Synthesis and GIAO NMR Calculations for Some Novel 4-Heteroarylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives: Comparison of Theoretical and Experimental 1Hand 13C- Chemical Shifts
1
Education Faculty, Kafkas University, 36100 Kars, Turkey
2
Department of Chemistry, Kafkas University, 36100 Kars, Turkey
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2005, 6(6), 219-229; https://doi.org/10.3390/i6060219
Submission received: 7 April 2005
/
Accepted: 21 August 2005
/
Published: 25 August 2005
Abstract
:3-Alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) reacted with 5-methylfuran-2-carboxyaldehyde to afford the corresponding 3-alkyl(aryl)-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (2). Four newly synthesized compounds have been characterized by elemental analyses, IR, 1H-NMR, 13C-NMR and UV spectral data. In addition, isotropic 1H- and 13C-nuclear magnetic shielding constants of compounds 3 were calculated by employing the direct implementation of the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional and HF levels of the theory. The geometry of each compound has been optimized using a 6-311G basis set. Nuclear shielding constants were also calculated by using 6-311G basis set. Theoretical values are compared to the experimental data.
Introduction
Several articles on the synthesis of some N-arylidenamino-1,2,4-triazole and N-arylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives have been published [1,2,3,4,5,6]. In addition, 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives are reported to show a broad spectrum of biological activities such as antifungal, antimicrobial, hypoglycemic, antihypertensive, analgesic, antiparasitic, hypocholesteremic, antiviral, anti-inflammatory, antitumor and anti-HIV properties [7,8,9,10,11,12]. These reports prompted us to synthesize some new potential biological active 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives.
Besides, NMR spectroscopy has proved to be an exceptional tool to elucidate structure and molecular conformation. Ab initio and DFT calculation of NMR shielding at very accurate levels of approximation are available in literature [13]. The widely used methods to calculate chemical shifts are as follows: IGLO (individual gauge localized orbital), LORG (localized or Loacaorbital origin) and GIAO (gauge independent or invariant or including atomic orbital). The GIAO approach [14] is known to give satisfactory chemical shifts for different nuclei [14,15,16] with larger molecules, yet these quantum chemical calculations often have to be limited to isolated (gas-phase) molecules in some preferred (optimized) structures, while experimental NMR spectra are commonly statically averages affected by dynamic process such as conformational equilibria as well as intra and/or intramolecular interactions.
In the present paper DFT and Ab inito method was used to analyze the experimental 1H and 13C data of four novel 3-alkyl(aryl)-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (2), which were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 5-methylfuran-2-carboxyaldehyde (Scheme 1).
Scheme 1.
Experimental
General
IR spectra were recorded using potassium bromide disks on a Perkin-Elmer 1000 FTIR spectrometer. 1H-NMR and 13C-NMR spectra were recorded in deuterated dimethyl sulfoxide with tetramethylsilane as internal standard on a Gemini-Varian spectrometer at 200 MHz and 50 MHz, respectively. UV absorption spectra were measured for ethanol solutions in 10 mm quartz cells between 200 and 400 nm using a Shimadzu-3101 PC UV-VIS-NIR spectrophotometer. Melting points were taken on a Electrothermal 9100 digital melting point apparatus. Chemicals were supplied from Fluka and Merck. The starting compounds 1a-d were prepared from the reactions of the corresponding ester ethoxy-carbonylhydrazones with hydrazine hydrate according to the literature [17].
General Method for the Preparation of 3-Alkyl(aryl)-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (2)
3-Alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-one (1) (0.01 mol) was dissolved in acetic acid (15 mL) and treated with methyl 5-methylfuran-2-carboxyaldehyde (1.10 mL, 0.01 mol). The mixture was refluxed for 1 h and then evaporated at 50-55 °C in vacuo. Several recrystallizations of the residue from an appropriate solvent gave pure compound 2.
3-Methyl-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-one (2a).
White crystals, yield 90 %; m.p. 164 °C (H2O); Calculated for C9H10N4O2 (206.20): 52.42% C, 4.89% H, 27.17% N; found: 52.60% C, 5.05% H, 27.44% N; 1H-NMR: δ 2.23 (s, 3H, CH3), 3.38 (s, 3H, CH3), 6.34 (d, 1H, Ar-H; J=2.44 Hz), 7.06 (d, 1H, Ar-H; J=3.22 Hz), 9.50 (s, 1H, N=CH), 11.81 (s, 1H, NH); 13C-NMR: δ 13.02, 15.38 (2CH3), 110.90, 121.35, 144.78, 158.10 (heteroaromatic carbons), 145.90 (triazole C-3), 148.64 (N=CH), 153.10 (triazole C-5); IR: 3218 (NH), 1697 (C=O), 1593 (C=N) cm-1; UV λmax (ε, L·mol-1·cm-1): 312 (23375) nm.
3-Ethyl-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-one (2b).
White crystals, yield 80 %; m.p. 179 °C (EtOH-H2O, 1:3); Calculated for C10H12N4O2 (220.23): 54.54% C, 5.49% H, 25.44% N; found: 54.38% C, 5.55% H, 25.38% N; 1H-NMR: δ 1.18 (t, 3H, CH3), 2.37 (s, 3H, CH3), 2.62 (q, 2H, CH2), 6.32 (d, 1H, Ar-H), 7.03 (d, 1H, Ar-H), 9.49 (s, 1H, N=CH), 11.82 (s, 1H, NH); 13C-NMR: δ 11.62, 15.33 (2CH3), 20.26 (CH2), 110.85, 121.09, 144.77, 158.03 (heteroaromatic carbons), 148.71 (triazole C-3), 149.65 (N=CH), 153.25 (triazole C-5); IR: 3199 (NH), 1701 (C=O), 1593 (C=N) cm-1; UV λmax (ε, L·mol-1·cm-1: 312 (24846) nm.
3-Benzyl-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-one (2c).
White crystals, yield 85 %; m.p. 166 °C (acetic acid-H2O, 1:3). Calculated for C15H14N4O2 (282.30): 63.82% C, 5.00% H, 19.85% N; found: 63.66% C, 4.86% H, 19.72% N; 1H-NMR: δ 2.38 (s, 3H, CH3), 4.00 (s, 2H, CH2), 6.33 (d, 1H, Ar-H; J=3.30 Hz), 7.05 (d, 1H, Ar-H; J=3.30 Hz),7.23-7.33 (m, 5H, Ar-H), 9.49 (s, 1H, N=CH), 11.97 (s, 1H, NH); 13C-NMR: δ 15.37 (CH3), 32.73 (CH2), 128.47, 130.14 (2C), 130.77 (2C), 137.41 (aromatic carbons), 110.92, 120.96, 144.72, 158.11 (heteroaromatic carbons), 147.86 (triazole C-3), 148.75 (N=CH), 153.09 (triazole C-5); IR: 3210 (NH), 1682 (C=O), 1574 (C=N), 755, 695 (monosubstituted benzenoid ring) cm-1; UV λmax (ε, L·mol-1·cm-1: 311 (28235), 205 (24846) nm.
3-Phenyl-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-one (2d).
White crystals, yield 65 %; m.p. 217 °C (acetic acid-H2O, 1:3); Calculated for C14H12N4O2 (268.28): 62.68% C, 4.51% H, 20.88% N; found: 62.20% C, 5.23% H, 20.77% N; 1H-NMR: δ 2.36 (s, 3H, CH3), 6.36 (d, 1H, Ar-H; J=3.22 Hz), 7.12 (d, 1H, Ar-H; J=3.30 Hz),7.50-7.92 (m, 5H, Ar-H), 9.39 (s, 1H, N=CH), 12.37 (s, 1H, NH); 13C-NMR: δ 15.39 (CH3), 128.52, 129.64 (2C), 130.26 (2C), 131.82 (aromatic carbons), 111.06, 121.64, 146.26, 158.44 (heteroaromatic carbons), 147.63 (triazole C-3), 148.59 (N=CH), 153.26 (triazole C-5); IR: 3160 (NH), 1697 (C=O), 1582 (C=N), 750, 690 (monosubstituted benzenoid ring) cm-1. UV λmax (ε, L·mol-1·cm-1: 313 (21712), 228 (12430), 202 (26032) nm.
Computational Methods
The calculations of the new compounds are given in Table 1, Table 2, Table 3 and Table 4. The numbering system is shown in Scheme 1. All the structures were fully optimized with the Gaussian 03 program[18]. After the optimization, 1H- and 13C- chemical shifts were calculated with GIAO method [19,20], using corresponding TMS shielding calculated at the same theoretical levels as the reference. All the computations were done using an IBM x225 Xeon computer that has 2048 MB ram. Linear correlation analyses were carried out using SigmaPlot program. The quality of each correlation was judged examining R, the Pearson correlation coefficient [21].
| Nuclei | Experimental | B3LYP/6-311G | Diff | HF/6-311G | Diff |
|---|---|---|---|---|---|
| C-2 | 153.10 | 156.22 | -3.12 | 166.13 | -13.03 |
| C-1 | 145.90 | 157.21 | -11.31 | 163.06 | -17.16 |
| C-9 | 13.02 | 14.51 | -1.49 | 14.39 | -1.37 |
| C-3 | 148.64 | 153.12 | -4.48 | 168.01 | -19.37 |
| C-5 | 121.35 | 131.09 | -9.74 | 135.58 | -14.23 |
| C-4 | 144.78 | 161.44 | -16.66 | 153.37 | -8.59 |
| C-7 | 158.10 | 169.97 | -11.87 | 170.68 | -12.58 |
| C-6 | 110.90 | 118.13 | -7.23 | 115.65 | -4.75 |
| C-8 | 15.38 | 15.70 | -0.32 | 15.74 | -0.36 |
| H-16 | 11.81 | 6.98 | 4.83 | 6.96 | 4.85 |
| H-23 | 2.23 | 2.10 | 0.13 | 2.30 | -0.07 |
| H-24 | 2.23 | 2.07 | 0.16 | 2.04 | 0.19 |
| H-25 | 2.23 | 2.55 | -0.32 | 2.60 | -0.37 |
| H-17 | 9.50 | 8.50 | 1.00 | 9.32 | 0.18 |
| H-18 | 7.06 | 6.65 | 0.41 | 7.25 | -0.19 |
| H-19 | 6.34 | 6.21 | 0.13 | 6.37 | -0.03 |
| H-20 | 2.38 | 2.59 | -0.21 | 2.67 | -0.29 |
| H-21 | 2.38 | 2.53 | -0.15 | 2.59 | -0.21 |
| H-22 | 2.38 | 2.19 | 0.19 | 2.32 |
| Nuclei | Experimental | B3LYP/6-311G | Diff | HF/6-311G | Diff |
|---|---|---|---|---|---|
| C-2 | 153.25 | 156.43 | -3.18 | 166.21 | -12.96 |
| C-1 | 148.71 | 161.11 | -12.40 | 166.41 | -17.70 |
| C-9 | 20.26 | 24.85 | -4.59 | 20.72 | -0.46 |
| C-3 | 149.65 | 153.17 | -3.52 | 168.08 | -18.43 |
| C-5 | 121.09 | 131.05 | -9.96 | 135.42 | -14.33 |
| C-4 | 144.77 | 161.39 | -16.62 | 153.45 | -8.68 |
| C-7 | 158.03 | 169.85 | -11.82 | 170.59 | -12.56 |
| C-6 | 110.85 | 117.91 | -7.06 | 115.63 | -4.78 |
| C-8 | 15.33 | 15.70 | -0.37 | 15.74 | -0.41 |
| C10 | 11.62 | 10.00 | 1.62 | 9.64 | 1.98 |
| H-16 | 11.82 | 6.99 | 4.83 | 6.95 | 4.87 |
| H-23 | 2.62 | 2.43 | 0.19 | 2.22 | 0.40 |
| H-24 | 2.62 | 2.99 | -0.37 | 2.84 | -0.22 |
| H-17 | 9.49 | 8.48 | 1.01 | 9.32 | 0.17 |
| H-18 | 7.03 | 6.66 | 0.37 | 7.22 | -0.19 |
| H-19 | 6.32 | 6.21 | 0.11 | 6.37 | -0.05 |
| H-20 | 2.37 | 2.59 | -0.22 | 2.67 | -0.30 |
| H-21 | 2.37 | 2.54 | -0.17 | 2.58 | -0.21 |
| H-22 | 2.37 | 2.20 | 0.17 | 2.31 | 0.06 |
| H-25 | 1.18 | 1.02 | 0.16 | 1.09 | 0.09 |
| H-26 | 1.18 | 1.45 | -0.27 | 1.60 | -0.42 |
| H-27 | 1.18 | 1.50 | -0.32 | 1.55 | -0.37 |
| Nuclei | Experimental | B3LYP/6-311G | Diff | HF/6-311G | Diff |
|---|---|---|---|---|---|
| C-2 | 153.09 | 159.30 | -6.21 | 166.94 | -13.85 |
| C-1 | 147.86 | 159.77 | -11.91 | 164.70 | -16.84 |
| C-9 | 32.73 | 37.84 | -5.11 | 32.66 | 0.07 |
| C-3 | 148.73 | 148.40 | 0.33 | 157.99 | -9.26 |
| C-5 | 120.96 | 118.92 | 2.04 | 122.18 | -1.22 |
| C-4 | 144.72 | 164.44 | -19.72 | 158.32 | -13.60 |
| C-7 | 158.11 | 170.31 | -12.20 | 169.14 | -11.03 |
| C-6 | 110.92 | 117.05 | -6.13 | 115.29 | -4.37 |
| C-8 | 15.37 | 15.62 | -0.25 | 15.69 | -0.32 |
| C-10 | 137.41 | 142.28 | -4.87 | 144.01 | -6.60 |
| C-11 | 130.77 | 137.36 | -6.59 | 140.57 | -9.80 |
| C-12 | 130.14 | 134.64 | -4.50 | 138.41 | -8.27 |
| C-16 | 128.47 | 133.57 | -5.10 | 137.07 | -8.60 |
| C-14 | 130.14 | 134.64 | -4.50 | 138.41 | -8.27 |
| C-15 | 130.77 | 137.36 | -6.59 | 140.57 | -9.80 |
| H-16 | 11.97 | 6.94 | 5.03 | 6.92 | 5.05 |
| H-23 | 4.00 | 3.91 | 0.09 | 3.93 | 0.07 |
| H-24 | 4.00 | 3.91 | 0.09 | 3.93 | 0.07 |
| H-17 | 9.49 | 10.50 | -1.01 | 10.73 | -1.24 |
| H-18 | 7.05 | 7.15 | -0.10 | 7.56 | -0.51 |
| H-19 | 6.33 | 6.20 | 0.13 | 6.38 | -0.05 |
| H-20 | 2.38 | 2.58 | -0.20 | 2.65 | -0.27 |
| H-21 | 2.38 | 2.58 | -0.20 | 2.65 | -0.27 |
| H-22 | 2.38 | 2.15 | 0.23 | 2.27 | 0.11 |
| H-25 | 7.23 | 7.23 | 0 | 7.74 | -0.51 |
| H-26 | 7.33 | 7.33 | 0 | 7.84 | -0.51 |
| H-27 | 7.30 | 7.27 | 0.03 | 7.77 | -0.47 |
| H-28 | 7.33 | 7.33 | 0 | 7.84 | -0.51 |
| H-29 | 7.23 | 7.23 | 0 | 7.74 | -0.51 |
| Nuclei | Experimental | B3LYP/6-311G | Diff | HF/6-311G | Diff |
|---|---|---|---|---|---|
| C-2 | 153.26 | 159.80 | -6.54 | 167.27 | -14.01 |
| C-1 | 147.63 | 156.02 | -8.39 | 162.39 | -14.76 |
| C-9 | 130.26 | 134.41 | -4.15 | 134.60 | -4.34 |
| C-3 | 148.59 | 148.96 | -0.37 | 158.14 | -9.55 |
| C-5 | 121.64 | 119.29 | 2.35 | 122.35 | -0.71 |
| C-4 | 146.26 | 164.62 | -18.36 | 158.57 | -12.31 |
| C-7 | 158.44 | 170.46 | -12.02 | 169.08 | -10.64 |
| C-6 | 111.06 | 117.09 | -6.03 | 115.29 | -4.23 |
| C-8 | 15.39 | 15.73 | -0.34 | 15.69 | -0.30 |
| C-10 | 129.64 | 134.89 | -5.25 | 141.15 | -11.51 |
| C-11 | 129.64 | 134.20 | -4.56 | 136.67 | -7.03 |
| C-12 | 131.82 | 136.36 | -4.54 | 141.72 | -9.90 |
| C-13 | 128.52 | 133.61 | -5.09 | 135.51 | -6.99 |
| C-14 | 130.26 | 135.89 | -5.63 | 142.08 | -11.82 |
| H-16 | 12.37 | 7.27 | 5.10 | 7.27 | 5.10 |
| H-17 | 9.39 | 10.72 | -1.33 | 10.87 | -1.48 |
| H-18 | 7.12 | 7.16 | -0.04 | 7.48 | -0.36 |
| H-19 | 6.36 | 6.22 | 0.14 | 6.36 | 0 |
| H-20 | 2.36 | 2.59 | -0.23 | 2.65 | -0.29 |
| H-21 | 2.36 | 2.59 | -0.23 | 2.65 | -0.29 |
| H-22 | 2.36 | 2.16 | 0.20 | 2.26 | 0.10 |
| H-23 | 7.90 | 8.28 | -0.38 | 8.70 | -0.80 |
| H-24 | 7.54 | 7.42 | 0.12 | 7.92 | -0.38 |
| H-25 | 7.50 | 7.39 | 0.11 | 8.04 | -0.54 |
| H-26 | 7.54 | 7.41 | 0.13 | 7.90 | -0.36 |
| H-27 | 7.92 | 8.43 | -0.51 | 8.57 | -0.65 |
Results and Discussion
The geometry optimizations were performed at the B3LYP/6-311G and HF/6-311G levels [22] with the Gaussian G03 program package [18]. The 1H- and 13C- chemical shifts were calculated with the B3LYP/6-311G HF/6-311G optimized geometries by GIAO method [19]. In order to obtain the calculated results comparable with the experimental data, we have transformed the absolute shieldings returned by the program in chemical shifts subtracting to the absolute shielding of TMS and the absolute shieldings of the molecule in exam. σrel. = σrel - σabs . In particular, each value of the absolute shieldings of the TMS was obtained with the same level of the absolute shieldings of the TMS, which was found with the same level of theory used in the determination of absolute shieldings of the compounds. The experimental and theoretical results, along with the error for each compound, are presented in Table 1, Table 2, Table 3 and Table 4. A least squares fit of all data, as shown in Figure 1, shows a strong linear relationship with an R-square value of 0.997 at B3LYP/6-311G and 0.998 at HF/6-311G basis set, respectively.
Figure 1.
Plot of overall 1H- and 13C- data
This relationship is also reflected in the results for the individual compounds, in which R-square values are consistently above 0.727. The overall standard error of estimate is 3.43 and 2.78 at B3LYP/6-311G and HF/6-311G basis sets, respectively. The approach of Forsyth and Sebag [23] for emprically scaling theoretical data linear regressions, δcalc = a + bδexp was made and details are summarized in Table 5.
Table 5.
Linear regression between experimental chemical shifts and calculated isotropic shielding constants (ppm), δcalc = a + bδexp , ( r= correlation coefficient, SE=standard error).
| Compd. no | Parameter | B3LYP/6-311G 13C | B3LYP /6-311G 1H | HF/6-311G 13C | HF/6-311G 1H |
|---|---|---|---|---|---|
| 2a | a | 0.386 | 1.049 | -0.879 | 1.087 |
| b | 1.062 | 0.656 | 1.098 | 0.691 | |
| r | 0.998 | 0.934 | 0.998 | 0.912 | |
| SE | 4.408 | 0.954 | 4.012 | 1.179 | |
| 2b | a | 0.313 | 0.847 | -2.282 | 0.875 |
| b | 1.062 | 0.678 | 1.107 | 0.716 | |
| r | 0.998 | 0.944 | 0.998 | 0.926 | |
| SE | 4.572 | 0.887 | 3.595 | 1.090 | |
| 2c | a | 0.124 | 1.250 | -3.353 | 1.345 |
| b | 1.049 | 0.750 | 1.094 | 0.777 | |
| r | 0.993 | 0.870 | 0.997 | 0.853 | |
| SE | 5.180 | 1.251 | 3.166 | 1.400 | |
| 2d | a | -2.657 | 1.280 | -3.340 | 1.345 |
| b | 1.065 | 0.750 | 1.093 | 0.776 | |
| r | 0.992 | 0.870 | 0.996 | 0.852 | |
| SE | 4.734 | 1.251 | 3.348 | 1.400 |
A linear correlation between theoretical and experimental carbon and proton chemical shifts is clearly seen in Table 1, Table 2, Table 3 and Table 4. A good quantitative agreement within 1-10 ppm at Table 3 and Table 4 is observed for the aromatic carbons of these compounds, which appear to be very satisfactory. It is due to the fact that the experimental chemical shifts in solution are subject to solvent, concentration and temperature effects. Differences are particularly apparent in the aromatic carbons in which chemical shifts are sensitive to substitution. It can also be seen that chemical shifts of the aromatic carbon atoms are not well produced by 6-311G basis set. This is probably due to the sensitivity of the calculations to geometry and rapid rotation of these groups, particularly NMR time scale.
As can be seen at Table 1, Table 2, Table 3 and Table 4, the errors range between 3.12-6.21 ppm at B3LYP/6-311G and 12.46-13.85 ppm at HF/6-311G ppm for C-2 atom which belongs to carbonyl group. The carbonyl carbon atom C-2 is more deshielded as a consequence of binding to the oxygen atoms. Similar effect was also observed for C-4 and C-7 atoms connected to the oxygen atom.. All the statistical calculations were affected by these results. In particular, the large differences calculated for the C-4, C-5, C-6 and C-7 carbons in all compounds were observed between 2 and 19 ppm. This deviation is due to the geometric distortions of furan ring caused by steric hinderance of the methyl substituent. A good quantitative agreement within 4.5-6.0 ppm at B3LYP/6-311G and 6.60-11.82 ppm at HF/6-311G at Table 3 and Table 4 were observed for aromatic carbons of 2c and 2d compounds, which appeared very satisfactory. This situation derives from the fact that the experimental chemical shifts in solution are subject to solvent, concentration and temperature effects.
The standard errors (SE) and regression coefficients (r) given in Table 5 indicate that HF method provides a some-what better fit for 13C chemical shifts than the DFT(B3LYP) method. In Table 5, the regression coefficient of r=0.99 for B3LYP and HF methods were found for all compounds. From these results, it is understood that the calculated values by both methods are almost close to each other, but some calculated chemical shifts with HF/6-311G show good agreement with experimental data if compared to the B3LYP/6-311G method. SE values are about compunds 2c and 2d for HF and B3LYP methods, respectively shown in Table 5. Besides, the best values reached for σcalc= a + bδexp equation are a=0 and b=1 respectively. As shown in Table 5, b values of 1.06 for B3LYP and 0.99 for HF methods were calculated. The b values were found close to 1 by B3LYP, while chemical shifts which were found by B3LYP method showed much better fitting to that of experimental data if compared to HF method. However, there are no big differences between both methods if compared to each other. With the exception of the N-H protons, both HF and DFT methods are in good agreement with the 1H spectrum of compounds 2a-d. There has occurred an important difference between experimental and theoretical results more than it is expected. The reason why such a result has come into being is that the N-H hydrogen in 4,5-dihydro-1H-1,2,4-triazol-5-one ring has acidic properties, so that some 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives were titrated potentiometrically with tetrabutylammonium hydroxide in different non-aqueous solvents, and the pKa values were found between 8.69 and 16.75 [3,4,5,6,24,25,26,27]. Thus, in the 1H-NMR spectra of the 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives, the signals of N-H protons were observed between δ 11.43 and 12.80 ppm [1,2,3,4,5,6,7,11,12,25,26,27,28,29,30]. This situation can be attributed to the resonance of the negatively formed ions (Scheme 2).
Scheme 2.
Conclusions
In this study, the structures of four novel 3-alkyl(aryl)-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) synthesized from the reactions of compounds 1 with 5-methylfuran-2-carboxyaldehyde were identified by using elemental analysis and IR, 1H-NMR, 13C-NMR and UV spectral data, and these obtained spectral values were seen as compatible with literature [3,4,5,25,26,27,28,29,30]. Correlations between experimental chemical shifts and GIAO-calculated isotropic shielding constants of protons and carbons as obtained from four new 3-alkyl(aryl)-4-(5-methyl-2-furylmethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones were established in order to assess the performance of NMR spectral calculations. DFT-B3LYP and HF levels of the theory 6-311G basis set were considered for geometry optimization and spectral calculations. Depending on computational levels, linear regressions, σcalc= a + bδexp, yield standard deviations of 0.954-5.18 ppm for hydrogen and carbon atoms.
References
- Ikizler, A. A.; Ikizler, A.; Yıldırım, N. Antitumor activities of some 4,5-dihydro-1H-1,2,4-triazol-5-ones. Monatsh. Chem. 1991, 122, 557–33. [Google Scholar] [CrossRef]
- Ikizler, A. A.; Yüksek, H. Reaction of 4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones with 2,5-dimethoxytetrahydrofuran. Collect. Czech. Chem. Commun. 1994, 59, 731–735. [Google Scholar] [CrossRef]
- Bahçeci, Ş.; Yüksek, H.; Ocak, Z.; Azaklı, A.; Alkan, M.; Ozdemir, M. Synthesis and potentiometric titrations of some new 4-(benzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives in non-aqueous media. Collect. Czech. Chem. Commun. 2002, 67, 1215–1222. [Google Scholar] [CrossRef]
- Bahçeci, Ş.; Yüksek, H.; Ocak, Z.; Köksal, C.; Ozdemir, M. Synthesis and non-aqueous medium titrations of some new 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Acta Chim. Slov. 2002, 49, 783–794. [Google Scholar]
- Yüksek, H.; Ocak, Z.; Özdemir, M.; Ocak, M.; Bekar, M.; Aksoy, M. A study on novel 4-heteroarylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones. Indian J. Heterocycl. Ch. 2003, 13, 49–52. [Google Scholar]
- Yüksek, H.; Bahçeci, Ş.; Ocak, Z.; Alkan, M.; Ermiş, B.; Mutlu, T.; Ocak, M.; Özdemir, M. Synthesis of some 4,5-dihydro-1H-1,2,4-triazol-5-ones. Indian J. Heterocycl. Ch. 2004, 13, 369–372. [Google Scholar]
- Ikizler, A. A.; Uçar, F.; Yüksek, H.; Aytin, A.; Yasa, I.; Gezer, T. Synthesis and antifungal activity of some new arylidenamino compounds. Acta Pol. Pharm.-Drug Res. 1997, 54, 135–140. [Google Scholar]
- Yüksek, H.; Demibaş, A.; Ikizler, A.; Johansson, C. B.; Çelik, C.; Ikizler, A. A. Synthesis and antibacterial activities of some 4,5-dihydro-1H-1,2,4-triazol-5-ones. Arzneim.-Forsch./Drug Res. 1997, 47, 405–409. [Google Scholar]
- Burzozowski, Z. Synthesis and anti-HIV activity of some new 2-mercapto-N-(1,2,4-triazol-3-yl)benzenesulfonamide derivatives containing the 1,2,4-triazole moiety fused with variety of heteroaromatic rings. Acta Pol. Pharm.-Drug Res. 1998, 55, 473–480. [Google Scholar]
- Bhat, A. R.; Bhat, G. V.; Shenoy, G. G. Synthesis and in-vitro antimicrobial activity of new 1,2,4-triazoles. J. Pharm. Pharmacol. 2001, 53, 267–272. [Google Scholar] [CrossRef] [PubMed]
- Ikizler, A. A.; Ikizler, A.; Yüksek, H.; Serdar, M. Antitumor activities of some 4,5-dihydro-1H-1,2,4-triazol-5-ones. Model. Measur. Control, Ser. C. 1998, 1, 25–33. [Google Scholar]
- Ikizler, A. A.; Demibaş, A.; Johansson, C. B.; Çelik, C.; Serdar, M.; Yüksek, H. Synthesis and biological activities of some 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Acta Pol. Pharm.-Drug Res. 1998, 55, 117–123. [Google Scholar]
- Schleyer, P.V.R.; Allinger, N.L.; Clark, T.; Gasteiger, J.; Kolmann, P.A.; Schaefer, H.F.; Schreiner, P.R. (Eds.) The encyclopedia of computational chemistry; John Wiley & Sons: Chichester, 1998.
- Ditchfield, R. Self-consistent perturbation theory of diamagnetism. I A gauge-invariant LCAO method for N.M.R. chemical shifts. Mol. Phys. 1974, 27, 789–807. [Google Scholar] [CrossRef]
- Barfiled, M.; Fagerness, P. J. Density Functional Theory/GIAO Studies of the 13C, 15N, and 1H NMR chemical shifts in aminopyrimidines and aminobenzenes: relationships to electron densities and amine group orientations. J. Am. Chem. Soc. 1977, 119, 8699–8711. [Google Scholar] [CrossRef]
- Manaj, J. M.; Maciewska, D.; Waver, I. 1H, 13C and 15N NMR and GIAO CPHF calculations on two quinoacridinium salts. Magn. Reson. Chem. 2000, 38, 482–485. [Google Scholar] [CrossRef]
- Ikizler, A. A.; Un, R. Reactions of ester ethoxycarbonylhydrazones with some amine type compounds. Chim. Acta Turc. 1979, 7, 269–290, [Chem. Abstr. 1991, 94, 15645d]. [Google Scholar]
- Frisch, M. J.; et al. Gaussian 03, Revision C. 02; Gaussian, Inc.: Pittsburgh PA, 2003. [Google Scholar]
- Hameka, H. F. On the magnetic shielding in the hydrogen molecule. Mol. Phys. 1958, 1, 203–215. [Google Scholar]
- Wolinski, K.; Hilton, K. J. F.; Pulay, P. Efficient Implementation of the Gauge-Independent Atomic Orbital Method for NMR Chemical Shift Calculations. J. Am. Chem.Soc. 1990, 12, 8251–8260. [Google Scholar]
- Womacott, T. M.; Womacott, R. J. Introductory Statistics, 5th edn; Wiley: New York, 1990. [Google Scholar]
- Poirer, R.; Kari, R.; Csizmadia, I.G. Handbook of Gaussian Basis Sets: A compendium for Ab Initio Molecular Orbital Calculations; Elsevier Science Publishing: New York, 1985. [Google Scholar]
- Forsyth, D A.; Sebag, A. B. Computed 13C-NMR Chemical Shifts via Empirically Scaled GIAO Shieldings and Molecular Mechanics Geometries. Conformation and Configuration from 13C Shifts. J. Am. Chem. Soc. 1997, 119, 9483–9494. [Google Scholar]
- Ikizler, A. A.; Ikizler, A.; Şentürk, H. B.; Serdar, M. The pKa values of some 1,2,4-triazole and 1,2,4-triazolin-5-one derivatives in nonaqueous media. Doğa-Tr. Kimya D. 1988, 12, 57–66, [Chem. Abstr. 1988, 109, 238277q]. [Google Scholar]
- Yüksek, H.; Alkan, M.; Ocak, Z.; Bahçeci, Ş.; Ocak, M.; Özdemir, M. Synthesis and acidic properties of some new potential biologically active 4-acylamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Indian J. Chem. 2004, 43B, 1527–1531. [Google Scholar]
- Yüksek, H.; Ocak, Z.; Alkan, M.; Bahçeci, Ş.; Özdemir, M. Synthesis and determination of pKa values of some new 3,4-disubstituted-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives in non-aqueous solvents. Molecules 2004, 9, 232–240. [Google Scholar]
- Yüksek, H.; Bahçeci, Ş.; Ocak, Z.; Özdemir, M.; Ocak, M.; Ermiş, B.; Mutlu, T. Synthesis and determination of acid dissociation constants of some new 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Asian J. Chem. 2005, 17, 195–201. [Google Scholar]
- Ikizler, A. A.; Yüksek, H. A study on 4,5-dihydro-1H-1,2,4-triazol-5-ones. Rev. Roum. Chim. 1996, 41, 585–590. [Google Scholar]
- Ikizler, A. A.; Yüksek, H. Acylation of 4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones. Org. Prep. Proced. Int. 1993, 25, 99–105. [Google Scholar] [CrossRef]
- Ikizler, A. A.; Ikizler, A.; Yüksek, H. 1H NMR spectra of some 4,5-dihydro-1,2,4-triazol-5-ones. Magn. Reson. Chem. 1993, 31, 1088–1094. [Google Scholar] [CrossRef]
© 2005 by MDPI (http://www.mdpi.org).
Share and Cite
MDPI and ACS Style
Yüksek, H.; Cakmak, I.; Sadi, S.; Alkan, M.; Baykara, H. Synthesis and GIAO NMR Calculations for Some Novel 4-Heteroarylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives: Comparison of Theoretical and Experimental 1Hand 13C- Chemical Shifts. Int. J. Mol. Sci. 2005, 6, 219-229. https://doi.org/10.3390/i6060219
AMA Style
Yüksek H, Cakmak I, Sadi S, Alkan M, Baykara H. Synthesis and GIAO NMR Calculations for Some Novel 4-Heteroarylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives: Comparison of Theoretical and Experimental 1Hand 13C- Chemical Shifts. International Journal of Molecular Sciences. 2005; 6(6):219-229. https://doi.org/10.3390/i6060219
Chicago/Turabian StyleYüksek, Haydar, Ismail Cakmak, Sibel Sadi, Muzaffer Alkan, and Haci Baykara. 2005. "Synthesis and GIAO NMR Calculations for Some Novel 4-Heteroarylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives: Comparison of Theoretical and Experimental 1Hand 13C- Chemical Shifts" International Journal of Molecular Sciences 6, no. 6: 219-229. https://doi.org/10.3390/i6060219
