Catalytic production of urethanes from amines and alkyl halides in supercritical carbon dioxide

Article abstract of DOI:10.1039/a908819i

Some common onium salts catalysed selective urethane production from amines and alkyl halides in supercritical carbon dioxide, which acted not only as an alternative to organic solvents but also as a phosgene replacement; the reaction efficiency was 50-10

Full text of DOI:10.1039/a908819i

Catalytic production of urethanes from amines and alkyl halides in
supercritical carbon dioxide
Masaaki Yoshida,* Namiko Hara and Sanae Okuyama
Applied Chemistry, Faculty of Engineering, Utsunomiya University, Utsunomiya 321-8585, Japan.
E-mail: yoshidam@cc.utsunomiya-u.ac.jp
Received (in Cambridge, UK) 5th November 1999, Accepted 7th December 1999
1
2
3
Some common onium salts catalysed selective urethane
production from amines and alkyl halides in supercritical
carbon dioxide, which acted not only as an alternative to
organic solvents but also as a phosgene replacement; the
reaction efficiency was 50–100 times higher than that
attained in heptane.
Table 1 Bu
4
NBr catalysed urethane production from R R NH, R X and
K CO
2 3
in scCO a
2
4
Bu NBr/
mol%
R1
R2
R X
3
t/h
Yield (%)b
–
–
(CH
(CH
2
)
)
4
–
–
BuCl
5
5
5
2
2
2
2
2
2
2
2
2
2
1
1
1
4
quant. (85)
76
2
4
CH
Bu
3
(CH
Br
2 7
) Cl
The most widely utilized method for the synthesis of urethanes
uses highly toxic phosgene as a reagent in organic solvents,
which are also toxic and flammable. Therefore the conventional
method involves environmental and safety problems.
–(CH ) –
–(CH
s
73
2
4
2
)
5
–
BuCl
BuCl
BuCl
BuCl
BuCl
BuCl
BuCl
BuBr
BuBr
BuBr
BuCl
5
15
5
5
5
5
5
5
5
quant. (85)
72 (62)
86 (81)
90 (82)
74
–(CH
2
)
2
O(CH
Me
Et
Bu
6
2 2
) –
Me
Et
Bu
Owing to the above mentions, much effort has been directed
toward alternative routes for preparation of urethanes using
carbon dioxide as a phosgene replacement.1 Carbon dioxide is
well known to react rapidly with amines to form carbamic acid
ammonium salts.9 However, as the nucleophilicity of the
carbamate anion is lower than that of the amine formed in the
equilibrium of the salt formation reaction, the reaction of the
carbamate salts with alkyl halides does not selectively afford
urethanes.2 So, the activation of the carbamate anion was
attempted by addition of crown ethers and strong bases.4
Monsanto’s chemists have achieved a highly selective urethane
synthesis process using very strong bases (e.g. CyTMG: N-
C H
6 11
C
H
11
72
–8
Ph
Me
H
H
H
H
quant. (94)
quant. (90)
quant. (90)
91 (85)
75
Bu
CH
Bn
Ph
2
NCHCH
2
5
20
a
Reaction was conducted at 100 °C, 80 atm in a 50 ml stainless steal
autoclave containing amine (5 mmol), alkyl halide (8 mmol) and K CO (10
mmol). b Estimated by H NMR, isolated yield in parentheses.
2
3
5
1
7
cyclohexyl-NA,NA,NB,NB-tetramethylguanidine). However, be-
carbonate. From the resulting 98% yield of urethane, it was
confirmed that scCO acts not only as a solvent but also as a
direct starting material for the urethane in our reaction
cause a stoichiometric amount of CyTMG was necessary in the
reaction, the Monsanto process could not replace the conven-
tional method.
2
10
system.
We have successfully synthesized urethanes in high yields
from amines, alkyl halides, potassium carbonate and a catalytic
amount of an onium salt in supercritical carbon dioxide
Consequently, the mechanism of the reaction could be
explained as follows (Scheme 1). First, the amine readily forms
the carbamic acid ammonium salt upon the introduction of
2
(scCO ) [eqn. (1)]. Supercritical carbon dioxide is an attractive
2
liquid carbon dioxide. The salt starts to dissolve in scCO as the
1
2
3
onium salt
1
2
3
temperature increases. At the reaction temperature (100 °C), the
ion exchange reaction takes place between the carbamate salt
and tetrabutylammonium bromide. As a result, the carbamate
anion is activated by the tetrabutylammonium ion and readily
reacts with alkyl halide to form urethane and potassium halide
in the presence of potassium carbonate. At the same time,
tetrabutylammonium bromide is regenerated to complete the
catalytic reaction cycle. If tetrabutylammonium bromide is
absent, the amine formed by the reverse reaction of the
equilibrium of the carbamate salt formation attacks alkyl halide
R R NH + R X + K CO æææææÆ R R NCOOR
2
3
(1)
scCO
2
alternative to organic solvents as it is environmentally benign,
essentially nontoxic, inexpensive, nonflammable and has rela-
tively low critical conditions (P = 73 atm, T = 31 °C).†
c c
The results of the one-pot urethane production are summa-
rized in Table 1. Not only aliphatic primary and secondary
amines but also aromatic amines reacted well. As these are
catalytic reactions, the low yields should be improved by
increasing the amount of catalyst or extending the reaction
time.
Table 2 Effect of catalyst on conversion of pyrrolidine, butyl chloride and
The effect of catalyst on the conversion of a pyrrolidine, butyl
chloride and potassium carbonate system in scCO is given in
2
a
2 3 2
K CO in scCO
Table 2. The reaction could be catalysed by amonium salts and
a phosphonium salt. Among these, the catalysts that afforded
the best results were tetrabutylammonium bromide and trioctyl-
ammonium chloride, which are commonly used in industry.
Sanchez and co-workers also reported a phosgene-replaced
urethane synthesis in heptane using amines, alkyl halides,
potassium carbonate and tetrabutylammonium hydrogensulfate,
Yield (%)b
Catalyst
Bu
4
Bu
4
Bu
4
Bu
4
NHSO
NBr
NI
4
69
74
51
48
66
73
PBr
[
[
CH
CH
3
(CH
(CH
2
)15NMe
2
Et]Br
MeNCl
3
2
) ]
7 3
as a solid/liquid phase-transfer reagent, without any additional
a
carbon dioxide.3 In their system, the carbonyl source was
Reaction was conducted at 100 °C, 80 atm in a 50 ml stainless steal
CO
10 mmol) and catalyst (0.5 mmol) without stirring for 2 h. b Estimated by
autoclave containing pyrrolidine (5 mmol), butyl chloride (6 mmol), K
2
3
potassium carbonate. In order to determine the carbonyl source
(
2
in our system, we tried a reaction in scCO with pyrrolidine,
1
H NMR.
butyl chloride and potassium phosphate in place of potassium
Chem. Commun., 2000, 151–152
This journal is © The Royal Society of Chemistry 2000
151

Notes and references
†
2
Typical experimental procedure: For carrying out the reactions in scCO ,
a 50 ml stainless steel autoclave (Taiatsu Techno portable reactor TVS-N2)
was used. Potassium carbonate (10 mmol), tetrabutylammonium bromide
(0.25 mmol), pyrrolidine (5 mmol) and butyl chloride (8 mmol) were
successively placed in the reaction vessel. The vessel was sealed and then
liquid carbon dioxide (ca. 12.3 g) was introduced from a cylinder at room
temperature. The reaction system was heated with a boiling water bath (ca.
1
00 °C). The pressure of the mixture reached ca. 80 atm and the mixture was
stirred magnetically for 2 h. In completion, the reaction vessel was cooled
with an ice bath and the pressure was released slowly to atmospheric
pressure. The residual mixture was extracted with chloroform and the yields
1
of urethane were estimated by H NMR.
1
2
T. Tsuda, H. Washita, K. Watanabe, M. Miwa and T. Saegusa, J. Chem.
Soc., Chem. Commun., 1978, 815; T. Tsuda, K. Watanabe, K. Miyata,
H. Yamamoto and T. Saegusa, Inorg. Chem., 1981, 20, 2728.
Y. Yoshida, S. Ishii and T. Yamashita, Chem. Lett., 1984, 1571; Y.
Yoshida, S. Ishii, M. Watanabe and T. Yamashita, Bull. Chem. Soc.
Jpn., 1989, 62, 1534.
Scheme 1
3
4
V. G. Parra, F. Sanchez and T. Torres, Synthesis, 1985, 282.
Y. Hori, Y. Nagano, J. Nakao, T. Fukuhara and H. Taguchi, Chem.
Express, 1986, 1, 224.
to form highly alkylated amines, and as a result the selectivity of
the urethane formation decreases.
Our reaction system is the first example of catalytic urethane
production. Also we found that the efficiency of the reaction in
5
M. Aresta and E. Quaranta, J. Org. Chem., 1988, 53, 4153; M. Aresta
and E. Quaranta, J. Chem. Soc., Dalton Trans., 1992, 1893; M. Aresta
and E. Quaranta, Tetrahedron, 1992, 48, 1515.
6
7
K. J. Butcher, Synthesis, 1994, 825.
2
scCO is 50–100 times higher than that attained in heptane.
W. D. McGhee, B. L. Parnas, D. P. Riley and J. J. Talley, U.S. Patent
No. 5,223,638, June 29, 1993; W. McGhee, Y. Pan and D. P. Riley,
J. Chem. Soc., Chem. Commun., 1994, 699; W. McGhee, D. P. Riley, K.
Christ, Y. Pan and B. Parnas, J. Org. Chem., 1995, 60, 2820.
Indeed, the urethane yield was less than 2% with pyrrolidine and
butyl chloride, and less than 1% with butylamine and butyl
bromide, in heptane.
In conclusion, we have achieved catalytic one-pot urethane
synthesis from amines and alkyl halides in supercritical carbon
dioxide and also achieved a phosgene replacement and organic
solvent replacement by using common onium salts as catalysts.
Our process is environmentally benign and also has benefits
economically.
8 A. Inesi, V. Mucciante and L. Rossi, J. Org. Chem., 1998, 63, 1337.
9 J. T. Edsall, Biophysical Chemistry, Academic Press, New York, 1958,
vol. 1, 571.
1
0 We also tried the reaction without potassium carbonate in scCO
2
, and
the urethane was obtained in a yield of 8%.
Communication a908819i
152
Chem. Commun., 2000, 151–152