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Chapter 5
Acrylonitrile derivatives
Acrylonitrile is a structurally novel compound. The use of the nitrile func-tion for C-C bond formation reaction occupies an important position inorganic chemistry. 2,3-disubstituted acrylonitriles represent an interest-ing class of biologically active compounds and are capable of undergoingmany useful organic transformations and many have been transformed intobioactive heterocycles [1]. It is well known that acrylonitriles are usefulintermediates in organic synthesis and capable of undergoing many use-ful organic transformations [2] and have been transformed into pyrazole,isoxazole and pyrimidine derivatives [3]. Many derivatives of acryloni-triles have been shown to possess anti-tumor [4], anti-tubercular, and anti-proliferative activities [5]. It is found from the literature that, the olefinicbond had Z-configuration irrespective of the size of the substituents on theheterocyclic rings. Recently, the crystal structures of some bioactive het-eroarylacrylonitriles, which reflect the olefinic bond geometry, and otherstructural details of the molecules have been reported [6].
161
162 Acrylonitrile derivatives
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile
The compound (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile (9), wassynthesised and crystallised according to the procedure reported in the [10].
5.1.1 Crystal and Molecular Structure
Experimentally data is collected and the same is reduced as explained insection 3.1 of chapter 3. The crystal data and structure refinement detailsare given in table 5.1.1. The values of Rint and Rsigma are 0.0407 and0.0489 respectively. The structure was solved using SHELXS-97. 2000phase sets were refined with the best phase set having a CFOM of 0.0542.Using the normalised structure factors with these phases, a total of 1731phases were generated with the final RE value of 21.9%.
The non-hydrogen atoms were refined anisotropically. The hydrogenatoms were fixed at chemically acceptable positions and were allowed toride on the parent atom during successive refinements. 328 parameterswere refined with 7204 reflections using SHELXL-97. ORTEP of themolecule is shown in figure 5.1.1 and 5.1.2.
The atomic coordinates and equivalent thermal parameters of non-hydrogen atoms of 9A and 9B are listed in the tables 5.1.2 and 5.1.3respectively. Tables 5.1.4 and 5.1.5 list the atomic coordinates and equiv-alent thermal parameters of hydrogen atoms of 9A and 9B respectively.The anisotropic thermal parameters of the non-hydrogen atoms of 9A and9B are listed in the tables 5.1.6 and 5.1.7 respectively. The bond lengthsof 9A and 9B are listed in tables 5.1.8 and 5.1.8 respectively. The bondangles of 9A and 9B are listed in tables 5.1.10 and 5.1.11 respectively. Se-lected torsion angles are listed in the tables 5.1.12 and 5.1.13 for 9A and9B respectively.
The packing of the molecules down a, b and c axes are shown in figures5.1.3 to 5.1.5 respectively.
There are two molecules in the asymmetric unit. In the molecule,the olefinic bond connecting the 4-methoxyphenyl acrylonitrile and phenylgroups has Z geometry. Significant deviations from the ideal bond-anglegeometry around the Csp2 atoms of the double bond are observed. Thebond angles in 9A, C13A-C12A=C9A equal to 130.39(2)◦ , C12A=C9A-C6A equal to 125.10(2)◦ and C10A-C9A-C6A equal to 114.1(2)◦
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 163
(in 9B, C13B-C12B=C9B equal to 130.4(2)◦ , C12B= C9B-C6B equalto 124.6(2)◦ and C10B-C9B-C6B equal to 114.6(2)◦) are distorted dueto the steric hindrance of the double bond linking the two ring systems.The olefinic double bond bearing the three conjugated substituents inthe molecule has a length of 1.345(2) A which is comparable with (Z)-2-(3-Thienyl)-3-(3,4,5-trimethoxy-phenyl) acrylonitrile with bond length1.353(3) A [7], and 2-styrylbenzimidazole with bond length 1.304(4) A [8],suggesting some delocalization in the unsaturated bridging unit [10].
The O-CH3 group substituted on ring 1 (phenylacrylonitrile) is in anti-periplanar conformation with respect to the phenyl ring C3-C4-C5-C6-C7-C8 as the torsion angle about atoms C4-C3-O2-C1 is 178.3(2)◦ in 9Aand 177.3(2)◦ in 9B. The oxygen atom O2 of this molecule participatesin intermolecular hydrogen bonding. The torsion angle of 23.14(2)◦ in9A and 26.59(2)◦ in 9B about the atoms C5-C6-C9-C10 indicates thesyn-periplanar conformation of acrylonitrile group with respect to themethoxyphenyl ring.
The plane of the olefinic double bond deviates with that of the sub-stituted phenyl ring which is given by the torsion angle of 23.5(3)◦ aboutthe atoms C9A=C12A-C13A-C14A in 9A and 25.0(3)◦ about the atomsC9B=C12B-C13B-C14B in 9B. This deviation is minimun in 9 when com-pared to the other three molecules studied in this class.
The structure exhibits intermolecular hydrogen bonds of the type C-H· · ·O which helps in stabilizing the crystal structure. The details of thisare given in the table 5.1.14. The molecules form hydrogen binded dimersand are stacked in pairs.
164 Acrylonitrile derivatives
Table 5.1.1: Crystal and structure refinement data for 9.
Empirical formula C16H13NOFormula weight 235.27Temperature 293(2)KWavelength 0.71073 ACrystal system TriclinicSpace group P1Cell dimensions
a = 7.362(9) Ab = 11.859(1) Ac = 14.481(1) Aα = 89.658(6)◦
β = 82.467(6)◦
γ = 89.604(5)◦
Volume 1253.3(2) A3
Z 4Density(calculated) 1.247 Mg/m3
Absorption coefficient 0.078 mm−1
F000 496Crystal size 0.3 × 0.27 × 0.25 mmθ range for data collection 2.22◦ to 32.45◦
Index ranges −11 ≤ h ≤ 11−17 ≤ k ≤ 17−20 ≤ l ≤ 20
Reflections collected 11308Independent reflections 7204 [Rint = 0.0425]Refinement method Full-matrix least-squares on F 2
Data / restraints / parameters 7204 / 0 / 328Goodness-of-fit on F 2 1.068Final R indices [I > 2σ(I)] R1 = 0.0595, wR2 = 0.1528R indices (all data) R1 = 0.1048, wR2 = 0.1925Extinction coefficient 0.079(8)
Largest diff. peak and hole 0.297 and −0.236 e. A−3
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 165
Table 5.1.2: Atomic coordinates and equivalent thermal parameters of thenon-hydrogen atoms for 9A.
Atom x y z Ueq
C1A 0.2925(4) 0.1649(2) 1.0317(2) 0.0730(6)O2A 0.3440(2) 0.2492(1) 0.9633(9) 0.0642(4)C3A 0.3187(2) 0.2273(1) 0.8737(1) 0.0486(4)C4A 0.3664(3) 0.3134(1) 0.8099(1) 0.0512(4)C5A 0.3396(2) 0.3016(1) 0.7184(1) 0.0484(4)C6A 0.2667(2) 0.2029(1) 0.6865(1) 0.0441(4)C7A 0.2213(2) 0.1174(1) 0.7514(1) 0.0493(4)C8A 0.2465(3) 0.1281(1) 0.8436(1) 0.0510(4)C9A 0.2404(2) 0.1904(1) 0.5871(1) 0.0460(4)C10A 0.2255(3) 0.2955(2) 0.5388(1) 0.0556(4)N11A 0.2127(3) 0.3821(2) 0.5055(1) 0.0844(6)C12A 0.2357(3) 0.0917(2) 0.5423(1) 0.0500(4)C13A 0.2161(2) 0.0682(1) 0.4450(1) 0.0475(4)C14A 0.1362(3) 0.1413(2) 0.3862(1) 0.0555(4)C15A 0.1309(3) 0.1148(2) 0.2941(1) 0.0604(5)C16A 0.2049(3) 0.0142(2) 0.2585(1) 0.0601(5)C17A 0.2809(3) −0.0602(2) 0.3154(1) 0.0611(5)C18A 0.2852(3) −0.0344(2) 0.4084(1) 0.0555(4)
Ueq = (1/3)∑
i
∑
jUij(a
∗i a
∗j )(ai · aj)
166 Acrylonitrile derivatives
Table 5.1.3: Atomic coordinates and equivalent thermal parameters of thenon-hydrogen atoms for 9B.
Atom x y z Ueq
C1B 0.2982(3) 0.6606(2) 0.4995(1) 0.0667(5)O2B 0.3439(2) 0.7468(1) 0.5601(9) 0.0595(4)C3B 0.3113(2) 0.7272(1) 0.6537(1) 0.0458(4)C4B 0.3654(2) 0.8117(1) 0.7098(1) 0.0486(4)C5B 0.3350(2) 0.8014(1) 0.8049(1) 0.0478(4)C6B 0.2512(2) 0.7058(1) 0.8478(1) 0.0438(4)C7B 0.1964(2) 0.6225(1) 0.7902(1) 0.0496(4)C8B 0.2260(3) 0.6319(1) 0.6944(1) 0.0501(4)C9B 0.2290(2) 0.6927(1) 0.9505(1) 0.0467(4)C10B 0.2199(3) 0.7972(2) 1.0012(1) 0.0560(4)N11B 0.2134(3) 0.8835(2) 1.0357(1) 0.0865(7)C12B 0.2281(2) 0.5927(2) 0.9958(1) 0.0496(4)C13B 0.2174(2) 0.5676(1) 1.0951(1) 0.0455(4)C14B 0.1399(3) 0.6386(2) 1.1661(1) 0.0524(4)C15B 0.1429(3) 0.6093(2) 1.2583(1) 0.0578(5)C16B 0.2204(3) 0.5092(2) 1.2823(1) 0.0585(5)C17B 0.2953(3) 0.4374(2) 1.2129(1) 0.0589(5)C18B 0.2926(3) 0.4652(2) 1.1207(1) 0.0530(4)
Ueq = (1/3)∑
i
∑
jUij(a
∗i a
∗j )(ai · aj)
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 167
Table 5.1.4: Atomic coordinates and equivalent thermal parameters of thehydrogen atoms for both 9A.
Atom x y z Uiso
H1A1 0.1645 0.1487 1.0334 0.110H1A2 0.3151 0.1915 1.0916 0.110H1A3 0.3630 0.0976 1.0164 0.110H4A 0.4169 0.3795 0.8293 0.061H5A 0.3705 0.3606 0.6768 0.058H7A 0.1724 0.0508 0.7320 0.059H8A 0.2154 0.0694 0.8853 0.061H12A 0.2466 0.0280 0.5791 0.060H14A 0.0855 0.2091 0.4095 0.067H15A 0.0773 0.1647 0.2557 0.073H16A 0.2032 −0.0029 0.1960 0.072H17A 0.3298 −0.1282 0.2917 0.073H18A 0.3347 −0.0862 0.4468 0.067
Table 5.1.5: Atomic coordinates and equivalent thermal parameters of thehydrogen atoms for both 9B.
Atom x y z Uiso
H1B1 0.3684 0.5939 0.5085 0.100H1B2 0.3252 0.6857 0.4360 0.100H1B3 0.1699 0.6441 0.5129 0.100H4B 0.4227 0.8757 0.6828 0.058H5B 0.3708 0.8592 0.8416 0.057H7B 0.1382 0.5587 0.8170 0.060H8B 0.1891 0.5747 0.6574 0.060H12B 0.2354 0.5298 0.9575 0.060H14B 0.0858 0.7063 1.1513 0.063H15B 0.0917 0.6579 1.3049 0.069H16B 0.2223 0.4902 1.3446 0.070H17B 0.3481 0.3696 1.2285 0.071H18B 0.3416 0.4152 1.0746 0.064
168 Acrylonitrile derivatives
Table 5.1.6: Anisotropic thermal parameters of the non-hydrogen atomsfor both 9A.
Atom U11 U22 U33 U12 U13 U23
C1A 0.095(2) 0.075(1) 0.052(1) -0.017(1) -0.020(1) 0.004(1)O2A 0.094(1) 0.054(7) 0.047(7) -0.013(7) -0.017(6) -0.005(6)C3A 0.054(1) 0.046(9) 0.047(9) -0.001(7) -0.010(7) -0.008(7)C4A 0.060(1) 0.040(8) 0.055(1) -0.009(7) -0.010(7) -0.007(7)C5A 0.054(1) 0.040(8) 0.052(1) -0.005(7) -0.007(7) -0.001(7)C6A 0.043(9) 0.042(8) 0.048(9) -0.001(6) -0.008(6) -0.004(7)C7A 0.056(1) 0.042(8) 0.051(1) -0.010(7) -0.009(7) -0.007(7)C8A 0.064(1) 0.041(8) 0.048(1) -0.007(7) -0.007(7) -0.002(7)C9A 0.046(9) 0.046(8) 0.047(9) -0.002(6) -0.008(6) -0.001(7)C10A 0.067(1) 0.049(1) 0.053(1) -0.005(8) -0.017(8) -0.001(8)N11A 0.129(2) 0.057(1) 0.075(1) -0.009(1) -0.039(1) 0.008(1)C12A 0.057(1) 0.047(9) 0.047(9) -0.001(7) -0.010(7) -0.002(8)C13A 0.049(9) 0.047(9) 0.047(9) -0.004(7) -0.007(7) -0.005(7)C14A 0.060(1) 0.055(1) 0.053(1) 0.008(8) -0.015(8) -0.009(8)C15A 0.065(1) 0.068(1) 0.052(1) -0.000(9) -0.019(8) -0.004(9)C16A 0.066(1) 0.070(1) 0.046(1) -0.009(9) -0.009(8) -0.010(9)C17A 0.067(1) 0.053(1) 0.063(1) -0.004(9) -0.007(9) -0.017(9)C18A 0.064(1) 0.045(9) 0.059(1) -0.004(8) -0.012(8) -0.007(8)
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 169
Table 5.1.7: Anisotropic thermal parameters of the non-hydrogen atomsfor both 9B.
Atom U11 U22 U33 U12 U13 U23
C1B 0.082(2) 0.069(1) 0.049(1) -0.011(1) -0.008(9) -0.011(1)O2B 0.081(1) 0.055(7) 0.044(7) -0.011(6) -0.008(6) 0.000(6)C3B 0.050(9) 0.046(8) 0.042(9) -0.001(7) -0.007(6) -0.000(7)C4B 0.054(1) 0.041(8) 0.052(1) -0.007(7) -0.008(7) 0.002(7)C5B 0.055(1) 0.039(8) 0.051(1) -0.005(7) -0.012(7) -0.006(7)C6B 0.046(9) 0.041(8) 0.045(9) -0.003(6) -0.007(6) -0.004(7)C7B 0.056(1) 0.045(8) 0.049(1) -0.012(7) -0.010(7) -0.001(7)C8B 0.060(1) 0.044(8) 0.048(9) -0.010(7) -0.011(7) -0.005(7)C9B 0.049(9) 0.044(8) 0.047(9) -0.003(7) -0.007(6) -0.008(7)C10B 0.070(1) 0.048(9) 0.049(1) -0.005(8) -0.003(8) -0.004(8)N11B 0.134(2) 0.055(1) 0.066(1) -0.011(1) 0.006(1) -0.013(9)C12B 0.056(1) 0.045(9) 0.048(9) -0.001(7) -0.007(7) -0.007(7)C13B 0.048(9) 0.046(8) 0.043(9) -0.004(7) -0.006(6) -0.002(7)C14B 0.054(1) 0.054(1) 0.048(1) 0.006(8) -0.004(7) -0.004(8)C15B 0.061(1) 0.067(1) 0.044(1) 0.001(9) -0.002(7) -0.007(9)C16B 0.063(1) 0.067(1) 0.047(1) -0.010(9) -0.012(8) 0.008(9)C17B 0.066(1) 0.050(1) 0.062(1) -0.001(8) -0.012(9) 0.006(9)C18B 0.063(1) 0.044(9) 0.051(1) -0.001(7) -0.005(8) -0.002(8)
170 Acrylonitrile derivatives
Figure 5.1.1: ORTEP of the residue A of the molecule 9 at 50% probability.
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 171
Figure 5.1.2: ORTEP of the residue B of the molecule 9 at 50% probability.
172 Acrylonitrile derivatives
Table 5.1.8: Bond Lengths of 9A (A).
Atoms Length Atoms Length
C1A-O2A 1.421(3) C10A-N11A 1.141(2)O2A-C3A 1.361(2) C12A-C13A 1.463(2)C3A-C4A 1.389(3) C13A-C14A 1.393(3)C3A-C8A 1.390(2) C13A-C18A 1.397(2)C4A-C5A 1.373(2) C14A-C15A 1.378(2)C5A-C6A 1.398(2) C15A-C16A 1.382(3)C6A-C7A 1.391(2) C16A-C17A 1.370(3)C6A-C9A 1.485(2) C17A-C18A 1.386(3)C7A-C8A 1.378(2) C9A-C10A 1.436(2)C9A-C12A 1.345(2)
Table 5.1.9: Bond Lengths of 9B (A).
Atoms Length Atoms Length
C1B-O2B 1.421(2) C9B-C10B 1.441(2)O2B-C3B 1.364(2) C10B-N11B 1.139(2)C3B-C8B 1.388(2) C12B-C13B 1.458(2)C3B-C4B 1.388(2) C13B-C14B 1.394(2)C4B-C5B 1.371(2) C13B-C18B 1.399(2)C5B-C6B 1.397(2) C14B-C15B 1.380(3)C6B-C7B 1.393(2) C15B-C16B 1.376(3)C6B-C9B 1.483(2) C16B-C17B 1.376(3)C7B-C8B 1.380(2) C17B-C18B 1.377(3)C9B-C12B 1.350(2)
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 173
Table 5.1.10: Bond Angles of 9A (◦).
Atoms Angle Atoms Angle
C3A-O2A-C1A 118.0(2) C12A-C9A-C6A 125.1(2)O2A-C3A-C4A 115.8(1) C10A-C9A-C6A 114.1(1)O2A-C3A-C8A 124.9(2) N11A-C10A-C9A 175.9(2)C4A-C3A-C8A 119.2(2) C9A-C12A-C13A 130.4(2)C5A-C4A-C3A 120.4(2) C14A-C13A-C18A 117.8(2)C4A-C5A-C6A 121.4(2) C14A-C13A-C12A 124.8(2)C7A-C6A-C5A 117.2(2) C18A-C13A-C12A 117.4(2)C7A-C6A-C9A 121.8(1) C15A-C14A-C13A 121.0(2)C5A-C6A-C9A 121.0(2) C14A-C15A-C16A 120.2(2)C8A-C7A-C6A 122.1(2) C17A-C16A-C15A 119.9(2)C7A-C8A-C3A 119.6(2) C16A-C17A-C18A 120.2(2)C12A-C9A-C10A 120.8(2) C17A-C18A-C13A 120.9(2)
Table 5.1.11: Bond Angles of 9B (◦).
Atoms Angle Atoms Angle
C3B-O2B-C1B 117.9(1) C12B-C9B-C6B 124.6(2)O2B-C3B-C8B 124.6(2) C10B-C9B-C6B 114.6(2)O2B-C3B-C4B 115.8(1) N11B-C10B-C9B 175.4(2)C8B-C3B-C4B 119.6(2) C9B-C12B-C13B 130.4(2)C5B-C4B-C3B 120.4(2) C14B-C13B-C18B 117.7(2)C4B-C5B-C6B 121.3(1) C14B-C13B-C12B 124.8(2)C7B-C6B-C5B 117.4(2) C18B-C13B-C12B 117.5(2)C7B-C6B-C9B 121.8(1) C15B-C14B-C13B 120.5(2)C5B-C6B-C9B 120.8(1) C16B-C15B-C14B 121.0(2)C8B-C7B-C6B 121.9(2) C17B-C16B-C15B 119.2(2)C7B-C8B-C3B 119.5(2) C16B-C17B-C18B 120.5(2)C12B-C9B-C10B 120.7(2) C17B-C18B-C13B 121.0(2)
174 Acrylonitrile derivatives
Table 5.1.12: Torsion Angles of 9A (◦).
Atoms Angle
C4A-C3A-O2A-C1A 178.3(2)C5A-C6A-C9A-C12A 154.9(2)C7A-C6A-C9A-C12A −24.8(3)C9A-C12A-C13A-C18A 155.5(2)C7A-C6A-C9A-C10A 157.2(2)C9A-C12A-C13A-C14A −23.5(3)
Table 5.1.13: Torsion Angles of 9B (◦).
Atoms Angle
C4B-C3B-O2B-C1B 177.3(2)C5B-C6B-C9B-C12B −149.5(2)C7B-C6B-C9B-C12B 28.1(2)C9B-C12B-C13B-C18B −154.2(2)C7B-C6B-C9B-C10B −155.9(2)C9B-C12B-C13B-C14B 25.0(3)
Table 5.1.14: Hydrogen bond geometry for 9 (A, ◦).
Atoms D–H· · ·A Angle
C18A–H18A· · ·O2B1 3.451(2) 158C18B–H18B· · · O2A 3.425(2) 157
Symmetry1. x, − 1 + y, z
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 175
Figure 5.1.3: Packing of the molecules of 9 when viewed down a-axis.
176 Acrylonitrile derivatives
Figure 5.1.4: Packing of the molecules of 9 when viewed down b-axis.
5.1 (Z)-2-(4-Methoxyphenyl)-3-phenyl acrylonitrile 177
Figure 5.1.5: Packing of the molecules of 9 when viewed down c-axis.
178 Acrylonitrile derivatives
5.2 3-(2-Chloro-6-fluoro phenyl)-2-(4-methoxyphenyl)
acrylonitrile
The synthesis and crystallisation of 3-(2-Chloro-6-fluoro phenyl) -2-(4-methoxyphenyl) acrylonitrile (10), was done according to the procedurereported in the [13].
5.2.1 Crystal and Molecular Structure
For data collection and data reduction, the experimental procedure fol-lowed is explained in section 3.1 of chapter 3. The crystal data and struc-ture refinement details are given in table 5.2.1. The values of Rint andRsigma are 0.0733 and 0.1283 respectively. The structure was solved usingSHELXS-97. 2000 phase sets were refined with the best phase set hav-ing a CFOM of 0.0488. Using the normalised structure factors with thesephases, a total of 1384 phases were generated with the final RE value of22.7%.
The non-hydrogen atoms were refined anisotropically. The hydrogenatoms were fixed at chemically acceptable positions and were allowed toride on the parent atom during successive refinements. 183 parameterswere refined with 2790 reflections using SHELXL-97. ORTEP of themolecule is shown in figure 5.2.1.
The atomic coordinates and equivalent thermal parameters of non-hydrogen and hydrogen atoms are listed in the tables 5.2.2 and 5.2.3 re-spectively. Table 5.2.4 gives the anisotropic thermal parameters of thenon-hydrogen atoms. The bond lengths and bond angles are listed in ta-bles 5.2.5 and 5.2.6 respectively. Selected torsion angles are listed in thetable 5.2.7.
Figures 5.2.2 to 5.2.4 show the packing of the molecules down a, b andc axes respectively.
The dihedral angle between the least squares planes of the methoxyphe-nyl ring and the chlorofluorophenyl ring is 57.43(19)◦ . This value is largewhen compared to the corresponding value for other three molecules ofacrylonitrile derivatives studied here. This might be due to the sterichindrance caused by the bulky chloro and the fluoro groups at the secondand sixth position of the phenyl ring C13-C14-C15-C16-C17-C18.
5.2 3-(2-Chloro-6-fluoro phenyl)-2-(4-methoxyphenyl) acrylonitrile 179
The olefinic bond connecting the 4-methoxyphenyl acrylonitrile and 2-chloro-6-fluorophenyl groups has Z geometry. Significant deviations fromthe ideal bond-angle geometry around the Csp2 atoms of the double bondare observed. The bond angles C13-C12=C9 is 127.6(4)◦ , C12=C9-C6is 124.4(4)◦ and C10-C9-C6 is 115.6(3)◦ are distorted due to the sterichindrance caused by the electronic effect of the double bond linking thetwo ring systems. The olefinic double bond bearing the three conjugatedsubstituents has a length of 1.345(6) A which is slightly lesser than thecorresponding value of 1.353(3) A and greater than 1.304(4) A reportedfor (Z)-2-(3-Thienyl)-3-(3,4,5-trimethoxyphenyl)-acrylonitrile [7], and 2-styrylbenzimidazole [8] respectively indicating some delocalization in theunsaturated bridging units [13].
The torsion angle of 136.4(4)◦ about the atoms C9=C12-C13-C14 in-dicates the deviation of 2-chloro-6-fluoro phenyl ring from the plane of theolefinic double bond. The torsion angle value of 179.1(4)◦ for the planecontaining the atoms C1-O2-C3-C4 indicates the anti-periplanar confor-mation of the methoxy group with the phenyl ring C3-C4-C5-C6-C7-C8 asin other molecules. Similarly, the acrylonitrile group is in syn-periplanarconformation (C5-C6-C9-C10) with respect to the methoxyphenyl ring asin other three molecules.
The structure exhibits intermolecular hydrogen bond of the type C-H· · ·N (table 5.2.8). The packing of the molecules indicates that the mole-cules are stacked in pairs and they are interlinked by hydrogen bonds toform a linear polymeric chain.
180 Acrylonitrile derivatives
Table 5.2.1: Crystal and structure refinement data for 10.
Empirical formula C16H11ClFNOFormula weight 287.71Temperature 293(2)KWavelength 0.71073 ACrystal system OrthorhombicSpace group Pca21
Cell dimensionsa = 29.143(3) Ab = 4.129(2) Ac = 11.205(4) A
Volume 1348.3(7) A3
Z 4Density(calculated) 1.417 Mg/m3
Absorption coefficient 0.288 mm−1
F000 592Crystal size 0.3 × 0.27 × 0.25 mmθ range for data collection 3.34◦ to 32.45◦
Index ranges −43 ≤ h ≤ 44−4 ≤ k ≤ 4−13 ≤ l ≤ 14
Reflections collected 1645Independent reflections 1048 [Rint = 0.0199]Refinement method Full-matrix least-squares on F 2
Data / restraints / parameters 2790 / 1 / 183Goodness-of-fit on F 2 1.060Final R indices [I > 2σ(I)] R1 = 0.0494, wR2 = 0.1257R indices (all data) R1 = 0.0865, wR2 = 0.1609Absolute structure parameter 0.44(12)Extinction coefficient 0.039(5)Largest diff. peak and hole 0.168 and −0.302 e. A−3
5.2 3-(2-Chloro-6-fluoro phenyl)-2-(4-methoxyphenyl) acrylonitrile 181
Table 5.2.2: Atomic coordinates and equivalent thermal parameters of thenon-hydrogen atoms for 10.
Atom x y z Ueq
C1 0.3968(1) −0.6840(1) 0.4638(6) 0.0717(1)O2 0.4178(8) −0.5023(7) 0.3702(3) 0.0710(1)C3 0.4619(1) −0.4034(8) 0.3845(4) 0.0538(1)C4 0.4888(1) −0.4751(9) 0.4829(5) 0.0601(1)C5 0.5345(1) −0.3739(9) 0.4865(5) 0.0611(1)C6 0.5536(1) −0.2000(7) 0.3933(4) 0.0501(1)C7 0.5256(1) −0.1246(9) 0.2972(4) 0.0578(1)C8 0.4805(1) −0.2238(9) 0.2918(5) 0.0592(1)C9 0.6024(1) −0.0925(8) 0.3966(4) 0.0500(9)C10 0.6193(1) 0.0500(9) 0.2893(5) 0.0596(1)N11 0.6303(1) 0.1680(1) 0.2015(6) 0.0810(1)C12 0.6300(1) −0.1182(8) 0.4925(5) 0.0569(1)C13 0.6789(1) −0.0360(8) 0.5005(4) 0.0509(1)C14 0.6964(1) 0.1312(9) 0.5975(5) 0.0563(1)C15 0.7426(1) 0.2037(9) 0.6112(5) 0.0660(1)C16 0.7728(1) 0.0989(1) 0.5239(5) 0.0702(1)C17 0.7578(1) −0.0738(1) 0.4284(5) 0.0655(1)C18 0.7116(1) −0.1367(9) 0.4186(4) 0.0562(1)F19 0.6976(7) −0.3176(6) 0.3245(3) 0.0752(9)Cl20 0.6581(3) 0.2641(3) 0.7074(2) 0.0698(4)
Ueq = (1/3)∑
i
∑
jUij(a
∗i a
∗j )(ai · aj)
182 Acrylonitrile derivatives
Table 5.2.3: Atomic coordinates and equivalent thermal parameters of thehydrogen atoms for 10.
Atom x y z Uiso
H1A 0.4141 −0.8778 0.4780 0.108H1B 0.3660 −0.7404 0.4411 0.108H1C 0.3960 −0.5558 0.5353 0.108H4 0.4765 −0.5904 0.5465 0.072H5 0.5524 −0.4242 0.5526 0.073H7 0.5376 −0.0035 0.2346 0.069H8 0.4626 −0.1703 0.2261 0.071H12 0.6164 −0.1970 0.5618 0.068H15 0.7530 0.3195 0.6771 0.079H16 0.8038 0.1475 0.5308 0.084H17 0.7782 −0.1478 0.3709 0.079
5.2 3-(2-Chloro-6-fluoro phenyl)-2-(4-methoxyphenyl) acrylonitrile 183
Table 5.2.4: Anisotropic thermal parameters of the non-hydrogen atomsfor 10.
Atom U11 U22 U33 U12 U13 U23
C1 0.050(2) 0.083(3) 0.082(4) -0.011(2) 0.008(2) -0.006(2)O2 0.046(1) 0.087(2) 0.080(3) -0.010(1) -0.007(1) 0.006(2)C3 0.043(1) 0.062(2) 0.057(4) -0.000(1) -0.002(2) -0.004(2)C4 0.057(2) 0.072(2) 0.051(4) -0.004(1) -0.002(2) 0.013(2)C5 0.052(2) 0.075(2) 0.056(4) -0.006(1) -0.010(2) 0.013(2)C6 0.042(1) 0.060(2) 0.049(3) 0.001(1) -0.002(1) 0.000(2)C7 0.050(2) 0.075(2) 0.048(4) -0.003(1) -0.001(2) 0.006(2)C8 0.048(2) 0.078(2) 0.052(4) 0.001(1) -0.008(2) 0.003(2)C9 0.042(1) 0.061(2) 0.047(3) 0.002(1) -0.001(1) 0.004(2)C10 0.046(2) 0.076(2) 0.056(4) -0.002(1) -0.001(2) 0.002(2)N11 0.068(2) 0.108(3) 0.067(4) -0.010(2) 0.007(2) 0.019(3)C12 0.045(2) 0.072(2) 0.055(4) 0.000(1) 0.004(2) 0.004(2)C13 0.042(1) 0.062(2) 0.048(3) 0.001(1) -0.004(1) 0.006(2)C14 0.053(2) 0.070(2) 0.046(4) 0.003(1) -0.003(2) 0.006(2)C15 0.059(2) 0.084(2) 0.055(4) -0.010(2) -0.014(2) 0.003(2)C16 0.045(2) 0.090(3) 0.075(5) -0.008(2) -0.008(2) 0.012(3)C17 0.046(2) 0.085(2) 0.066(4) 0.005(1) 0.004(2) 0.010(2)C18 0.052(2) 0.062(2) 0.055(4) 0.002(1) -0.000(2) -0.001(2)F19 0.062(1) 0.093(2) 0.071(3) 0.008(1) 0.003(1) -0.023(1)Cl20 0.069(5) 0.090(6) 0.050(1) 0.008(4) -0.002(5) -0.004(6)
184 Acrylonitrile derivatives
Figure 5.2.1: ORTEP of the molecule 10 at 50% probability.
5.2 3-(2-Chloro-6-fluoro phenyl)-2-(4-methoxyphenyl) acrylonitrile 185
Table 5.2.5: Bond Lengths of 10 (A).
Atoms Length Atoms Length
C1-O2 1.427(6) C10-N11 1.143(7)O2-C3 1.360(4) C12-C13 1.470(4)C3-C4 1.385(6) C13-C14 1.385(6)C3-C8 1.386(6) C13-C18 1.385(6)C4-C5 1.395(5) C14-C15 1.387(5)C5-C6 1.384(6) C14-Cl20 1.750(5)C6-C7 1.386(6) C15-C16 1.385(7)C6-C9 1.490(4) C16-C17 1.359(7)C7-C8 1.379(5) C17-C18 1.375(5)C9-C12 1.346(6) C18-F19 1.354(5)C9-C10 1.426(7)
Table 5.2.6: Bond Angles of 10 (◦).
Atoms Angle Atoms Angle
C3-O2-C1 118.5(4) N11-C10-C9 176.0(4)O2-C3-C4 124.4(4) C9-C12-C13 127.5(4)O2-C3-C8 116.2(4) C14-C13-C18 114.7(3)C4-C3-C8 119.3(3) C14-C13-C12 121.3(4)C3-C4-C5 119.9(4) C18-C13-C12 123.8(4)C6-C5-C4 121.2(4) C13-C14-C15 123.4(4)C5-C6-C7 117.7(3) C13-C14-Cl20 118.3(3)C5-C6-C9 121.4(4) C15-C14-Cl20 118.3(4)C7-C6-C9 120.9(4) C16-C15-C14 118.1(5)C8-C7-C6 121.9(4) C17-C16-C15 121.1(4)C7-C8-C3 119.9(4) C16-C17-C18 118.5(4)C12-C9-C10 120.0(3) F19-C18-C17 117.4(4)C12-C9-C6 124.4(4) F19-C18-C13 118.4(3)C10-C9-C6 115.6(4) C17-C18-C13 124.2(4)
186 Acrylonitrile derivatives
Table 5.2.7: Torsion Angles of 10 (◦).
Atoms Angle Atoms Angle
C4-C3-O2-C1 2.0(5) C14-C13-C18-F19 176.4(3)C7-C6-C9-C10 −8.2(5) C7-C6-C9-C12 170.8(4)C9-C12-C13-C14 136.4(4) C12-C13-C14-Cl20 −3.6(5)C6-C9-C12-C13 176.1(3) C10-C9-C12-C13 −4.9(6)C7-C6-C9-C10 −8.2(5) C5-C6-C9-C12 −8.2(5)
Table 5.2.8: Hydrogen bond geometry for 10 (A, ◦).
Atoms D–H· · ·A Angle
C20–H20C· · ·N111 3.498(7) 162
Symmetry1. 1 − x,−y, 1/2 + z
5.2 3-(2-Chloro-6-fluoro phenyl)-2-(4-methoxyphenyl) acrylonitrile 187
Figure 5.2.2: Packing of the molecules of 10 when viewed down a-axis.
188 Acrylonitrile derivatives
Figure 5.2.3: Packing of the molecules of 10 when viewed down b-axis.
5.2 3-(2-Chloro-6-fluoro phenyl)-2-(4-methoxyphenyl) acrylonitrile 189
Figure 5.2.4: Packing of the molecules of 10 when viewed down c-axis.
190 Acrylonitrile derivatives
5.3 2-(4-Methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)
acrylonitrile
The synthesis and crystallisation of the compound 2-(4-Methoxyphenyl)3-(3,4,5-trimethoxyphenyl) acrylonitrile (11), was done according to theprocedure reported in [12].
5.3.1 Crystal and Molecular Structure
The experimental procedure for data collection and data reduction areexplained in section 3.1 of chapter 3. The crystal data and structure re-finement details are given in table 5.3.1. The values of Rint and Rsigma are0.0302 and 0.0342 respectively. The structure was solved using SHELXS-97. 2000 phase sets were refined with the best phase set having a CFOM of0.0468. Using the normalised structure factors with these phases, a totalof 1134 phases were generated.
The final RE value was 23.0%. The non-hydrogen atoms were refinedanisotropically. The hydrogen atoms were fixed at chemically acceptablepositions and were allowed to ride on the parent atom during succes-sive refinements. 222 parameters were refined with 3922 reflections usingSHELXL-97. ORTEP of the molecule is shown in figure 5.3.1.
Tables 5.3.2 and 5.3.3 list the atomic coordinates and equivalent ther-mal parameters of non-hydrogen and hydrogen atoms respectively. Ta-ble 5.3.4 gives the anisotropic thermal parameters of the non-hydrogenatoms. The bond lengths and bond angles are listed in tables 5.3.5 and5.3.6 respectively. Selected torsion angles are listed in the table 5.3.7.
Figures 5.3.2 to 5.3.4 show the packing of the molecules down a, b andc axes respectively.
The title compound was designed as an analog of compound [9] inwhich 3-hydroxy-4-methoxy phenyl moiety was replaced by 4-methoxyphenyl moiety and the olefinic bond carrying nitrile group. The dihedralangle between the methoxyphenyl ring and the trimethoxyphenyl ring is18.16(16)◦ . The methoxy group substituted on ring 1 (phenylacrylonitrile)is in anti-periplanar conformation (C4-C3-O2-C1=177.5(3)◦) with respectto the phenyl ring C3-C4-C5-C6-C7-C8 as in other molecules.
5.3 2-(4-Methoxyphenyl)-3- (3,4,5-trimethoxyphenyl) acrylonitrile 191
The olefinic bond connecting the 4-methoxyphenyl acrylonitrile and3,4,5-trimethoxyphenyl groups has Z geometry. Significant deviations fromthe ideal bond-angle geometry around the Csp2 atoms of the double bondare observed. The bond angles C9=C12-C13 is 130.3(3)◦ , C12=C9-C6is 125.4(3)◦ and C10-C9-C6 is 114.6(2)◦ are distorted due to the sterichindrance of the double bond linking the two ring systems. The olefinicdouble bond bearing the three conjugated substituents has a length of1.351(3) A which is comparable with the corresponding values of 1.353(3) Aand 1.304(4) A reported for (Z)-2-(3-Thienyl)-3-(3,4,5-trimethoxyphenyl)acrylonitrile [7] and 2-styrylbenzimidazole [8] respectively indicating somedelocalization in the unsaturated bridging units.
The torsion angle of −160.8(3)◦ for the plane containing the atomsC9=C12-C13-C14 indicates the deviation of 3,4,5-trimethoxyphenyl ringfrom the plane of the olefinic double bond. The torsion angles of −10.6(5)◦
and −5.1(5)◦ for the planes of atoms C18-C17-O23-C24 and C14-C15-O19-C20 respectively, indicate that the methoxy groups at C17 and C15 arealmost in the plane of phenyl ring. But the methoxy group at C16 isin −anti-clinal conformation with the phenyl ring C13-C14-C15-C16-C17-C18 [12] as the torsion angle about C15-C16-O21-C22 is −104.2(3)◦. Thismolecule was tested and evaluated in vitro against bacterial and fungalstrains and confirmed that this molecule exhibited a broad spectrum ofanti-bacterial activity when compared with standard drugs.
The structure exhibits both inter and intramolecular hydrogen bondsof the type C-H· · ·O and C-H· · ·N (table 5.3.8). The molecules form hy-drogen bonded dimers.
192 Acrylonitrile derivatives
Table 5.3.1: Crystal and structure refinement data for 11.
Empirical formula C19H19NO4
Formula weight 325.35Temperature 293(2)KWavelength 0.71073 ACrystal system MonoclinicSpace group P21/cCell dimensions
a = 7.288(4) Ab = 8.103(9) Ac = 28.460(3) Aβ = 94.018(5)◦
Volume 1676.6(3) A3
Z 4Density(calculated) 1.289 Mg/m3
Absorption coefficient 0.091 mm−1
F000 688Crystal size 0.3 × 0.27 × 0.25 mmθ range for data collection 2.61◦ to 32.48◦
Index ranges −8 ≤ h ≤ 9−10 ≤ k ≤ 11−42 ≤ l ≤ 42
Reflections collected 6771Independent reflections 3922 [Rint = 0.0302]Refinement method Full-matrix least-squares on F 2
Data / restraints / parameters 3922 / 0 / 222Goodness-of-fit on F 2 1.100Final R indices [I > 2σ(I)] R1 = 0.0886, wR2 = 0.2534R indices (all data) R1 = 0.1196, wR2 = 0.3039Extinction coefficient 0.098(15)Largest diff. peak and hole 0.393 and −0.442 e. A−3
5.3 2-(4-Methoxyphenyl)-3- (3,4,5-trimethoxyphenyl) acrylonitrile 193
Table 5.3.2: Atomic coordinates and equivalent thermal parameters of thenon-hydrogen atoms for 11.
Atom x y z Ueq
C1 −0.8063(5) 0.6544(6) 0.5157(1) 0.0882(1)O2 −0.7650(3) 0.6046(3) 0.4695(7) 0.0787(8)C3 −0.6016(4) 0.6552(4) 0.4538(8) 0.0646(8)C8 −0.5693(4) 0.6101(4) 0.4080(9) 0.0667(8)C7 −0.4128(4) 0.6586(4) 0.3879(8) 0.0661(8)C6 −0.2796(3) 0.7541(4) 0.4129(7) 0.0579(7)C5 −0.3119(4) 0.7939(5) 0.4591(8) 0.0668(8)C4 −0.4712(4) 0.7448(5) 0.4793(8) 0.0714(9)C9 −0.1163(4) 0.8185(4) 0.3909(8) 0.0585(7)C10 −0.0081(4) 0.9345(5) 0.4194(9) 0.0722(9)N11 0.0727(5) 1.0274(5) 0.4425(1) 0.1048(1)C12 −0.0731(4) 0.7875(4) 0.3464(8) 0.0595(7)C13 0.0727(3) 0.8568(4) 0.3193(8) 0.0558(7)C14 0.0503(3) 0.8408(4) 0.2703(8) 0.0546(6)C15 0.1742(3) 0.9135(4) 0.2420(7) 0.0529(6)C16 0.3209(4) 1.0043(4) 0.2620(8) 0.0549(7)C17 0.3460(4) 1.0153(4) 0.3111(8) 0.0574(7)C18 0.2249(4) 0.9412(4) 0.3394(8) 0.0582(7)O19 0.1649(3) 0.9072(3) 0.1939(6) 0.0644(6)C20 0.0274(5) 0.8092(6) 0.1709(9) 0.0850(1)O21 0.4336(2) 1.0869(3) 0.2337(6) 0.0640(6)C22 0.6078(4) 1.0106(5) 0.2293(1) 0.0807(1)O23 0.4942(3) 1.1067(3) 0.3276(7) 0.0763(7)C24 0.5083(5) 1.1505(5) 0.3757(1) 0.0818(1)
Ueq = (1/3)∑
i
∑
jUij(a
∗i a
∗j )(ai · aj)
194 Acrylonitrile derivatives
Table 5.3.3: Atomic coordinates and equivalent thermal parameters of thehydrogen atoms for 11.
Atom x y z Uiso
H1A −0.7199 0.6048 0.5384 0.132H1B −0.9285 0.6194 0.5215 0.132H1C −0.7984 0.7723 0.5181 0.132H4 −0.6555 0.5459 0.3907 0.080H5 −0.3948 0.6275 0.3571 0.079H7 −0.2245 0.8551 0.4769 0.080H8 −0.4889 0.7730 0.5104 0.086H12 −0.1477 0.7100 0.3303 0.071H14 −0.0484 0.7809 0.2567 0.065H18 0.2447 0.9475 0.3719 0.070H20A 0.0386 0.6979 0.1823 0.128H20B 0.0410 0.8106 0.1376 0.128H20C −0.0913 0.8519 0.1771 0.128H22A 0.6731 1.0042 0.2598 0.121H22B 0.6778 1.0748 0.2086 0.121H22C 0.5899 0.9014 0.2167 0.121H24A 0.3996 1.2093 0.3832 0.123H24B 0.6141 1.2196 0.3821 0.123H24C 0.5206 1.0525 0.3946 0.123
5.3 2-(4-Methoxyphenyl)-3- (3,4,5-trimethoxyphenyl) acrylonitrile 195
Table 5.3.4: Anisotropic thermal parameters of the non-hydrogen atomsfor 11.
Atom U11 U22 U33 U12 U13 U23
C1 0.095(2) 0.104(4) 0.070(2) -0.001(2) 0.034(2) -0.002(2)O2 0.080(1) 0.091(2) 0.068(1) -0.007(1) 0.023(9) -0.002(1)C3 0.076(2) 0.067(3) 0.053(1) 0.003(1) 0.014(1) 0.005(1)C8 0.079(2) 0.066(3) 0.056(1) -0.008(1) 0.009(1) -0.004(1)C7 0.080(2) 0.072(3) 0.047(1) -0.004(1) 0.012(1) -0.005(1)C6 0.076(2) 0.055(2) 0.044(1) 0.002(1) 0.010(9) -0.000(9)C5 0.083(2) 0.070(3) 0.049(1) -0.005(1) 0.010(1) -0.007(1)C4 0.088(2) 0.079(3) 0.049(1) -0.002(2) 0.016(1) -0.005(1)C9 0.073(2) 0.056(2) 0.048(1) 0.001(1) 0.010(9) -0.003(1)C10 0.081(2) 0.081(3) 0.057(1) -0.010(2) 0.016(1) -0.013(1)N11 0.109(2) 0.129(4) 0.079(2) -0.038(2) 0.027(2) -0.045(2)C12 0.072(2) 0.057(2) 0.051(1) -0.001(1) 0.009(9) -0.003(1)C13 0.069(2) 0.049(2) 0.051(1) 0.002(1) 0.011(9) -0.000(1)C14 0.065(1) 0.049(2) 0.051(1) 0.000(1) 0.007(8) -0.003(9)C15 0.064(1) 0.047(2) 0.048(1) 0.004(1) 0.005(8) 0.000(9)C16 0.062(1) 0.049(2) 0.054(1) 0.003(1) 0.009(9) 0.005(1)C17 0.061(2) 0.054(2) 0.057(1) 0.001(1) 0.001(9) -0.003(1)C18 0.067(1) 0.058(2) 0.049(1) 0.004(1) 0.005(9) 0.001(1)O19 0.080(1) 0.065(2) 0.049(8) -0.009(1) 0.006(7) 0.002(8)C20 0.093(2) 0.108(4) 0.055(1) -0.026(2) 0.006(1) -0.018(2)O21 0.068(1) 0.062(2) 0.063(1) -0.005(9) 0.011(7) 0.010(8)C22 0.070(2) 0.090(3) 0.084(2) -0.006(2) 0.021(1) -0.002(2)O23 0.076(1) 0.089(2) 0.063(1) -0.019(1) 0.001(8) -0.008(1)C24 0.089(2) 0.085(3) 0.069(2) -0.005(2) -0.009(1) -0.013(2)
196 Acrylonitrile derivatives
Figure 5.3.1: ORTEP of the molecule 11 at 50% probability.
5.3 2-(4-Methoxyphenyl)-3- (3,4,5-trimethoxyphenyl) acrylonitrile 197
Table 5.3.5: Bond Lengths of 11 (A).
Atoms Length Atoms Length
C1-O2 1.426(3) C13-C18 1.391(4)O2-C3 1.364(3) C13-C14 1.399(3)C3-C4 1.365(4) C14-C15 1.383(3)C3-C8 1.390(3) C15-O19 1.368(3)C8-C7 1.369(4) C15-C16 1.387(4)C7-C6 1.397(4) C16-O21 1.365(3)C6-C5 1.389(3) C16-C17 1.399(3)C6-C9 1.479(4) C17-O23 1.365(3)C5-C4 1.390(4) C17-C18 1.374(4)C9-C12 1.351(3) O19-C20 1.403(4)C9-C10 1.440(4) O21-C22 1.425(4)C10-N11 1.136(4) O23-C24 1.413(3)C12-C13 1.467(3)
198 Acrylonitrile derivatives
Table 5.3.6: Bond Angles of 11 (◦).
Atoms Angle Atoms Angle
C3-O2-C1 117.6(3) C18-C13-C12 124.0(2)O2-C3-C4 125.2(2) C14-C13-C12 116.7(2)O2-C3-C8 116.0(3) C15-C14-C13 120.4(2)C4-C3-C8 118.8(2) O19-C15-C14 125.4(2)C7-C8-C3 121.2(3) O19-C15-C16 114.4(2)C8-C7-C6 121.0(2) C14-C15-C16 120.2(2)C5-C6-C7 117.0(2) O21-C16-C15 119.8(2)C5-C6-C9 120.9(2) O21-C16-C17 121.1(3)C7-C6-C9 122.1(2) C15-C16-C17 119.1(2)C6-C5-C4 121.8(3) O23-C17-C18 124.1(2)C3-C4-C5 120.1(2) O23-C17-C16 115.0(2)C12-C9-C10 119.7(2) C18-C17-C16 120.9(3)C12-C9-C6 125.4(3) C17-C18-C13 120.1(2)C10-C9-C6 114.7(2) C15-O19-C20 118.1(2)N11-C10-C9 178.0(3) C16-O21-C22 114.5(2)C9-C12-C13 130.2(3) C17-O23-C24 118.2(2)C18-C13-C14 119.2(2)
5.3 2-(4-Methoxyphenyl)-3- (3,4,5-trimethoxyphenyl) acrylonitrile 199
Table 5.3.7: Torsion Angles of 11 (◦).
Atoms Angle Atoms Angle
C4-C3-O2-C1 2.5(5) C5-C6-C9-C10 −5.5(4)C7-C6-C9-C12 −3.3(5) C9-C12-C13-C18 16.7(5)C9-C12-C13-C14 −160.8(3) C18-C17-O23-C24 −10.6(5)C17-C16-O21-C22 78.5(4) C14-C15-O19-C20 −5.1(5)
Table 5.3.8: Hydrogen bond geometry for 11 (A, ◦).
Atoms D–H· · ·A Angle
C12–H12· · ·O191 3.343(4) 143C18–H18· · ·N11 3.285(4) 139C22–H22A· · ·O23 3.071(4) 115
Symmetry1. − x, − /2 + y, 1/2 − z
200 Acrylonitrile derivatives
Figure 5.3.2: Packing of the molecules of 11 when viewed down a-axis.
5.3 2-(4-Methoxyphenyl)-3- (3,4,5-trimethoxyphenyl) acrylonitrile 201
Figure 5.3.3: Packing of the molecules of 11 when viewed down b-axis.
202 Acrylonitrile derivatives
Figure 5.3.4: Packing of the molecules of 11 when viewed down c-axis.
5.4 3-(N,N-Dimethylamino-phenyl) -2-(4-methoxyphenyl) acrylonitrile 203
5.4 3-(N,N-Dimethylamino-phenyl)-2-(4-methoxyphenyl)
acrylonitrile
The 3-(N,N-Dimethylamino-phenyl)-2-(4-methoxyphenyl) acrylonitrile(12), was synthesised and crystallised according to the procedure reportedin the [11].
5.4.1 Crystal and Molecular Structure
The experimental procedure for data collection and data reduction areexplained in section 3.1 of chapter 3. The crystal data and structure re-finement details are given in table 5.4.1. The values of Rint and Rsigma are0.0199 and 0.0312 respectively. The structure was solved using SHELXS-97. 2000 phase sets were refined with the best phase set having a CFOM of0.0441. Using the normalised structure factors with these phases, a totalof 1447 phases were generated.
The final RE value was 38.0%. The non-hydrogen atoms were refinedanisotropically. The hydrogen atoms were fixed at chemically acceptablepositions and were allowed to ride on the parent atom during succes-sive refinements. 194 parameters were refined with 4761 reflections usingSHELXL-97. ORTEP of the molecule is shown in figure 4.2.1.
Tables 5.4.2 and 5.4.3 list the atomic coordinates and equivalent ther-mal parameters of non-hydrogen and hydrogen atoms respectively. Ta-ble 5.4.4 gives the anisotropic thermal parameters of the non-hydrogenatoms. The bond lengths and bond angles are listed in tables 5.4.5 and5.4.6 respectively. Selected torsion angles are listed in the table 5.4.7
Figures 5.4.2 to 5.4.4 show the packing of the molecules down a, b andc axes respectively.
In this molecule, the dihedral angle between the least squares planes ofmethoxyphenyl group and N,N-dimethylamino-phenyl group is 10.26(8)◦
which is very small compared to the other three derivatives studied here.This may be due to the presence of dimethylamino group. The methoxygroup substituted on ring 1 (phenylacrylonitrile) is in anti-periplanar con-formation (C4-C3-O2-C1=177.8(2)◦) with respect to the phenyl ring C3-C4-C5-C6-C7-C8.
The olefinic bond connecting the 4-methoxyphenyl acrylonitrile and3-N,N-dimethylaminophenyl groups has Z geometry. Significant devia-
204 Acrylonitrile derivatives
tions from the ideal bond-angle geometry around the Csp2 atoms of thedouble bond are observed. The bond angles C13-C12=C9 is 132.01(2)◦ ,C12=C9-C6 is 125.73(2)◦ and C10-C9-C6 is 114.17(2)◦ are distorted dueto the steric hindrance of the double bond linking the two ring systems.The olefinic double bond bearing the three conjugated substituents in themolecule has a length of 1.3514(3) A which is comparable with (Z)-2-(3-Thienyl)-3-(3,4,5-trimethoxyphenyl)-acrylonitrile of bond length 1.353(3)A [7], and 2-styrylbenzimidazole of bond length 1.304(4) A [8], suggestingsome delocalization in the unsaturated bridging unit.
The torsion angle of 169.52(2)◦ for the plane of atoms C14-C13-C12=C9 indicates the deviation of the N,N-dimethylamino-phenyl ring from theplane of the olefinic double bond [11] which is maximum with respect tothe other three molecules studied. The torsion angle about the atomsC15-C16-N19-C20 is 4.33(3)◦ indicating that the dimethylamino group isalmost in the same plane of the phenyl ring C13-C14-C15-C16-C17-C18.This molecule exhibited a broad spectrum of anti-fungal activity whencompared with standard drugs.
The structure exhibits intramolecular hydrogen bonds of the type C-H· · ·N (C18-H18· · ·N11) with a bond length of 3.417(3) A and a bondangle of 146◦. The packing of the molecules indicates that the moleculesare interlinked by hydrogen bonds.
5.4 3-(N,N-Dimethylamino-phenyl) -2-(4-methoxyphenyl) acrylonitrile 205
Table 5.4.1: Crystal and structure refinement data for 12.
Empirical formula C18H18N2OFormula weight 278.34Temperature 293(2)KWavelength 0.71073 ACrystal system MonoclinicSpace group P21/cCell dimensions
a = 11.736(9) Ab = 7.646(8) Ac = 19.932(1) Aβ = 123.379(5)◦
Volume 1493.5(2) A3
Z 4Density(calculated) 1.238 Mg/m3
Absorption coefficient 0.078 mm−1
F000 592Crystal size 0.25 × 0.25 × 0.2 mmθ range for data collection 2.08◦ to 32.42◦
Index ranges −17 ≤ h ≤ 17−8 ≤ k ≤ 11−30 ≤ l ≤ 29
Reflections collected 6864Independent reflections 4761 [Rint = 0.0199]Refinement method Full-matrix least-squares on F 2
Data / restraints / parameters 4761 / 0 / 194Goodness-of-fit on F 2 1.039Final R indices [I > 2σ(I)] R1 = 0.0629, wR2 = 0.1584R indices (all data) R1 = 0.0995, wR2 = 0.1932Extinction coefficient 0.079(8)Largest diff. peak and hole 0.194 and −0.202 e. A−3
206 Acrylonitrile derivatives
Table 5.4.2: Atomic coordinates and equivalent thermal parameters of thenon-hydrogen atoms for 12.
Atom x y z Ueq
C1 −0.1359(2) −0.0334(3) 0.0249(1) 0.0867(7)O2 −0.0094(1) 0.0531(2) 0.0764(7) 0.0716(4)C3 0.0493(2) 0.0427(2) 0.1573(9) 0.0537(3)C4 −0.0039(2) −0.0495(2) 0.1938(1) 0.0580(4)C5 0.0617(2) −0.0477(2) 0.2765(1) 0.0580(4)C6 0.1823(2) 0.0458(2) 0.3258(9) 0.0503(3)C7 0.2349(2) 0.1355(2) 0.2874(1) 0.0567(4)C8 0.1702(2) 0.1343(2) 0.2050(1) 0.0581(4)C9 0.2509(2) 0.0534(2) 0.4143(9) 0.0529(3)C10 0.3695(2) 0.1638(2) 0.4543(1) 0.0621(4)N11 0.4615(2) 0.2569(3) 0.4823(1) 0.0875(6)C12 0.2081(2) −0.0273(2) 0.4570(1) 0.0586(4)C13 0.2619(2) −0.0292(2) 0.5422(9) 0.0555(4)C14 0.1811(2) −0.1029(2) 0.5671(1) 0.0608(4)C15 0.2224(2) −0.1081(2) 0.6464(1) 0.0591(4)C16 0.3495(2) −0.0399(2) 0.7072(9) 0.0511(3)C17 0.4321(2) 0.0302(2) 0.6826(1) 0.0594(4)C18 0.3892(2) 0.0351(2) 0.6034(1) 0.0605(4)N19 0.3923(1) −0.0419(2) 0.7863(8) 0.0575(3)C20 0.3113(2) −0.1263(3) 0.8113(1) 0.0699(5)C21 0.5276(2) 0.0169(2) 0.8484(1) 0.0649(4)
Ueq = (1/3)∑
i
∑
jUij(a
∗i a
∗j )(ai · aj)
5.4 3-(N,N-Dimethylamino-phenyl) -2-(4-methoxyphenyl) acrylonitrile 207
Table 5.4.3: Atomic coordinates and equivalent thermal parameters of thehydrogen atoms for 12.
Atom x y z Uiso
H1A −0.1247 −0.1565 0.0362 0.130H1B −0.1659 −0.0142 −0.0300 0.130H1C −0.2027 0.0122 0.0339 0.130H4 −0.0840 −0.1131 0.1625 0.070H5 0.0243 −0.1104 0.2999 0.070H7 0.3158 0.1977 0.3184 0.068H8 0.2078 0.1951 0.1813 0.070H12 0.1295 −0.0939 0.4260 0.070H14 0.0966 −0.1499 0.5285 0.073H15 0.1653 −0.1576 0.6600 0.071H17 0.5178 0.0743 0.7212 0.071H18 0.4467 0.0828 0.5897 0.073H20A 0.2222 −0.0741 0.7838 0.105H20B 0.3549 −0.1123 0.8682 0.105H20C 0.3029 −0.2486 0.7985 0.105H21A 0.5944 −0.0567 0.8490 0.097H21B 0.5381 0.0109 0.8997 0.097H21C 0.5401 0.1354 0.8378 0.097
208 Acrylonitrile derivatives
Table 5.4.4: Anisotropic thermal parameters of the non-hydrogen atomsfor 12.
Atom U11 U22 U33 U12 U13 U23
C1 0.078(1) 0.113(2) 0.059(1) -0.032(1) 0.031(1) -0.009(1)O2 0.069(8) 0.091(9) 0.053(6) -0.020(6) 0.032(6) -0.003(6)C3 0.058(9) 0.054(8) 0.054(8) -0.001(6) 0.033(7) -0.001(6)C4 0.057(9) 0.059(9) 0.058(8) -0.009(7) 0.033(8) -0.003(7)C5 0.061(9) 0.058(9) 0.060(9) -0.008(7) 0.036(8) 0.002(7)C6 0.055(8) 0.044(7) 0.056(8) 0.002(6) 0.033(7) 0.000(6)C7 0.056(8) 0.056(9) 0.060(8) -0.007(6) 0.033(7) -0.002(7)C8 0.060(9) 0.060(9) 0.061(9) -0.009(7) 0.038(8) -0.001(7)C9 0.057(8) 0.047(7) 0.056(8) 0.001(6) 0.032(7) -0.001(6)C10 0.072(1) 0.062(1) 0.056(8) -0.009(8) 0.038(8) -0.003(7)N11 0.097(1) 0.097(1) 0.066(9) -0.040(1) 0.043(9) -0.010(8)C12 0.060(9) 0.059(9) 0.057(8) -0.005(7) 0.032(8) -0.001(7)C13 0.060(9) 0.054(8) 0.054(8) -0.001(6) 0.032(7) 0.002(6)C14 0.057(9) 0.066(1) 0.059(9) -0.009(7) 0.031(8) -0.002(7)C15 0.057(9) 0.062(9) 0.061(9) -0.001(7) 0.034(8) 0.002(7)C16 0.056(8) 0.046(7) 0.055(8) 0.001(6) 0.033(7) 0.002(6)C17 0.057(9) 0.064(1) 0.057(8) -0.009(7) 0.032(8) -0.000(7)C18 0.062(1) 0.067(1) 0.058(8) -0.010(7) 0.036(8) 0.001(7)N19 0.058(8) 0.064(8) 0.054(7) -0.003(6) 0.033(6) 0.001(6)C20 0.069(1) 0.084(1) 0.066(1) -0.000(9) 0.044(9) 0.009(9)C21 0.065(1) 0.071(1) 0.057(9) -0.005(8) 0.032(8) -0.005(7)
5.4 3-(N,N-Dimethylamino-phenyl) -2-(4-methoxyphenyl) acrylonitrile 209
Figure 5.4.1: ORTEP of the molecule 12 at 50% probability.
210 Acrylonitrile derivatives
Table 5.4.5: Bond Lengths of 12 (A).
Atoms Length Atoms Length
C1-O2 1.421(2) C10-N11 1.149(2)O2-C3 1.365(2) C12-C13 1.449(2)C3-C4 1.383(2) C13-C18 1.399(2)C3-C8 1.387(2) C13-C14 1.408(2)C4-C5 1.384(2) C14-C15 1.375(2)C5-C6 1.396(2) C15-C16 1.407(2)C6-C7 1.399(2) C16-N19 1.367(2)C6-C9 1.483(2) C16-C17 1.410(2)C7-C8 1.380(2) C17-C18 1.369(2)C9-C12 1.353(2) N19-C20 1.446(2)C9-C10 1.437(2) N19-C21 1.447(2)
Table 5.4.6: Bond Angles of 12 (◦).
Atoms Angle Atoms Angle
C3-O2-C1 118.2(1) C9-C12-C13 132.0(2)O2-C3-C4 124.8(1) C18-C13-C14 115.9(1)O2-C3-C8 116.1(1) C18-C13-C12 125.9(2)C4-C3-C8 119.0(1) C14-C13-C12 118.3(2)C3-C4-C5 120.3(2) C15-C14-C13 122.5(2)C4-C5-C6 121.8(1) C14-C15-C16 121.1(1)C5-C6-C7 116.6(1) N19-C16-C15 122.2(1)C5-C6-C9 122.3(1) N19-C16-C17 121.3(1)C7-C6-C9 121.1(1) C15-C16-C17 116.6(1)C8-C7-C6 121.9(1) C18-C17-C16 121.6(2)C7-C8-C3 120.3(1) C17-C18-C13 122.4(2)C12-C9-C10 120.0(2) C16-N19-C20 120.6(1)C12-C9-C6 125.7(1) C16-N19-C21 121.1(1)C10-C9-C6 114.2(1) C20-N19-C21 117.7(1)N11-C10-C9 176.2(2)
5.4 3-(N,N-Dimethylamino-phenyl) -2-(4-methoxyphenyl) acrylonitrile 211
Table 5.4.7: Torsion Angles of 12 (◦).
Atoms Angle Atoms Angle
C4-C3-O2-C1 1.48(3) C15-C16-N19-C20 4.33(3)C5-C6-C9-C12 0.65(3) C7-C6-C9-C10 2.19(2)C9-C12-C13-C18 −11.01(3) C17-C16-N19-C21 −4.23(2)C7-C6-C9-C10 2.19(2) C10-C9-C12-C13 −1.35(3)
212 Acrylonitrile derivatives
Figure 5.4.2: Packing of the molecules of 12 when viewed down a-axis.
5.4 3-(N,N-Dimethylamino-phenyl) -2-(4-methoxyphenyl) acrylonitrile 213
Figure 5.4.3: Packing of the molecules of 12 when viewed down b-axis.
214 Acrylonitrile derivatives
Figure 5.4.4: Packing of the molecules of 12 when viewed down c-axis.
5.5 Results 215
5.5 Results
Crystal and molecular structures of the samples 9, 10, 11 and 12 have beenstudied. The olefinic bond connecting the 4-methoxyphenyl acrylonitrilewith different groups has Z geometry. Significant deviations from theideal bond-angle geometry around the Csp2 atoms of the double bond areobserved. The bond angles are distorted due to the steric hindrance of thedouble bond linking the two ring systems.
The structures of the compounds 9 and 10 exhibit intermolecular hy-drogen bond of the type C-H· · ·O and C-H· · ·N respectively, the sample12 shows intramolecular hydrogen bonds of the type C-H· · ·N where asthe sample 11 exhibits both inter and intramolecular hydrogen bond ofthe type C-H· · ·O and C-H· · ·N.
The torsion angle for the plane containing the atoms C9=C12-C13-C14with the plane of the olefinic double bond in molecules 9, 10, 11 and 12was studied and found to vary. These discrepancies might be due to thesubstitutions for the ring 2.
These compounds were studied for biological activity and evaluated invitro against bacterial strains of Bacillus subtilis, Escherichia coli, Salmon-ella typhimurium, Pseudomonas aeruginosa, and Staphylococcus aureusand fungi like Aspergillus niger, Cephalosporium acremonium, and Fusar-ium moniliforme. The molecule 11 exhibited a broad spectrum of anti-bacterial activity when compared with standard drugs, which might bedue to the presence of three methoxy groups on the ring 2. Also, molecule12 exhibited a broad spectrum of anti-fungal activity when compared withstandard drugs. This can be attributed for the presence of dimethylaminogroup on the ring 2.
The olefinic double bond length bearing the three conjugated sub-stituents varies from one another in the above studied molecules and alsofrom (Z)-2-(3-Thienyl)-3-(3,4,5-trimethoxyphenyl) -acrylonitrile [7] and 2-styrylbenzimidazole [8] indicating some delocalization in the unsaturatedbridging units.
216 Acrylonitrile derivatives
5.6 References
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2. Ambrosi H. D., Duczek W., and Jahnisch K., Liebigs Ann. Chem.,1013, 1994.
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5. Carta A., Sanna P., Palomba M., Vargiu L., Colla M. L., and LoddoR., Eur. J. Med. Chem., 37, 891–900, 2002.
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9. El-Zayat A. A., Degen D., Drabek S., Clark G. M., Pettit G. R., andVon Hoff D. D., Anticancer Drugs, 4, 19, 1993.
10. Sarala G., Kavitha C. V., Rangappa K. S., Sridhar M. A., andShashidhara Prasad J., Acta Cryst., E62, o3998–o4000, 2006.
11. Sarala G., Kavitha C. V., Naveen S., Rangappa K. S., Sridhar M.A., and Shashidhara Prasad J., J. Anal. Sci., 22, 291–292, 2006.
12. Kavitha C. V., Sarala G., Naveen S., Rangappa K. S., Sridhar M.A., and Shashidhara Prasad J., J. Anal. Sci., 22, 265–267, 2006.
13. Kavitha C. V., Sarala G., Rangappa K. S., Sridhar M. A., andShashidhara Prasad J., Acta Cryst., E62, o4345–o4347, 2006.