Solvent-free Dieckmann condensation reactions of diethyl adipate
and pimelate
Fumio Toda,* Takaaki Suzuki and Satoru Higa
Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyma,
Ehime 790-8577, Japan
Received 28th July 1998, Accepted 22nd September 1998
Table 1 Yields of solvent-free Dieckmann condensation reaction
Dieckmann condensation reactions of diethyl adipate and
pimelate proceeded efficiently in the absence of solvent,
and the reaction products were collected by a direct
distillation from the solvent-free reaction mixture.
products 2a and 2ba
Base
Yield of 2a (%)
Yield of 2b (%)
ButOK
ButONa
EtOK
82
74
63
61
69
68
56
60
Dieckmann condensation reactions of diesters should be carried
out in dried solvent under reflux in an inert atmosphere.1,2
Furthermore, Dieckmann reactions are often carried out under
high dilution conditions in order to avoid intramolecular reac-
tion.1,2 We found, however, that the reaction of diethyl adipate
1a and pimelate 1b (diethyl hexanedioate and heptanedioate,
EtONa
a All reactions were carried out at room temperature for 10 min and the
reaction mixture was kept in a desiccator for 60 min.
Table 2 Yields of 2a and 2b obtained by Dieckmann condensation
reaction in toluenea
Base
Yield of 2a (%)
Yield of 2b (%)
ButOK
ButONa
EtOK
98
69
41
58
63
56
60
60
EtONa
a All reactions were carried out in toluene under reflux for 3 h.
Scheme 1
The solvent-free Dieckmann condensation of 1a and 1b also
proceeds efficiently in the presence of powdered ButONa,
EtOK and EtONa as summarized in Table 1. For comparison
with the solvent-free reaction, the Dieckmann condensation
of 1a and 1b with the same base in toluene under reflux was
studied. As shown in Table 2, there is no marked difference
between the yields of solvent-free and solvent reactions. This
clearly shows that the solvent-free reaction is much better than
the other in terms of simplicity, cleanliness and economy.
In order to accomplish an enantioselective solvent-free
Dieckmann reaction, the condensation was carried out in an
respectively) proceeds efficiently in the absence of solvent under
air. We also succeeded in isolating the reaction products from
the reaction mixture directly by distillation. These results
establish a completely solvent-free procedure throughout the
reaction and work-up of the reaction mixture. This is a very
clean, green, simple and economical procedure.
After mixing 1a and powdered ButOK for 10 min at room
temperature using a mortar and pestle, the solidified reaction
mixture was kept in a desiccator for 60 min in order to complete
the reaction and evaporate the ButOH formed. The dried reac-
tion mixture was neutralized by addition of p-TsOHؒH2O and
distilled under reduced pressure to give 2a in 82% yield. The
details of the procedure are given in the Experimental section.
In contrast to the simple solvent-free procedure, the normal
reaction of 1a is carried out in dried toluene under reflux
using Na metal under an N2 atmosphere and the reaction
product 2a is isolated in 74–81% yield by the following suc-
cessive work-up: neutralization with AcOH, evaporation of
toluene and distillation.2 The residue left after the distillation
contains some recovered ester. When the solvent-free reaction
mixture of 1a and ButOK is distilled after neutralization with
p-TsOHؒH2O, 2a was obtained in 82% yield by the solvent-free
procedure and isolation of the product has many advantages.
The same treatment of 1b with ButOK in the absence of solvent
followed by distillation gave 2b in 69% yield.
Ph2C
OH
O
H
(R, R) - ( – ) -
H
O
Ph2C OH
3
OEt
CH2
O
O
C
C
CH2
CH2
CH2
OEt
Solvent-free and solid–solid organic reactions have been well
established.3 However, the reaction products are isolated from
the reaction mixture by extraction with solvent in most cases,
although the reaction product can be separated by filtration
in some special cases, such as those where the reaction can be
carried out in a water suspension.4 In contrast to these solid
state reactions, the solvent-free Dieckmann condensation needs
no liquid throughout the entire process.
Ph2C OH
1a
O
H
(R, R) - ( – ) -
H
O
3
Ph2C OH
4
J. Chem. Soc., Perkin Trans. 1, 1998, 3521–3522
3521