reactions
of Benzylamino Alcohols under Microwave Irradiation†
Michel Bortolussi,* Robert Bloch and Andr e´ Loupy
1
998, 34–35†
R e´ activit e´ et Synth e` se S e´ lective (UA CNRS 478), I.C.M.O., B aˆ t. 420, Universit e´ de Paris-Sud,
91405 Orsay, France
Microwave activation under solvent-free conditions is shown to be the best procedure for performing retro-Diels–Alder
reactions.
Retro Diels–Alder reactions often require drastic conditions,
high temperatures and even sometimes flash vacuum ther-
molysis (FVT). Such thermolytic procedures have been
used to prepare unsaturated amino alcohols from a variety of
amino alcohols (Scheme 1).
of 6–10 h were necessary to obtain acceptable yields (how-
ever always lower than under microwaves) of less pure
products. The specific effect of microwaves is here very
important, although not always obvious under homogeneous
1
–4
10
conditions. It is interesting to note that such an intrinsic
effect of microwaves occurs in the most difficult cases yet
R
11
observed for other types of solvent-free reactions. Such an
O
H
R′
12
N
CH2Ph
observation is coherent with a remark of Lewis who under-
R′
CH2OH
CH2Ph
heat
+
H
lined a generalization which has recently become obvious,
stating that the more important microwave effects are con-
nected to the more difficult reactions.
N
O
R
CH2OH
Scheme 1
Microwave activation coupled with solvent-free conditions
is shown to be by far the most efficient method for perform-
ing these retro Diels–Alder reactions. The improvements are
remarkable if we consider that both classical thermolysis and
FVT (leading to decomposition) are poorly productive (or
non-operative). Especially for monobenzylated amino com-
pounds 1c–e, solvent-free conditions plus microwave irradia-
tion constitute the only method of giving fast and clean
reactions.
In the case of dibenzylamino alcohols (R = PhCH ), satis-
2
factory yields are obtained by refluxing in xylene solution for
rather long times (6 h). However, these conditions prove
unsuccessful in the case of monobenzylamino compounds
(
R = H) where only a solvent-free method (heating of the
neat product for 6 h at 160 °C) leads to a mostly clean reac-
tion. Owing to the lack of volatility of these compounds, FVT
is not useful in this case, since decomposition occurs before
evaporation in the hot tube. A dry technique, coupled with
microwave activation, has been advocated in the case of high-
O
H
R3
R1
6
,7
temperature transformations and for the displacement of
N
R2
8
volatile polar molecules.
CH2OH
Several reactions were therefore performed under micro-
wave irradiation for a variety of neat liquid adducts 1 using a
single mode reactor (Synthewave 402 apparatus from Pro-
labo) in order to control precisely the experimental condi-
tions (power and temperature). To check the possible
specific effects (non-thermal) of microwaves, the results were
compared with those obtained under conventional heating in
a thermostatted oil bath, conditions elsewhere being equal.
Yields were quantitative for all five desired products within
very short times (10 or 15 min) and at relatively low tempera-
tures (120–140 °C). A very important specific effect of micro-
waves is clearly exemplified, as on conventional heating
under strictly otherwise identical conditions yields were less
than 2%. Under classical thermal conditions, reaction times
1
a R1 = R2 = CH2Ph, R3 = Bun
b R = R2 = CH2Ph, R3 = [CH2]3OCH2Ph
1
c R = H, R2 = CH2Ph, R3 = Bun
1
d R1 = H, R2 = CH2
OMe, R3 = [CH2]3OCH2Ph
d R1 = H, R2 = CH2
OMe, R3 = Bun
R3
CH2OH
H
+
1
N
O
R1
R2
2
Scheme 2
Table 1 Microwave-assisted thermolysis of neat benzylamino alcohols 1a–e
Microwave activation
Classical heating
a
Time
(t/min)
Yield (%)
of 2
Time
(t/min)
a
Substrate
T/°C
T/°C
Yield (%)
1
a
120
15
10
10
15
15
15
15
66
P98
P98
P98
P98
P65
P98
140
140
180
480
70
84
1
40
1
1
1
1
b
c
d
e
140
120
120
100
160
360
74
120
120
180
600
50
84
1
20
a
Isolated yield of pure product.
*
To receive any correspondence (e-mail: mbortolu@icmo.u-
Experimental
psud.fr).
Focused microwave irradiations were carried out with a Synthe-
wave S402 single mode reactor from Prolabo (2450 MHz, 300 W)
†This is a Short Paper as defined in the Instructions for Authors,
9
Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
with irradiation monitoring by PC, infrared measurement and
continual feedback temperature control. Indicated temperatures