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Synthesis, crystal structure, Hirshfeld surface studies and frontier orbitals analysis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine
Accepted Manuscript
Synthesis, Crystal structure, Hirshfeld surface studies and frontier orbitals analysis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine G. Krishnaswamy , P. Krishna Murthy , P.A. Suchetan , Nivedita R Desai , D.B. Aruna Kumar , R. Sreenivasa Rao PII: DOI: Reference:
S2405-8300(17)30025-3 10.1016/j.cdc.2017.06.001 CDC 58
To appear in:
Chemical Data Collections
Received date: Revised date: Accepted date:
25 January 2017 30 May 2017 2 June 2017
Please cite this article as: G. Krishnaswamy , P. Krishna Murthy , P.A. Suchetan , Nivedita R Desai , D.B. Aruna Kumar , R. Sreenivasa Rao , Synthesis, Crystal structure, Hirshfeld surface studies and frontier orbitals analysis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine, Chemical Data Collections (2017), doi: 10.1016/j.cdc.2017.06.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Synthesis, Crystal structure, Hirshfeld surface studies and frontier orbitals analysis of 4-(1-benzofuran2-yl)-2-methyl-6-phenylpyrimidine G. Krishnaswamy,1 P. Krishna Murthy,2 P.A. Suchetan,1 Nivedita R Desai,1 D.B. Aruna Kumar,*1R. Sreenivasa Rao3 1
Department of Studies and Research in Chemistry, University College of Science, Tumkur University, Tumakuru-572 103, Karnataka, India
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Department of Chemistry, Bapatla Engineering College (Autonomous), Acharaya Nagarjuna University Post Graduate Research Centre, Bapatla-522 102, A.P., India
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Department of Chemistry, Bapatla College of Arts and Sciences, Baptla-522 101, A.P., India
Contact email: [email protected]
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Abstract
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4-(benzofuran-2-yl)-2-methyl-6-phenylpyrimidine(BFMPP) has been synthesized and characterized by FTIR, 1H &13CNMR and Mass spectrometry techniques. Single crystals of title compound were grown by slow evaporation solution growth technique at room temperature and crystal structure has been determined by single crystal X-ray diffraction technique. The title compound(BFMPP) crystallizes in monoclinic space group P21, with cell dimensions a = 4.803(3) Å, b = 9.498(5) Å, c = 15.557(9) Å, β= 93.25 (4)o and Z = 2. The crystal structure is stabilized by weak C-H…N intermolecular interactions generating a one dimensional C(4) network propagating along the *100+ direction and two pi…pi interactions. Further, a detailed analysis of the Hirshfeld surfaces facilitating an understanding of the type and nature of intermolecular interactions in the supramolecular structure is made. The calculated HOMO-LUMO energy gap discloses that charge transfer occurs within the molecule.
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Keywords: BFMPP, Crystal structure, X-ray diffraction, Hirshfeld analysis, HOMO-LUMO plots. Specifications Table Subject area X-ray crystallography Compounds 4-(benzofuran-2-yl)-2-methyl-6-phenylpyrimidine Data category Crystallographic data Data acquisition format CIF for crystallography Data type Analyzed Procedure The unit cell parameters and the intensity data at 298K for the title compound was obtained on an Oxford Diffraction Xcalibur Gemini single crystal X-ray diffractometer using graphite monochromated Mo Kα radiation (λ = 0.71073 Å). The CrysAlisPro software was used for data collection, reduction and absorption correction. Data accessibility CCDC:1411045 URL:https://www.ccdc.cam.ac.uk/conts/retrieving.html
1. Rationale
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Heterocycles hold a key point in organic and medicinal chemistry as they act as a bridge between life sciences and biochemical investigations. A significant amount of contemporary investigation is being currently pursued on these compounds worldwide. The pyrimidine rings are nitrogen rich heterocycles, key constituent of many natural, synthetic compounds and shows very interesting pharmacological activity [1-4]. In recent years, pyrimidine derivatives have received significant attention owing to their diverse biological properties, particularly as cytostatic [5-8], immune modulating [9], antitubercular, calcium channel blockers [10], antimicrobial properties [11], herbicides [12] and pesticides [13]. The biological importance of pyrimidine derivatives has motivated significant interest towards the synthesis of 4-(benzofuran-2-yl)-2-methyl-6-phenylpyrimidine(BFMPP) and the structure was characterized well as it would be more useful. Further, various intermolecular interactions are well supported by Hirshfeld surface and fingerprint plots analysis.
2. Experimental 2.1. General remarks
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The reagents and solvents used for synthesis were procured from Spectrochem, Sigma Aldrich and used as such received. Reactions were monitor by analytical thin layer chromatography (TLC) and TLC plates were visualized by exposing UV light, KMnO4 solution or by iodine vapors. The FT-IR spectrum was recorded in KBr pellets using JASCO FTIR-4100 spectrometer in the range of 4000 – 400 cm -1 1
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resolution of ± 2 cm . H & C-NMR spectrum was recorded on JEOL-400 MHz NMR instrument using CDCl3 as solvent. The chemical shifts values (δ) are reported in parts per million (ppm) using TMS as an
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internal standard. Mass spectrum was recorded on Shimadzu-2010EV with APCI and ESI probes.
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2.2. Synthesis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine To a stirred solution of (1-benzofuran-2-yl)-3-phenylprop-2-en-1-one (0.5g, 2.06mmol) in mixture of ethanol: water (4:1, 5 mL), acetamidine hydrochloride (0.11g, 2.06 mmol), KOH (0.12g, 2.2mmol) was added and the reaction mixture refluxed for 6 hours. After completion of reaction indicated by TLC, the reaction mixture was poured into ice cold water and extracted to ethyl acetate (3 x 20 mL). The organic layer washed with water, brine and dried over anhydrous Na2SO4. Evaporate the organic layer under reduced pressure to get crude product. The crude product was purified by column chromatography using silica 60-120 mesh and ethyl acetate: petroleum ether (1:9) as eluent to get desire product (0.39g, yield: 68.4%, M.p: 130-133oC).
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Method of crystallization
100mg of compound was dissolved in 15mL of ethyl acetate and warmed for 5 minutes. The solution was filtered through Whatmann filter paper and resulting solution was kept at room temperature in conical flask with stopper slightly open. After 5 days, the crystals of BFPP were developed; filtered and suitable crystals for single crystal analysis were selected (Scheme-1). 1
H NMR (400MHz, CDCl3): δ 8.20-8.17 (2H, m, Ar-H), 8.05 (1H, s, Py-H), 7.71-7.69 (2H, dd,Ar-H), 7.62-
7.53 (4H, m, Ar-H), 7.43-7.39 (1H, m, Ar-H), 7.32 (1H, m, Ar-H), 2.86 (3H, s, Py-CH3). 2
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C NMR (100 MHz, CDCl3): δ 168.576 (C12), 165.217 (C9), 156.213 (C11), 155.642 (C1), 153.310 (C8),
136.973 (C13), 130.901 (C14 & C18), 128.915 (C15 & C17), 128.295 (C16), 127.278 (C5), 126.313 (C4), 123.510 (C2), 122.248 (C3), 111.670 (C6), 108.906(C7), 108.124 (C10), 26.204 (C19). 3
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Mass (m/z): Calculated: 286.32, Found: 287.59 (M+1)
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Scheme. Synthesis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine
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2.3. X-Ray Crystallography A suitable colourless, needle shaped single crystal of the title compound with dimensions of0.36mm x 0.20mm x 0.16mm was selected and data was collected on an Oxford diffraction X caliber Gemini diffractometer with graphite monochromated Mo Kα radiation (λ = 0.71073 Å) at 293 K. The CrysAlisProsoftware [14] was used for data collection, reduction and absorption correction. The structure was solved by direct method and refined by full-matrix least-squares methods on F2 using SHELX-97 [15] available in the WinGX package [16]. All the non-hydrogen atoms were refined with anisotropic thermal parameters. The hydrogen atoms were included in the structure factor calculations and treated using a riding model. Molecular graphics and crystal packing were created using ORTEP [17] and MERCURY [18] packages. The parameter for data collection and structure refinement of compound BFMPP are listed in Table 1.
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2.4. Hirshfeld surfaces The Hirshfeld surface analyses were carried out and fingerprint plots were plotted using Crystal Explorer 3.0 [19-25]. When the CIF files were uploaded into the Crystal-Explorer software, all bond lengths to hydrogen were automatically modified to standard neutron diffraction values, i.e. C–H = 1.083 Å. 3. Data, value and validation 3.1. Crystal and molecular structure description of BFMPP The molecular structure of BFMPP determined by X-ray diffraction is depicted in Figure 1. BFMPP crystallizes in the monoclinic space group P21with cell dimensions a = 4.803(3) Å, b = 9.498(5) Å, c = 15.557(9) Å, β= 93.25 (4)o and Z = 2.The molecule is almost planar with root mean squared deviation (considering non-H atoms) being 0.101 Å. The dihedral angle between the benzene (A), the pyrimidine 3
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ring (B) and the benzofuran ring (C) are 4.79 (A/B), 10.76 (A/C) and 8.42(1)o(B/C) respectively. The crystal structure is stabilized by weak C-H…N intermolecular interactions (Table 2 and Figure 2) running into C(4) chains along *100+ and two pi…pi interactions. Hence, the supra molecular architecture exhibited is one dimensional.
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Figure 1. ORTEP view of the molecule with atom numbering scheme for non-hydrogen atoms
Figure 2. Crystal packing of BFMPP
3.2. Hirshfeld surface analysis The Hirshfeld surfaces of title compound illustrated in Figure 3, showing surfaces that have been mapped over a dnorm(A), shape index (B) and curvedness (C) range of -0.111 to 1.143 Å, -1.0 to 1.0 Å and -4.0 to 0.4 Å, respectively. The predominant interactions between the methyl hydrogen of pyrimidine ring and the nitrogen of pyrimidine ring, which can be seen in the Hirshfeld surfaces as the bright red spot marked as A in Figure 3 and clearly seen in Figure 4. In the 2D fingerprint plots (Figure 5), the C4
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H···N intermolecular interactions appear as two distinct spikes circled with green color. Prominent pairs of sharp spikes of almost equal lengths in the fingerprint plots (Figure 5) are characteristics of nearly equal C(donor)···N(acceptor) distances and generate a one dimensional C(4) network propagating along the [100] direction. The upper spike (Figure 5) corresponds to the donor spike (H atom of methyl group interacting with N-atoms of the pyrimidine ring), with the lower spike being an acceptor spike (Natomsof the pyrimidine ring interacting with H- atom of methyl group). The wings marked in Figure 5 (circled with black) are due to the C···H contacts. A significant difference in terms of H···H contacts appears asspikes (marked as red circles in Figure 5). The relative contribution of the different interactions to the Hirshfeld surface was calculated for title compound. It is evident that the H···H contacts can account forabout 50.5% of the Hirshfeld surface area; the remaining contribution was mostly due to C···H 28.2%,N···H 6.5%, O···H 3.3% and C···C 6.0% interactions, with only minor contribution from C···N, O···C and O···N (maximum 5.5%).
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Figure 3. Hirshfeld surfaces of BFMPP.
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Figure 4. C-H…N intermolecular interactions mapped on dnorm surface.
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Figure 5. 2D Fingerprint plots of BFMPP.
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3.3.Frontier molecular orbital analysis The HOMO-LUMO energy plots of BFMPP has been obtained from Crystal Explorer with Tonto program using DFT/Becke88LYP/6-31G(d) method and the pictorial representation shown in Figure 6. The HOMO (MO 75) lies at -6.28 eV and whereas the LUMO (MO 76) is located at -2.2 eV. In the title compound, the HOMO of π nature is delocalized all over the molecule except phenyl ring, methyl group and LUMO in addition to this on the phenyl ring except methyl group. Accordingly, the HOMO-LUMO transition implies an electron density transfer from the benzofuran ring to phenyl ring through the pyrimidine ring, and that the frontier orbital energy gap is 4.08 eV. The global chemical descriptors associated with a molecular system are: ionization potential (I) = -EHOMO= 6.28, electron affinity (A) = -ELUMO= 2.2, chemical potential (μ) = - (I+A)/2 = -4.24, the global hardness (η) = (I-A)/2 = 2.04 ,softness (ν)= 1/ η = 0.49, electronegativity (χ) = (I+A)/2 = 4.24 and electrophilicity index (ω) = µ2/2η = 4.406 *26,27+. It is seen that the chemical potential of the title compound is negative and it implies that the molecular system is stable. They do not decompose spontaneously into the elements they are made up of. The hardness signifies the resistance towards the deformation of electron cloud of chemical system under small perturbation encountered during the chemical process. 3.4. UV-Visible spectral analysis
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The electronic spectra of title compound calculated at TD-DFT/B3LYP/SDD method using optimized geometry and the calculation are performed in methanol. The electronic spectra of title compound shows an electronic absorption band with maxima 344 nm (Figure S5)and this transition mainly due to the transition HOMO-LUMO that is the π-π transition predicted. The excitation transitions, CI coefficient, excitation energies, oscillator strengths and wavelength can be seen in Table S1.
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Figure 6. HOMO plot and LUMO plot of the title compound (BFMPP).
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3.5. FT-IR spectral analysis FT-IR spectrum of title compound is shown in Figure S1. Vibrational frequencies of title compound calculated at ground state by using B3LYP/DFT/SDD basic set in gas phase(Table S2).The CH stretching frequency of aromatic rings are theoretically assigned at 3181, 3117, 3090 cm-1 for benzofuran ring and 3150 cm-1 for pyrimidine ring. For mono-substituted phenyl ring, the CH stretching modes are expected above 3000 cm-1[28, 29] and DFT calculations give these modes in the range 3120, 3106, 3094 cm -1 and experimentally bands are observed at 3051 cm-1. The CH3 stretching modes are expected in the region 2900-3050 cm-1[28]. The bands observed at 2925 cm-1 and in the range 3060-2939 cm-1 (DFT) are assigned as stretching modes of the methyl group. The aromatic ring stretching modes are observed in the range 1585, 1558cm-1 and 1598, 1569 cm-1 theoretically expected. The C=N stretching modes is observed at1528cm-1experimentally and computed 1528 cm-1. In present case in-plane and out-of-plane CH deformation observed at above and below 1000 cm-1 and good agreement literature values.
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4. Conclusion 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine(BFMPP)has been synthesized and characterized by single crystal X-ray diffraction, FT-IR, 1H & 13CNMR and Mass spectrometry. The X-ray diffraction studies showed that the title BFMPP crystallized in monoclinic space group P21, with cell dimensions a = 4.803(3) Å, b = 9.498(5) Å, c = 15.557(9) Å, β= 93.25 (4)o and Z = 2.The difference in HOMO and LUMO energies supports the charge transfer interaction within the molecule. The calculated HOMO and LUMO energies were used to semi-quantitatively estimate the ionization potential, electron affinity, electronegativity, electrophilicity index, hardness and chemical potential. The crystal surface analysis carried out by Hirshfeld surface studies and fingerprint plots analysis, which facilitates to understanding the type and nature of intermolecular interactions and as well as packing in the solid-state. Acknowledgments The authors are highly thankful to Prof. T.N. Guru Row, SSCU, IISC, Bangalore, India for the collection of diffraction data. Authors are also thankful to the Department of Science and Technology, New Delhi, 7
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Government of India for providing financial assistance and Tumkur University to carry out the project under the DST FAST TRACK [SR/FT/CS-81/2010 (G)] scheme.
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Table 1. Crystallographic data and structure refinement of BFMPP
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C19H14N2O 286.32 0.71073 Monoclinic 4.803(3) 9.498(5) 15.557(9) 93.25(4) 708.6(6) P21 2 293(2) 0.36 x 0.20 x 0.16 1.342 0.084 2.62 to 61.5 -6 ≤ h ≤ 6, -12 ≤ k ≤ 13, -22 ≤ l ≤ 22 14129 4208 0.937 R1 = 0.0609, wR2 = 0.1518 R1 = 0.1665, wR2 = 0.1719 0.15/-0.22
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Formula Formula weight Wavelength(Å) Crystal system a (Å) b (Å) c (Å) β (°) V (Å3) Space group Z T(K) Crystal size (mm3) ρcalcd (g cm-3) μ (mm-1) θ range (°) h / k / l indices Reflections collected Unique reflection, Rint GooF R1[I > 2σ(I)] wR2[all data] Δρmax, Δρmin (e Å-3)
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Table 2. Hydrogen bond geometry (o, Å) in the BFMPP. D–H…A D–H (Å) H...A (Å) D…A (Å) D–H…A (o) i C33-H33B-N31 0.96 2.61(1) 3.5355(1) 162(1) ii Cg1…Cg2 3.5644(1) Cg1…Cg3i 3.6945(1) Cg1, Cg2 and Cg3 are the centroid of the furan ring, pyrimidine and the benzene ring of benzofuran ring respectively. Symmetry codes: (i) -1+x, y, z; (ii) 1+x, y, z;
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Graphical abstract
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Synthesis, Crystal structure, Hirshfeld surface studies and frontier orbitals analysis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine G. Krishnaswamy , P. Krishna Murthy , P.A. Suchetan , Nivedita R Desai , D.B. Aruna Kumar , R. Sreenivasa Rao PII: DOI: Reference:
S2405-8300(17)30025-3 10.1016/j.cdc.2017.06.001 CDC 58
To appear in:
Chemical Data Collections
Received date: Revised date: Accepted date:
25 January 2017 30 May 2017 2 June 2017
Please cite this article as: G. Krishnaswamy , P. Krishna Murthy , P.A. Suchetan , Nivedita R Desai , D.B. Aruna Kumar , R. Sreenivasa Rao , Synthesis, Crystal structure, Hirshfeld surface studies and frontier orbitals analysis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine, Chemical Data Collections (2017), doi: 10.1016/j.cdc.2017.06.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Synthesis, Crystal structure, Hirshfeld surface studies and frontier orbitals analysis of 4-(1-benzofuran2-yl)-2-methyl-6-phenylpyrimidine G. Krishnaswamy,1 P. Krishna Murthy,2 P.A. Suchetan,1 Nivedita R Desai,1 D.B. Aruna Kumar,*1R. Sreenivasa Rao3 1
Department of Studies and Research in Chemistry, University College of Science, Tumkur University, Tumakuru-572 103, Karnataka, India
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Department of Chemistry, Bapatla Engineering College (Autonomous), Acharaya Nagarjuna University Post Graduate Research Centre, Bapatla-522 102, A.P., India
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Department of Chemistry, Bapatla College of Arts and Sciences, Baptla-522 101, A.P., India
Contact email: [email protected]
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4-(benzofuran-2-yl)-2-methyl-6-phenylpyrimidine(BFMPP) has been synthesized and characterized by FTIR, 1H &13CNMR and Mass spectrometry techniques. Single crystals of title compound were grown by slow evaporation solution growth technique at room temperature and crystal structure has been determined by single crystal X-ray diffraction technique. The title compound(BFMPP) crystallizes in monoclinic space group P21, with cell dimensions a = 4.803(3) Å, b = 9.498(5) Å, c = 15.557(9) Å, β= 93.25 (4)o and Z = 2. The crystal structure is stabilized by weak C-H…N intermolecular interactions generating a one dimensional C(4) network propagating along the *100+ direction and two pi…pi interactions. Further, a detailed analysis of the Hirshfeld surfaces facilitating an understanding of the type and nature of intermolecular interactions in the supramolecular structure is made. The calculated HOMO-LUMO energy gap discloses that charge transfer occurs within the molecule.
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Keywords: BFMPP, Crystal structure, X-ray diffraction, Hirshfeld analysis, HOMO-LUMO plots. Specifications Table Subject area X-ray crystallography Compounds 4-(benzofuran-2-yl)-2-methyl-6-phenylpyrimidine Data category Crystallographic data Data acquisition format CIF for crystallography Data type Analyzed Procedure The unit cell parameters and the intensity data at 298K for the title compound was obtained on an Oxford Diffraction Xcalibur Gemini single crystal X-ray diffractometer using graphite monochromated Mo Kα radiation (λ = 0.71073 Å). The CrysAlisPro software was used for data collection, reduction and absorption correction. Data accessibility CCDC:1411045 URL:https://www.ccdc.cam.ac.uk/conts/retrieving.html
1. Rationale
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Heterocycles hold a key point in organic and medicinal chemistry as they act as a bridge between life sciences and biochemical investigations. A significant amount of contemporary investigation is being currently pursued on these compounds worldwide. The pyrimidine rings are nitrogen rich heterocycles, key constituent of many natural, synthetic compounds and shows very interesting pharmacological activity [1-4]. In recent years, pyrimidine derivatives have received significant attention owing to their diverse biological properties, particularly as cytostatic [5-8], immune modulating [9], antitubercular, calcium channel blockers [10], antimicrobial properties [11], herbicides [12] and pesticides [13]. The biological importance of pyrimidine derivatives has motivated significant interest towards the synthesis of 4-(benzofuran-2-yl)-2-methyl-6-phenylpyrimidine(BFMPP) and the structure was characterized well as it would be more useful. Further, various intermolecular interactions are well supported by Hirshfeld surface and fingerprint plots analysis.
2. Experimental 2.1. General remarks
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The reagents and solvents used for synthesis were procured from Spectrochem, Sigma Aldrich and used as such received. Reactions were monitor by analytical thin layer chromatography (TLC) and TLC plates were visualized by exposing UV light, KMnO4 solution or by iodine vapors. The FT-IR spectrum was recorded in KBr pellets using JASCO FTIR-4100 spectrometer in the range of 4000 – 400 cm -1 1
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resolution of ± 2 cm . H & C-NMR spectrum was recorded on JEOL-400 MHz NMR instrument using CDCl3 as solvent. The chemical shifts values (δ) are reported in parts per million (ppm) using TMS as an
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internal standard. Mass spectrum was recorded on Shimadzu-2010EV with APCI and ESI probes.
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2.2. Synthesis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine To a stirred solution of (1-benzofuran-2-yl)-3-phenylprop-2-en-1-one (0.5g, 2.06mmol) in mixture of ethanol: water (4:1, 5 mL), acetamidine hydrochloride (0.11g, 2.06 mmol), KOH (0.12g, 2.2mmol) was added and the reaction mixture refluxed for 6 hours. After completion of reaction indicated by TLC, the reaction mixture was poured into ice cold water and extracted to ethyl acetate (3 x 20 mL). The organic layer washed with water, brine and dried over anhydrous Na2SO4. Evaporate the organic layer under reduced pressure to get crude product. The crude product was purified by column chromatography using silica 60-120 mesh and ethyl acetate: petroleum ether (1:9) as eluent to get desire product (0.39g, yield: 68.4%, M.p: 130-133oC).
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Method of crystallization
100mg of compound was dissolved in 15mL of ethyl acetate and warmed for 5 minutes. The solution was filtered through Whatmann filter paper and resulting solution was kept at room temperature in conical flask with stopper slightly open. After 5 days, the crystals of BFPP were developed; filtered and suitable crystals for single crystal analysis were selected (Scheme-1). 1
H NMR (400MHz, CDCl3): δ 8.20-8.17 (2H, m, Ar-H), 8.05 (1H, s, Py-H), 7.71-7.69 (2H, dd,Ar-H), 7.62-
7.53 (4H, m, Ar-H), 7.43-7.39 (1H, m, Ar-H), 7.32 (1H, m, Ar-H), 2.86 (3H, s, Py-CH3). 2
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C NMR (100 MHz, CDCl3): δ 168.576 (C12), 165.217 (C9), 156.213 (C11), 155.642 (C1), 153.310 (C8),
136.973 (C13), 130.901 (C14 & C18), 128.915 (C15 & C17), 128.295 (C16), 127.278 (C5), 126.313 (C4), 123.510 (C2), 122.248 (C3), 111.670 (C6), 108.906(C7), 108.124 (C10), 26.204 (C19). 3
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Mass (m/z): Calculated: 286.32, Found: 287.59 (M+1)
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Scheme. Synthesis of 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine
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2.3. X-Ray Crystallography A suitable colourless, needle shaped single crystal of the title compound with dimensions of0.36mm x 0.20mm x 0.16mm was selected and data was collected on an Oxford diffraction X caliber Gemini diffractometer with graphite monochromated Mo Kα radiation (λ = 0.71073 Å) at 293 K. The CrysAlisProsoftware [14] was used for data collection, reduction and absorption correction. The structure was solved by direct method and refined by full-matrix least-squares methods on F2 using SHELX-97 [15] available in the WinGX package [16]. All the non-hydrogen atoms were refined with anisotropic thermal parameters. The hydrogen atoms were included in the structure factor calculations and treated using a riding model. Molecular graphics and crystal packing were created using ORTEP [17] and MERCURY [18] packages. The parameter for data collection and structure refinement of compound BFMPP are listed in Table 1.
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2.4. Hirshfeld surfaces The Hirshfeld surface analyses were carried out and fingerprint plots were plotted using Crystal Explorer 3.0 [19-25]. When the CIF files were uploaded into the Crystal-Explorer software, all bond lengths to hydrogen were automatically modified to standard neutron diffraction values, i.e. C–H = 1.083 Å. 3. Data, value and validation 3.1. Crystal and molecular structure description of BFMPP The molecular structure of BFMPP determined by X-ray diffraction is depicted in Figure 1. BFMPP crystallizes in the monoclinic space group P21with cell dimensions a = 4.803(3) Å, b = 9.498(5) Å, c = 15.557(9) Å, β= 93.25 (4)o and Z = 2.The molecule is almost planar with root mean squared deviation (considering non-H atoms) being 0.101 Å. The dihedral angle between the benzene (A), the pyrimidine 3
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ring (B) and the benzofuran ring (C) are 4.79 (A/B), 10.76 (A/C) and 8.42(1)o(B/C) respectively. The crystal structure is stabilized by weak C-H…N intermolecular interactions (Table 2 and Figure 2) running into C(4) chains along *100+ and two pi…pi interactions. Hence, the supra molecular architecture exhibited is one dimensional.
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Figure 1. ORTEP view of the molecule with atom numbering scheme for non-hydrogen atoms
Figure 2. Crystal packing of BFMPP
3.2. Hirshfeld surface analysis The Hirshfeld surfaces of title compound illustrated in Figure 3, showing surfaces that have been mapped over a dnorm(A), shape index (B) and curvedness (C) range of -0.111 to 1.143 Å, -1.0 to 1.0 Å and -4.0 to 0.4 Å, respectively. The predominant interactions between the methyl hydrogen of pyrimidine ring and the nitrogen of pyrimidine ring, which can be seen in the Hirshfeld surfaces as the bright red spot marked as A in Figure 3 and clearly seen in Figure 4. In the 2D fingerprint plots (Figure 5), the C4
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H···N intermolecular interactions appear as two distinct spikes circled with green color. Prominent pairs of sharp spikes of almost equal lengths in the fingerprint plots (Figure 5) are characteristics of nearly equal C(donor)···N(acceptor) distances and generate a one dimensional C(4) network propagating along the [100] direction. The upper spike (Figure 5) corresponds to the donor spike (H atom of methyl group interacting with N-atoms of the pyrimidine ring), with the lower spike being an acceptor spike (Natomsof the pyrimidine ring interacting with H- atom of methyl group). The wings marked in Figure 5 (circled with black) are due to the C···H contacts. A significant difference in terms of H···H contacts appears asspikes (marked as red circles in Figure 5). The relative contribution of the different interactions to the Hirshfeld surface was calculated for title compound. It is evident that the H···H contacts can account forabout 50.5% of the Hirshfeld surface area; the remaining contribution was mostly due to C···H 28.2%,N···H 6.5%, O···H 3.3% and C···C 6.0% interactions, with only minor contribution from C···N, O···C and O···N (maximum 5.5%).
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Figure 3. Hirshfeld surfaces of BFMPP.
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Figure 4. C-H…N intermolecular interactions mapped on dnorm surface.
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Figure 5. 2D Fingerprint plots of BFMPP.
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3.3.Frontier molecular orbital analysis The HOMO-LUMO energy plots of BFMPP has been obtained from Crystal Explorer with Tonto program using DFT/Becke88LYP/6-31G(d) method and the pictorial representation shown in Figure 6. The HOMO (MO 75) lies at -6.28 eV and whereas the LUMO (MO 76) is located at -2.2 eV. In the title compound, the HOMO of π nature is delocalized all over the molecule except phenyl ring, methyl group and LUMO in addition to this on the phenyl ring except methyl group. Accordingly, the HOMO-LUMO transition implies an electron density transfer from the benzofuran ring to phenyl ring through the pyrimidine ring, and that the frontier orbital energy gap is 4.08 eV. The global chemical descriptors associated with a molecular system are: ionization potential (I) = -EHOMO= 6.28, electron affinity (A) = -ELUMO= 2.2, chemical potential (μ) = - (I+A)/2 = -4.24, the global hardness (η) = (I-A)/2 = 2.04 ,softness (ν)= 1/ η = 0.49, electronegativity (χ) = (I+A)/2 = 4.24 and electrophilicity index (ω) = µ2/2η = 4.406 *26,27+. It is seen that the chemical potential of the title compound is negative and it implies that the molecular system is stable. They do not decompose spontaneously into the elements they are made up of. The hardness signifies the resistance towards the deformation of electron cloud of chemical system under small perturbation encountered during the chemical process. 3.4. UV-Visible spectral analysis
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The electronic spectra of title compound calculated at TD-DFT/B3LYP/SDD method using optimized geometry and the calculation are performed in methanol. The electronic spectra of title compound shows an electronic absorption band with maxima 344 nm (Figure S5)and this transition mainly due to the transition HOMO-LUMO that is the π-π transition predicted. The excitation transitions, CI coefficient, excitation energies, oscillator strengths and wavelength can be seen in Table S1.
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Figure 6. HOMO plot and LUMO plot of the title compound (BFMPP).
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3.5. FT-IR spectral analysis FT-IR spectrum of title compound is shown in Figure S1. Vibrational frequencies of title compound calculated at ground state by using B3LYP/DFT/SDD basic set in gas phase(Table S2).The CH stretching frequency of aromatic rings are theoretically assigned at 3181, 3117, 3090 cm-1 for benzofuran ring and 3150 cm-1 for pyrimidine ring. For mono-substituted phenyl ring, the CH stretching modes are expected above 3000 cm-1[28, 29] and DFT calculations give these modes in the range 3120, 3106, 3094 cm -1 and experimentally bands are observed at 3051 cm-1. The CH3 stretching modes are expected in the region 2900-3050 cm-1[28]. The bands observed at 2925 cm-1 and in the range 3060-2939 cm-1 (DFT) are assigned as stretching modes of the methyl group. The aromatic ring stretching modes are observed in the range 1585, 1558cm-1 and 1598, 1569 cm-1 theoretically expected. The C=N stretching modes is observed at1528cm-1experimentally and computed 1528 cm-1. In present case in-plane and out-of-plane CH deformation observed at above and below 1000 cm-1 and good agreement literature values.
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4. Conclusion 4-(1-benzofuran-2-yl)-2-methyl-6-phenylpyrimidine(BFMPP)has been synthesized and characterized by single crystal X-ray diffraction, FT-IR, 1H & 13CNMR and Mass spectrometry. The X-ray diffraction studies showed that the title BFMPP crystallized in monoclinic space group P21, with cell dimensions a = 4.803(3) Å, b = 9.498(5) Å, c = 15.557(9) Å, β= 93.25 (4)o and Z = 2.The difference in HOMO and LUMO energies supports the charge transfer interaction within the molecule. The calculated HOMO and LUMO energies were used to semi-quantitatively estimate the ionization potential, electron affinity, electronegativity, electrophilicity index, hardness and chemical potential. The crystal surface analysis carried out by Hirshfeld surface studies and fingerprint plots analysis, which facilitates to understanding the type and nature of intermolecular interactions and as well as packing in the solid-state. Acknowledgments The authors are highly thankful to Prof. T.N. Guru Row, SSCU, IISC, Bangalore, India for the collection of diffraction data. Authors are also thankful to the Department of Science and Technology, New Delhi, 7
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Government of India for providing financial assistance and Tumkur University to carry out the project under the DST FAST TRACK [SR/FT/CS-81/2010 (G)] scheme.
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Table 1. Crystallographic data and structure refinement of BFMPP
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C19H14N2O 286.32 0.71073 Monoclinic 4.803(3) 9.498(5) 15.557(9) 93.25(4) 708.6(6) P21 2 293(2) 0.36 x 0.20 x 0.16 1.342 0.084 2.62 to 61.5 -6 ≤ h ≤ 6, -12 ≤ k ≤ 13, -22 ≤ l ≤ 22 14129 4208 0.937 R1 = 0.0609, wR2 = 0.1518 R1 = 0.1665, wR2 = 0.1719 0.15/-0.22
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Formula Formula weight Wavelength(Å) Crystal system a (Å) b (Å) c (Å) β (°) V (Å3) Space group Z T(K) Crystal size (mm3) ρcalcd (g cm-3) μ (mm-1) θ range (°) h / k / l indices Reflections collected Unique reflection, Rint GooF R1[I > 2σ(I)] wR2[all data] Δρmax, Δρmin (e Å-3)
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Table 2. Hydrogen bond geometry (o, Å) in the BFMPP. D–H…A D–H (Å) H...A (Å) D…A (Å) D–H…A (o) i C33-H33B-N31 0.96 2.61(1) 3.5355(1) 162(1) ii Cg1…Cg2 3.5644(1) Cg1…Cg3i 3.6945(1) Cg1, Cg2 and Cg3 are the centroid of the furan ring, pyrimidine and the benzene ring of benzofuran ring respectively. Symmetry codes: (i) -1+x, y, z; (ii) 1+x, y, z;
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Graphical abstract
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