Annular Tautomerism of 3(5)-Disubstituted-1H-pyrazoles with Ester and Amide Groups
Abstract
:1. Introduction
2. Results and Discussion
2.1. X-Ray Results
2.2. Theoretical Calculations
2.3. Study in Solution
3. Experimental Section
3.1. Synthesis
3.2. X-Ray
3.3. Computational Procedures
3.4. NMR Spectroscopy
3.5. FT-IR Spectroscopy
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 1a, 1-3b, and 4 are available from the authors. |
1a | 1b | 2b | 3b | 4 | |
---|---|---|---|---|---|
Chemical formula | C6H9N3O | C7H10N2O2 | C5H7N3O2 | C5H5N3O4 | C5H8N4O4 |
Mr | 139.16 | 154.17 | 141.14 | 171.12 | 188.15 |
Crystal system, space group | Monoclinic, P21/c | Monoclinic, P21/n | Monoclinic, P21/n | Monoclinic, P21/m | Monoclinic, P21/n |
a, b, c (Å) | 14.7736 (4), 7.2104 (2), 13.6295 (4) | 9.7186 (7), 6.0828 (4), 13.4976 (11) | 10.8040 (5), 13.6444 (5), 13.8883 (6) | 5.5232 (3), 6.1484 (3), 10.8318 (5) | 3.7803 (1), 22.9836 (7), 9.0425 (3) |
β (°) | 90.800 (3) | 102.810 (7) | 110.173 (5) | 102.679 (5) | 98.082 (3) |
V (Å3) | 1451.72 (7) | 778.07 (10) | 1921.74 (15) | 358.87 (3) | 777.85 (4) |
Z | 8 | 4 | 12 | 2 | 4 |
µ (mm−1) | 0.09 | 0.1 | 0.12 | 0.14 | 0.14 |
Crystal size (mm) | 0.5 × 0.4 × 0.2 | 0.5 × 0.3 × 0.1 | 0.4 × 0.3 × 0.2 | 0.5 × 0.4 × 0.2 | 0.4 × 0.3 × 0.2 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9524, 2826, 2196 | 5041, 1523, 1130 | 9264, 3742, 2660 | 2439, 776, 685 | 5234, 1530, 1186 |
Rint | 0.024 | 0.037 | 0.027 | 0.013 | 0.027 |
(sin θ/λ)max (Å−1) | 0.617 | 0.616 | 0.617 | 0.617 | 0.617 |
Refinement | |||||
R[F2 > 2σ(F2)], wR(F2), S | 0.037, 0.103, 1.08 | 0.038, 0.103, 0.88 | 0.034, 0.085, 0.77 | 0.027, 0.076, 1.11 | 0.029, 0.070, 0.95 |
No. of reflections | 2826 | 1523 | 3742 | 776 | 1530 |
No. of parameters | 185 | 102 | 292 | 79 | 120 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.26, −0.26 | 0.20, −0.27 | 0.17, −0.25 | 0.29, −0.19 | 0.24, −0.24 |
X-Pz-CO- | Tautomer (T3/5)/Conformer (c/t) | |||
---|---|---|---|---|
X- | T3c | T3t | T5c | T5t |
Me- | 7 | |||
H- | 2 | 3 | ||
Ph- | 12 | 1 | 3 | 2 |
OOC-Pz-COOH | 11 | 5 | 1 | 2 |
NC- | 1 | 3 | ||
-CF- | 6 | 2 | ||
HO- | 1 |
In Vacuo | Chloroform | Acetonitrile | Water | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ψ | Energy | ΔE | ψ | Energy | ΔE | ψ | Energy | ΔE | ψ | Energy | ΔE | |
Conformer Code↓ | (°) | (Ha) | (kcal/mol) | (°) | (Ha) | (kcal/mol) | (°) | (Ha) | (kcal/mol) | (°) | (Ha) | (kcal/mol) |
(1a) CH3-Pz-CONHCH3 | ||||||||||||
T3c | 0.0 | −473.322883 | 0.00 | 0.0 | −473.340504 | 0.00 | 0.0 | −473.344429 | 0.00 | 0.0 | −473.344742 | 0.00 |
T3t | 180.0 | −473.312263 | 6.66 | 180.0 | −473.334178 | 3.97 | 180.0 | −473.340706 | 2.34 | 180.0 | −473.342131 | 1.64 |
T5c | 24.4 | −473.314249 | 5.42 | 24.1 | −473.333208 | 4.58 | 17.6 | −473.338227 | 3.89 | 18.4 | −473.339003 | 3.60 |
T5t | 180.0 | −473.321441 | 0.90 | 180.0 | −473.337598 | 1.82 | 180.0 | −473.341534 | 1.82 | 180.0 | −473.341632 | 1.95 |
(1b) CH3-Pz-COOCH2CH3 | ||||||||||||
T3c | 0.0 | −532.474789 | 1.83 | 0.0 | −532.492603 | 0.00 | 0.0 | −532.496648 | 0.00 | 0.0 | −532.494392 | 0.00 |
T3t | 180.0 | −532.473347 | 2.73 | 180.0 | −532.491806 | 0.50 | 180.0 | −532.496280 | 0.23 | 180.0 | −532.494119 | 0.17 |
T5c | 0.2 | −532.477188 | 0.32 | 0.4 | −532.491509 | 0.69 | 0.3 | −532.494031 | 1.64 | 0.0 | −532.490849 | 2.22 |
T5t | 180.0 | −532.477703 | 0.00 | 180.0 | −532.491767 | 0.52 | 180.0 | −532.494172 | 1.55 | 180.0 | −532.490747 | 2.29 |
(2a) H2N-Pz-CONHCH3 | ||||||||||||
T3c | 0.0 | −489.374774 | 1.25 | 0.0 | −489.397950 | 0.00 | 0.0 | −489.404669 | 0.00 | 0.0 | −489.405337 | 0.00 |
T3t | −179.9 | −489.365033 | 7.36 | −180.0 | −489.392782 | 3.24 | −180.0 | −489.402127 | 1.59 | −180.0 | −489.404202 | 0.71 |
T5c | 24.2 | −489.371558 | 3.26 | 25.3 | −489.393897 | 2.54 | 18.1 | −489.400630 | 2.53 | 5.1 | −489.401874 | 2.17 |
T5t | −180.0 | −489.376759 | 0.00 | 180.0 | −489.397510 | 0.28 | 180.0 | −489.403626 | 0.65 | −180.0 | −489.404197 | 0.72 |
(2b) H2N-Pz-COOCH3 | ||||||||||||
T3c | 0.0 | −509.246751 | 4.67 | 0.0 | −509.267576 | 1.80 | 0.0 | −509.274622 | 0.43 | 0.0 | −509.273901 | 0.27 |
T3t | 180.0 | −509.245885 | 5.21 | 180.0 | −509.267586 | 1.80 | 180.0 | −509.275108 | 0.13 | 180.0 | −509.274337 | 0.00 |
T5c | 0.0 | −509.253108 | 0.68 | 0.4 | −509.270059 | 0.25 | 0.4 | −509.275012 | 0.19 | 0.2 | −509.273864 | 0.30 |
T5t | 180.0 | −509.254195 | 0.00 | 179.9 | −509.270450 | 0.00 | 179.8 | −509.275315 | 0.00 | −179.9 | −509.273994 | 0.22 |
(3a) O2N-Pz-CONHCH3 | ||||||||||||
T3c | 0.0 | −638.517709 | 0.63 | 0.0 | −638.535327 | 2.29 | 0.0 | −638.539811 | 3.59 | 0.0 | −638.538274 | 3.81 |
T3t | −155.5 | −638.508452 | 6.43 | −174.4 | −638.529928 | 5.68 | −174.3 | −638.536869 | 5.44 | −170.8 | −638.536671 | 4.82 |
T5c | 26.8 | −638.510067 | 5.42 | 24.8 | −638.533577 | 3.39 | 22.6 | −638.541327 | 2.64 | 20.4 | −638.540059 | 2.69 |
T5t | 180.0 | −638.518707 | 0.00 | −177.3 | −638.538973 | 0.00 | 180.0 | −638.545531 | 0.00 | −179.9 | −638.544350 | 0.00 |
(3b) O2N-Pz-COOCH3 | ||||||||||||
T3c | 0.0 | −658.389922 | 2.95 | 0.0 | −658.404657 | 3.63 | 0.0 | −658.409316 | 3.72 | 0.0 | −658.405911 | 3.65 |
T3t | 180.0 | −658.389303 | 3.34 | 180.0 | −658.404464 | 3.75 | 180.0 | −658.409578 | 3.56 | 180.0 | −658.406313 | 3.40 |
T5c | 0.0 | −658.393160 | 0.92 | 0.0 | −658.409513 | 0.59 | 0.0 | −658.414409 | 0.53 | 0.0 | −658.411099 | 0.39 |
T5t | 180.0 | −658.394621 | 0.00 | 180.0 | −658.410447 | 0.00 | 180.0 | −658.415251 | 0.00 | 180.0 | −658.411725 | 0.00 |
Compound | NICS(0) | NICS(1) | NICS(1)zz |
---|---|---|---|
Pyrazole | −13.51 | −11.37 | −33.87 |
3-Methyl-1H-pyrazole | −12.57 | −13.22 | −31.38 |
5-Methyl-1H-pyrazole | −12.13 | −12.12 | −30.52 |
1H-pyrazol-3-amine (3-Aminopyrazole) | −11.97 | −8.93 | −26.42 |
1H-pyrazol-5-amine (5-Aminopyrazole) | −11.94 | −8.72 | −25.71 |
3-Nitro-1H-pyrazole | −13.50 | −10.63 | −29.74 |
5-Nitro-1H-pyrazole | −12.43 | −10.36 | −28.76 |
N-Methyl-1H-pyrazole-3-carboxamide (ψ = 0°) | −12.81 | −10.89 | −30.98 |
N-Methyl-1H-pyrazole-3-carboxamide (ψ = 180°) | −12.95 | −10.99 | −31.00 |
N-Methyl-1H-pyrazole-5-carboxamide (ψ = 0°) | −12.61 | −10.90 | −32.07 |
N-Methyl-1H-pyrazole-5-carboxamide (ψ = 180°) | −12.28 | −10.86 | −30.69 |
Methyl 1H-pyrazole-3-carboxylate (ψ = 0°) | −12.88 | −10.98 | −31.14 |
Methyl 1H-pyrazole-3-carboxylate (ψ = 180°) | −12.88 | −11.03 | −31.16 |
Methyl 1H-pyrazole-5-carboxylate (ψ = 0°) | −12.29 | −10.89 | −30.85 |
Methyl 1H-pyrazole-5-carboxylate (ψ = 180°) | −12.21 | −10.88 | −30.68 |
Code | NICS(0) | NICS(1) | NICS(1)zz | ∆NICS(1)zz |
---|---|---|---|---|
(1a) CH3-Pz-CONHCH3 | ||||
T3c | −11.57 | −10.08 | −27.86 | 0.00 |
T3t | −11.68 | −10.12 | −27.88 | −0.02 |
T5c | −11.57 | −10.05 | −27.94 | −0.08 |
T5t | −11.35 | −10.23 | −28.09 | −0.23 |
(1b) CH3-Pz-COOCH2CH3 | ||||
T3c | −11.61 | −10.06 | −27.93 | 0.00 |
T3t | −11.65 | −10.19 | −28.02 | −0.08 |
T5c | −11.37 | −10.76 | −28.3 | −0.36 |
T5t | −11.33 | −10.29 | −28.12 | −0.18 |
(2a) H2N-Pz-CONHCH3 | ||||
T3c | −11.48 | -8.45 | -23.36 | 0.00 |
T3t | −11.64 | -8.56 | -23.44 | -0.08 |
T5c | −11.45 | -8.95 | -25.81 | -2.44 |
T5t | −11.09 | -8.75 | -24.01 | -0.65 |
(2b) H2N-Pz-COOCH3 | ||||
T3c | −11.70 | −8.61 | −23.60 | 0.00 |
T3t | −11.72 | −8.63 | −23.71 | −0.11 |
T5c | −11.43 | −9.08 | −24.84 | −1.24 |
T5t | −11.40 | −9.10 | −24.86 | −1.26 |
(3a) O2N-Pz-CONHCH3 | ||||
T3c | −12.12 | −10.00 | −26.33 | 0.00 |
T3t | −12.50 | −10.28 | −27.40 | −1.07 |
T5c | −13.06 | −10.29 | −27.99 | −1.66 |
T5t | −12.72 | −10.33 | −27.16 | −0.82 |
(3b) O2N-Pz-COOCH3 | ||||
T3c | −12.30 | −10.17 | −26.60 | 0.00 |
T3t | −12.36 | −10.22 | −26.72 | −0.12 |
T5c | −12.77 | −10.33 | −27.28 | −0.68 |
T5t | −12.76 | −10.35 | −27.22 | −0.62 |
Code | Chloroform | Acetonitrile | ||||
---|---|---|---|---|---|---|
Calc. | Scaled a | Measured | Calc. | Scaled b | Measured | |
(1b) CH3-Pz-COOCH2CH3 | ||||||
T3c | 1803.76 | 1715 | 1720 | 1799.13 | 1716 | 1718 |
T3t | 1824.47 | 1735 | 1814.27 | 1731 | 1730 | |
(2b) H2N-Pz-COOCH3 | ||||||
T3c | 1807.09 | 1718 | 1801.77 | 1719 | 1721 | |
T3t | 1826.99 | 1737 | 1818.40 | 1735 | 1731 | |
T5c | 1827.74 | 1737 | 1820.13 | 1736 | 1731 | |
T5t | 1808.87 | 1720 | 1725 | 1805.58 | 1723 | 1721 |
(3b) O2N-Pz-COOCH3 | ||||||
T5c | 1840.61 | 1750 | 1751 | 1831.87 | 1748 | 1747 |
T5t | 1824.01 | 1734 | 1734 | 1822.54 | 1739 | 1739 |
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Kusakiewicz-Dawid, A.; Porada, M.; Dziuk, B.; Siodłak, D. Annular Tautomerism of 3(5)-Disubstituted-1H-pyrazoles with Ester and Amide Groups. Molecules 2019, 24, 2632. https://doi.org/10.3390/molecules24142632
Kusakiewicz-Dawid A, Porada M, Dziuk B, Siodłak D. Annular Tautomerism of 3(5)-Disubstituted-1H-pyrazoles with Ester and Amide Groups. Molecules. 2019; 24(14):2632. https://doi.org/10.3390/molecules24142632
Chicago/Turabian StyleKusakiewicz-Dawid, Anna, Monika Porada, Błażej Dziuk, and Dawid Siodłak. 2019. "Annular Tautomerism of 3(5)-Disubstituted-1H-pyrazoles with Ester and Amide Groups" Molecules 24, no. 14: 2632. https://doi.org/10.3390/molecules24142632
APA StyleKusakiewicz-Dawid, A., Porada, M., Dziuk, B., & Siodłak, D. (2019). Annular Tautomerism of 3(5)-Disubstituted-1H-pyrazoles with Ester and Amide Groups. Molecules, 24(14), 2632. https://doi.org/10.3390/molecules24142632