β–Cyclodextrin–Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
Entry | Solvents | Temp (°C) | Amount (mol %) | Time (min) | Yield (%) b |
---|---|---|---|---|---|
1 | No Solvent | rt. | -- | 150 | No reaction |
2 | No Solvent | 80 | -- | 150 | No reaction |
3 | No Solvent | rt. | 2 | 150 | 28 |
4 | No Solvent | 50 | 2 | 40 | 55 |
5 | No Solvent | 80 | 2 | 30 | 85 |
6 | No Solvent | 100 | 2 | 20 | 96 |
7 | No Solvent | 80 | 1 | 70 | 74 |
8 | No Solvent | 80 | 3 | 50 | 92 |
9 | Water | 80 | 2 | 30 | 63 |
10 | CH3CH2OH | reflux | 2 | 40 | 78 |
11 | ClCH2CH2Cl | reflux | 2 | 40 | 45 |
12 | EtOAc | reflux | 2 | 40 | 70 |
13 | THF | reflux | 2 | 40 | 56 |
14 | CH3CN | 100 | 2 | 40 | 64 |
15 | DMF | 100 | 2 | 40 | 72 |
Entry | Catalyst | Solvent | Condition | Yield (in %) b | Time | Ref. |
---|---|---|---|---|---|---|
1 | Zeolite HY | - | MW | 42–85 | 6 min | [12] |
2 | Silica gel | - | MW | 60–90 | 6 min | [12] |
3 | Silica gel/NaHSO4 | DCM | reflux | 85–90 | 2.5 h | [13] |
4 | HClO4–SiO2 | - | 140 °C | 60–94 | 15–20 min | [14] |
5 | I2 | Ethanol | 75°C | 97–99 | 15–20 min | [15] |
6 | K5CoW12O40·3H2O | DCM | 140 °C | 15–95 | 2.5 h | [8] |
7 | BF3·SiO2 | - | 140 °C | 80–96 | 2 h | [16] |
8 | InCl3·3H2O | MeOH | r.t. | 47–84 | 6–9 h | [17] |
10 | [(CH2)4SO3HMIM] | - | 140 °C | 85–95 | 2–2.5 h | [20] |
11 | MCM-41 | - | 140 °C | 74–82 | 1.92–2.25 h | [21] |
12 | MCM-41 | AcOH | reflux | 75–85 | 25–35 min | [21] |
13 | p-TsOH | - | 140 °C | 75–82 | 1.92–2.17 h | [21] |
14 | p-TsOH | EtOH | reflux | 73–83 | 13–23 min | [21] |
15 | - | 1-Butyl-3-methylimidazolium bromide | 140 °C | 82–93 | 1.5–5 h | [22] |
16 | - | 1-Butyl-3-methylimidazolium bromide | MW | 82–93 | 3–8 min | [22] |
17 | P2O5/SiO2 | - | 100 °C | 87–98 | 15–55 min | [23] |
18 | - | - | 140 °C | 0 | 3 h | [20] |
19 | SiO2-Pr-SO3H | - | 140 °C | 85–98 | 10 min–3 h | [19] |
20 | β-CD-Pr-SO3H | - | 100 °C | 68–96 | 15 min–4 h | (This work) |
Entry | R1 | R2 | Product | Time | Yield (in %) b | M.P. in °C (Observed) | M.P. in °C (in Literature) |
---|---|---|---|---|---|---|---|
1 | 4-Cl | C6H5 | 5a | 30 min | 96 | 158–160 | 157–159 |
2 | 3-NO2 | C6H5 | 5b | 15 min | 93 | 247–249 | 249–250 |
3 | 4-OCH3 | C6H5 | 5c | 3 h | 90 | 180–182 | 181–183 |
4 | 4-CH3 | C6H5 | 5d | 2.5 h | 90 | 188–190 | 189–190 |
5 | 4-Cl | -CH2C6H5 | 5e | 3 h | 89 | 166–168 | 163–165 |
6 | 4-OH | -CH2C6H5 | 5f | 3 h | 80 | 132–134 | 131–132 |
7 | -CH2C6H5 | 5g | 3.5 h | 73 | 154–155 | 155–157 | |
8 | 4-CH3 | -CH2C6H5 | 5h | 3.5 h | 75 | 160–162 | 163–165 |
9 | 3-OCH3 | -CH2C6H5 | 5i | 4 h | 70 | 115–117 | 128–129 |
10 | 3,4-OCH3 | -CH2C6H5 | 5j | 4 h | 68 | 189–191 | 188–190 |
2.2. Reusability of the Catalyst
No. of Runs | Percentage Yield |
---|---|
1 | 96 |
2 | 94 |
3 | 90 |
4 | 90 |
2.3. Pharmacology
Local Anesthetic Activity
Compound | Corneal Anesthesia a | Mouse Tail Anesthesia b |
---|---|---|
5a | 20.3 ± 8.6 | 11.3 (±0.11) × 10−2 |
5b | 12.4 ± 9.3 | 5.7 (±0.42) × 10−2 |
5c | 15.5 ± 12.3 | 6.5 (±0.23) × 10−2 |
5d | 10.32 ± 0.12 | 4.3 (±0.54) × 10−2 |
5e | 21.65 ± 4.7 | 3.4 (±0.32) × 10−2 |
5f | 5.5 ± 3.5 | 5.4 (±0.14) × 10−2 |
5g | 121.23 ± 12.3 | 1.6 (±0.26) × 10−2 |
5h | 65.65 ± 5.8 | 9.2 (±0.16) × 10−2 |
5i | 95.4 ± 13.2 | 7.4 (±0.18) × 10−2 |
5j | 20.3 ± 10.3 | 4.1 (±0.45) × 10−2 |
Lidocaine HCl c | 100 | 2.1 (±0.25) × 10−2 |
3. Experimental Section
3.1. General Information
3.1.1. Synthesis of β-CD-PSA
3.1.2. General Procedure for the Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles 5(a–j)
3.2. Pharmacology
3.2.1. Corneal Anesthesia
3.2.2. Mouse Tail Anesthesia
3.2.3. Rat Sciatic Nerve Block
3.2.4. Acute Toxicity
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Ran, Y.; Li, M.; Zhang, Z.-Z. β–Cyclodextrin–Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents. Molecules 2015, 20, 20286-20296. https://doi.org/10.3390/molecules201119696
Ran Y, Li M, Zhang Z-Z. β–Cyclodextrin–Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents. Molecules. 2015; 20(11):20286-20296. https://doi.org/10.3390/molecules201119696
Chicago/Turabian StyleRan, Yan, Ming Li, and Zong-Ze Zhang. 2015. "β–Cyclodextrin–Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents" Molecules 20, no. 11: 20286-20296. https://doi.org/10.3390/molecules201119696