Cobalt carbonyl as an effective CO source in one-pot synthesis of esters from aryl halides

Article abstract of DOI:10.1039/c3nj00548h

For the first time, we have successfully applied Co₂(CO) ₈ as an effective carbonyl source for the Pd catalysed alkoxycarbonylation of aryl halides affording the corresponding aryl esters under mild microwave conditions. A wide variety of esters and carbonyl derivatives were prepared using this protocol.

Full text of DOI:10.1039/c3nj00548h

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Cobalt carbonyl as an effective CO source in one-pot
synthesis of esters from aryl halides†
P. Baburajan,a R. Senthilkumaranb and Kuppanagounder P. Elango*a
Cite this: NewJ.Chem., 2013,
37, 3050
Received (in Porto Alegre, Brazil)
22nd May 2013,
For the first time, we have successfully applied Co2(CO)8 as an effective carbonyl source for the Pd
catalysed alkoxycarbonylation of aryl halides affording the corresponding aryl esters under mild
microwave conditions. A wide variety of esters and carbonyl derivatives were prepared using this
protocol.
Accepted 5th July 2013
DOI: 10.1039/c3nj00548h
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is a highly toxic compound and also the reaction requires high
temperatures {Mo(CO)6 – m.p. 150 1C}, if not higher equivalents.
Introduction
Palladium catalysed carbonylation reactions play an important
role in organic synthesis. Heck and co-workers introduced this
methodology in 1974 using a large excess of carbon monoxide
gas.1 Though carbon monoxide is a very handy molecule in
organic synthesis, it is toxic to humans and also to the
environment. Very strict regulations have to be followed to
use carbon monoxide in laboratories and hence most labora-
tories are reluctant to use this frequently in small scale pre-
parations. On the other hand, the synthesis of carbonyl
derivatives like esters, amides and acids is very significant in
organic and medicinal chemistry. Over the years many carbo-
nylation methods have been developed using carbon monoxide
gas under high pressure and temperature for long time dura-
tions.2 Also, such procedures needs initial evacuation of CO
from the reaction vessel, which is hazardous to the environ-
ment. Recently, Buchwald et al. reported relatively mild reac-
tion conditions.3 However, this methodology also requires
excess amounts of CO and initial evacuation of the vessel.
Recently, alternative sources of CO, such as formic acid deri-
vatives,4 aldehydes5 and acid halides,6 for the preparation of
carbonyl derivatives have also been reported in the literature.
These methods have their own disadvantages such as either they
are reactant specific or work under high temperatures or both.
Alternatively a few attempts have also been made to use
transition-metal carbonyls like Ni, Mo, W, Cr, or Fe carbonyls as
the CO source in the reaction. Mats Larhed and co-workers
proved that Mo(CO)6 exhibited better results, and recently
successfully summarised this in a review article.7 However, it
Therefore, the main objective of the present endeavour is to use
the relatively low melting solid Co2(CO)8 (m.p. 55 1C) as an
environmentally safe reagent for the CO source in the carbonyla-
tion of aryl halides to yield esters and carbonyl derivatives.
Though this carbonyl has been reported in literature as a catalyst8
in such a reaction in the presence of CO gas, this is the first
attempt to use this as a successful CO source (without external
CO gas) in the reaction under mild microwave conditions.
Result and discussion
Herein, we have successfully developed a convenient method
for ethoxycarbonylation of ethyl-4-bromobenzoate using Co2(CO)8
(nearly stoichiometric amounts) as the carbonyl source under
microwave irradiation (Scheme 1). We have opted for micro-
wave irradiation for this reaction as it is safe and fast and the
most convenient over traditional thermal heating methods.
Also, it includes faster reaction times, controlled reaction
conditions, and the opportunity to change the reaction para-
meters. Initial screening studies to find a suitable base for the
ethoxycarbonylation of ethyl-4-bromobenzoate were carried out
using various organic and inorganic bases (Table 1, entries
1–6). The results indicated that dimethylaminopyridine (DMAP;
Table 1, entry 4) was found to be a relatively good base yielding
75% of the desired ester. The results of Pd catalyst variation
studies (Table 1, entries 7–12) showed that Pd(OAc)2 was found
a Department of Chemistry, Gandhigram Rural Institute-Deemed University,
Gandhigram 624302, India. E-mail: drkpelango@rediffmail.com
b Syngene International Ltd, Bangalore 560099, India
† Electronic supplementary information (ESI) available: Microwave irradiation
parameters, safety parameters, characterization of the products, 1H & 13C NMR
spectra. See DOI: 10.1039/c3nj00548h
Scheme 1 General reaction scheme.
c
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Table 1 Optimisation of ethoxy carbonylation reactiong
Table 2 Synthesis of ethyl esters from aryl bromides and aryl iodidesd
Entry Aryl halides (1a–u) Co2(CO)8 a (eq.) Product (2a–u)
Yield (%)
95b
88c
1
2
3
0.25
0.25
0.25
Temp.
Time Yieldd
(min) (%)
Entry Pd sourcea
Solventb (1C)
Basec
89b
82c
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)2Cl2
Pd(PPh3)4
Pd(dppf)Cl2
Ethanol 120
Ethanol 120
Ethanol 120
Ethanol 120
Ethanol 120
Ethanol 120
Ethanol 120
Ethanol 120
Ethanol 120
Na2CO3 30
14
15
46
75
64
25
68
35
61
52
35
ND
45
62
48
44
84
65
ND
94e
68f
K2CO3
TEA
DMAP
DBU
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
91b
93c
—
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
9
4
5
0.25
0.25
84
10
11
12
13
14
15
16
17
18
19
20
21
Pd(CH3CN)2Cl2 Ethanol 120
Pd2(dba)3
—
Ethanol 120
Ethanol 120
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
THF
120
77b, 75c
Dioxane 120
DMSO
DMF
Toluene
Toluene
120
120
90
6
7
8
9
0.25
0.25
0.25
0.25
82
70
Toluene RT
95b, 84c
Toluene
Toluene
90
90
a
b
5 mol% of Pd source was used. All the solvents were freshly distilled
and used. 2 eq. of base was used. Yield of isolated product. 0.25 eq.
of Co2(CO)8 was used. 0.2 eq. Co2(CO)8 was used. All the reactions
were executed with 1 mmol of ethyl-4-bromobenzoate, 10 mol%
of xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) and
0.3 mmol of Co2(CO)8 at microwave irradiation for 30 min.
c
d
e
93
f
g
90b
76c
10
11
0.25
0.25
82
to be more effective. The reaction has also been carried out in
different solvents (entries 13–17) keeping the ratio as 3 : 1
(solvent : ethanol). Based on the results obtained, we selected
a toluene–ethanol mixture as the medium and 90 1C as the
optimum temperature (Table 1, entry 17) for the reaction.
Studies varying the amount of cobalt carbonyl indicated that
0.25 eq. of it is necessary for complete conversion with high
yield (Table 1, entry 20). However, based on this requirement
up to 0.3 eq. of the cobalt carbonyl has been used in selected
cases. It is interesting to note that, in the present study, during
the course of the reaction no pressure was developed (Fig. S1,
ESI†) and hence it is safe to use Co2(CO)8 as a carbonyl source.
With the optimized reaction conditions, we extended the
scope of ethoxycarbonylation to various aryl halides possessing
different functional groups and hetero halides, and the results
are collected in Table 2. In general, ethoxycarbonylation of
various aryl halides afforded the desired ester in good to
excellent yields (Scheme 2). The results also indicated that aryl
iodides gave relatively lower yields than the corresponding aryl
bromides. In the case of aryl halides, both compounds with
electron donating and with electron withdrawing substituents
gave good yields. One of the most interesting results of the
present study is that aryl halides possessing nucleophiles (OH,
NH2, CONH2, COOH) as substituents can be effectively con-
verted into the corresponding esters smoothly (entries 14, 16–19).
2-Bromophenylmethanol (entry 21) was found to form a cyclic
12
13
14
0.25
0.25
0.25
65
78
75
15
0.25
69
16
17
0.25
0.30
70
62
18
0.25
68
c
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Table 3 Synthesis of carbonyl derivativesc
Table 2 (continued )
a
Entry Aryl halides (1a–u) Co2(CO)8 a (eq.) Product (2a–u)
Yield (%)
65
Entry R-NuH
Co2(CO)8 (eq.) Product (3a–j)
Yieldb (%)
19
20
0.25
1
2
3
4
5
–OH
0.25
0.25
0.25
0.30
0.25
90
94
85
84
92
0.25
0.25
84
92
21
a
b
The eq. of Co2(CO)8 is relative to the eq. of aryl halide used. Isolated
c
yield when aryl bromide used. Isolated yield when aryl iodide used.
d
Reaction conditions: (1 mmol) of aryl halide, 5 mol% of Pd(OAc)2,
10 mol% xantphos, 2 mmol DMAP, toluene : ethanol (3 : 1, 4 mL), M/W
90 1C, 30 min.
6
7
0.25
95
82
Scheme 2 Carbonylation of aryl halides.
0.30
0.25
8
9
–NH2
80
84
0.25
0.25
Scheme 3 Carbonylation of aryl halides with different nucleophiles.
10
H2O
71
phthalide derivative. The carbonylation of ethyl 4-bromobenzoate
has also been carried out with different nucleophiles, such as
alcohols, primary and secondary amines and water, under identical
experimental conditions (Scheme 3). The percentage yields of the
carbonyl compounds obtained are given in Table 3. The results
detailed in Table 3 indicated that the carbonylation of ethyl 4-bromo-
benzoate with the chosen nucleophiles gave excellent yields.
a
b
The eq. of Co2(CO)8 is relative to the eq. of aryl halide used. Isolated
c
yield. Reaction conditions: 1 mmol of aryl halide (1 eq.), 5 mol% of
Pd(OAc)2, 10 mol% of xantphos, 2 mmol DMAP (2 eq.), toluene : ethanol
(3 : 1, 4 mL), M/W 90 1C, 30 min.
Purification of products was performed by silica gel column
chromatography. 1H NMR spectra were obtained using a 300 MHz
spectrometer. 13C NMR spectra were obtained from a 75 MHz
Conclusions
spectrometer. All H and 13C NMR experiments are reported in
1
In summary, we have demonstrated a simple, safe and environ-
mentally friendly method of carbonylation of aryl halides to give
esters and carbonyl derivatives using Co2(CO)8 as the carbonyl
source by exploiting in situ carbon monoxide liberation. This
protocol is a CO gas free method which can be easily automated
and which can be carried out with short reaction times.
parts per million (ppm) downfield from tetramethylsilane and
were measured relative to the signals for residual chloroform in
the deuterated solvents. The mass spectra were recorded on
an Ultra Performance Liquid Chromatography (UPLC) or gas
chromatography-mass spectrometry (GC-MS). All the spectral
data matched well with the literature descriptions.
Experimental section
General procedures
General section
Method A: the synthesis of aryl esters from aryl bromides. To
Commercially available reagents were used as received in this a stirred solution of aryl bromide (1 mmol) in toluene : EtOH
work. Toluene and ethanol were freshly distilled and used. mixture (3 : 1, 4 mL) taken in a 8 mL microwave vial, Pd(OAc)2
c
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(5 mol%), xantphos (10 mol%) and DMAP (2 mmol) were added obtained as a colorless liquid. Yield: (146 mg, 89% in Method
followed by Co2(CO)8 (0.25 mmol). The vial was sealed imme- A & 134 mg, 82% in Method B).
diately and microwave irradiated at 90 1C for 30 min. The
1H-NMR (300 MHz, CDCl3): d 1.38 (t, 3H, J = 7.2 Hz), 2.39
reaction mixture was concentrated under reduced pressure and (s, 3H), 4.36 (q, 2H, J = 7.1 Hz), 7.22 (d, 2H, J = 8.4 Hz), 7.93
diluted with ethyl acetate, washed with 10% aq. citric acid (d, 2H, J = 8.4 Hz). 13C-NMR (75 MHz, CDCl3, d ppm): 14.4, 21.5,
solution and brine solution and the organic layer was dried over 60.6, 127.7, 129.0 (2C), 129.6 (2C), 143.3, 166.4.
Na2SO4, and concentrated under reduced pressure. The result-
4-Methoxybenzoic acid ethyl ester (2c). Compound 2c was
ing crude product was purified by silica gel (60–120 mesh) prepared according to the general procedure described in
column chromatography using ethyl acetate and hexane as Methods A and B by using 1-bromo-4-methoxybenzene (187 mg,
eluents.
1 mmol) and 1-iodo-4-methoxybenzene (234 mg, 1 mmol) respec-
Method B: the synthesis of aryl esters from aryl iodides. To a tively in toluene : EtOH (3 : 1, 4 mL), Pd(OAc)2 (12 mg, 5 mol%),
stirred solution of aryl iodide (1 mmol) in toluene : EtOH xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and
mixture (3 : 1, 4 mL) taken in a 8 mL microwave vial, Pd(OAc)2 Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2c was obtained
(5 mol%), xantphos (10 mol%), and DMAP (2 mmol) were as a yellow liquid. Yield: (164 mg, 91% in Method A & 149 mg, 83%
1
added followed by Co2(CO)8 (0.2 mmol). The vial was sealed in Method B). H-NMR (300 MHz, CDCl3): d 1.39 (t, J = 7.11 Hz,
immediately and microwave irradiated at 90 1C for 30 min. The 3H), 3.87 (s, 3H), 4.35 (q, J = 7.14 Hz, 2H), 6.92 (d, J = 8.64 Hz, 2H),
reaction mixture was concentrated under reduced pressure and 8.01 (d, J = 8.61 Hz, 2H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.3,
diluted with ethyl acetate, washed with 10% aq. citric acid 55.3, 60.5, 113.5 (2C), 122.9, 131.4 (2C), 163.1, 166.3.
solution and brine solution and the organic layer was dried over
3-Methoxybenzoic acid ethyl ester (2d). Compound 2d was
Na2SO4, and concentrated under reduced pressure. The result- prepared according to the general procedure described in
ing crude product was purified by silica gel (60–120 mesh) Method A by using 1-bromo-3-methoxybenzene (187 mg, 1 mmol)
column chromatography using ethyl acetate and hexane as in toluene : EtOH (3: 1, 4 mL), Pd(OAc)2 (12 mg, 5 mol%),
eluents.
xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and
Method C: the synthesis of carbonyl derivatives from aryl Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2d was
halides. To a stirred solution of aryl halide (1 mmol) in toluene obtained as a colorless liquid. Yield: (151 mg, 84%).
(4 mL), in a 8 mL microwave vial, R-Nu (2 mmol), Pd(OAc)2
1H-NMR (400 MHz, CDCl3): d 1.41 (t, J = 7.12 Hz, 3H), 3.87
(5 mol%), xantphos (10 mol%), and DMAP (2 mmol) were (s, 3H), 4.39 (q, J = 7.16 Hz, 2H), 7.10–7.12 (m, 1H), 7.34–7.36
added followed by Co2(CO)8 (0.2 mmol). The vial was sealed (m, 1H), 7.57–7.58 (m, 1H), 7.58–7.65 (m, 1H). 13C-NMR (75 MHz,
immediately and microwave irradiated at 90 1C for 30 min. The CDCl3, d ppm): 14.2, 55.3, 60.9, 113.9, 119.2, 121.8, 129.2, 131.8,
reaction mixture was concentrated under reduced pressure and 159.4, 166.4.
diluted with ethyl acetate, washed with 10% aq. citric acid
4-tert-Butylbenzoic acid ethyl ester (2e). Compound 2e was
solution and brine solution and the organic layer was dried over prepared according to the general procedure described in
Na2SO4, and concentrated under reduced pressure. The resulting Methods A and B by using 1-bromo-4-(tert-butyl)benzene (213 mg,
crude product was purified by silica gel (60–120 mesh) column 1 mmol) and 1-iodo-4-(tert-butyl)benzene (274 mg, 1 mmol)
chromatography using ethyl acetate and hexane as eluents.
respectively in toluene : EtOH (3 : 1, 4 mL), Pd(OAc)2 (12 mg,
5 mol%), xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol)
and Co2(CO)8 (100 mg, 0.3 mmol). The title compound 2e was
Synthesis and characterization of the products
Benzoic acid ethyl ester (2a). Compound 2a was prepared obtained as a colorless solid. Yield: (158.6 mg, 77% in Method
according to the general procedure described in Methods A and A & 154.5 mg, 75% in Method B).
B by using bromobenzene (157 mg, 1 mmol) and iodobenzene
1H-NMR (400 MHz, CDCl3): d 1.35 (s, 9H), 1.40 (t, J = 6.48 Hz,
(205 mg, 1 mmol) respectively in toluene : EtOH (3 : 1, 4 mL), 3H), 4.38 (q, J = 7.12 Hz, 2H), 7.46 (d, J = 8.56 Hz, 2H), 7.99
Pd(OAc)2 (12 mg, 5 mol%), xantphos (58 mg, 10 mol%), DMAP (d, J = 8.60 Hz, 2H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.3, 31
(244 mg, 2 mmol) and Co2(CO)8 (85 mg, 0.25 mmol). The title (3C), 35, 60.6, 125.2 (2C), 129.2 (2C), 156.3, 166.6.
compound 2a was obtained as a colourless liquid. Yield:
4-Fluorobenzoic acid ethyl ester (2f). Compound 2f was
(143 mg, 95% in Method A & 132 mg, 88% in Method B).
prepared according to the general procedure described in
1H-NMR (400 MHz, CDCl3): d 1.42 (t, J = 7.12 Hz, 3H), 4.40 Method A by using 1-bromo-4-fluorobenzene (175 mg, 1 mmol)
(q, J = 7.12 Hz, 2H), 7.44–7.46 (m, 2H), 7.55–7.56 (m, 1H), 8.06– in toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%),
8.06 (m, 2H), 13C-NMR (75 MHz, CDCl3, d ppm): 14.3, 60.9, xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and
128.2, 129.4, 130.4, 132.7, 166.5.
Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2f was
4-Methylbenzoic acid ethyl ester (2b). Compound 2b was obtained as a colorless liquid. Yield: (137.7 mg, 82%).
prepared according to the general procedure described in
1H-NMR (300 MHz, CDCl3): d 1.40 (t, J = 7.14 Hz, 3H), 4.37
Methods A and B by using 1-bromo-4-methylbenzene (171 mg, (q, J = 7.11 Hz, 2H), 7.08–7.09 (m, 2H), 8.05–8.06 (m, 2H). 13C-NMR
1 mmol) and 1-iodo-4-methylbenzene (218 mg, 1 mmol) respec- (75 MHz, CDCl3, d ppm): 14.2, 61.0, 115.2, 115.5, 126.7, 131.9,
tively in toluene: EtOH (3: 1, 4 mL), Pd(OAc)2 (12 mg, 5 mol%), 132.0, 163.9, 165.6, 167.3.
xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and
4-Chlorobenzoic acid ethyl ester (2g). Compound 2g was
Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2b was prepared according to the general procedure described in
c
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Methods A and B by using 1-bromo-4-chlorobenzene (191 mg,
2-Formylbenzoic acid ethyl ester (2l). Compound 2l was
1 mmol) and 4-chloro-1-iodobenzene (238 mg, 1 mmol) respec- prepared according to the general procedure described in
tively in toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), Method A by using 2-bromobenzaldehyde (185 mg, 1 mmol)
xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and in toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%),
Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2g was xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and
obtained as an off-white solid. Yield: (174.8 mg, 95% in Method Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2l was
A & 147 mg, 80% in Method B).
obtained as a colorless liquid. Yield: (115 mg, 65%).
1H-NMR (400 MHz, CDCl3): d 1.39 (t, 3H, J = 7.0 Hz), 4.37
1H-NMR (400 MHz, CDCl3): d 1.44 (t, J = 7.16 Hz, 3H), 4.46
(q, 2H, J = 7.1 Hz), 7.38–7.42 (m, 2H), 7.96–7.99 (m, 2H). 13C-NMR (q, J = 7.16 Hz, 2H), 7.65–7.66 (m, 2H), 7.95–7.96 (m, 2H), 10.64
(75 MHz, CDCl3, d ppm): 14.2, 61.1, 128.6, 128.9, 131.2, 139.1, 165.7. (s, 1H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.2, 61.9, 128.3,
4-Formylbenzoic acid ethyl ester (2h). Compound 2h was 130.2, 132.2, 132.4, 132.8, 136.9, 166.2, 192.0.
prepared according to the general procedure described in
3-Pyridinecarboxylic acid ethyl ester (2m). Compound 2m
Method A by using 4-bromobenzaldehyde (185 mg, 1 mmol) was prepared according to the general procedure described in
in toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), Method A by using 3-bromopyridine (158 mg, 1 mmol) in
xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos
Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2h was (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8
obtained as a colorless liquid. Yield: (166 mg, 95%).
(85 mg, 0.25 mmol). The title compound 2m was obtained as a
1H-NMR (400 MHz, CDCl3): d 1.42 (t, J = 7.16 Hz, 3H), 4.42 colorless liquid. Yield: (117.7 mg, 78%).
(q, J = 7.16 H, 2H), 7.94–7.95 (m, 2H), 8.15–8.16 (m, 2H), 10.10
1H-NMR (400 MHz, CDCl3): d 1.42 (t, J = 7.12 Hz, 3H), 4.43
(s, 1H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.2, 61.5, 129.4, (q, J = 7.16 Hz, 2H), 7.38–7.39 (m, 1H), 8.30–8.30 (m, 1H), 8.77–
130.5, 135.4, 139.0, 165.5, 191.6.
4-Nitrobenzoic acid ethyl ester (2i). Compound 2i was pre- d ppm): 14.2, 61.3, 123.2, 126.3, 136.9, 150.8, 153.2, 165.2.
pared according to the general procedure described in Methods 4-Hydroxybenzoic acid ethyl ester (2n). Compound 2n was
8.78 (m, 1H), 9.24 (d, J = 1.64 Hz, 1H). 13C-NMR (75 MHz, CDCl3,
A and B by using 1-bromo-4-nitrobenzene (202 mg, 1 mmol) prepared according to the general procedure described in
and 1-iodo-4-nitrobenzene (249 mg, 1 mmol) respectively in Method A by using 4-bromophenol (173 mg, 1 mmol) in
toluene : EtOH (3 : 1, 4 mL), Pd(OAc)2 (12 mg, 5 mol%), xant- toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos
phos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8 (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8
(85 mg, 0.25 mmol). The title compound 2i was obtained as a (100 mg, 0.30 mmol). The title compound 2n was obtained as
yellow solid. Yield: (175.5 mg, 90% in Method A & 148 mg, 76% an off-white solid. Yield: (125 mg, 75%).
in Method B).
1H-NMR (400 MHz, CDCl3): d 1.40 (t, J = 6.80 Hz, 3H), 4.37
1H-NMR (300 MHz, CDCl3): d 1.44 (t, J = 7.14 Hz, 3H), 4.45 (q, (q, J = 7.20 Hz, 2H), 5.49 (s, 1H), 6.89 (d, J = 2.80 Hz, 2H), 6.89
J = 7.11 Hz, 2H), 8.24–8.28 (m, 4H). 13C-NMR (75 MHz, CDCl3, d (d, J = 2.80 Hz, 2H).
ppm): 14.1, 62.0, 123.4, 130.6, 135.8, 150.4, 164.6.
3-Fluorobenzoic acid ethyl ester (2o). Compound 2o
3-Formylbenzoic acid ethyl ester (2j). Compound 2j was was prepared according to the general procedure described
prepared according to the general procedure described in in Method A by using 1-bromo-3-fluorobenzene (175 mg,
Method A by using 3-bromobenzaldehyde (185 mg, 1 mmol) 1 mmol) in toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg,
in toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), 5 mol%), xantphos (58 mg, 10 mol%), DMAP (244 mg,
xantphos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and 2 mmol) and Co2(CO)8 (85 mg, 0.25 mmol). The title com-
Co2(CO)8 (85 mg, 0.25 mmol). The title compound 2j was pound 2o was obtained as a colorless liquid. Yield: (116 mg,
obtained as a colorless liquid. Yield: (146 mg, 82%).
69%).
1H-NMR (400 MHz, CDCl3): d 1.41 (t, J = 7.16 Hz, 3H), 4.40
1H-NMR (300 MHz, CDCl3): d 1.42 (t, 3H, J = 8.17 Hz),
4.42 (q, 2H, J = 8.16 Hz), 7.59–7.64 (m, 1H), 7.92–8.19 (q, J = 7.16 Hz, 2H), 7.24–7.24 (m, 1H), 7.40–7.41 (m, 1H), 7.72–
(m, 1H), 8.29–8.41 (m, 1H), 8.41–8.62 (1H), 10.08 (s, 1H). 13C-NMR 7.72 (m, 1H), 7.84–7.84 (m, 1H). 13C-NMR (75 MHz, CDCl3,
(75 MHz, CDCl3, d ppm): 14.2, 61.4, 129.2, 131.0, 134.4, 135.0, d ppm): 14.2, 61.2, 116.2, 116.5, 119.6, 119.9, 125.1, 125.2,
165.4, 191.5.
Biphenyl-4-carboxylic acid ethyl ester (2k). Compound 2k
129.8, 129.9, 132.5, 132.7, 160.8, 164.1, 165.4.
4-Aminobenzoic acid ethyl ester (2p). Compound 2p was
was prepared according to the general procedure described in prepared according to the general procedure described in
Method A by using 4-bromo-1,10-biphenyl (233 mg, 1 mmol) in Method A by using 4-bromoaniline (172 mg, 1 mmol) in
toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos
(58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8 (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8
(100 mg, 0.3 mmol). The title compound 2k was obtained as a (85 mg, 0.25 mmol). The title compound 3p was obtained as a
white solid. Yield: (176 mg, 78%).
colorless solid. Yield: (120 mg, 62%).
1H-NMR (400 MHz, CDCl3): d 1.43 (t, J = 7.12 Hz, 3H), 4.42
1H-NMR (300 MHz, CDCl3): d 1.36 (t, J = 6.54 Hz, 3H), 4.06
(q, J = 7.04 Hz, 2H), 7.39–7.41 (m, 3H), 7.63–7.65 (m, 4H), 8.13 (s, 2H), 4.31 (q, J = 6.63 Hz, 2H), 6.64 (d, J = 8.16 Hz, 2H), 7.86
(d, J = 8.08 Hz, 2H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.3, (d, J = 8.13 Hz, 2H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.3,
60.9, 126.9, 127.2, 128.0, 128.8, 129.2, 130.0, 140.0, 145.4, 166.4. 60.2, 113.7, 129.5, 120.0, 131.5, 150.7, 166.7.
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Terephthalamic acid ethyl ester (2q). Compound 2q was using ethyl 4-bromobenzoate (115 mg, 0.5 mmol) in toluene :
prepared according to the general procedure described in MeOH (3 : 1, 4 mL), Pd(OAc)2 (6 mg, 5 mol%), xantphos (30 mg,
Method A by using 4-bromobenzamide (200 mg, 1 mmol) in 10 mol%), DMAP (122 mg, 1 mmol) and Co2(CO)8 (43 mg,
toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos 0.125 mmol). The title compound 3a was obtained as an off-
(58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8 white semisolid. Yield: (94 mg, 90%).
(100 mg, 0.30 mmol). The title compound 2q was obtained as
off-white solid. Yield: (120 mg, 62%).
1H-NMR (300 MHz, CDCl3): d 1.39 (t, J = 7.11 Hz, 3H), 4.35
(q, J = 7.14 Hz, 2H), 6.92 (d, J = 8.64 Hz, 2H), 8.01 (d, J = 8.61 Hz,
1H-NMR (300 MHz, CDCl3): d 1.42 (t, J = 7.14 Hz, 3H), 4.41 2H). 13C-NMR (100 MHz, CDCl3, d ppm): 14.2, 52.3, 61.3, 129.4,
(q, J = 7.14 Hz, 2H), 6.08 (s, 2H), 7.46–7.49 (m, 1H), 7.82–7.84 133.7, 134.2, 165.7, 166.2.
(m, 2H), 7.89–8.11 (m, 2H). 13C-NMR (75 MHz, CDCl3, d ppm):
Diethyl terephthalate (3b). Compound 3b was prepared
14.2, 61.3, 127.3, 128.6, 129.8, 132.0, 133.5, 165.6.
according to the general procedure described in Methods A–C by
4-Carboxybenzoic acid ethyl ester (2r). Compound 2r was using ethyl 4-bromobenzoate (115 mg, 0.5 mmol) in toluene : EtOH
prepared according to the general procedure described in (3 : 1, 4 mL), Pd(OAc)2 (6 mg, 5 mol%), xantphos (30 mg, 10 mol%),
Method A by using 4-bromobenzoic acid (201 mg, 1 mmol) in DMAP (122 mg, 1 mmol) and Co2(CO)8 (43 mg, 0.125 mmol).
toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos The title compound 3b was obtained as a white semisolid.
(58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8 Yield: (105 mg, 94%).
(85 mg, 0.25 mmol). The title compound 2r was obtained as a
1H-NMR (300 MHz, CDCl3): d 1.42 (t, J = 7.11 Hz, 3H), 4.41
(q, J = 7.11 Hz, 2H), 8.11 (s, 4H). 13C-NMR (100 MHz, CDCl3,
white solid. Yield: (132 mg, 68%).
1H-NMR (300 MHz, CDCl3): d 1.45 (t, J = 3.15 Hz, 3H), 4.43 d ppm): 14.2, 61.3, 129.4 (4C), 134.1, 165.8.
(q, J = 5.37 Hz, 2H), 8.14–8.17 (m, 4H). 13C-NMR (75 MHz,
CDCl3, d ppm): 14.2, 61.4, 129.5, 130.2, 134.9, 165.6.
Ethyl isopropyl terephthalate (3c). Compound 3c was pre-
pared according to the general procedure described in Method
3-Carboxybenzoic acid ethyl ester (2s). Compound 2s was C by using ethyl 4-bromobenzoate (115 mg, 0.5 mmol) in
prepared according to the general procedure described in toluene : IPA (3 : 1, 4 mL), Pd(OAc)2 (6 mg, 5 mol%), xantphos
Method A by using 3-bromobenzoic acid (201 mg, 1 mmol) in (30 mg, 10 mol%), DMAP (122 mg, 1 mmol) and Co2(CO)8
toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos (43 mg, 0.125 mmol). The title compound 3c was obtained as a
(58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8 colorless liquid. Yield: (101 mg, 85%).
(100 mg, 0.30 mmol). The title compound 2s was obtained as a
white solid. Yield: (126 mg, 65%).
1H-NMR (400 MHz, CDCl3): d 1.39–1.40 (m, 9H), 4.41
(q, J = 7.12 Hz, 2H), 5.25–5.26 (m, 1H), 8.10 (s, 4H). 13C-NMR
1H-NMR (300 MHz, CDCl3): d 1.45 (t, J = 5.34 Hz, 3H), 4.45 (100 MHz, CDCl3, d ppm): 14.2, 21.8, 61.3, 68.9, 129.3 (4C),
(q, J = 5.34 Hz, 2H), 7.60 (t, J = 5.82 Hz, 1H), 8.31–8.31 (m, 2H), 133.9, 134.5, 165.2, 165.8.
8.79 (s, 1H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.2, 61.4,
Butyl ethyl terephthalate (3d). Compound 3d was prepared
128.7, 129.5, 131.1, 131.3, 134.2, 134.6, 165.6.
according to the general procedure described in Method C by
4-Ethoxycarbonylbenzophenone (2t). Compound 2t was pre- using ethyl 4-bromobenzoate (115 mg, 0.5 mmol) in toluene :
pared according to the general procedure described in Method n-BuOH (3 : 1, 4 mL), Pd(OAc)2 (6 mg, 5 mol%), xantphos
A by using (4-bromophenyl)(phenyl)methanone (261 mg, 1 mmol) (30 mg, 10 mol%), DMAP (122 mg, 1 mmol) and Co2(CO)8
in toluene : EtOH 1 : 1 (4 mL), Pd(OAc)2 (12 mg, 5 mol%), xant- (43 mg, 0.125 mmol). The title compound 3d was obtained as a
phos (58 mg, 10 mol%), DMAP (244 mg, 2 mmol) and Co2(CO)8 colorless liquid. Yield: (105 mg, 84%).
(85 mg, 0.25 mmol). The title compound 2t was obtained as a
white solid. Yield: (214.2 mg, 84%).
1H-NMR (300 MHz, CDCl3): d 1.00 (t, J = 7.16 Hz, 3H), 1.43
(t, J = 7.11 Hz, 3H), 1.47–1.50 (m, 2H), 1.72–1.75 (m, 2H), 4.33–
1H-NMR (400 MHz, CDCl3): d 1.44 (t, J = 7.12 Hz, 3H), 4.44 4.35 (m, 4H), 8.10 (s, 4H). 13C-NMR (100 MHz, CDCl3, d ppm):
(q, J = 7.12 Hz, 2H), 7.50–7.52 (m, 2H), 7.62–7.62 (m, 1H), 7.81– 13.6, 14.2, 19.2, 30.6, 61.3, 65.2, 129.4 (4C), 134.1, 165.8.
7.81 (m, 4H), 8.16–8.18 (m, 2H).
13C-NMR (100 MHz, CDCl3, d ppm): 14.2, 61.4, 128.4, 129.4, according to the general procedure described in Method C by
129.7, 130.0, 132.9, 133.5, 137.0, 141.1, 165.8, 196.0. using ethyl 4-bromobenzoate (115 mg, 0.5 mmol) in toluene
Benzyl ethyl terephthalate (3e). Compound 3e was prepared
1(3H)-Isobenzofuranone (2u). Compound 2u was prepared (3 mL), benzyl alcohol (108 mg, 1 mmol) Pd(OAc)2 (6 mg, 5 mol%),
according to the general procedure described in Method A by xantphos (30 mg, 10 mol%), DMAP (122 mg, 1 mmol) and
using 2-bromophenylmethanol (187 mg, 1 mmol) in toluene Co2(CO)8 (43 mg, 0.125 mmol). The title compound 3e was
(4 mL), Pd(OAc)2 (12 mg, 5 mol%), xantphos (58 mg, 10 mol%), obtained as a colorless liquid. Yield: (132.5 mg, 92%).
DMAP (244 mg, 2 mmol) and Co2(CO)8 (85 mg, 0.25 mmol). The
title compound 2u was obtained as an off-white powder. Yield: (q, J = 9.52 Hz, 2H), 5.40 (s, 2H), 7.39–7.41 (m, 5H), 8.09–8.10
(123 mg, 92%).
(m, 4H). 13C-NMR (75 MHz, CDCl3, d ppm): 14.3, 61.4, 67.1,
1H-NMR (400 MHz, CDCl3): d 1.42 (t, J = 9.52 Hz, 3H), 4.41
1H-NMR (300 MHz, CDCl3): d 5.33 (s, 2H), 7.50–7.52 (m, 2H), 128.3, 128.6, 129.6, 133.8, 134.4, 135.7, 165.7.
7.68–7.70 (m, 1H), 7.92–7.94 (m, 1H). 13C-NMR (100 MHz,
CDCl3, d ppm): 69.6, 122.0, 125.7, 129.0, 133.9, 146.5, 171.0.
Ethyl phenyl terephthalate (3f). Compound 3f was prepared
according to the general procedure described in Method C by
Ethyl methyl terephthalate (3a). Compound 3a was prepared using ethyl 4-bromobenzoate (115 mg, 0.5 mmol) in toluene
according to the general procedure described in Method C by (3 mL), phenol (94 mg, 1 mmol), Pd(OAc)2 (6 mg, 5 mol%),
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xantphos (30 mg, 10 mol%), DMAP (122 mg, 1 mmol) and d ppm): 14.2, 35.2, 39.3, 61.1, 126.9 (2C), 129.6 (2C), 131.2,
Co2(CO)8 (43 mg, 0.125 mmol). The title compound 3f was 140.5, 165.8, 170.5.
obtained as a white solid. Yield: (129 mg, 95%).
4-Carboxybenzoic acid ethyl ester (3j). Compound 3j was
1H-NMR (400 MHz, CDCl3): d 0.00 (t, J = 7.12 Hz, 3H), 0.00 prepared according to the general procedure described in
(q, J = 7.12 Hz, 2H), 7.44–7.46 (m, 2H), 7.55–7.56 (m, 1H), 8.06– Method C by using ethyl 4-bromobenzoate (115 mg, 0.5 mmol)
8.06 (m, 2H). 13C-NMR (100 MHz, CDCl3, d ppm): 14.3, 61.5, in toluene : water (9 : 1, 3 mL), Pd(OAc)2 (6 mg, 5 mol%),
121.6, 126.1, 129.6, 130.1, 133.2, 134.9, 150.8, 164.4, 165.7.
xantphos (30 mg, 10 mol%), DMAP (122 mg, 1 mmol) and
Ethyl 4-(phenylcarbamoyl)benzoate (3g). Compound 3g was Co2(CO)8 (43 mg, 0.125 mmol). The title compound 3j was
prepared according to the general procedure described in obtained as a colorless liquid. Yield: (70 mg, 71%).
Method C by using ethyl 4-bromobenzoate (115 mg, 0.5 mmol)
1H-NMR (400 MHz, CDCl3): d 1.43 (t, J = 7.16 Hz, 3H), 4.43
in toluene (3 mL), aniline (93 mg, 1 mmol) Pd(OAc)2 (6 mg, (q, J = 7.16 Hz, 2H), 3.12 (s, 3H), 8.14–8.17 (m, 4H). 13C-NMR
5 mol%), xantphos (30 mg, 10 mol%), DMAP (122 mg, 1 mmol) (100 MHz, CDCl3, d ppm): 14.2, 61.4, 129.5, 130.2, 134.9, 165.6.
and Co2(CO)8 (43 mg, 0.125 mmol). The title compound 3g was
obtained as a colorless liquid. Yield: (111 mg, 82%).
References
1H-NMR (300 MHz, CDCl3): d 1.42 (t, J = 7.14 Hz, 3H), 4.41
(q, J = 7.11 Hz, 2H), 7.15–7.17 (m, 1H), 7.38 (t, J = 8.16 Hz, 2H), 1 (a) A. Schoenberg, I. Bartoletti and R. F. Heck, J. Org. Chem.,
7.66 (d, J = 7.71 Hz, 2H), 7.91 (d, J = 8.28 Hz, 2H), 8.07–8.09
(m, 3H). 13C-NMR (100 MHz, CDCl3, d ppm): 14.2, 61.4, 120.4,
124.8, 127.0, 129.0, 129.8, 133.2, 137.6, 138.7, 165.0, 165.7.
Ethyl 4-(methylcarbamoyl)benzoate (3h). Compound 3h was
prepared according to the general procedure described in
1974, 39, 3318; (b) A. Schoenberg and R. F. Heck, J. Org.
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2 (a) A. Brennfu¨hrer, H. Neumann and M. Beller, Angew. Chem.,
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Method C by using ethyl 4-bromobenzoate (115 mg, 0.5 mmol) 3 R. H. Munday, J. R. Martinelli and S. L. Buchwald, J. Am.
in toluene (3 mL), 2 M methylamine in THF solution (0.5 mL, Chem. Soc., 2008, 130, 2754–2755.
1 mmol), Pd(OAc)2 (6 mg, 5 mol%), xantphos (30 mg, 10 mol%), 4 (a) T. Schareina, A. Zapf, A. Cotte, M. Gotta and M. Beller,
´
DMAP (122 mg, 1 mmol) and Co2(CO)8 (43 mg, 0.125 mmol).
The title compound 3h was obtained as a colorless liquid. Yield:
(84 mg, 81%). 1H-NMR (400 MHz, CDCl3): d 1.43 (t, J = 7.16 Hz,
3H), 3.06 (d, J = 4.84 Hz, 3H), 4.42 (q, J = 7.12 Hz, 2H), 6.22
(s broad, 1H), 7.83 (d, J = 8.40 Hz, 2H), 8.12 (d, J = 8.40 Hz, 2H).
13C-NMR (100 MHz, CDCl3, d ppm): 14.2, 26.8, 29.6, 61.2, 126.8
(2C), 129.7 (2C), 132.8, 138.3, 165.8, 167.3.
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Ethyl 4-(dimethylcarbamoyl)benzoate (3i). Compound 3i was
prepared according to the general procedure described in 5 (a) T. Morimoto, K. Fuji, K. Tsutsumi and K. Kakiuchi, J. Am.
Method C by using ethyl 4-bromobenzoate (115 mg, 0.5 mmol)
(229 mg, 1 mmol) in toluene (3 mL), 2 M dimethylamine in THF
solution (0.5 mL, 1 mmol), Pd(OAc)2 (6 mg, 5 mol%), xantphos
Chem. Soc., 2002, 124, 3806; (b) T. Shibata, N. Toshida and
K. Takagi, J. Org. Chem., 2002, 67, 7446; (c) T. Shibata,
N. Toshida and K. Takagi, Org. Lett., 2002, 4, 1619.
(30 mg, 10 mol%), DMAP (122 mg, 1 mmol) and Co2(CO)8 6 (a) P. Hermange, T. M. Gøgsig, A. T. Lindhardt, R. H. Taaning
(43 mg, 0.125 mmol). The title compound 3i was obtained as a
colorless liquid. Yield: (87 mg, 84%).
and T. Skrydstrup, Org. Lett., 2011, 13, 2444; (b) T. Morimoto
and K. Kakiuchi, Angew. Chem., Int. Ed., 2004, 43, 5580.
1H-NMR (400 MHz, CDCl3): d 1.39 (t, J = 9.52 Hz, 3H), 2.94 7 R. L. Odell, F. Russo and M. Larhed, Synlett, 2012, 685.
(s, 3H), 3.12 (s, 3H), 4.38 (q, J = 9.52 Hz, 2H), 7.46 (d, J = 9.00 Hz, 8 J. Brunet, C. Sidot and P. Caubere, J. Org. Chem., 1983,
2H), 8.07 (d, J = 11.28 Hz, 2H). 13C-NMR (100 MHz, CDCl3,
48, 1166.
c
3056 New J. Chem., 2013, 37, 3050--3056
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2013