Suzuki–Miyaura Coupling Using Monolithic Pd Reactors and Scaling-Up by Series Connection of the Reactors
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preparation of Lithium Arylborates Using Flow Microreactors
2.2. Preparation of Polymer Monolith and Immobilization of Pd Catalyst
2.3. Suzuki–Miyaura Coupling Using the Pd Catalyst Supported by Polymer Monolith A
2.4. Suzuki–Miyaura Coupling Using the Pd Catalyst Supported by Monolith B
2.5. Series Connection
2.6. Recyclability of Monolithic Pd Catalysts
3. Materials and Methods
3.1. General
3.2. Preparation of the Pd Catalysts Supported by Monolith A and Monolith B
3.3. Cross-Coupling of Bromobenzene and p-Iodobenzonitrile by the Space Integation of Lithiation, Borylation, and Suzuki–Miyaura Coupling
3.4. Cross-Coupling of Aryl Bromides (Ar1–Br) and Aryl Halides (Ar2–X) by the Integration of Lithiation, Borylation and Suzuki–Miyaura Coupling in a Flow (Monolith A Reactor)
3.5. Cross-Coupling of Aryl Bromides (Ar1–Br) and Aryl Halides (Ar2–X) by the Integration of Lithiation, Borylation, and Suzuki–Miyaura Coupling Using a Single Monolith B Reactor or Three Monolith B Reactors Connected in Series
3.6. Cross-Coupling of Bromobenzene and p-Iodobenzonitrile by the Integration of Lithiation, Borylation, and Suzuki–Miyaura Coupling Using Multiple Monolith B Reactors Connected in Series
3.7. Synthesis of Adapalene
3.8. Recyclability of the Polymer Monolith A and Monolith B Reactors
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Ar1-X | Conditions of Lithiation and Borylation | Ar2-X | Product | Yield (%) a | ||
---|---|---|---|---|---|---|
tR1 (s) | Temperature (°C) | Condition (a) c | Condition (b) d | |||
| 1.7 | 0 | | | 96 | 100 |
1.7 | 0 | | | 0 | 3 | |
1.7 | 0 | | | 76 | 87 | |
1.7 | 0 | | | 6 | 41 | |
1.7 | 0 | | | 1 | 29 | |
1.7 | 0 | | | 86 | 92 | |
| 0.059 | 0 | | | 68 | 91 |
0.059 | 0 | | | 17 | 83 | |
0.059 | 0 | | | 12 | 91 | |
0.059 | 0 | | | 34 | 84 | |
| 0.059 | 0 | | | 63 | 97 |
0.059 | 0 | | | 15 | 87 | |
| 0.059 | 24 | | | 63 | 98 |
0.059 | 24 | | | 2 | 52 | |
| 0.059 | 0 | | | 0 | 54 b |
| 1.7 | 0 | | | 83 | 94 |
1.7 | 0 | | | 78 | 87 | |
1.7 | 0 | | | 71 | 86 |
Reactor | n (Number of Reactors) | Flow Rate (mL/min) | Residence Time (min) | Pressure Drop (MPa) | Yield (%) | Productivity (mg/h) |
---|---|---|---|---|---|---|
A | 1 | 0.2 | 9.4 | 0.9 | 96 | 52 |
A | 1 | 0.4 | 4.7 | 1.7 | 96 | 100 |
A | 1 | 1.0 | 1.9 | 3.9 | 81 | 220 |
A | 1 | 1.5 | 1.3 | 5.9 | 66 | 270 |
B | 1 | 0.2 | 9.6 | 0.3 | 98 | 53 |
B | 1 | 0.4 | 4.8 | 0.4 | 100 | 110 |
B | 1 | 1.0 | 1.9 | 0.7 | 87 | 230 |
B | 1 | 1.5 | 1.3 | 0.9 | 67 | 270 |
B | 3 | 0.6 | 9.6 | 1.4 | 98 | 160 |
B | 3 | 1.2 | 4.8 | 3.0 | 97 | 310 |
B | 3 | 3.0 | 1.9 | 6.8 | 86 | 690 |
B | 3 | 4.5 | 1.3 | 9.0 | 55 | 670 |
B | 5 | 1.0 | 9.6 | 3.3 | 100 | 270 |
B | 5 | 2.0 | 4.8 | 6.6 | 99 | 530 |
B | 5 | 5.0 | 1.9 | 14 | 75 | 1000 |
B | 5 | 7.5 | 1.3 | 19 | 52 | 1000 |
Ar1-X | Conditions of Lithiation and Borylation | Ar2-X | Product | Yield (%) a | ||
---|---|---|---|---|---|---|
tR1 (s) | Temperature (°C) | n = 1 | n = 3 | |||
| 1.7 | 0 | | | 62 | 87 |
1.7 | 0 | | | 41 | 74 | |
| 0.059 | 24 | | | 26 | 65 |
0.059 | 24 | | | 63 | 94 | |
0.059 | 24 | | | 43 | 82 |
Cycle Number | Yield (%) a | |
---|---|---|
Monolith A | Monolith B | |
1 | 97 | 97 |
2 | 96 | 100 |
3 | 96 | 96 |
4 | 100 | 97 |
5 | 97 | 100 |
6 | 94 | 97 |
7 | 93 | 93 |
8 | 95 | 96 |
9 | 98 | 96 |
10 | 99 | 99 |
11 | 99 | 98 |
12 | 99 | 99 |
13 | 97 | 99 |
14 | 99 | 99 |
15 | 95 | 98 |
T (°C) | Flow Rate (mL/min) | tR (min) | Yield (%) |
---|---|---|---|
60 | 0.2 | 9.4 | 37 |
0.4 | 4.7 | 14 | |
1.0 | 1.9 | 0 | |
1.5 | 1.3 | 0 | |
80 | 0.2 | 9.4 | 81 |
0.4 | 4.7 | 81 | |
1.0 | 1.9 | 39 | |
1.5 | 1.3 | 30 | |
100 | 0.2 | 9.4 | 96 |
0.4 | 4.7 | 96 | |
1.0 | 1.9 | 81 | |
1.5 | 1.3 | 66 | |
120 | 0.2 | 9.4 | 100 |
0.4 | 4.7 | 95 | |
1.0 | 1.9 | 93 | |
1.5 | 1.3 | 96 |
T (°C) | Flow Rate (mL/min) | tR (min) | Yield (%) |
---|---|---|---|
60 | 0.2 | 9.6 | 50 |
0.4 | 4.8 | 60 | |
1.0 | 1.9 | 76 | |
1.5 | 1.3 | 82 | |
80 | 0.2 | 9.6 | 61 |
0.4 | 4.8 | 74 | |
1.0 | 1.9 | 92 | |
1.5 | 1.3 | 100 | |
100 | 0.2 | 9.6 | 67 |
0.4 | 4.8 | 87 | |
1.0 | 1.9 | 100 | |
1.5 | 1.3 | 98 | |
120 | 0.2 | 9.6 | 89 |
0.4 | 4.8 | 92 | |
1.0 | 1.9 | 99 | |
1.5 | 1.3 | 99 |
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Nagaki, A.; Hirose, K.; Moriwaki, Y.; Takumi, M.; Takahashi, Y.; Mitamura, K.; Matsukawa, K.; Ishizuka, N.; Yoshida, J.-i. Suzuki–Miyaura Coupling Using Monolithic Pd Reactors and Scaling-Up by Series Connection of the Reactors. Catalysts 2019, 9, 300. https://doi.org/10.3390/catal9030300
Nagaki A, Hirose K, Moriwaki Y, Takumi M, Takahashi Y, Mitamura K, Matsukawa K, Ishizuka N, Yoshida J-i. Suzuki–Miyaura Coupling Using Monolithic Pd Reactors and Scaling-Up by Series Connection of the Reactors. Catalysts. 2019; 9(3):300. https://doi.org/10.3390/catal9030300
Chicago/Turabian StyleNagaki, Aiichiro, Katsuyuki Hirose, Yuya Moriwaki, Masahiro Takumi, Yusuke Takahashi, Koji Mitamura, Kimihiro Matsukawa, Norio Ishizuka, and Jun-ichi Yoshida. 2019. "Suzuki–Miyaura Coupling Using Monolithic Pd Reactors and Scaling-Up by Series Connection of the Reactors" Catalysts 9, no. 3: 300. https://doi.org/10.3390/catal9030300