Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution
Abstract
:1. Introduction
2. Results and Discussion
2.1. Methods and Energy Calculations
2.2. Equilibration Mechanism
2.3. Solution Structure Simulations
3. Conclusions
Acknowledgments
Conflicts of Interest
References
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Gas | CH2Cl2 | Water | |||||
---|---|---|---|---|---|---|---|
ΔGgint | ΔGsint | ΔGsolv | ΔGstot | ΔGsint | ΔGsolv | ΔGstot | |
2OH oxazole | |||||||
2OH, trans | 7.8 | 10.0 | −6.6 | 3.4 | 11.2 | −9.1 | 2.1 |
2-one, NH | −52.0 | −45.4 | −17.0 | −62.4 | −42.7 | −21.9 | −64.6 |
2-one, C5H | −23.6 | −16.8 | −20.6 | −37.4 | −13.4 | −26.8 | −40.2 |
2OH thiazole | |||||||
2OH, trans | 12.6 | 17.1 | −11.2 | 5.9 | 18.8 | −11.5 | 7.3 |
2-one, NH | −45.9 | −40.7 | −14.2 | −54.9 | −38.2 | −14.7 | −52.9 |
2-one, C5H | −9.1 | −1.8 | −17.8 | −19.6 | 1.6 | −19.8 | −18.2 |
4OH oxazole | |||||||
4OH, trans | 11.5 | 15.1 | −10.8 | 4.3 | 16.9 | −14.4 | 2.5 |
4-one, C5H | −29.5 | −23.6 | −16.3 | −39.9 | −21.0 | −20.8 | −41.8 |
4OH thiazole | |||||||
4OH, trans | 11.9 | 16.2 | −11.6 | 4.6 | 18.3 | −15.6 | 2.7 |
4-one, C5H | −8.0 | −1.7 | −16.5 | −18.2 | 1.3 | −21.8 | −20.5 |
Gas | CH2Cl2 | Water | |||||
---|---|---|---|---|---|---|---|
ΔGgint | ΔGsint | ΔGsolv | ΔGstot | ΔGsint | ΔGsolv | ΔGstot | |
3OH isoxazole | |||||||
3OH, trans | 13.5 | 17.9 | −12.7 | 5.2 | 20.1 | −17.2 | 2.9 |
3-one, NH | 4.6 b | 9.8 | −11.2 | −3.1 b | 11.3 | −14.3 | −4.7 b |
3OH isothiazole | |||||||
3OH, trans | 14.9 | 19.3 | −12.9 | 6.4 | 21.6 | −17.5 | 4.1 |
3-one, NH | 4.6 | 13.6 | −19.2 | −5.6 | 16.4 | −24.7 | −8.2 |
4OH isoxazole | |||||||
4OH, trans | 0.0 | 0.1 | −0.2 | −0.1 | 0.1 | −0.2 | −0.1 |
4-one, C5H | 1.9 | −0.6 | 6.6 | 6.0 | −1.6 | 9.2 | 7.6 |
4OH isothiazole | |||||||
4OH, trans | −0.4 | 0.8 | −1.1 | −0.3 | 1.0 | −1.6 | −0.6 |
4-one, C5H | 12.9 | 12.7 | 3.3 | 15.9 | 12.3 | 4.8 | 17.1 |
CH2Cl2 | Water | Exp b,c | |
---|---|---|---|
2OH | |||
oxazole | 2-one, NH | 2-one, NH | 2-one, NH |
thiazole | 2-one, NH | 2-one, NH | 2-one, NH |
3OH | |||
isoxazole | 3-one, NH/3OH cis | 3-one, NH | Mainly 3OH in all media |
isothiazole | 3-one, NH | 3-one, NH | 3OH |
4OH | |||
oxazole | 4-one, C5H | 4-one, C5H | 4-one, C5H |
thiazole | 4-one, C5H | 4-one, C5H | 4OH and 4-one, C5H no ratio provided |
isoxazole | 4OH, trans/4OH, cis | 4OH, trans/4OH, cis | 4OH |
isothiazole | 4OH, trans/4OH, cis | 4OH, trans/4OH, cis | 4OH |
5OH d | |||
oxazole | 5-one, C4H | 5-one, C4H | 5-one, C4H (in crystal) |
thiazole | 5-one, C4H | 5-one, C4H | |
isoxazole | 5-one, C4H/5-one, NH | 5-one, C4H/5-one, NH | 5-one, C4H in CH3Cl3, NH/CH 55:45 in water e |
isothiazole | 5-one, NH | 5-one, NH | 5-one, NH f |
3CH3,5OH isoxazole | 5-one, C4H | C4H/NH 70:30 in water | |
4CH3,5OH isoxazole | 5-one, NH | 5-one, NH |
CH2Cl2 | Water | |||||
---|---|---|---|---|---|---|
PCM | MC | DM | PCM | MC | DM | |
Oxazole | ||||||
1a → 1c | −17.0 | 0.25, 6.21 | −21.9 | −22.4 | 0.35, 6.52 | |
1c → 1d | −3.6 | 0.7 | 6.21, 7.35 | −4.9 | 9.1 | 6.52, 7.71 |
3b → 3c | −5.5 | 3.35, 5.15 | −6.4 | −7.6 | 3.54, 5.43 | |
Thiazole | ||||||
2a → 2c | −14.2 | 0.58, 5.59 | −14.7 | −23.7 | 0.62, 5.90 | |
2c → 2d | −1.8 | 0.3 | 5.59, 7.08 | −5.1 | 8.1 | 5.90, 7.48 |
4b → 4c | −4.9 | 3.51, 5.33 | −6.2 | −5.8 | 3.75, 5.70 | |
Isoxazole | ||||||
5a → 5c | −11.2 | −9.9 | 2.31, 4.88 | −14.3 | −17.7 | 2.43, 5.14 |
7b → 7c | 6.8 | 4.46, 0.89 | 9.4 | 8.1 | 4.67, 0.92 | |
Isothiazole | ||||||
6a → 6c | −19.2 | 1.73, 5.34 | −24.7 | −40.3 | 1.84, 5.69 | |
8b → 8c | 4.4 | −1.9 | 4.27, 2.05 | 6.4 | 5.8 | 4.51, 2.17 |
Oring/Hw | Sring/Hw | N/Hw | NH/Ow | −O/Hw | OH/Ow | =O/Hw | nHB(E) | |
---|---|---|---|---|---|---|---|---|
Oxazole | ||||||||
1a | --- b | 1.4 | 0.6 | 1.0 | 2.1(−14.6) | |||
1c | 0.3 c | 1.1 | 2.3 | 2.8(−16.7) | ||||
1d | 0.1 c | 0.6 | 1.9 | 2.1(−16.7 d) | ||||
3b | 0.4 | 1.3 | 0.8 e | 1.0 | 2.6(−14.6) | |||
3c | 0.1 f | 0.9 | 1.9 | 2.4(−16.7) | ||||
Thiazole | ||||||||
2a | --- b | 1.3 g | 0.7 | 1.0 | 1.7(−14.6) | |||
2c | --- b | 1.0 | 2.1 | 2.7(−16.7) | ||||
2d | --- b | 1.0 | 1.9 | 2.2(−16.7 d) | ||||
4b | --- b | 1.6 | 0.9 | 1.0 | 2.7(−14.6) | |||
4c | --- b | 1.0 | 2.1 | 2.8(−14.6) | ||||
Isoxazole | ||||||||
5a | 1.9 h | 2.0 i | 0.7 | 1.0 | 2.5(−14.6) | |||
5c | --- b | 1.0 | 2.4 | 3.2(−16.7) | ||||
7b | 1.1 | 1.7 | 0.8 | 1.0 | 2.2(−16.7) | |||
7c | 0.7 j | 1.1 | 1.5 | 2.2(−12.6 d) | ||||
Isothiazole | ||||||||
6a | (0.2) k | 1.5 g | 0.9 | 1.0 | 2.8(−10.5) | |||
6c | --- b | 1.0 | 2.6 | 3.5(−16.7) | ||||
8b | --- b | 1.5 | 0.9 | 1.0 | 1.9(−16.7 d) | |||
8c | --- b | 0.4 l | 1.7 | 1.3(−16.7) |
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Nagy, P.I. Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution. Int. J. Mol. Sci. 2016, 17, 1094. https://doi.org/10.3390/ijms17071094
Nagy PI. Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution. International Journal of Molecular Sciences. 2016; 17(7):1094. https://doi.org/10.3390/ijms17071094
Chicago/Turabian StyleNagy, Peter I. 2016. "Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution" International Journal of Molecular Sciences 17, no. 7: 1094. https://doi.org/10.3390/ijms17071094
APA StyleNagy, P. I. (2016). Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution. International Journal of Molecular Sciences, 17(7), 1094. https://doi.org/10.3390/ijms17071094