Vibrational spectra and normal coordinate analysis on structure of nitrazepam

Indian Journal of Pure & Applied Physics Vol. 46, March 2008, pp. 162-168 Vibrational spectra and normal coordinate analysis on structure of nitrazepam S Gunasekaran*, R Arunbalaji*, S Seshadri + & S Muthu *Spectrophysics Research Laboratory, Department of Physics, Pachaiyappa s College, Chennai 600 030 +Department of Physics, Sri Chandrasekharendra Saraswathi Viswa Maha Vidyalaya, Enathur, Kanchipuram 631 561 Department of Applied Physics, Sri Venkateswara College of Engineering, Sriperumbudur 602 105 Email: arunbalaji_81@yahoo.com Received 14 February 2006; revised 18 July 2007; accepted 12 December 2007 A normal coordinate analysis on nitrazepam has been carried out with a set of symmetry co-ordinates following Wilson's F-G matrix method. The potential constants evaluated for the molecule are found to be in good agreement with literature values thereby conforming the vibrational assignments. To check whether the chosen set of vibrational frequencies contributes maximum to the potential energy associated with the normal co-ordinates of the molecule, the potential energy distribution has been evaluated. Keywords: Fourier Transform infrared spectrum, Fourier Transform Raman spectrum, Nitrazepam, Normal coordinate analysis, potential energy distribution 1 Introduction Nitrazepam, a derivative of benzodiazepine has more prominent anticonvulsant activity than any other derivative of benzodiazepine. Nitrazepam has been shown to actually increase rapid eye movement (REM) sleep. It is taken at bedtime and induces sleep 1,2 in 20-30min with duration of up to 8 h. The molecular formula of nitrazepam is (C 15 H 11 N 3 O 3 ) which is chemically known as 9-nitro-6-phenyl-2, 5-diazabicycio[5,4,0]undeca-5,8,10,12-tetraen-3-one. Recent spectroscopic studies of benzene and its derivatives have been carried out due to their biological and pharmaceutical importance. An extensive work has been carried out on the title compound and its derivatives in the recent year 3,4. But so far no work has been done on vibrational spectra and normal co-ordinate analysis of this drug, because of their high complexity and low symmetry and it is also difficult to interpret the spectra of this molecule. The FTIR and FT Raman spectra are recorded for these molecule and complete vibrational band assignments have been made. A systematic set of symmetry co-ordinates has been constructed on the basis of C s symmetry and a normal co-ordinate analysis of this molecule has been carried out using Wilson's F-G matrix method. The potential energy distribution has been evaluated. 2 Experimental Details Spectroscopic grade pure sample of nitrazepam procured from Sigma Chemical Company, USA and used as such without further purification. The FTIR spectrum of the compound has been recorded in the region 4000 400 cm -1 in evacuation mode using KBr pellet pressed technique with 4.0 cm -1 resolution, at Dr. CEEAL Laboratories, Chennai, India. The FT Raman spectrum has been recorded in the region 4000 100 cm -1 in purge mode using YAG laser of 200 mw at Central Electro Chemical Research Institute, Karaikudi, Tamil Nadu. FTIR and FT Raman spectra of nitrazepam are shown in Figures 1 and 2, 3 Normal Coordinate Analysis Nitrazepam has 60 fundamental modes of vibration under C s symmetry point group which are distributed as Г vib = 40 A' + 20 A". All the fundamental modes are active both in FTIR and Raman. Out of forty modes of vibrations, 29 modes in A' species and only 12 in A" species are considered in the present work. The structure, orientation of the principle axes and the nomenclature of the parameters of the nitrazepam molecule are shown in Fig. 3. The molecular

GUNASEKARAN et al.: VIBRATIONAL SPECTRA AND NORMAL COORDINATE ANALYSIS 163 Fig. 1 FTIR spectrum of nitrazepam Fig. 2 FT Raman Spectrum of nitrazepam parameters (bond angle and bond lengths) are taken from ChemSoft Trial version10.0 and are presented in Table1. 3.1 Symmetry coordinates The symmetry coordinates of the compound under study are constructed using the internal coordinates with the knowledge of the projection operator and with the help of the character table. The following are the set of orthonormal symmetry co-ordinates considered in the present work. A' species S 1 = 1/ 6 [Δp 1 + Δp 2 + Δp 3 + Δp 4 + Δp 5 + Δp 6 ] S 2 = 1/ 3 [Δb 1 + Δb 2 + Δb 3 ]

164 INDIAN J PURE & APPL PHYS, VOL 46, MARCH 2008 Fig. 3 Structure, nomenclature of parameters and the orientation of the principal axes of nitrazepam and 3D view S 3 = 1/ 3 [Δg 1 + Δg 2 + Δg 3 ] S 4 = 1/ 2 [Δc 1 + Δc 2 ] S 5 = 1/ 2 [Δe 1 + Δe 2 ] S 6 = 1/ 2 [Δr 1 + Δr 2 ] S 7 = Δj S 8 = Δa S 9 = Δd S 10 = Δt S 11 = Δh S 12 = 1/ 6 [Δα 1 + Δα 2 + Δα 3 + Δα 4 + Δα 5 + Δα 6 ] S 13 = 1/ 6 [Δβ 1 + Δβ 2 + Δβ 3 + Δβ 4 + Δβ 5 + Δβ 6 ] S 14 = 1/ 3 [Δτ 1 + Δτ 2 + Δτ 2 ] S 15 = 1/ 2 [Δσ 1 + Δσ 2 ] S 16 = 1/ 2 [Δθ 1 + Δθ 2 ] Table 1 Molecular parameters of nitrazepam Nature of bond length/bond angle Description Molecular Parameters N 1 C 2 b 2 1.2660 Å N 1 C 8 b 1 1.2660 Å N 1 H 16 a 1.0500 Å C 2 C 3 c 1 1.4802 Å C 2 O 12 d 1.2080 Å C 3 N 4 b 3 1.4700 Å C 3 H 18 e 1 1.1130 Å C 3 H 19 e 2 1.1130 Å N 4 C 5 t 1.2600 Å C 5 C 6 c 2 1.3370 Å C 5 X 17 h 1.7700 Å C 6 C 17 p 2 1.3370 Å C 6 C 8 p 3 1.3370 Å C 7 C 11 p 1 1.3370 Å C 8 C 9 p 4 1.3370 Å C 8 H 20 g 1 1.1000 Å C 9 C 10 p 5 1.4200 Å C 9 N 13 j 1.1683 Å C 10 C 11 p 6 1.3370 Å C 10 H 21 g 2 1.1000 Å C 11 H 22 g 3 1.1000 Å N 13 O 14 r 1 1.2566 Å N 13 O 15 r 2 1.2739 Å C 3 C 2 N 1 τ 2 118.00 O 12 C 2 N 1 χ 122.60 O 12 C 2 C 3 ψ 122.50 C 7 N 1 C 2 Σ 124.00 H 16 N 1 C 2 θ 2 118.00 H 16 N 1 C 7 θ 1 118.00 C 6 C 7 N 1 τ 1 120.00 C 11 C 7 N 1 ξ 119.99 C 11 C 7 C 6 α 2 120.00 C 8 C 6 C 7 α 3 120.00 C 10 C 11 C 7 α 1 119.99 H 22 C 11 C 7 β 6 120.00 H 22 C 11 C 10 β 5 119.99 C 6 C 5 N 4 γ 120.00 X 17 C 5 N 4 ρ 119.98 X 17 C 5 C 6 ϕ 120.00 C 9 C 8 C 6 α 4 119.99 H 20 C 8 C 6 β 1 119.90 H 20 C 8 C 9 β 2 120.00 C 10 C 9 C 8 α 5 119.99 N 13 C 9 C 8 σ 1 120.00 N 13 C 9 C 10 σ 2 121.30 C 11 C 10 C 9 α 6 121.35 H 21 C 10 C 9 β 3 117.38 H 21 C 10 C 11 β 4 121.30 C 5 N 4 C 3 λ 108.00 O 14 N 13 C 9 η 1 118.99 O 15 N 13 C 9 η 2 118.99 O 15 N 13 O 14 φ 127.00 N 4 C 3 C 2 τ 3 103.85 H 18 C 3 C 2 π 112.72 H 19 C 3 N 4 μ 112.72 H 19 C 3 H 18 ω 109.40

GUNASEKARAN et al.: VIBRATIONAL SPECTRA AND NORMAL COORDINATE ANALYSIS 165 S 17 = 1/ 2 [Δη 1 + Δη 2 ] S 18 = Δφ S 19 = Δξ S 20 = Δ S 21 = Δχ S 22 = Δψ S 23 = Δπ S 24 = Δω S 25 = Δμ S 26 = Δλ S 27 = Δρ S 28 = Δγ S 29 = Δϕ A" species S 30 = 1/ 12 [2Δp 1 Δp 2 Δp 3 + 2Δp 4 Δp 5 Δp 6 ] S 31 = 1/ 6 [2Δb 1 Δb 2 Δb 3 ] S 32 = 1/6 [2Δg 1 Δg 2 Δg 3 ] S 33 = 1/ 2 [Δc 1 Δc 2 ] S 34 = 1/ 2 [Δe 1 Δe 2 ] S 35 = 1/ 2 [Δr 1 Δr 2 ] S 36 = 1/ 12 [2Δα 1 Δα 2 Δα 3 + 2Δα 4 Δα 5 Δα 6 ] S 37 = 1/ 12 [2Δβ 1 Δβ 2 Δβ 3 + 2Δβ 4 Δβ 5 Δβ 6 ] S 38 = 1/ 6 [Δτ 1 Δτ 2 Δτ 2 ] S 39 = 1/ 2 [Δσ 1 Δσ 2 ] S 40 = 1/ 2 [Δθ 1 Δθ 2 ] S 41 = 1/ 2 [Δη 1 - Δη 2 ] where Δ s represent changes in the corresponding bond distances and bond angles. 3.2 FTIR and FT Raman spectra and vibrational band assignment The infrared and Raman spectra contain a number of bands at specific wave numbers. The vibrational analysis indicate which of the vibrational modes represent these observed bands. The assignments for the fundamental modes of vibrations have been made on basis of the position shape, intensity and vibrational frequencies of similar compounds like derivatives of benzene, pyridine and pyrimidine compounds 5,6. Aromatic CC stretching The ring carbon-carbon stretching vibrations 6,7 occur in the region 1625-1430 cm -1. Mohan and Settu 7 have identified the IR bands at 1470, 1484, 1561 and 1575 cm -1 in diazepam and closely related compound of benzodiazepines due to aromatic CC stretching vibrations. Based on these factors, the FTIR bands at 1455 and 1469 cm -1 are assigned to aromatic CC symmetric stretching and bands at 1513 cm -1 and 1550 cm -1 are assigned to aromatic CC asymmetric stretching vibrations. The Raman bands for symmetric stretching observed at 1458 and 1460 cm -1 and the asymmetric stretching assigned in the region 1520-1560 cm -1, C H stretching The heterocyclic aromatic compounds and its derivatives are structurally very close to benzene. The C-H stretching vibrations of aromatic and hetero aromatic structures 8-10 occur in the region 3000-3100 cm -1. Neville and Shurvell 11 have identified the FTIR bands at 3023, 3056, and 3073 cm -1 in Fourier Transform Raman and infrared vibrational study of diazepam and four closely related derivatives of 1,4-benzodiazepine due to the C-H stretching vibrations. Hence, in the present investigation, the bands observed at 3025 and 3085 cm -1 in the FTIR spectra and the bands found at 3029 and 3085 cm -1 in the FT Raman spectra are due to C-H symmetric and asymmetric stretching vibrations, C N and C=N stretching The ring C=N stretching vibrations 12,13 occur in the region 1615-1575cm -1 and 1520-1465 cm -1. The medium to weak absorption bands for the C-N linkages in amines appear in the region 1200-1020 cm -1. Mohan et al 14. have identified the stretching frequency of C=N bond in benzimidazole at 1617 cm -1. Gunasekaran et al 15. have observed the C-N stretching band at 1312cm -1 in benzocaine. Referring to the above assignments, the FTIR bands at 1341 and 1359 cm -1 are attributed to C-N symmetric and asymmetric stretching vibrations, In Raman spectra, the bands observed at 1338 cm -1 are due to C-N symmetric stretching vibrations, Also the bands observed at 1315 cm -1 for IR and 1309 cm -1 for Raman could be attributed to C-N stretching vibrations and the bands present at 1607 cm -1 could be attributed to C=N stretching vibrations.

166 INDIAN J PURE & APPL PHYS, VOL 46, MARCH 2008 Table 2 Vibrational band Assignments, Potential Constants (10 2 N/m) and PED Values of nitrazepam Symmetry Frequency (cm -1 ) Assignment Force Constant PED % Coordinate FTIR FT Raman (10 2 N/m) A' species S 1 1455 (w) 1458 (m) Ring C C symmetric stretching 6.4766 96 S 2 1341 (s) 1338 (s) C N symmetric stretching 5.9596 96 S 3 3025 (m) 3029 (w) C H symmetric stretching 5.1110 87 S 4 1469 (m) 1460 (w) C C symmetric stretching 6.4760 98 S 5 2977 (s) 2976 (s) C H symmetric stretching 5.1112 88 S 6 1480 (w) 1475 (w) N O symmetric stretching 10.1782 93 S 7 1315 (s) 1309 (w) C N stretching 5.9008 90 S 8 3380 (s) 3363 (w) N H stretching 6.9124 94 S 9 1682 (w) 1689 (w) C = O stretching 11.1121 93 S 10 1607 (w) 1610 (w) C = N stretching 13.2222 91 S 11 1250 (s) 1255 (m) C C (X) stretching 5.5999 87 S 12 540 (w) 541 (w) C C = C symmetric bending 0.9147 57 S 13 1090 (w) 1095 (w) C C H symmetric bending 0.5330 62 S 14 940 (w) 949 (w) C C N symmetric bending 1.3366 56 S 15 915 (w) 908 (w) C C N symmetric bending 1.3301 56 S 16 1573(w) 1570 (w) C N H symmetric bending 0.3560 35 S 17 S 18 701(w) 620(w) 693 (w) 620(w) C N O symmetric bending O - N O bending 0.7566 0.8104 42 57 S 19 899 (s) ------ C C N bending 0.3173 37 S 20 814 (vs) 814 (s) C N C bending 0.9143 50 S 21 750 (w) 752 (w) N C = O bending 0.7612 78 S 22 669 (s) 677 (w) C C = O bending 0.7988 65 S 23 953 (w) 950 (w) C C - H bending 0.6424 52 S 24 1389 (w) 1388 (s) H C - H bending 0.5620 60 S 25 1405 (w) 1408 (s) N C H bending 0.5354 53 S 26 838 (w) ------ C N C bending 0.9144 44 S 27 511 (w) 510 (w) C C = N bending 1.3306 58 S 28 520 (m) 520 (m) C C = N bending 1.3318 58 S 29 669 (w) 665 (w) C C C bending 1.1538 81 A" species S 30 1513 (w) 1520 (w) Ring C C asymmetric stretching 6.4880 92 S 31 1359 (m) ------ C N asymmetric stretching 5.9847 79 S 32 3085 (s) 3085 (w) C H asymmetric stretching 5.2827 92 S 33 1550 (w) 1560 (s) C C asymmetric stretching 6.4981 74 S 34 2985(w) 2999 (ms) C H asymmetric stretching 5.2820 94 S 35 1530 (w) 1528 (w) N O asymmetric stretching 10.3110 88 578 (w) 580 (w) C C - C asymmetric bending 0.9838 48 S 36 S 37 1210 (w) 1210 (w) C C - H asymmetric bending 0.5440 38 S 38 1004 (m) 1004 (w) C C - N asymmetric bending 1.3898 40 S 39 989 (m) ------ C C N asymmetric bending 1.3894 40 1596 (w) ------ C N H asymmetric bending 0.3840 50 S 41 724(s) ------ C N O asymmetric bending 0.7748 56 S 40 vs: very strong; s: strong; m: medium; ms: medium strong; w: weak

GUNASEKARAN et al.: VIBRATIONAL SPECTRA AND NORMAL COORDINATE ANALYSIS 167 C=O stretching The band due to C=O stretching vibration is observed in the region1850-1550 cm -1 due to tautomerism, pyrimidines substituted with hydroxyl groups are generally in the keto form and therefore, have a strong band due to carbonyl group 16,17. In the present work, the bands observed at 1682 cm -1 in FTIR spectrum and 1689 cm -1 in Raman are assigned to C=O stretching mode of vibrations, C C H bending The C H deformation 18,19 frequencies in benzene and its derivatives are found to occur in the region 1200-1050 cm -1. In the present work, the bands observed at 1090 cm -1 and 1210 cm -1 in FTIR spectrum are assigned to C-C-H symmetric and asymmetric bending and the bands observed at 1095 and 1210 cm -1 in FT Raman spectrum are assigned to C-C-H symmetric and asymmetric bending, Also the bands observed at 953 cm -1 for IR and 950cm -1 for Raman are assigned to C-C-H bending vibrations, C C C bending The C C C bending bands 20-22 always occur below 600 cm -1. Isopropyl benzenes 23 have a medium intensity of band in the region 560-480 cm -1. In the present work, the band observed at 540 cm -1 and 578 cm -1 are assigned to C C C symmetric and asymmetric bending in FTIR spectra, respectively and the bands at 541 and 580 cm -1 are assigned to C C C symmetric and asymmetric bending in FT Raman spectra, 4 Results and Discussion A normal coordinate analysis of nitrazepam has been carried out using the observed wave numbers from FTIR and FT Raman spectra. The evaluation of force constants is made on the basis of general valence force field by applying Wilson s FG matrix method 14. The potential energy associated with the normal coordinates of the molecule has been calculated using the relation PED = F 2 ij L ij /λ j. The calculated force constants and the % potential energy distribution are presented in Table 2. The initial set of force constants for the nitrazepam has been taken from related molecules 15. This set of force constants was subsequently refined by keeping a few interaction constants fixed through out the refinement process using successive approximation technique. The force constant of C C stretching vibration of the compound is found to be around 6.4766 x 10 2 N/m as expected and they contribute PED value of more than 96%. The symmetric and asymmetric C H stretching vibrations of the molecule exhibit a force constant around 5.1110x10 2 N/m and 5.2829 x 10 2 N/m, respectively, contributing to the PED value of more than 90 %. Similarly, the force constant of C N symmetric stretching vibration of the compound is found to be around 5.9596 x 10 2 N/m and it contributes PED value of more than 96 %. A PED value of around 93 % has been calculated for C=O stretching vibrations whose frequency is assigned around 1682 cm -1. In addition to the stretching force constants, the force constants for bending vibrations have also been calculated and are in good agreement with the literature values 16 5 Conclusion Thus, a complete vibrational band assignment of nitrazepam has been carried out using infrared and Raman spectra on the basis of C s point group symmetry. A symmetric set of potential constants has been computed and it is found to be in good agreement with literature. The PED calculation with respect to normal modes of vibration, provides a strong support for the frequency assignment on the highly complex molecule. References 1 Tripathi K D, Medical Pharmacology, Jaypee (Brothers Medical Publishers, New Delhi), 1995. 2 Indian Pharmacopoeia, Controller of Publication, Civil Lines, Delhi, Vol I & II (1996). 3 Gunasekaran S, Ponnambalam U, Muthu S & An Gand, Indian J Phys, 12 (2003) 51. 4 Acheson R M, An Introduction of Chemistry of Heterocyclic Compounds, 3 rd Ed (John Wiley, New York), 1977. 5 Colthup N B, Daly L H & Wiberly S E, Introduction to infrared & Raman spectroscopy, 2 nd Ed (Academic Press, New York), 1975. 6 Socrates G, Infrared characteristic Group frequencies, 1 st Ed, John Wiley, (1980). 7 Mohan S & Settu K, Indian J Pure & Appl Phys, 35 (1997) 1. 8 Puviarasan N, Arjunan V & Mohan S, Turk J Chem, 26 (2002) 323. 9 Chithambarathanu T, Umayourbaghan V & Krishnakumar V, Indian J Pure & Appl Phys, 41 (2003) 844. 10 Gunasekaran S, Natarajan R K & Santhosam K, Asian J Chem, 15 (2003) 1347. 11 Neville G A & Shervell H F, J Raman Spectrosc, 21 (1990) 9. 12 Pouchert C J, Aldrich Library of Infrared Spectra, Aldrich Chemical, Milwakee, Wisconsin, USA (1975).

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