Palladium-catalyzed amidocarbonylation improved by recyclable ionic liquids

Article abstract of DOI:10.1055/s-2006-950270

Two types of ionic liquids (halide anion ionic liquids and Brensted acidic ionic liquids) were first applied to improve the palladium-catalyzed amidocarbonylation. Both the palladium catalyst and the ionic liquids could be recycled at least five times without significant loss in catalytic activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950270

LETTER
2795
Palladium-Catalyzed Amidocarbonylation Improved by Recyclable Ionic
Liquids
A
B
midocarbonylat
i
ion Im
p
n
roved by Io
gn ic Liquids chun Zhu, Xuanzhen Jiang*
Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, P. R. of China
Fax +86(571)87951611; E-mail: chejiang@zju.edu.cn
Received 3 July 2006
R3
N
O
Abstract: Two types of ionic liquids (halide anion ionic liquids and
Brønsted acidic ionic liquids) were first applied to improve the pal-
ladium-catalyzed amidocarbonylation. Both the palladium catalyst
and the ionic liquids could be recycled at least five times without
significant loss in catalytic activity.
O
O
PdBr2, PPh3, CO
IL, 100 °C, 15 h
R2
R3
R2
OH
+
N
H
R1
H
R1
O
Equation 1
Key words: amidocarbonylation, ionic liquids, amino acids, palla-
dium, catalysis
8
high thermal stability and ease of recyclability. They are
attractive especially for the immobilization of transition-
9
metal-based catalysts, Lewis acids and enzymes. Specif-
ically functionalized ionic liquids, such as Brønsted acidic
ionic liquids have been reported recently to serve as both
Amino acids and their derivatives are unequivocally one
of the most important classes of organic compounds. The
1
transition-metal-catalyzed three-component reaction of
aldehydes, amides, and carbon monoxide, so-called ami-
docarbonylation, is a versatile one step approach to the
synthesis of racemic N-acyl-a-amino acids. Cobalt cata-
lysts were originally discovered by Wakamatsu and co-
10
reaction medium and catalysts. The properties of ionic
liquids can be tailored by the fine-tuning of parameters
such as the choice of organic cation, inorganic anion and
the length of alkyl chain. Hence, there is significant inter-
est in using ionic liquids as replacements of conventional
organic solvents. However, there are no examples of the
use of ionic liquids as solvents for the amidocarbonylation
so far.
2
workers in the early 1970s, and then palladium catalyst
systems consisting of main catalyst (PdCl or PdBr ),
2
2
ligand (PPh ), co-catalysts (LiBr and H SO ) and polar
3
2
4
3
solvent NMP (N-methylpyrrolidone) were revealed. Re-
cently, the catalytic activities of rhodium, iridium, ruthe-
nium and platinum in amidocarbonylation were also
N
Bu
4
reported. Among these transition metals, the most active
N
Et
N
N
i-Pent
N
N
Me
X
metal so far is palladium, although palladium catalysts are
expensive and unrecoverable in many cases. To solve
these problems the heterogeneous catalyst Pd/C in ami-
docarbonylation was reported by Beller et al. and another
heterogeneous catalyst (polymer-incarcerated palladium)
was reported by Akiyama et al. The heterogeneous cata-
lyst can be recovered by filtering but there is no experi-
mental evidence to show the reuse of these catalysts.
Me
Me
Br
Br
X = Br, Cl, PF6, BF4
[
i-pmim]Br
[emim]Br
[bmim]X
5
Br
N
Oct
N
N
Me
Bu
6
Br
[omim]Br
[N-butylpyridine]Br
Scheme 1
7
Recently our group has developed a new heterogeneous
HZSM-5-supported palladium catalyst, which can be re-
covered and reused in amidocarbonylation by simple fil-
tration. The other components of the catalyst system,
however, could not be recycled. An attempt was made to
search a novel environmentally benign and economic way
to recycle the catalyst system for amidocarbonylation.
The application of ionic liquids (ILs) would be a suitable
choice.
In the present study, we would like to report, for the first
time, the use of halide anion ionic liquids as solvent and
halide ions co-catalyst, and the use of Brønsted acidic ion-
ic liquids as strong acid co-catalyst instead of sulfuric acid
in the palladium-catalyzed amidocarbonylation (Equation
1
).
Several halide anion ionic liquids (Scheme 1) and Brøn-
sted acidic ionic liquids (Scheme 2) were examined.
Ionic liquids are emerging as a set of green solvents with
unique properties such as good solvating ability, wide liq-
uid range, tunable polarity, negligible vapor pressure,
Meanwhile the catalyst system, PdBr –PPh –ILs, could
2
3
be directly reused after products separation.
Preliminary results to evaluate the performance of the two
types of ionic liquids in amidocarbonylation are summa-
rized in Table 1. The special significance of halide ions as3
co-catalyst for palladium-catalyzed amidocarbonylation
SYNLETT 2006, No. 17, pp 2795–2798
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950270; Art ID: W13406ST
1
7
.1
0
.2
0
0
6
©
Georg Thieme Verlag Stuttgart · New York

2
796
B. Zhu, X. Jiang
LETTER
SO3H
HSO4
Table 1 Amidocarbonylation of Cyclohexanecarboxaldehyde in
SO3H
HSO4
Ionic Iiquidsa
N
N
Me
N
Entry Solvent
Brønsted Additive
acidic IL
Yield
(%)
IL 1
IL 2
b
Ph
Ph
P
SO3H
SO3
1
2
3
[emim]Br
[emim]Br
[emim]Br
IL 1
IL 1
IL 1
–
84
85
P
SO3H
HSO4
Ph
Ph
Ph
Ph
Me
LiBr (35 mol%)
IL 3
IL 4
N-acetylcyclohexyl- 87
glycine (3 mol%)
Scheme 2
4c
5
6
7
8
9
0
1
2
3
4
[bmim]Br
[bmim]Br
[bmim]Br
[bmim]Br
[bmim]Br
[i-pmim]Br
[omim]Br
H SO
–
27
75
10
71
19
53
38
70
29
–
2
4
IL 1
IL 2
IL 3
IL 4
IL 1
IL 1
–
O
PdBr , PPh , CO
COOH
2
3
CHO
+
H2N
[
emim]Br, acidic IL
00 °C, 15 h
–
Me
NHCOMe
1
–
Equation 2
–
–
suggests that ionic liquids with halide anions could be
used as both reaction medium and halide ions co-catalyst.
Investigations showed that the use of bromide anion ionic
liquids, such as [emim]Br, as solvent afford activities as
high as NMP in palladium-catalyzed amidocarbonylation.
In the reaction of cyclohexanecarboxaldehyde with acet-
amide in [emim]Br (Equation 2), the corresponding N-
acetylcyclohexylglycine can be obtained in 84% yield
1
1
1
1
1
–
[N-butylpyridine]Br IL 2
–
[bmim]Cl
IL 1
IL 1
IL 1
IL 1
LiBr (35 mol%)
LiBr (35 mol%)
LiBr (35 mol%)
LiBr (35 mol%)
[bmim]PF6
[bmim]BF4
–
(
Table 1, entry 1). The addition of 35 mol% lithium bro-
mide to the catalyst system gave 85% yield (Table 1, entry 15d
); hence, the increase in yield was negligible. This dem-
onstrated that the presence of halide ions co-catalyst could
IL 1
–
2
a
Reagents and conditions: Cyclohexanal (20 mmol), acetamide (22
mmol), PdBr (0.2 mmol), PPh (0.2 mmol), Brønsted acidic IL (2
2
3
be omitted by using halide anion ionic liquids. Among the mmol), ionic liquids solvent (25 mL), CO (60 bar), at 100 °C for 15 h.
b
Brønsted acidic ionic liquids tested, Brønsted acidic IL 1
gave the best result (Table 1, entries 5–8). Brønsted acidic
IL 2 showed good performance only when used with [N-
butylpyridine]Br (Table 1, entry 11). When sulfuric acid
was used as strong acid co-catalyst instead of Brønsted
acidic ionic liquids, the amidocarbonylation yield de-
creased significantly (Table 1, entry 4). This indicated that
Brønsted acidic ionic liquids showed much better compat-
ibility with halide anion ionic liquids than sulfuric acid
did. Ionic liquids with short alkyl-chain substituents dis-
played better performance, the order of activity is ranked
as follows: [emim]Br > [bmim]Br, [N-butylpyridine]Br >
Isolated yield.
c
H SO (0.6 mmol).
2
4
d
Brønsted acidic IL 1 was used as solvent.
After each run, the N-acyl-a-amino acid products were re-
moved by tetrahydrofuran extraction. The rest of the ILs
and catalyst were recovered and reused in the next cycle
without further addition of [emim]Br, PdBr and PPh in
2
3
each alternative run. As shown in Table 2, the yields grad-
ually increased from cycles 1 to 3 and then decreased from
cycles 4 to 5. The maximum conversion was obtained in
cycle 3. This is probably because the N-acyl-a-amino acid
remaining in the ionic liquid solvent improved the reac-
tion yield in the recycled runs. This is also in accordance
with the result (Table 1, entry 3) that the addition of 3
mol% N-acetylcyclohexylglycine to the catalyst system
gave increased yields. Compared to conventional sol-
vents, the solubility of gases in ionic liquids is generally
[
i-pmim]Br > [omim]Br (Table 1, entries 1, 5 and 9–11).
The use of halide-free ionic liquids, for instance
bmim]PF and [bmim]BF , as solvent resulted in no
[
6
4
product, even though lithium bromide was added (Table
, entries 13 and 14). In addition, the catalyst system
1
showed no catalytic activity when Brønsted acidic ionic
11
high. The increased solubility of carbon monoxide in the
ionic liquids is another advantage of the use of ionic liq-
uids as solvent. Meanwhile the catalyst system remained
yellow throughout the whole recycling, suggesting that
the catalyst remained intact. The catalyst/ionic liquids so-
lution could be reused at least five times without signifi-
cant loss in catalytic activity.
liquids, such as Brønsted acidic IL 1, were used as solvent
(
Table 1, entry 15).
The major advantage of the use of ionic liquids as reaction
media and co-catalysts is that this catalytic system can be
easily recovered and recycled in subsequent runs. The re-
usability of the catalytic system was tested in the ami-
docarbonylation of cyclohexanecarboxaldehyde. The
results are presented in Table 2.
To establish the generality of the present protocol, a vari-
ety of aldehydes was examined, and the obtained results
Synlett 2006, No. 17, 2795–2798 © Thieme Stuttgart · New York

LETTER
Amidocarbonylation Improved by Ionic Liquids
2797
1
2
Table 2 Recyclability of PdBr –PPh –[emim]Br for Amidocarbonylation of Cyclohexanecarboxaldehyde
2
3
Cycle
0
1
2
3
4
5
Yield (%)a
82 (84)
86
89
91
87
82
a
Extracted yield; isolated yield is given in parentheses.
are summarized in Table 3. Under the optimized reaction In conclusion, the current study presents the realization of
conditions, a wide range of aldehydes underwent the cat- palladium-catalyzed amidocarbonylation improved by
alytic amidocarbonylation in ionic liquids to produce the two types of ionic liquids. Halide anion ionic liquids were
corresponding N-acyl-a-amino acids. All aliphatic and ar- used as both the solvent and halogen source; environmen-
omatic aldehydes tested here gave amidocarbonylation tally friendly Brønsted acidic ionic liquids played a role of
products in moderate to good yields.
strong acid co-catalyst. Efficiencies comparable to non-IL
are observed. This method is tolerant to a range of func-
tional aldehydes and affords fairly good yields of N-acyl-
a-amino acids. Recycling of the entire reaction media (IL
solvent, palladium–phosphine catalyst, and IL halogen
source) can be implemented by extraction of the product
and remaining substrates. Of particular note is the fact that
this novel protocol is economical and environmentally be-
nign and shows potential utility in industry.
Table 3 Amidocarbonylation of Aldehydes in [emim]Bra
Entry Aldehyde
1
Product
Yield (%)b
84
COOH
CHO
CHO
NHCOMe
a
b
c
2
3
COOH
82
63
56
60
NHCOPh
Acknowledgment
We are grateful for the financial support of the National Natural Sci-
ence Foundation of China (No. 20376071).
COOH
CHO
NHCOMe
COOH
References and Notes
4
5
CHO
(
(
(
1) Szmant, H. H. Organic Building Blocks for the Chemical
Industry; Wiley: New York, 1989.
2) Wakamatsu, H.; Uda, J.; Yamakami, N. J. Chem. Soc.,
Chem. Commun. 1971, 1540.
3) (a) Jägers, E.; Koll, H.-P. Ger. Offen., DE 3812737, 1989;
Chem. Abstr. 1990, 112, 77951. (b) Beller, M.; Eckert, M.;
Vollmuller, F.; Bogdanovic, S.; Geissler, H. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1494.
NHCOMe
d
COOH
NHCOMe
CHO
e
f
6
7
53
47
COOH
(4) (a) Drauz, K.; Burkhardt, O.; Beller, M.; Eckert, M. Ger.
Offen., DE 10012251, 1999; Chem. Abstr. 2001, 134,
56964. (b) Sagae, T.; Sugiura, M.; Hagio, H.; Kobayashi, S.
Chem. Lett. 2003, 32, 160. (c) Enzmann, A.; Eckert, M.;
Ponikwar, W.; Polborn, K.; Schneiderbauer, S.; Beller, M.;
Beck, W. Eur. J. Inorg. Chem. 2004, 1330.
CHO
NHCOMe
OMe
OMe
OMe
COOH
CHO
(
5) Beller, M.; Moradi, W. A.; Eckert, M.; Neumann, H.
Tetrahedron Lett. 1999, 40, 4523.
(6) Akiyama, R.; Sagae, T.; Sugiura, M.; Kobayashi, S. J.
Organomet. Chem. 2004, 689, 3806.
NHCOMe
OMe
g
(7) Yang, K. W.; Jiang, X. Z. Bull. Chem. Soc. Jpn. 2006, 79,
806.
8
9
COOH
41
52
CHO
(
8) (a) Böhm, V. P. W.; Herrmann, W. A. Chem. Eur. J. 2000,
NHCOMe
6, 1017. (b) Audic, N.; Clavier, H.; Mauduit, M.; Guillemin,
h
J.-C. J. Am. Chem. Soc. 2003, 125, 9245. (c) Park, S. B.;
Alper, H. Org. Lett. 2003, 5, 3209. (d) Xiao, J. C.;
Twamley, B.; Shreeve, J. M. Org. Lett. 2004, 6, 3845.
CHO
HOOC
NHCOMe
(
e) Gordon, C. M. Appl. Catal. A: Gen. 2001, 222, 101.
9) (a) Dupont, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. Rev.
002, 102, 3667. (b) Wilkes, J. S. J. Mol. Catal. A: Chem.
(
2
i
2004, 214, 11. (c) Song, C. E. Chem. Commun. 2004, 1033.
(d) Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S.
Tetrahedron 2005, 61, 1015.
a
Reagents and conditions: Aldehyde (20 mmol), amide (22 mmol),
PdBr (0.2 mmol), PPh (0.2 mmol), Brønsted acidic IL 1 (2 mmol),
emim]Br (25 mL), CO (60 bar), at 100 °C for 15 h.
2
3
(
10) (a) Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.; Weaver,
[
b
K. J.; Forbes, D. C.; Davis, J. H. Jr. J. Am. Chem. Soc. 2002,
Isolated yield.
124, 5962. (b) Gui, J. Z.; Cong, X. H.; Liu, D.; Zhang, X. T.;
Synlett 2006, No. 17, 2795–2798 © Thieme Stuttgart · New York

2
798
B. Zhu, X. Jiang
LETTER
Hu, Z. D.; Sun, Z. L. Catal. Commun. 2004, 5, 473. (c)Wu,
H. H.; Sun, J.; Yang, F.; Tang, J.; He, M. Y. Chin. J. Chem.
134.2, 131.3, 128.2, 127.7, 57.9, 29.4, 28.8, 25.7, 25.6. MS:
+
m/z = 105 (100), 261 [M ], 262 [M + 1]. IR (KBr): 3292,
–
1
2
004, 22, 619. (d) Wu, H. H.; Yang, F.; Cui, P.; Tang, J.; He,
2920, 2853, 1702, 1638, 1535, 1334, 1276, 932, 697 cm .
1
M. Y. Tetrahedron Lett. 2004, 45, 4963. (e) Qiao, K.;
Yokoyama, C. Chem. Lett. 2004, 33, 472. (f) Zhu, H. P.;
Yang, F.; Tang, J.; He, M. Y. Green Chem. 2003, 5, 38.
N-Acetyl-a-norvaline (d): white solid; mp 111–114 °C. H
NMR (400 MHz, DMSO-d ): d = 8.07 (d, J = 7.6 Hz, 1 H),
6
4.17 (q, J = 7.6 Hz, 1 H), 1.83 (s, 3 H), 1.50–1.65 (m, 2 H),
1
3
(
11) (a) Sheldon, R. Chem. Commun. 2001, 2399. (b) Ansari, I.
1.26–1.31 (m, 2 H), 0.83–0.87 (t, 3 H). C NMR (100 MHz,
A.; Gree, R. Org. Lett. 2002, 4, 1507.
DMSO-d ): d = 174.0, 169.4, 51.6, 33.2, 22.3, 18.7, 13.5.
6
+
(
12) General Procedure and Recycling Process:
A 60-mL autoclave with a magnet-driven propeller stirrer
was used for the high-pressure amidocarbonylation.
MS: m/z = 72 (100), 159 [M ], 160 [M + 1]. IR (KBr): 3345,
2962, 2936, 2875, 2456, 1928, 1717, 1595, 1543, 1237, 997,
–
1
612 cm .
Aldehyde (20 mmol), amide (22 mmol), PdBr (0.2 mmol),
N-Acetyl-a-phenylglycine (f): white solid; mp 199–201 °C.
2
1
PPh (0.2 mmol), Brønsted acidic ionic liquid (2 mmol), and
H NMR (400 MHz, DMSO-d ): d = 12.34 (s, 1 H), 8.65 (d,
3
6
[emim]Br (25 mL) were transferred into the autoclave and
J = 7.6 Hz, 1 H), 7.32–7.42 (m, 5 H) 5.37 (d, J = 7.6 Hz, 1
1
3
allowed to react under 60 bar CO at 100 °C for 15 h. After
the reaction the recycling process began with refluxing the
reaction mixture with THF (3 × 30 mL). Then the THF
phases were combined and the volatile components were
removed in a rotary evaporator, and the residue was taken up
H), 1.91 (s, 3 H). C NMR (100 MHz, DMSO-d ): d =
6
172.2, 169.3, 137.4, 128.7, 128.1, 127.8, 56.4, 22.4. MS:
m/z = 106 (100), 193 [M ], 194 [M + 1]. IR (KBr): 3342,
+
3032, 2484, 1922, 1716, 1602, 1544, 1258, 1179, 1003, 719,
–
1
614 cm .
in a sat. aq solution of NaHCO , and then washed with
N-Acetyl-a-phenylalanine (h): white solid; mp 171–173 °C.
3
1
CHCl and EtOAc. The aqueous phase was adjusted to pH 2
H NMR (400 MHz, DMSO-d ): d = 12.70 (s, 1 H), 8.21 (d,
3
6
with phosphoric acid and extracted with EtOAc. Then the
J = 8.0 Hz, 1 H), 7.18–7.30 (m, 5 H), 4.39–4.45 (m, 1 H),
1
3
organic phases were combined and dried over MgSO , and
3.03–3.07 (q, 1 H), 2.81–2.87 (q, 1 H), 1.79 (s, 3 H). C
4
the solvent was removed in vacuum. The product was
purified by recrystallization with a suitable solvent mixture.
The remaining ionic liquid was dried in vacuum and then
poured into the autoclave reactor containing fresh aldehyde
NMR (100 MHz, DMSO-d ): d = 173.2, 169.3, 137.8, 129.1,
6
128.2, 126.5, 53.6, 36.8, 22.4. MS: m/z = 148 (100), 207
+
[M ], 208 [M + 1]. IR (KBr): 3331, 2913, 2458, 1699, 1621,
–
1
1553, 1437, 1244, 978, 908, 704 cm .
(
20 mmol), amide (22 mmol) and Brønsted acidic ionic
liquid (2 mmol) for the next run, but there was no need to add
emim]Br, PdBr or PPh . Finally the reaction was restarted.
N-Acetyl-a-(a-naphthyl)glycine (i): white solid; mp: 222–
1
224 °C. H NMR (400 MHz, DMSO-d ): d = 8.22 (d, 1 H),
6
[
7.90–8.08 (m, 3 H), 7.49–7.61 (m, 4 H), 6.12–6.14 (m, 1 H),
2
3
1
3
N-Benzoyl-a-cyclohexylglycine (b): white solid; mp 193–
1.91 (s, 3 H). C NMR (100 MHz, DMSO-d ): d = 172.8,
6
1
1
8
3
96 °C. H NMR (400 MHz, DMSO-d ): d = 12.56 (s, 1 H),
170.3, 133.9, 133.7, 131.2, 129.2, 129.1, 127.3, 126.6,
6
.42 (d, J = 7.6 Hz, 1 H), 7.88–7.90 (m, 2 H), 7.44–7.55 (m,
H), 4.32 (t, J = 7.6 Hz, 1 H), 1.59–1.87 (m, 6 H), 1.08–1.18
126.1, 125.9, 123.7, 53.3, 22.6. MS: m/z = 156 (100), 243
+
[M ], 244 [M + 1]. IR (KBr): 3348, 2878, 2787, 2486, 1916,
m, 5 H). 13C NMR (100 MHz, DMSO-d ): d = 173.2, 166.9,
1704, 1615, 1535, 1289, 1261, 776, 663 cm .
–1
(
6
Synlett 2006, No. 17, 2795–2798 © Thieme Stuttgart · New York