C 2005) Journal of Chemical Crystallography, Vol. 35, No. 3, March 2005 ( DOI: 10.1007/s10870-005-2953-6
Synthesis and crystal structure of 5-allyl-5Hdibenzo[b,f]azepine M.P. Sadashiva,(1) B.H. Doreswamy,(2) Basappa,(1) K.S. Rangappa,(1)∗ M.A. Sridhar,(2) and J. Shashidhara Prasad(2) Received June 3, 2004; accepted October 17, 2004
The crystals 5H-dibenzo[b,f]azepine 2 and 5-allyl-5H-dibenzo[b,f]azepine 3 were synthesized and characterized by X-ray crystallography. The compound 3 is a novel synthon for the construction of unusual isoxazoli(ne)dine rings bearing at the 5th position of dibenzo[b,f]azepine moiety. The compound 2 (C14 H11 N) crystallizes in the orthorhom˚ b = 8.250(7) A, ˚ c= bic space group P21 21 21 with the parameters a = 6.036(1) A, ˚ Z = 4 and the final R factor is R1 = 0.0544. The compound 3 (C17 H15 N) 20.528(4) A, ˚ crystallizes in the Hexagonal space group P61 with the parameters a = 11.043(9) A, ˚ Z = 6 and the final R factor is R1 = 0.0373. c = 18.575 A, KEY WORDS: Dibenzoazepine; allyldibenzoazepine; isoxazoli(ne)dine; crystal structure.
derivatives using 5-allyl-5H-dibenzo[b,f]azepine 3 as a suitable synthon for the construction of biologically active rings such as 5-substituted isoxazoli(ne)dines.6–8 So herein, we report the synthesis and crystal structure of 3 and a known compound crystal structure of 2. The title compound was synthesized as per Scheme 1 and characterized by X-ray diffraction studies.
Introduction Carbamazepine (dibenzo[b,f]azepine-5caarboxamide) has become established as an effective agent in the management of epilepsy, trigeminal neuralgia and effective disorders.1 However, administration of this drug in human is complicated by adverse central nervous system effects and frequent and serious idiosyncratic reactions.2–4 5H-dibenzo[b,f]azepine 2 is a common basic fused tricyclic ring for various therapeutics such as carbamazepine and oxcarbazepine.5 Due to other side effects associated with these antiepileptic drugs, we intend to synthesize dibenzo[b,f]azepine 2
Chemistry Synthesis of 5-allyl-5H-dibenzo[b,f]azepine 3, a novel dipolarophile for the synthesis of dibenzo[b,f]azepine bearing isoxazoli(ne)dines began with the synthesis of dinitroiminodibenzyl using orthonitro toluene. The subsequent reduction, cyclization and dehydrogenation of dinitroiminodibenzyl yielded 2, previously reported by Loiseau et al. The synthesis of 3 is obtained by allylation of the n-terminal dibenzo[b,f]azepine 2
(1)
Department of Studies in Chemistry, University of Mysore, Mysore 570 006, India. (2) Department of Studies in Physics, University of Mysore, Mysore 570 006, India. ∗ To whom correspondence should be addressed; e-mail:
[email protected].
171 C 2005 Springer Science+Business Media, Inc. 1074-1542/05/0300-0171/0
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Sadashiva, Doreswamy, Basappa, Rangappa, Sridhar, and Prasad Synthesis and characterisation of 3
Scheme 1
with allyl bromide in the presence of sodium carbonate (Scheme 1). Reaction condition: (i) allyl bromide, Na2 CO3 and Methanol at 60◦ C (N2 atmosphere). The allylated dibenzo[b,f]azepine 3 is found to be a suitable synthon for the construction of isoxazoli(ne)dine via 1,3-dipolarcycloaddition reactions with the nitrones (aldoximes) and a suitable oxidant/catalyst.9,10 Novel isoxazoli(ne)dines are reported to be the bioisosteric replacements when this ring is incorporated to the nucleotides in place of sugar moiety. We reported various heterocyclic ring fused isoxazoli(ne)dines,11 which enable us to find a new therapeutic agent bearing both the dibenzo[b,f]azepine and the bioactive isoxazoli(ne)dines. Experimental Reaction monitoring and determination of the products were accomplished by TLC. The melting points were determined on SELACO650 hot stage apparatus and are uncorrected. The IR (KBr cm−1 ) spectra were measured on shimadzu 8300 IR spectrophotometer, 1 H NMR were recorded on Shimadzu AMX 400-Bruker, 400 MHz spectrometer by using CDCl3 as solvent and TMS as an internal standard (chemical shift in δ ppm). Elemental analyses were obtained on a Vario-EL instrument. The known compound 2 was prepared by using reported method1 and identified by comparing their spectra and physical data with the authentic sample and finally confirmed by its X-ray crystallographic studies.
Compound dibenzo[b,f]azepine 2 (0.5 g) was dissolved in 10 mL of methanol. Allyl bromide (2 eq. 0.4 mL) and powdered K2 CO3 (2 eq. 0.715 g) were added to the solution and refluxed the mixture for 4–6 h. After completion of the TLC, distilled the methanol and excess ally bromide completely under vacuo. 30 mL of chloroform was added and filtered. The organic layer is concentrated under vacuo and purified through silica gel (eluent n-hexane: ethyl acetate: 4:1). The obtained solid was recrystallized by slow evaporation method using methanol as a solvent. mp: 40–42◦ C. IR KBr (cm−1 ): 1315, 1642, 3040, 3072. 1 H NMR (AMX 400-Bruker, CDCl ): δ 4.4 3 (d, 2H J = 14 Hz), 5.12 (dd, 2H), 5.28 (dd, 2H), 5.8 (m, 1H), 6.76 (s, 2H), 7.08 (d, 2H J = 5 Hz), 6.98–7.12 (q, 4H), 7.2–7.3 (t, 2H) Anal. Calcd for C17 H15 N: C, 87.6; H, 6.49; N, 6.0; Found: C, 87.63; H, 6.43; N, 6.0. Crystal structure determination Single crystals of 2 and 3 of dimensions 0.25 mm × 0.2 mm × 0.2 mm and 0.3 mm × 0.25 mm × 0.2 mm were chosen for X-ray diffraction studies. The measurements were made on a DIPLabo Imaging Plate system with graphite monochromated radiation (MoKα). Thirty six frames of data were collected using oscillation method. Image processing and data reduction were done by using Denzo.12 The structure was solved and refined using maXus13–15 program. For the molecule 2, all the non-hydrogen atoms were revealed in the first map. Full-matrix least-squares refinement based on 1049 observed reflections (I > 2σ (I )) with isotropic temperature factors for all the atoms converged residual to R = 0.1685. Refinement of non-hydrogen atoms with anisotropic thermal parameters was started at this stage. After eight cycles of refinement the residuals saturated
5-allyl-5H-dibenzo[b,f]azepine
173
Table 1. Crystal Data and Structure Refinement for 2 and 3 2 Empirical formula Formula weight Temperature Wavelength Crystal system Space group Cell dimensions
Volume Z Density(calc) Absorption coefficient F000 Crystal size θ range for data collection Index ranges
Reflections collected Independent reflections Refinement method Data/restraints/parameters Goodness-of-fit on F 2 Final R indices [I > 2σ (I )] R indices (all data) Extinction coefficient Largest diff. peak and hole
3
C14 H11 N 193.24 293(2) K 0.71073 A˚ Orthorhombic P21 21 21 a = 6.036(1) A˚ b = 8.250(7) A˚ c = 20.528(4) A˚ 1022.2(3) A˚ 3 4 1.256 Mg/m3 0.073 mm−1 408 0.25 × 0.2 × 0.2 mm 3.17◦ to 23.24◦ −6 ≤ h ≤ 6 −8 ≤ k ≤ 8 −22 ≤ l ≤ 22 1309 1309 [R(int) = 0.0000] Full-matrix least-squares on F 2 1309 / 0 / 137 1.083 R1 = 0.0544, wR2 = 0.1531 R1 = 0.0642, wR2 = 0.1678 0.075(16) 0.302 and −0.413 e.A˚ −3
at R = 0.0544. For the molecule 3, all the non-hydrogen atoms were revealed in the first map. Full-matrix least-squares refinement based on 1496 observed reflections (I > 2σ (I )) with isotropic temperature factors for all the atoms converged residual to R = 0.1426. Refinement of non-hydrogen atoms with anisotropic thermal parameters was started at this stage. After ten cycles of refinement the residuals saturated at R = 0.0373. The hydrogen atoms were placed at calculated positions and were not refined. Table 1 gives the details of crystal data, data collection and refinement. Results and discussion Tables 2 and 3 give the bond distances and angles of non-hydrogen atoms respectively. The
C17 H15 N 233.30
Hexagonal P61 a = 11.043(9) A˚ c = 18.575 A˚
γ = 120◦ 1961.70(16) A˚ 3 6 1.185 Mg/m3 0.069 mm−1 744 0.3 × 0.25 × 0.2 mm 2.13◦ to 21.96◦ −11 ≤ h ≤ 11 −9 ≤ k ≤ 9 −18 ≤ l ≤ 19 3147 1588 [R(int) = 0.0150]
1588 / 1 / 164 1.144 R1 = 0.0373, wR2 = 0.0972 R1 = 0.0461, wR2 = 0.1273 0.077(8) 0.254 and −0.211 e.A˚ −3
bond lengths and bond angles agree with their standard values. Figures 1 and 2 represents the ORTEP16 diagram of the molecules 2 and 3 at 50% probability. The molecules appear stacked when viewed along a axis (Figures 3 and 4). The dihedral angles found between leastsquares planes 1(C2 C3 C4 C5 C6 C7) and 2(C10 C11 C12 C13 C14 C15) of 2, 1(C2 C7) and 2(C10 C15) of 3 are 35.7(2)◦ and 46.29(2)◦ respectively. The maximum deviation from the ˚ for C5 and mean plane 1 of 2 is −0.003(6) A ˚ for C10 in plane 2. The corresp0.012(4) A ˚ for ponding deviations in 3 are −0.014(2) A ˚ C2, and 0.008(4) A for C10 respectively. The seven membered ring of both the molecules are planar with their maximum deviations ˚ and −0.472(2) A, ˚ at N1 by −0.378(2) A respectively.
174
Sadashiva, Doreswamy, Basappa, Rangappa, Sridhar, and Prasad ˚ of 2 and 3 Table 2. Bond Lengths (A) Atoms
Length
Atoms
Length
2 N1 N1 C2 C2 C15 C15 C10 C10 C7
C15 C2 C3 C7 C14 C10 C11 C9 C6
1.409(5) 1.409(5) 1.400(6) 1.396(5) 1.374(6) 1.418(5) 1.404(6) 1.459(6) 1.398(6)
C7 C9 C3 C14 C11 C6 C12 C5
C8 C8 C4 C13 C12 C5 C13 C4
1.467(6) 1.333(3) 1.369(6) 1.383(6) 1.389(7) 1.375(7) 1.367(8) 1.370(8)
N1 N1 N1 C15 C15 C16 C7 C7 C7 C14
C2 C15 C16 C14 C10 C17 C6 C2 C8 C13
1.422(3) 1.428(3) 1.463(3) 1.373(4) 1.401(4) 1.486(4) 1.404(5) 1.401(4) 1.455(5) 1.392(5)
C11 C11 C3 C3 C13 C10 C9 C6 C17 C4
C12 C10 C4 C2 C12 C9 C8 C5 C18 C5
1.347(6) 1.408(6) 1.374(4) 1.376(4) 1.351(6) 1.448(5) 1.308(6) 1.370(6) 1.290(4) 1.355(6)
3
Fig. 1. ORTEP diagram of the molecule at 50% probability 2.
Table 3. Bond Angles (◦ ) of 2 and 3 Atoms
Angle
Atoms
Angle
2 C15 C3 C3 C7 C14 C14 N1 C11 C11 C15 C2 C2
N1 C2 C2 C7 C2 N1 C2 N1 C15 N1 C15 C10 C15 C10 C10 C15 C10 C9 C10 C9 C7 C6 C7 C8
124.1(2) 118.6(5) 118.7(4) 122.5(4) 119.2(3) 119.7(5) 121.0(4) 117.0(5) 120.2(5) 122.8(5) 117.5(5) 122.8(5)
C6 C8 C4 C9 C13 C12 C5 C13 C4 C12 C5
C7 C8 C9 C10 C3 C2 C8 C7 C14 C15 C11 C10 C6 C7 C12 C11 C5 C6 C13 C14 C4 C3
119.8(5) 130.0(5) 121.3(4) 128.8(5) 122.6(4) 121.3(6) 124.0(6) 121.0(6) 117.0(6) 118.2(5) 121.5(5)
C2 C2 C15 C14 C14 C10 N1 C6 C6 C2 C15 C12 C4 C3
N1 C15 N1 C16 N1 C16 C15 C10 C15 N1 C15 N1 C16 C17 C7 C2 C7 C8 C7 C8 C14 C13 C11 C10 C3 C2 C2 C7
117.5(2) 116.7(2) 116.2(2) 119.8(2) 121.4(2) 118.8(2) 111.3(2) 117.1(3) 119.9(3) 123.0(3) 121.1(3) 123.1(3) 120.9(3) 119.5(2)
C3 C7 C12 C11 C11 C15 C8 C9 C5 C18 C5 C4 C11
C2 N1 C2 N1 C13 C14 C10 C15 C10 C9 C10 C9 C9 C10 C8 C7 C6 C7 C17 C16 C4 C3 C5 C6 C12 C13
121.0(2) 119.2(2) 119.8(3) 116.5(3) 120.2(3) 123.3(3) 128.4(3) 127.5(3) 122.7(3) 125.6(4) 121.3(3) 118.4(3) 119.8(3)
Fig. 2. ORTEP diagram of the molecule at 50% probability 3.
3
Fig. 3. Packing of the molecules of 2 down a axis.
Fig. 4. Packing of the molecules of 3 down a axis.
5-allyl-5H-dibenzo[b,f]azepine Acknowledgments The authors would like to express their thanks to DST, Government of India for financial assistance under the project SP/I2/FOO/93. Supplementary material CCDC no’s. 239892, 239894 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033; e-mail:
[email protected]].
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