Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimizing the Synthesis of Aliphatic Isothiocyanates
2.2. Synthesis of Aliphatic Isothiocyanates 4a–j
2.3. Synthesis of Aromatic Isothiocyanates 7a–j
2.4. Synthesis of Isothiocyanate Derivatives of Natural 9a–j and Unnatural 11a–c Amino Acids
2.5. Determination of the Absolute Configuration Using Circular Dichroism
2.6. Proposed Mechanism of Synthesis of ITC Using DMT/NMM/TsO−
2.7. Comparison DMT/NMM/TsO− vs. Selected Desulfurating Agents
2.8. Antibacterial Activity
3. Materials and Methods
3.1. General Information
3.2. General Procedure and Characterization of Compounds 4a–ag
3.2.1. General Procedure for Compounds 4a–j—Method A
3.2.2. General Procedure for Compounds 4a, 4c, 4e, 4g and 4i—Method B
3.2.3. General Procedure for Compounds 7a–j
3.2.4. General Procedure for Compounds 9a–j
3.2.5. General Procedure for Compounds 11a–c
3.2.6. 2,4- dimethoxy-6-methylthio-1,3,5-triazine (14)
3.3. Study of Antimicrobial Activity
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Entry | MW Conditions | Base (Equiv.) | Solvent | DMT/NMM/TsO− (Equiv.) | Yield (%) b | |
---|---|---|---|---|---|---|
Time (min) | Temp (°C) | |||||
1 c | 3 | 90 | Et3N (4) | DCM | 1.0 | 90 |
2 | 3 | 90 | NMM (4) | DCM | 1.0 | 78 |
3 | 3 | 90 | DBU (4) | DCM | 1.0 | 69 |
4 | 3 | 90 | - | DCM | 1.0 | 51 |
5 | 3 | 90 | Et3N (3) | DCM | 1.0 | 92 |
6 d | 3 | 90 | Et3N (3) | DCM | 1.3 | 92 |
7 | 3 | 90 | Et3N (3) | DCM | 0.7 | 86 |
8 | 3 | 90 | Et3N (3) | DCM | 0 | 55 |
9 | 3 | 90 | Et3N (3) | H2O | 1.0 | 73 |
10 e | 3 | 90 | Et3N (3) | H2O | 1.3 | 89 |
11 f,g,h | 30 | rt | Et3N (3) | DCM | 1.0 | 82 |
Entry | MW Conditions | Base (Equiv.) | Solvent | DMT/NMM/TsO− (Equiv.) | Yield (%) b |
---|---|---|---|---|---|
Time (min) | |||||
1 | 3 | Et3N (3) | DCM | 1.0 | 30 |
2 | 3 | DBU (3) | DCM | 1.0 | 71 |
3 | 3 | DBU (4) | DCM | 1.0 | 67 |
4 | 3 | DBU (4) | DCM | 1.3 | 70 |
5 | 10 | DBU (3) | DCM | 1.0 | 67 |
6 | 3 | DBU (3) | H2O | 1.3 | 21 |
Entry | Compound | Absolute Configuration | [α]D (Concentration) |
---|---|---|---|
1 | 4c | R | −18.1 (1.0 CHCl3) |
2 | 4d | S | +17.5 (1.0 CHCl3) |
3 | 9a | S | +24.1 (0.32 CHCl3) |
4 | 9b | R | −23.3 (0.32 CHCl3) |
5 | 9c | S | +32.1 (0.31 CHCl3) |
6 | 9d | S | +21.4 (0.34 CHCl3) |
7 | 9e | S | +16.3 (1.0 EtOH) |
8 | 9f | S | −21.7 (0.32 CHCl3) |
9 | 9g | S | +23.5 (1.0 EtOH) |
10 | 9h | S | −60.0 (1.0 toluene) |
11 | 9i | S | −18.2 (0.5 CHCl3) |
Entry | DesulfuratingAgents | Yields (%) |
---|---|---|
1 b | DMT/NMM/TsO− | 92 |
2 | TCT | 87 |
3 | I2 | 86 |
4 | Boc2O, DMAPcat. | 84 |
5 | T3P® | 83 |
6 | TsCl | 81 |
7 | Ethyl chloroformate | 78 |
8 | H2O2 30% | 75 |
Entry | Compound (Concentration) | Structure | Growth Inhibition of E. coli (Mean ± DS) | Growth Inhibition of S. aureus (Mean ± DS) |
---|---|---|---|---|
1 | 9a (4 mg/mL, 27 μM) | 15.3 ± 0.3 | 16.1 ± 0.4 | |
2 | 9b (4 mg/mL, 27 μM) | 22.0 ± 0.4 | 22.7 ± 0.3 | |
3 | 9c (4 mg/mL, 18 μM) | 22.1 ± 0.1 | 18.4 ± 0.6 | |
4 | 9d (4 mg/mL, 21 μM) | 36.0 ± 0.7 | 25.1 ± 0.3 | |
5 | 9e (4 mg/mL, 23 μM) | 36.2 ± 0.2 | 32.3 ± 0.1 | |
6 | 9f (4 mg/mL, 21 μM) | 18.3 ± 0.3 | 25.2 ± 0.3 | |
7 | 9g (4 mg/mL, 21 μM) | 20.2 ± 0.2 | 17.5 ± 0.3 | |
8 | 9h (4 mg/mL, 18 μM) | 20.1 ± 0.3 | 24.5 ± 0.6 | |
9 | 9i (4 mg/mL, 16 μM) | 29.3 ± 0.1 | 28.3 ± 0.2 | |
10 | 9j (4 mg/mL, 27 μM) | 30.0 ± 0.4 | 32.1 ± 0.1 | |
11 | 11a (4 mg/mL, 20 μM) | 20.1 ± 0.3 | 32.3 ± 0.3 | |
12 | 11b (4 mg/mL, 18 μM) | 24.4 ± 0.6 | 16.3 ± 0.4 | |
13 | 11c (4 mg/mL, 17 μM) | 20.8 ± 0.2 | 15.5 ± 0.2 | |
15 | Negative control | sterile water | NO | NO |
14 | Positive control (20 μg/mL, 0.062 μM) | Chloramphenicol | 36.2 ± 0.2 | 38.8 ± 0.3 |
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Janczewski, Ł.; Kręgiel, D.; Kolesińska, B. Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent. Molecules 2021, 26, 2740. https://doi.org/10.3390/molecules26092740
Janczewski Ł, Kręgiel D, Kolesińska B. Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent. Molecules. 2021; 26(9):2740. https://doi.org/10.3390/molecules26092740
Chicago/Turabian StyleJanczewski, Łukasz, Dorota Kręgiel, and Beata Kolesińska. 2021. "Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent" Molecules 26, no. 9: 2740. https://doi.org/10.3390/molecules26092740