Is CO2 fixation promoted through the formation of DBU bicarbonate salt?

Article abstract of DOI:10.1002/hc.21014

The bicyclic amidines, 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) and 1,5-diazabicyclo[4.3.0] non-5-ene (DBN), were used for the chemical fixation of carbon dioxide. The promotion for CO₂ fixation is often reported through the formation of a thermally unstable DBU or DBN bicarbonate salt. To examine the effects of the DBU or DBN bicarbonate salt, reactions of 2-aminobenzonitrile with the DBU salt or DBN salt in dimethylformamide (DMF) were performed at 20°C for 24 h in argon or carbon dioxide (0.1 MPa). However, in all the cases, 1H-quinazoline-2,4-dione was not obtained completely. In contrast with room temperature reactions, 2-aminobenzonitriles and DBU bicarbonate salt in DMF reacted for 4 h under high temperature (80°C) and CO₂ atmosphere (0.1 MPa) gave 1H-quinazoline-2,4-diones in good to excellent yields. At high-temperature conditions, DBU bicarbonate salt is decomposed to DBU and carbon dioxide. Also, the carbonylation of 2-aminobenzonitrile using DBU and carbon dioxide afforded 1H-quinazoline-2,4- dione in good yields under similar reaction conditions. These results suggest that the combination of DBU or DBN as a strong base and carbon dioxide is much more important than the in situ formation of DBU or DBN bicarbonate salt for the acceleration of CO₂ fixation.

Full text of DOI:10.1002/hc.21014

Heteroatom Chemistry
Volume 23, Number 3, 2012
I
s CO Fixation Promoted through the
2
Formation of DBU Bicarbonate Salt?
Takumi Mizuno, Takeo Nakai, and Masatoshi Mihara
Osaka Municipal Technical Research Institute, 1-6-50, Morinomiya, Joto-ku,
Osaka 536-8553, Japan
Received 4 December 2011; revised 10 January 2012
INTRODUCTION
ABSTRACT: The bicyclic amidines, 1,8-diazabicyclo
[
5.4.0]undec-7-ene (DBU) and 1,5-diazabicyclo[4.3.0]
The activation of carbon dioxide with bi-
cyclic amidines, 1,8-diazabicyclo-[5.4.0]undec-7-ene
(DBU) and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)
non-5-ene (DBN), were used for the chemical fixation
of carbon dioxide. The promotion for CO fixation is
2
often reported through the formation of a thermally
unstable DBU or DBN bicarbonate salt.To examine the
effects of the DBU or DBN bicarbonate salt, reactions
of 2-aminobenzonitrile with the DBU salt or DBN salt
was achieved for the chemical fixation of CO . Car-
bon dioxide forms the thermally unstable complex
2
(1a) with DBU, which decomposes to DBU and car-
◦
bon dioxide at more than 58 C. Similarly, complex
◦
in dimethylformamide (DMF) were performed at 20 C
(1b) formed from CO and DBN decomposes at more
2
◦
for 24 h in argon or carbon dioxide (0.1 MPa). How-
ever, in all the cases, 1H-quinazoline-2,4-dione was
not obtained completely. In contrast with room tem-
perature reactions, 2-aminobenzonitriles and DBU bi-
than 30 C [1,2]. These complexes have often been
cited as an explanation for the promotion of CO fix-
2
ation [3–6]. Recently, Jessop et al. reported that the
DBU–CO complex (1a) is consistent with the for-
2
+
−
carbonate salt in DMF reacted for 4 h under high
mation of DBU bicarbonate salt, [DBU H ][HCO ],
3
◦
temperature (80 C) and CO
2
atmosphere (0.1 MPa)
in the presence of water [7].
gave 1H-quinazoline-2,4-diones in good to excellent
yields. At high-temperature conditions, DBU bicarbon-
ate salt is decomposed to DBU and carbon dioxide.
Also, the carbonylation of 2-aminobenzonitrile using
DBU and carbon dioxide afforded 1H-quinazoline-2,4-
dione in good yields under similar reaction conditions.
These results suggest that the combination of DBU or
DBN as a strong base and carbon dioxide is much
more important than the in situ formation of DBU or
In 2000, we reported a convenient synthesis
method of 1H-quinazoline-2,4-diones 2 from 2-
aminobenzonitriles 3 by the chemical fixation of car-
◦
bon dioxide under mild conditions (0.1 MPa, 20 C)
in the presence of excess amount of DBU or DBN in
dimethylformamide (DMF) [8,9]. Furthermore, we
also found that catalytic amount of DBU or DBN
2
has the exceptional ability for the fixation of CO to
◦
give 2 in excellent yields under 1.0 MPa at 80 C in
DBN bicarbonate salt for the acceleration of CO
ation. ꢀC 2012 Wiley Periodicals, Inc. Heteroatom Chem
3:276–280, 2012; View this article online at wileyonlineli-
2
fix-
DMF or DMSO [10].
Recently, solvent-free synthesis of substituted 2
in good yields from 3 with only carbon dioxide (0.1
MPa) and catalytic amount of DBU or DBN was es-
tablished [11]. This solvent-free synthesis of 2 was
2
brary.com. DOI 10.1002/hc.21014
◦
performed at high temperature (120–150 C) under
carbon dioxide (0.1 MPa) to avoid the solidification
of amidines with carbon dioxide. In these reaction
conditions, DBU bicarbonate salt (1a) and DBN bi-
carbonate salt (1b) are thermally unstable and easily
decompose to bases and carbon dioxide. Therefore,
Correspondence to: Takumi Mizuno; e-mail: tmizuno@
omtri.or.jp.
Contract grant sponsor: Ministry of Education, Culture, Sports,
Science and Technology, Japan.
Contract grant number: 22550144.
ꢀ
c 2012 Wiley Periodicals, Inc.
276

Is CO Fixation Promoted through the Formation of DBU Bicarbonate Salt? 277
2
◦
SCHEME 1 Reaction of amidine bicarbonate salts (1) with 2-aminobenzonitrile (3a) at 20 C.
SCHEME 2 High-temperature reactions of amidine bicarbonate salts (1).
the formation of these salts as active intermediates
is doubtful.
to afford 2a in good yield (87%). Similarly, using
DBN bicarbonate salt (1b) gave 2a in reasonable
yield (74%). Next, several 1H-quinazoline-2,4-diones
(
2
2b–e), which include the key intermediates (2b and
d) of medicines [11], were synthesized in good
RESULTS AND DISCUSSION
In this paper, the reactivity of DBU bicarbonate
salt (1a) and DBN bicarbonate salt (1b) with 2-
aminobenzonitriles 3 was examined. At first, DBU
salt (1a) and 2-aminobenzonitrile (3a) were mixed in
DMF and stirred at 20 C for 24 h in argon or carbon
dioxide atmosphere. Surprisingly, 1H-quinazoline-
to excellent yields from 2-aminobenzonitriles (3b–
e) and DBU bicarbonate salt (1a) in DMF with
carbon dioxide (0.1 MPa) under the similar high-
temperature conditions (Scheme 3).
◦
On the other hand, carbonylations of 3a with
◦
DBU and carbon dioxide (0.1 MPa) at 20 C for 24 h
◦
2,4-dione (2a) was not formed at all. Also, DBN salt
and 80 C for 4 h were performed to give 2a in
did not show the formation of 2a (Scheme 1).
good yields (88% and 89%, respectively) (Scheme 4).
These results strongly showed that the combination
of DBU or DBN and carbon dioxide seems to be criti-
Under the high-temperature conditions, unsta-
ble DBU bicarbonate salt (1a) and DBN bicarbon-
ate salt (1b) are decomposed to bases and carbon
dioxide [2]. Then, the reactions at high temperature
were tried. A mixture of 2-aminobenzonitrile (3a)
with DBU bicarbonate salt (1a) in DMF was stirred
cal for the promotion of CO fixation in this reaction
2
system.
Scheme 5 shows a plausible path for the for-
mation of 1H-quinazoline-2,4-dione (2a) from 2-
aminobenzonitrile (3a) with carbon dioxide in the
presence of DBU. At first, DBU reacts with 2-
aminobenzonitrile (3a) to give DBU salt of 2-
aminobenzonitrile (4a) predominantly, compared
with the formation of DBU bicarbonate salt (1a)
from DBU with carbon dioxide. The carbonyla-
tion of 4a with carbon dioxide generates a car-
bamate salt (5a). Then, nucleophilic cyclization of
5a into 6a, followed by rearrangement of 6a by
way of isocyanate intermediate (7a), gives 8a. By
the stabilization of 8a, the DBU salt of quinazo-
line (9a) is afforded. Finally, acidification of 9a gave
◦
at 80 C for 4 h in argon. 1H-Quinazoline-2,4-dione
(
2a) was formed in moderate yield (57%). Similarly,
by the reaction with DBN bicarbonate salt (1b) at
◦
8
0 C, 2a was obtained in 45% yield (Scheme 2).
Furthermore, high-temperature reactions of
DBU bicarbonate salt (1a) and DBN bicarbonate salt
1b) with 2-aminobenzonitriles 3 under carbon diox-
(
ide atmosphere (0.1 MPa) were also examined. The
synthesis of 1H-quinazoline-2,4-dione (2a) from 2-
aminobenzonitrile (3a) and DBU bicarbonate salt
◦
(
1a) was tried at 80 C under carbon dioxide (0.1
MPa) for 4 h. This reaction proceeded smoothly
Heteroatom Chemistry DOI 10.1002/hc

278 Mizuno, Nakai, and Mihara
◦
SCHEME 3 Reaction of DBU bicarbonate salt (1a) with 3a–e at 80 C in CO .
2
CO atmosphere (0.1 MPa) conditions, because of
2
thermal decomposition of DBU bicarbonate salt (1a)
to DBU and carbon dioxide. Also, carbonylation of
◦
3
a with DBU and carbon dioxide (0.1 MPa) at 20 C
◦
or 80 C afforded 2a in good yields.
In this reaction system, the combination of DBU
or DBN acted as a strong base and carbon dioxide
is more essential for chemical CO fixation than the
formation of DBU bicarbonate salt (1a) or DBN bi-
carbonate salt (1b).
2
SCHEME 4 Carbonylation of 3a with DBU and carbon
dioxide.
1
H-quinazoline-2,4-dione (2a). Therefore, the main
EXPERIMENTAL
role of DBU seems to be the generation of DBU salt
of 2-aminobenzonitrile (4a), and not the formation
of DBU bicarbonate salt (1a).
Melting points were determined on a Mettler FP
5
instrument (Switzerland) and were uncorrected.
FT-IR spectra were recorded on a JASCO FT/IR-
1
13
4
100 instrument (Tokyo, Japan). H and C NMR
CONCLUSION
spectra were obtained on a JEOL JNM-AL300 (300
MHz, 75 MHz) instrument (Tokyo, Japan). Chemi-
cal shifts were reported in ppm relative to tetram-
ethylsilane (δ units). Mass spectra were measured
In summary, 1H-quinazoline-2,4-diones (2a–e) were
obtained in good to excellent yields from 2-
aminobenzonitriles (3a–e) with 1a under 80 C and
◦
SCHEME 5 Possible reaction path.
Heteroatom Chemistry DOI 10.1002/hc

Is CO Fixation Promoted through the Formation of DBU Bicarbonate Salt? 279
2
1
on a JEOL JMS-600 spectrometer (Tokyo, Japan).
-Aminobenzonitriles (3a–e), amidines (DBU and
1626, 1468, 1438, 1266, 1100; H NMR (d -DMSO) δ
6
2
(ppm): 3.77 (s, 3H, CH ), 3.81 (s, 3H, CH ), 6.66 (s,
3
3
DBN), DMF, and carbon dioxide (99.8%) were used
as purchased. DBU bicarbonate salt (1a) and DBN
bicarbonate salt (1b) were prepared according to the
literature [7].
1H, CH), 7.24 (s, 1H, CH), 10.88 (s, 1H, NH), 11.06
13
(s, 1H, NH); C NMR (d -DMSO) δ (ppm): 55.7,
6
55.8, 97.7, 106.2, 107.2, 136.5, 145.0, 150.4, 154.9,
+
162.4; MS (EI) m/z (%): 222 (M ,100), 207 (38),
164 (22). Exact MS: calcd for C10
H
10
N
2
4
O : 222.0641,
found: 222.0642.
Reaction of DBU Bicarbonate Salt (1a) with
◦
2
-Aminobenzonitrile (3a) at 20 C
6-Chloro-1H-quinazoline-2,4-dione (2c). Yield:
◦
◦
2-Aminobenzonitrile (3a) (1.181 g, 10 mmol) and
1.957 g (100%); mp: >300 C (Lit. [10] >300 C); IR
−
1
DBU bicarbonate salt (1a) (2.143 g, 10 mmol) with
DMF (20 mL) were mixed in a 100-mL three-necked
flask under argon with a magnetic stirring bar. Then,
the mixture was vigorously stirred under argon (0.1
(KBr, cm )gν: 3199, 3059, 1743, 1713, 1668, 1483,
1
1429, 1285, 828; H NMR (d -DMSO) δ (ppm): 7.16
6
(d, J = 8.7 Hz, 1H, CH), 7.65 (d, J = 8.7 Hz, 1H, CH),
7.79 (s, 1H, CH), 11.24 (s, 1H, NH), 11.40 (s, 1H, NH);
◦
13
MPa) at 20 C for 24 h. The resulting white emulsion
C NMR (d -DMSO) δ (ppm): 115.7, 117.5, 125.9,
6
was then poured into 1 M HCl (100 mL). No solid was
precipitated, and 1H-quinazoline-2,4-dione (2a) was
not obtained completely. In the case of the reaction
126.2, 134.7, 139.7, 150.0, 161.8; MS (EI) m/z (%):
196 (M ,100), 153 (73), 125 (26). Exact MS: calcd
+
for C H ClN O : 196.0040, found: 196.0037.
8
5
2
2
◦
under carbon dioxide (0.1 MPa) at 20 C for 24 h, 2a
also did not form. Also, using DBN bicarbonate salt
7-Chloro-1H-quinazoline-2,4-dione (2d). Yield:
◦
◦
(
1b) and 3a in argon or CO
2
(0.1 MPa) under similar
1.605 g (82%); mp: >300 C (Lit.[10] >300 C); IR
−
1
reaction conditions afforded no formation of 2a.
(KBr, cm ) ν: 3306, 3054, 1743, 1686, 1618, 1431,
1
1
287, 864; H NMR (d -DMSO) δ (ppm): 7.15–7.21
6
(
1
m, 2H, CH), 7.86 (d, J = 8.4 Hz, 1H, CH), 11.20 (s,
Typical Procedure for the Reaction of DBU
13
H, NH), 11.36 (s, 1H, NH); C NMR (d -DMSO) δ
6
Bicarbonate Salt (1a) with 2-Aminobenzonitrile
(ppm): 113.3, 114.6, 122.4, 129.0, 139.2, 141.9, 150.1,
◦
(
3a) at 80 C under Carbon Dioxide Atmosphere
+
1
62.0; MS (EI) m/z (%): 196 (M ,100), 153 (91),
Into a 100-mL three-necked flask equipped with a
condenser, 2-aminobenzonitrile (3a) (1.181 g, 10
mmol), DBU bicarbonate salt (1a) (2.143 g, 10
mmol), and DMF (20 mL) were placed under argon
with a large magnetic stirring bar. Then the reac-
126 (49). Exact MS: calcd for C H ClN O : 196.0040,
found: 196.0036.
8
5
2
2
6-Nitro-1H-quinazoline-2,4-dione (2e). Yield:
◦
◦
1.469 g (71%); mp: >300 C (Lit. [10] >300 C); IR
◦
−1
1
tion mixture was heated to 80 C and carbon dioxide
(KBr, cm )gν: 3455, 1680; H NMR (d -DMSO)
6
(
0.1 MPa) was charged. The mixture was vigorously
δ (ppm): 7.31 (d, J = 9.0 Hz, 1H, CH), 8.41 (dd,
◦
stirred under CO
2
(0.1 MPa) at 80 C for 4 h. The re-
J = 2.7, 9.0 Hz, 1H, CH), 8.55 (d, J = 2.7 Hz,
13
sulting solution was then poured into 1 M HCl (100
mL) and washed with tert-butyl methyl ether (100
mL) to give pure 2a.
1H, CH), 11.67 (s, 1H, NH), 11.76 (s, 1H, NH);
C
NMR (d -DMSO) δ (ppm): 114.5, 116.6, 123.0, 129.5,
6
141.8, 145.6, 149.9, 161.6; MS (EI) m/z (%): 207
+
(
M , 100), 164 (27). Exact MS: calcd for C
8
H
5
N
3
4
O :
1
H-Quinazoline-2,4-dione (1a). Yield: 1.405 g
207.0280, found: 207.0271.
◦
◦
(
87%); mp: >300 C (Lit. [10] >300 C); IR (KBr,
−
1
cm ): ν: g254, 3056, 2847, 1720, 1705, 1670, 1617,
Carbonylation of 2-Aminobenzonitrile (3a) with
Carbon Dioxide in the Presence of DBU
1
1
(
444, 757; H NMR (d
6
-DMSO) δ (ppm): 7.14–7.18
m, 2H, CH), 7.62 (t, J = 7.7 Hz, 1H, CH), 7.87 (d,
J = 7.7 Hz, 1H, CH), 11.10 (s, 1H, NH), 11.24 (s,
A
DMF (20 mL) solution containing 2-
13
1
H, NH); C NMR (d
6
-DMSO) δ (ppm): 114.3, 115.3,
aminobenzonitrile (3a) (1.181 g, 10 mmol) and
1
22.3, 126.9, 134.9, 140.8, 150.2, 162.8; MS (EI) m/z
DBU (1.49 mL, 10 mmol) was stirred under argon
(0.1 MPa) at 20 C for 1 h. Into the resulting pale
+
◦
(
%): 162 (M ,100), 119 (48), 92 (17). Exact MS: calcd
for C
8
H
6
N
2
O
2
: 162.0429, found: 162.0408.
yellow solution, carbon dioxide (0.1 MPa) was
◦
charged at 20 C. The reaction was vigorously stirred
◦
6
,7-Dimethoxy-1H-quinazoline-2,4-dione (2b).
for 24 h at 20 C. Then, the resulting white emulsion
◦
◦
Yield: 2.145 g (97%); mp: >300 C (Lit. [10] >300 C);
IR (KBr, cm ) ν: 3470, 3375, 3296, 1708, 1651,
was poured into 1 M HCl (100 mL) and washed
with tert-butyl methyl ether (100 mL) to obtain
−
1
Heteroatom Chemistry DOI 10.1002/hc

280 Mizuno, Nakai, and Mihara
1
H-quinazoline-2,4-dione (2a) in 1.426 g (88%)
[4] Mizuno, T.; Iwai, T.; Ishino, Y. Tetrahedron Lett
004, 45, 7073.
[5] Kishimoto, Y.; Ogawa, I. Ind Eng Chem Res 2004, 43,
155.
2
yield. In a similar manner, carbonylation of 3a with
DBU and carbon dioxide (0.1 MPa) at 80 C for 4 h
gave 2a in 1.449 g (89%) yield.
◦
8
[6] Paddock, R. L.; Hiyama, Y.; McKay, J. M.; Nguyen,
S. T. Tetrahedron Lett 2004, 45, 2023.
[7] Heldebrant, D. J.; Jessop, P. G.; Thomas, C. A.;
Eckert C. A.; Liotta, C. L. J Org Chem 2005, 70,
REFERENCES
5
335.
[
[
[
1] P e´ rez, E. R.; Silva, M. O.; Costa, V. C.; Rodrigues-
Filho, U. P.; Franco, D. W. Tetrahedron Lett 2002,
[8] Mizuno, T.; Okamoto, N.; Ito, T.; Miyata, T. Tetrahe-
dron Lett 2000, 41, 1051.
[9] Mizuno, T.; Okamoto, N.; Ito, T.; Miyata, T. Het-
eroatom Chem 2000, 11, 428.
[10] Mizuno, T.; Ishino, Y. Tetrahedron 2002, 58, 3155.
[11] Mizuno, T.; Mihara, M.; Nakai, T.; Iwai, T.; Ito, T.
Synthesis 2007, 2524.
4
3, 4091.
2] P e´ rez, E. R.; Santos, R. H. A.; Gambardella, M. T.
P.; Macedo, L. G. M.; Rodrigues-Filho, U. P.; Launay,
J.-C.; Franco, D. W. J Org Chem 2004, 69, 8005.
3] Dinsmore, C. J.; Mercer, S. P. Org Lett 2004, 6, 2885.
Heteroatom Chemistry DOI 10.1002/hc