Ö.BAĞLAYAN a , G.KEŞAN c , C.PARLAK b and M.ŞENYELa

a Physics Department, Science Faculty, Anadolu University, Eskişehir, 26470, Turkeyb Department of Physics, Dumlupnar University, Kütahya, 43100, Turkey

c Faculty of Science, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic

• The optimized geometric parameters (bond lengths, bond and dihedral angles), conformational analysis, normal mode frequencies and corresponding vibrational assignments of 4-pypp (C8H17N3) are theoretically examined by means of B3LYP hybrid density functional theory (DFT) method together with 6−31++G(d,p) basis set.

• Furthermore, reliable vibrational assignments have been made on the basis of potential energy distribution (PED) and the thermodynamics functions, highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) of 4-pypp have been predicted.

ABSTRACT

ABSTRACT

• Calculations are employed for four different conformations of 4-pypp both in gas phase and in solution. Solvent effects are investigated using chloroform and dimethylsulfoxide.

• All results indicates that B3LYP method is able to provide satisfactory results for predicting vibrational frequencies and the structural parameters, mole fractions of stable conformers, vibrational frequencies and assignments, IR and Raman intensities of 4-pypp are solvent dependent.

INDEX

4-(1-PYRROLIDINYL)PIPERAZINE Theoretical Study

• Infrared Spectrum

• Raman Spectrum

• Vibrational Assignments

• Thermodynamics functions

• Homo-Lumo Orbitals Results

Molecular Formula: C8H17N3

Molecular Weight:154.241 g/mol

This molecule has 3N-6 vibrational modes.

So, there are 3x28-6=78 vibrational modes.

4-(1-PYRROLIDINYL)PIPERAZINE

4-(1-PYRROLIDINYL)PIPERAZINE

Why 4-pypp ?

It has been known that many piperazine derivatives are of great interest in pharmacy and notable successful drugs.

Piperazine and its derivatives have wide application potentials in the field of material science and organic synthesis. Furthermore, many piperazine derivatives are of great interest in pharmacy and notable successful drugs.

4-pypp has wide applications in medicine.

THEORETICAL STUDY

All the calculations were performed by using Gaussian 09.A1 program on a personal computer and GaussView 5.0.8 was used for visualization of the structure and simulated vibrational spectra. PED calculations were carried out by the VEDA 4 (Vibrational Energy Distribution Analysis) program.

Many possible conformers could be proposed for 4-pypp, but here the discussion was confined to e-e (equatorial-equatorial), e-a (equatorial-axial), a-a(axial-axial) and a-e (axial-equatorial) conformers of the title molecule where the former represents NH while the latter stands for pyrrolidinyl group.

Conformations of 4-pypp a-a & a-e

AXIEL-AXIEL AXIEL-EQUATORIAL

Conformations of 4-pypp e-a & e-e

EQUATORIAL-AXIEL EQUATORIAL-EQUATORIAL

THEORETICAL STUDY

• They are considered in axial and equatorial positions according to plane formed by C14, C15, C16 and C19 atoms of 4-pypp. For the calculations, all four forms of 4-pypp were first optimized in the gas phase, chloroform (chlf) and dimethylsulfoxide (dmso) at B3LYP level of theory using 6-31++G(d,p) basis set. The e-e and a-e conformations were found more stable than the other two forms.

Therefore, for the vibrational calculations, the vibrational frequencies of e-a form of 4-pypp were calculated by using the same method and basis set under the keyword freq = Raman, pop = full and then scaled by 0.955 (above 1800 cm-1) and 0.977 (under 1800 cm-1) for 6-31++G(d,p).

Optimized Parameters and Mole Fractions of Four Forms of 4-pypp

B3LYP / 6-31++G(d,p) e-e e-a a-a a-e

Gas  

ΔG (Hartree) -479.10037

9

-479.09799

5

-479.10011

9

-479.097060

Relative Stability (δΔG;kcal/mol)

0.00 1.496 0.163 2.083

Mole Fractions (%) 36.7 27.7 35.6 -Molar Volume (cm3/mol) 124.408 146.507 133.656 120.754Recommend a0 (Å) 4.54 4.76 4.63 4.50

Chloroform  

ΔG (Hartree) -479.10871

9

-479.10485

4

-479.10873

7

-479.104280

Relative Stability (δΔG;kcal/mol)

0.011 2.437 0.00 2.797

Mole Fractions (%) 50 - 50 0

Dimethylsulfoxide

 

ΔG (Hartree) -479.11292

3

-479.10814

4

-479.11301

5

-479.108094

Relative Stability (δΔG;kcal/mol)

0.058 3.057 0.00 3.088

Mole Fractions (%) 49.8 - 50.2 0

Optimized Geometric Parameters for e-e and e-a form of 4-pypp in various medium

ParametersB3LYP/6–31++G(d.p)

Gas phase Chloroform Dmso  e – e a – e e – e a – e e – e a – eBond Lenghts (Å)            

N27 – H26 1.016 1.018 1.022 1.024 1.025 1.027N27 – C16 1.462 1.462 1.464 1.466 1.465 1.467N27 – C19 1.462 1.463 1.464 1.466 1.465 1.467C14 – N28 1.475 1.473 1.477 1.475 1.477 1.476C15 – N28 1.475 1.473 1.477 1.475 1.477 1.476N28 – 1.471 1.472 1.473 1.474 1.473 1.474N13 – C4 1.477 1.477 1.479 1.480 1.481 1.481N13 – C3 1.477 1.477 1.479 1.480 1.481 1.481(C – C)pp 1.528 1.535 1.528 1.535 1.528 1.535(C – H)pp 1.099 1.098 1.099 1.098 1.100 1.098(C – C)py 1.542 1.542 1.542 1.542 1.543 1.542(C – H)py 1.096 1.096 1.096 1.096 1.096 1.096Bond Angles (o)            C14 – N28 – N13 108.92 109.05 108.85 108.97 108.85 108.98C15 – N28 – N13 108.92 109.04 108.84 108.97 108.86 108.98N28 – N13 – C4 110.86 110.88 110.80 110.78 110.80 110.76N28 – N13 – C3 110.86 110.88 110.79 110.79 110.81 110.81C4 – N13 – C3 102.99 102.96 102.90 102.88 102.85 102.84H26 – N27 – C16 110.79 109.66 110.29 109.28 110.05 109.11H26 – N27 – C19 110.79 109.66 110.29 109.28 110.04 109.11(H – C – H)pp 108.24 107.63 108.10 107.68 108.02 107.72(C – N – C)pp 109.43 109.25 109.21 109.08 109.16 109.04(C – C – N)pp 109.99 112.23 110.19 112.26 110.27 112.26(C – C – C)py 104.28 104.29 104.33 104.33 104.35 104.35(H – C – H)py 107.92 107.91 107.92 107.92 107.91 107.90

Dihedral Angles (o)            

C14 – N28 – N13 – C3 117.86 177.74 177.72 177.74 177.73 177.72C14 – N28 – N13 – C4 64.12 64.00 64.16 64.22 64.22 64.25C15 – N28 – N13 – C4 -177.85 -177.72 -177.87 -177.76 -177.73 -177.82C15 – N28 – N13 – C3 -64.11 -63.99 -64.32 -64.24 -64.22 -64.35

Thermodynamic Parameters for e-e and e-a form of 4-pypp

Parameters 4pypp

B3LYP/6-31++g(d.p)

Gas Phase Chloroform Dmso

e - e a - e e - e a - e e - e a - e

Thermal total energy (kcal / mol)167.730 167.699 167.624 167.610 167.510 167.512

Vibrational energy (kcal/mol)165.952 165.922 165.846 165.833 165.732 165.734

Zero point vibrational energy (kcal/mol)161.306 161.255 161.282 161.239 161.182 161.151

Dipole moment (Debye) 1.495 1.382 1.325 1.685 1.539 1.828

Heat capacity (kcal / mol.K) 40.470 40.597 40.295 40.439 40.285 40.433

Entropy (kcal / mol.K) 99.846 100.014 98.717 98.916 98.442 98.670

ModeAssignments

B3LYP/6–31++G(d.p)

e –e form in gas phase

PED (≥ 5 %) να νβ IIR IR

1 ν(NH) 100 3537 3378 0.000 27.724

2 ν(CH) 96 3122 2981 35.570 18.795

3ν(CH) 92 3117 2977 72.710 0.977

4ν(CH) 95 3116 2975 33.880 33.979

5ν(CH) 93 3103 2964 0.360 21.869

6ν(CH) 90 3101 2962 5.330 7.282

7ν(CH) 89 3093 2954 10.730 0.889

8ν(CH) 96 3077 2938 26.970 35.886

9ν(CH) 97 3076 2938 49.550 22.999

10ν(CH) 94 3073 2934 72.240 38.282

11ν(CH) 98 3062 2925 27.710 11.319

12 ν(CH) 93 2975 2841 109.670 27.222

13ν(CH) 93 2968 2835 11.990 7.025

14ν(CH) 96 2954 2821 137.850 41.663

15ν(CH) 97 2945 2813 45.570 6.644

16ν(CH) 93 2943 2811 68.400 47.051

17ν(CH) 94 2940 2808 43.720 3.971

18 δ(HCH) 85 1535 1499 2.890 4.284

19δ(HCH) 92 1517 1482 0.430 3.977

20δ(HCH) 78 1514 1479 3.510 4.330

21δ(HCH) 74 1511 1476 7.050 3.348

22δ(HCH) 74 1506 1471 16.010 1.064

23δ(HCH) 90 1497 1463 0.390 0.329

24δ(HCH) 82 1493 1459 0.780 15.944

25δ(HCH) 82 1492 1458 0.820 2.995

26 δ(HCN) 78 1481 1447 3.890 1.307

27 δ(HCC) 47 1429 1397 2.850 1.077

28δ(HCC) 56 1411 1378 1.100 1.426

29δ(HCC) 67 1384 1352 3.170 1.350

30δ(HCC) 59 1373 1342 0.450 1.116

Theoretical Vibrational frequencies (cm-1) for e–e form of 4-pypp in gas phase

να : Unscaled wavenumbers. νβ : scaled with 0.955 above 1800 cm−1, 0.977 under 1800 cm−1. IR and IR: Calculated infrared and Raman intensities. PED data are taken from VEDA4.

Theoretical Vibrational frequencies (cm-1) for a–e form of 4-pypp in chloroform

ModeAssignments

B3LYP/6–31++G(d.p)

a –e form in chloroform

PED (≥ 5 %) να νβ IIR IR

1 ν(NH) 100 / 100 3537 3284 0.400 22.440

2 ν(CH) 94 / 98 3122 2978 61.030 34.765

3 ν(CH) 93 / 92 3117 2973 108.190 3.606

4 ν(CH) 94 / 97 3116 2970 34.280 86.229

5 ν(CH) 88 / 95 3103 2960 4.020 50.273

6 ν(CH) 89 / 95 3101 2959 16.350 1.266

7 ν(CH) 89 / 93 3093 2953 10.760 1.814

8 ν(CH) 89 / 94 3077 2949 52.870 43.767

9 ν(CH) 89 / 94 3076 2949 45.080 29.692

10 ν(CH) 94 / 97 3073 2931 83.430 73.382

11 ν(CH) 98 / 97 3062 2921 39.050 17.461

12 ν(CH) 90 / 94 2975 2898 67.120 69.468

13 ν(CH) 91 / 95 2968 2895 49.100 9.254

14 ν(CH) 95 / 92 2954 2823 104.420 108.123

15 ν(CH) 97 / 97 2945 2815 49.890 15.546

16 ν(CH) 95 / 92 2943 2807 250.140 64.653

17 ν(CH) 97 / 97 2940 2800 47.290 10.279

18 δ(HCH) 64 / 94 1535 1498 6.070 11.737

19 δ(HCH) 74 / 94 1517 1477 0.300 8.018

20 δ(HCH) 72 / 87 1514 1474 12.830 5.723

21 ν(NH) 100 / 100 1511 1471 4.370 3.274

22 ν(CH) 94 / 98 1506 1466 8.740 1.850

23 ν(CH) 93 / 92 1497 1455 2.060 11.918

24 ν(CH) 94 / 97 1493 1452 10.280 8.291

25 ν(CH) 88 / 95 1492 1452 12.660 1.996

26 ν(CH) 89 / 95 1481 1443 1.010 15.986

27 ν(CH) 89 / 93 1429 1378 7.170 3.606

28 ν(CH) 89 / 94 1411 1366 4.550 3.649

29 ν(CH) 89 / 94 1384 1350 4.820 3.692

30 ν(CH) 94 / 97 1373 1346 4.490 0.743

να : Unscaled wavenumbers. νβ : scaled with 0.955 above 1800 cm−1, 0.977 under 1800 cm−1. IR and IR: Calculated infrared and Raman intensities. PED data are taken from VEDA4.

Theoretical Vibrational frequencies (cm-1) for a–e form of 4-pypp in dmso

ModeAssignments

B3LYP/6–31++G(d.p)

a –e form in dmso

PED (≥ 5 %) να νβ IIR IR

1 ν(NH) 100 / 100 3537 3251 0.260 33.161

2 ν(CH) 94 / 98 3122 2977 57.570 53.839

3 ν(CH) 93 / 92 3117 2973 125.060 4.208

4 ν(CH) 94 / 97 3116 2970 61.950 103.776

5 ν(CH) 88 / 95 3103 2961 2.260 67.023

6 ν(CH) 89 / 95 3101 2960 18.070 2.118

7 ν(CH) 89 / 93 3093 2952 13.220 4.009

8 ν(CH) 89 / 94 3077 2948 54.720 40.765

9 ν(CH) 89 / 94 3076 2948 61.420 52.241

10 ν(CH) 94 / 97 3073 2930 89.630 95.276

11 ν(CH) 98 / 97 3062 2919 44.000 19.862

12 ν(CH) 90 / 94 2975 2895 90.250 95.215

13 ν(CH) 91 / 95 2968 2892 52.140 9.551

14 ν(CH) 95 / 92 2954 2823 112.020 183.683

15 ν(CH) 97 / 97 2945 2815 57.850 22.636

16 ν(CH) 95 / 92 2943 2808 360.160 78.720

17 ν(CH) 97 / 97 2940 2802 56.140 13.628

18 δ(HCH) 64 / 94 1535 1492 5.900 12.641

19 δ(HCH) 74 / 94 1517 1475 0.280 9.914

20 δ(HCH) 72 / 87 1514 1472 13.690 6.852

21 ν(NH) 100 / 100 1511 1468 15.000 1.233

22 ν(CH) 94 / 98 1506 1468 5.650 3.361

23 ν(CH) 93 / 92 1497 1454 2.380 14.833

24 ν(CH) 94 / 97 1493 1453 8.230 11.032

25 ν(CH) 88 / 95 1492 1449 12.960 2.420

26 ν(CH) 89 / 95 1481 1441 0.540 21.380

27 ν(CH) 89 / 93 1429 1378 9.410 6.461

28 ν(CH) 89 / 94 1411 1365 5.120 4.513

29 ν(CH) 89 / 94 1384 1349 4.900 5.755

30 ν(CH) 94 / 97 1373 1345 5.330 0.750

να : Unscaled wavenumbers. νβ : scaled with 0.955 above 1800 cm−1, 0.977 under 1800 cm−1. IR and IR: Calculated infrared and Raman intensities. PED data are taken from VEDA4.

Theoretical Spectrum (e-e Gas IR-Raman)

Theoretical Spectrum (a-e Chloroform IR-Raman)

Theoretical Spectrum (a-e Dmso IR-Raman)

Homo & Lumo Orbitals (Gas)

Homo & Lumo Orbitals (Chloroform)

Homo & Lumo Orbitals (Dmso)

CONCLUSION

The theoretical vibrational investigations of 4-pypp are successfully performed by using quantum chemical calculations. In conclusion, following results can be summarized:Results of energy calculations for gas phase indicate that e-e form is the most stable conformer of 4-pypp. However, These calculations for solvations showed that a-e form is the most stable conformer for title molecule. So, the conformational energy barrier is dependent of the solvent. In generally, there are no significant changes in the geometric parameters when 4-pypp in solvated. From lower to higher dielectric, the dipole moment increases and there are some shifts in vibrational frequencies due to dielectric medium. Solvent effects on vibrational intensities are considerable and they increase as one goes from lower to higher dielectric constant.

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