1. DFT STUDY OF SOLVENT EFFECTS ON CONFORMATIONAL EQUILIBRIA AND
VIBRATIONAL SPECTRA OF 4-(1-PYRROLIDINYL)PIPERAZINE
Ö.BAĞLAYAN a , G.KEŞAN c , C.PARLAK b and M.ŞENYELa
a Physics Department, Science Faculty, Anadolu University, Eskişehir, 26470, Turkey
b Department of Physics, Dumlupnar University, Kütahya, 43100, Turkey
c Faculty of Science, University of South Bohemia, Branišovská 31, České Budějovice, Czech Republic

2. ABSTRACT
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 pypp have been predicted.

3. 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.

4. INDEX 4-(1-PYRROLIDINYL)PIPERAZINE Theoretical Study Infrared Spectrum
Raman Spectrum
Vibrational Assignments
Thermodynamics functions
Homo-Lumo Orbitals
Results

5. 4-(1-PYRROLIDINYL)PIPERAZINE
Molecular Formula: C8H17N3
Molecular Weight: g/mol
This molecule has 3N-6 vibrational modes.
So, there are 3x28-6=78 vibrational modes.

6. 4-(1-PYRROLIDINYL)PIPERAZINE

7. 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.

8. THEORETICAL STUDY
All the calculations were performed by using Gaussian 09.A1 program on a personal computer and GaussView 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.

9. Conformations of 4-pypp a-a & a-e
AXIEL-AXIEL
AXIEL-EQUATORIAL

10. Conformations of 4-pypp e-a & e-e
EQUATORIAL-AXIEL
EQUATORIAL-EQUATORIAL

11. 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 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 (above 1800 cm-1) and (under 1800 cm-1) for G(d,p).

12. Optimized Parameters and Mole Fractions of Four Forms of 4-pypp
B3LYP / G(d,p)
e-e
e-a
a-a
a-e
Gas
ΔG (Hartree)
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)
Recommend a0 (Å)
4.54
4.76
4.63
4.50
Chloroform
0.011
2.437
2.797 50
Dimethylsulfoxide
0.058
3.057
3.088
49.8
50.2

13. Optimized Geometric Parameters for e-e and e-a form of 4-pypp in various medium
B3LYP/6–31++G(d.p)
Gas phase
Chloroform
Dmso
e – e
a – e
Bond Lenghts (Å)
N27 – H26
1.016
1.018
1.022
1.024
1.025
1.027
N27 – C16
1.462
1.464
1.466
1.465
1.467
N27 – C19
1.463
C14 – N28
1.475
1.473
1.477
1.476
C15 – N28
N28 –
1.471
1.472
1.474
N13 – C4
1.479
1.480
1.481
N13 – C3
(C – C)pp
1.528
1.535
(C – H)pp
1.099
1.098
1.100
(C – C)py
1.542
1.543
(C – H)py
1.096
Bond Angles (o)
C14 – N28 – N13
108.92
109.05
108.85
108.97
108.98
C15 – N28 – N13
109.04
108.84
108.86
N28 – N13 – C4
110.86
110.88
110.80
110.78
110.76
N28 – N13 – C3
110.79
110.81
C4 – N13 – C3
102.99
102.96
102.90
102.88
102.85
102.84
H26 – N27 – C16
109.66
110.29
109.28
110.05
109.11
H26 – N27 – C19
110.04
(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
(C – C – N)pp
109.99
112.23
110.19
112.26
110.27
(C – C – C)py
104.28
104.29
104.33
104.35
(H – C – H)py
107.92
107.91
107.90
Dihedral Angles (o)
C14 – N28 – N13 – C3
117.86
177.74
177.72
177.73
C14 – N28 – N13 – C4
64.12
64.00
64.16
64.22
64.25
C15 – N28 – N13 – C4
C15 – N28 – N13 – C3
-64.11
-63.99
-64.32
-64.24
-64.22
-64.35

14. Thermodynamic Parameters for e-e and e-a form of 4-pypp
B3LYP/6-31++g(d.p)
Gas Phase
Chloroform
Dmso
e - e
a - e
Thermal total energy (kcal / mol)
Vibrational energy (kcal/mol)
Zero point vibrational energy (kcal/mol)
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
98.717
98.916
98.442
98.670

15. Theoretical Vibrational frequencies (cm-1) for e–e form of 4-pypp in gas phase
Mode
Assignments
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 3
ν(CH) 92
3117
2977
72.710
0.977 4
ν(CH) 95
3116
2975
33.880
33.979 5
ν(CH) 93
3103
2964
0.360
21.869 6
ν(CH) 90
3101
2962
5.330
7.282 7
ν(CH) 89
3093
2954
10.730
0.889 8
3077
2938
26.970
35.886 9
ν(CH) 97
3076
49.550
22.999
10
ν(CH) 94
3073
2934
72.240
38.282
11
ν(CH) 98
3062
2925
27.710
11.319
12
2841
27.222
13
2968
2835
11.990
7.025
14
2821
41.663
15
2945
2813
45.570
6.644
16
2943
2811
68.400
47.051
17
2940
2808
43.720
3.971
18
δ(HCH) 85
1535
1499
2.890
4.284
19
δ(HCH) 92
1517
1482
0.430
3.977
20
δ(HCH) 78
1514
1479
3.510
4.330
21
δ(HCH) 74
1511
1476
7.050
3.348
22
1506
1471
16.010
1.064
23
δ(HCH) 90
1497
1463
0.390
0.329
24
δ(HCH) 82
1493
1459
0.780
15.944
25
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
28
δ(HCC) 56
1411
1378
1.100
1.426
29
δ(HCC) 67
1384
1352
3.170
1.350
30
δ(HCC) 59
1373
1342
0.450
1.116
να : Unscaled wavenumbers. νβ : scaled with above 1800 cm−1, under 1800 cm−1. IR and IR: Calculated infrared and Raman intensities. PED data are taken from VEDA4.

16. Theoretical Vibrational frequencies (cm-1) for a–e form of 4-pypp in chloroform
Mode
Assignments
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
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
3076
45.080
29.692
10
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
15
ν(CH) 97 / 97
2945
2815
49.890
15.546
16
2943
2807
64.653
17
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
1511
1471
4.370
3.274
22
1506
1466
8.740
1.850
23
1497
1455
2.060
11.918
24
1493
1452
10.280
8.291
25
1492
12.660
1.996
26
1481
1443
1.010
15.986
27
1429
1378
7.170
28
1411
1366
4.550
3.649
29
1384
1350
4.820
3.692
30
1373
1346
4.490
0.743
να : Unscaled wavenumbers. νβ : scaled with above 1800 cm−1, under 1800 cm−1. IR and IR: Calculated infrared and Raman intensities. PED data are taken from VEDA4.

17. Theoretical Vibrational frequencies (cm-1) for a–e form of 4-pypp in dmso
Mode
Assignments
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
4.208 4
ν(CH) 94 / 97
3116
2970
61.950 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
3076
61.420
52.241
10
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
15
ν(CH) 97 / 97
2945
2815
57.850
22.636
16
2943
2808
78.720
17
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
1511
1468
15.000
1.233
22
1506
5.650
3.361
23
1497
1454
2.380
14.833
24
1493
1453
8.230
11.032
25
1449
12.960
2.420
26
1481
1441
0.540
21.380
27
1429
1378
9.410
6.461
28
1411
1365
5.120
4.513
29
1384
1349
4.900
5.755
30
1373
1345
5.330
0.750
να : Unscaled wavenumbers. νβ : scaled with above 1800 cm−1, under 1800 cm−1. IR and IR: Calculated infrared and Raman intensities. PED data are taken from VEDA4.

18. Theoretical Spectrum (e-e Gas IR-Raman)

19. Theoretical Spectrum (a-e Chloroform IR-Raman)

20. Theoretical Spectrum (a-e Dmso IR-Raman)

21. Homo & Lumo Orbitals (Gas)

22. Homo & Lumo Orbitals (Chloroform)

23. Homo & Lumo Orbitals (Dmso)

24. 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.

25. THANK YOU FOR YOUR PARTICIPATION..