Synthesis, structural elucidation and X-ray crystallographic studies of 1-(3,5-bis(trifluoromethyl)phenyl)-3-(dimethylamino)prop-2-en-1-one European Journal of Chemistry 10 (4) (2019) 381-385 European Journal of Chemistry View Journal Online View Article Online Synthesis, structural elucidation and X-ray crystallographic studies of 1-(3,5-bis(trifluoromethyl)phenyl)-3-(dimethylamino)prop-2-en-1-one Stability Nongrum , Susma Das , Shikpika Khanikar and Jai Narain Vishwakarma * Organic Research Laboratory, Department of Chemical Science, Assam Don Bosco University, Tapesia Gardens, Kamarkuchi, Sonapur, 782 402 Assam, India stabilitynongrum@gmail.com (S.N.), susmadas91@gmail.com (S.D.), shilpikakhanikar11@gmail.com (S.K.), jnvishwakarma@rediffmail.com (J.N.V.) * Corresponding author at: Organic Research Laboratory, Department of Chemical Science, Assam Don Bosco University, Tapesia Gardens, Kamarkuchi, Sonapur, 782 402 Assam, India. Tel: +91.91270.51222 Fax: +91.91270.51222 e-mail: jnvishwakarma@rediffmail.com (J.N. Vishwakarma). 10.5155/eurjchem.10.4.381-385.1922 Received: 03 September 2019 Received in revised form: 24 September 2019 Accepted: 06 October 2019 Published online: 31 December 2019 Printed: 31 December 2019 A new enaminone was synthesized by reacting 3,5-bis-(trifluoromethyl)acetophenones and N,N-dimethylformamide dimethyl acetal and its detailed structural and crystalline properties were studied. The crystal data were found to be as C13H11F6NO, monoclinic, space group P21/c (no. 14), a = 8.1556(8) Å, b = 24.877(3) Å, c = 7.6067(7) Å, β = 116.745(6)°, V = 1378.2(3) Å3, Z = 4, T = 293(2) K, μ(MoKα) = 0.150 mm-1, Dcalc = 1.500 g/cm3, 40777 reflections measured (5.594° ≤ 2Θ ≤ 56.786°), 3413 unique (Rint = 0.1040, Rsigma = 0.0584) which were used in all calculations. The final R1 was 0.0771 (I > 2σ(I)) and wR2 was 0.2541 (all data). Enaminones Acetophenone Trifluoromethyl X-ray crystallography Geometric parameters N,N-Dimethylformamide dimethyl acetal Cite this: Eur. J. Chem. 2019, 10(4), 381-385 Journal website: www.eurjchem.com 1. Introduction Fluorine containing naturally occurring compounds are very few to be found [1], however, about 25% of the marketed drug molecules are embedded with fluorine atoms [2]. Fluorine, the most electronegative element in periodic table and also capable of forming hydrogen-bond, can induce a strong plorization on its neighbouring elements [1]. Hence, the presence of fluorinated groups in biologically active molecular architectures should influence the electronic and binding properties, metabolic stability and lipophilicity enhancing the drug optimization capablities of a lead molecule. Trifluoro- methylated alkenes are considered very important pharma- cophores and have been gaining propularity in pharma- ceuticals and agro-sciences [3]. A number of fluorine substituted drugs are available in the market, which are prescribed to cure a wide range of diseases [4]. Encouraged by these advantages, a good degree of attention has been invested towards the development of newer synthetic strategies for mono-, di- and tri-fluorinated molecular entities [5,6]. Literature reveals that enaminones are very versatile predecessors for synthesizing novel heterocyclic systems as they can react with both electrophiles and nucleophiles [7,8]. They also process many biological properties like antitumor, antimicrobial, anti-inflammatory, analgesic, ulcerogenic agents [7]. Promoted by these observations and in continuation with our earlier studies on enaminones [9,10], we decided to synthesise the title compound, the results of which are presented herein (Scheme 1). 2. Experimental 2.1. Instrumentation 1H NMR (300 MHz) and 13C NMR (75 MHz) were recorded on Bruker AV II 300 MHz. The chemical shift (δ ppm) and the coupling constants (Hz) are reported in the standard fashion with reference to TMS as standard in CDCl3. The FT-IR spectra were recorded on Perkin Elmer Spectrum II spectrophoto- meter. The melting point was recorded using open capillary method and is uncorrected. X-ray diffraction data of the crystal were recorded using a Bruker APEX-II CCD diffractometer [11]. The electro spray mass spectra were recorded on a THERMO Finnigan LCQ Advantage max ion trap mass spectrometer. ABSTRACT RESEARCH ARTICLE KEYWORDS European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2019 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.10.4.381-385.1922 http://dx.doi.org/10.5155/eurjchem.10.4.381-385.1922 https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.4.381-385.1922&domain=pdf&date_stamp=2019-12-31 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.10.4.381-385.1922 mailto:stabilitynongrum@gmail.com mailto:susmadas91@gmail.com mailto:shilpikakhanikar11@gmail.com mailto:jnvishwakarma@rediffmail.com mailto:jnvishwakarma@rediffmail.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.4.381-385.1922&domain=pdf&date_stamp=2019-12-31� 382 Nongrum et al. / European Journal of Chemistry 10 (4) (2019) 381-385 CF3 F3C N Me Me O CF3 F3C Me O Toluene, Reflux 1 3 N CH OMe OMe Me Me 20 h 2 Scheme 1 Figure 1. Molecular structure of the title compound. 2.2. Synthesis A mixture of 3,5-bis-(trifluoromethyl)acetophenone (1) (1 mmol) and N,N-dimethylformamide dimethyl acetal (2) (2 mmol) in 3 mL toluene was refluxed for 20 hours. Completion of the reaction was monitored by TLC. At the end of the reaction, solvent was removed under reduced pressure to give a viscous mass which on trituration with hexane gave a practically pure yellow solid in 87% yield. Further purification was achieved by column chromatography on Silica Gel (60-120 mesh) using ethylacetate-hexane (20%) mixture as mobile phase. 1-(3, 5-Bis(trifluoromethyl)phenyl)-3-(dimethylamino)prop- 2-en-1-one (3): Colour: Yellow. Yield: 87%. M.p.: 95-96 °C. FT- IR (KBr, ν, cm-1): 1676 (C=O) (ketone), 1558 (C=C) (aromatic), 1348 (C-N) (amine), 1295 (C-F), 910 (C-H) (aromatic), 662 (C- H) (aromatic). 1H NMR (300 MHz, CDCl3, δ, ppm): 2.99 (s, 3H, CH3), 3.22 (s, 3H, CH3), 5.67 (d, 1H, J = 12 Hz, C2H), 7.91 (d, 1H, J = 12 Hz, C3H), 7.94 (s, 1H, Ar-H), 8.32 (s, 2H, Ar-H). 13C NMR (75 MHz, CDCl3, δ, ppm): 37.7 (1C, CH3), 45.5 (1C, CH3), 91.1 (1C, C2), 123.5 (2C, CF3), 124.3 (1C, C4’, Aromatic), 127.7 (2C, C2’, C6’, Aromatic), 131.7 (2C, C3’, C5’, Aromatic), 142.5 (1C, C1’, Aromatic), 155.7 (1C, C3), 184.7 (1C, C1). MS (ESI, m/z (%)): 312 ([MH]+, 100%), 313, 314, 334, 335. 2.3. Crystallographic details Block, colorless crystals of the compound were obtained by dissolving the compound in ethanol and then allowing it to recrystallize slowly. The structure was solved by direct methods (SHELXS97) [12] and refined by full-matrix least- squares based on F2. All calculations were carried out using the WinGX [13] system version 1.80.05. All the non-H-atoms were refined in the anisotropic approximation. The threshold expression of F2>2sigma(F2) is used only for calculating R- factors (gt) etc. H-atoms were located at calculated positions. Figure 2 shows the packing pattern of the crystal, of its components in three dimensional lattice. 3. Results and discussion 3.1. Spectral analysis The FT-IR spectra showed a bands at 1676 cm-1 for C=O, 1558 cm-1 for C=C, 1348 cm-1 for C-N, 1295 cm-1 for C-F and 910 cm-1 and 662 cm-1 for aromatic C-H bonds. The 1H NMR spectra of compound 3 exhibited two distinct singlets at δ 2.99 and 3.22 ppm for the two methyl protons of NMe2 group indicating that the two methyl groups are in different environments due the double bond character of the C-N bond. The vinylic protons resonated as doublets at δ 5.67 and 7.91 ppm with coupling constant of 12.0 Hz, thus supporting trans geometry. The aromatic protons appeared as singlets at δ 7.94 ppm for one proton and at δ 8.32 ppm for two protons. In the 13C NMR spectra of compound 3, the two methyl group carbon atoms showed signals at δ 37.7 and 45.5 ppm. The vinylic carbon atoms C3 and C2 resonated at δ 91.1 and 155.7 ppm, respectively. The carbonyl carbon signal was found at δ 184.7 ppm as expected. The 13C NMR spectra of the aromatic ring was very interesting due to coupling pattern with fluorine atoms. Thus, the carbon atoms of the CF3 groups gave quartet at δ 123.5 ppm with coupling constant of 270 Hz and the aromatic carbon atoms C3’ and C5’ appeared as quartet at δ 131.7 ppm with a coupling constant of 132 Hz. The C4’ of the aromatic ring resonated at δ 124.3 ppm as a septet with a coupling constant 3.75 Hz and C2’ and C6’ appeared as a doublet at δ 127.7 ppm with J = 3 Hz. The C1’ carbon was located at δ 142.5 ppm. The mass spectra of compound 3 showed a base peak for MH+ at 312 and other peaks at 313, 314, 334 and 335 m/z. Dimethylformamide-dimethylacetal undergoes cleavage under thermal conditions to give the oxo-stabilized carbenium ion A, which acting as an electrophile reacts with enolized acetophenone 1 to give an intermediate B. Assisted by the methoxide ion B is finally converted into the desired formaylated acetophenone 3 as shown in Scheme 2. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.381-385.1922 Nongrum et al. / European Journal of Chemistry 10 (4) (2019) 381-385 383 F3C CF3 C H2 O CF3 F3CH CH2 O + H F3C CF3 O H OMe NMe2 F3C CF3 O NMe2 1 3 N C Me Me OMe OMe H Heat N C Me Me OMe H N C Me Me OMe H 2 + A A B OMe OMe Scheme 2 3.2. Crystal structure The compound 1-(3,5-bis(trifluoromethyl)phenyl)-3-(di methylamino)prop-2-en-1-one (C13H11F6NO) crystallized in a monoclinic cell (space group P2(1)/c) obtained by phi and ῳ scans, refinement on F2, R[F2>2σ(F2)] = 0.0771, wR(F2) = 0.2541, 234 parameters and radiation source is from fine- focus sealed tube. All the conditions used for the measurement of the crystal structure is shown in Table 1 and 2 along with their atomic coordinates and displacement parameters. The structural parameters including bond distances and bond angles for compound 3 are listed in Table 3. In the crystal packing structure, no significant hydrogen bond was found. However, a short intermolecular contact is observed between O1 and H6 atoms. Table 1. Crystal data and structure refinement for the title compound. Parameters Obtained specification CCDC No 194391 Empirical formula C13H11F6NO Formula weight 311.23 Temperature (K) 293(2) Crystal system Monoclinic Space group P21/c a (Å) 8.1556(8) b (Å) 24.877(3) c (Å) 7.6067(7) α (°) 90 β (°) 116.745(6) γ (°) 90 Volume (Å3) 1378.2(3) Z 4 ρcalc (g/cm3) 1.500 μ (mm-1) 0.150 F(000) 632.0 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 5.594 to 56.786 Index ranges -10 ≤ h ≤ 10 -33 ≤ k ≤ 32 -10 ≤ l ≤ 10 Reflections collected 40777 Independent reflections 3413 [Rint = 0.1040, Rsigma = 0.0584] Data/restraints/parameters 3413/0/234 Goodness-of-fit on F2 1.051 Final R indexes [I≥2σ (I)] R1 = 0.0771, wR2 = 0.2062 Final R indexes [all data] R1 = 0.1600, wR2 = 0.2541 Largest diff. peak/hole (e.Å-3) 0.40/-0.37 (a) (b) Figure 2. (a) Packing of the crystal in three-dimensional lattice, (b) Short contact formed between oxygen and hydrogen. 4. Conclusion In this article, we report the successful synthesis of a new enaminone, which may act as a building block for numerous hitherto unreported novel molecules. Its spectral charac- terization has been studied. Its crystalline characterization shows that it adopts trans-configuration. The bond angles of C1-C7-C8, C7-C8-C9 and C8-C9-N1 are found to be 118.4(3)°, 119.8(3)°, and 128.2(3)°, respectively. These obtained values suggested that a planer structure in the molecule. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.381-385.1922 384 Nongrum et al. / European Journal of Chemistry 10 (4) (2019) 381-385 Table 2. Fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for compound 3. Ueq is defined as 1/3 of of the trace of the orthogonalized UIJ tensor. Atom x y z U(eq) O1 3230(3) 2259.4(9) 6561(3) 64.4(7) N1 -1553(4) 1721.1(11) 1929(4) 77.4(12) F1 6340(6) 4483.3(14) 10432(5) 171.6(18) F2 6980(5) 3681.5(16) 11068(5) 161.4(17) F3 4873(6) 4012(2) 11429(5) 170.5(18) F4 1000(5) 4321.5(11) 1441(4) 125.2(12) F5 3012(5) 4859.9(12) 3341(5) 136.5(14) F6 435(5) 4813.5(13) 3323(5) 138.7(13) C1 2592(4) 3177.6(12) 5857(5) 47.5(8) C2 3802(5) 3330.8(15) 7763(5) 53.2(8) C3 4321(5) 3861.5(14) 8190(5) 57.9(9) C4 3650(5) 4251.5(16) 6724(6) 63.3(10) C5 2465(5) 4099.9(13) 4826(5) 56.3(9) C6 1920(5) 3566.5(13) 4392(5) 50.8(8) C7 2107(4) 2591.0(12) 5458(4) 46.9(8) C8 385(4) 2451.2(14) 3854(5) 48.9(8) C9 -43(5) 1925.1(14) 3381(5) 48.8(8) C10 -1716(8) 1146.7(18) 1520(8) 80.9(13) C11 -3019(6) 2067(2) 602(7) 67.4(11) C12 1754(6) 4517.1(16) 3240(7) 56.8(8) C13 5627(7) 4013.7(19) 10238(7) 82.7(13) Table 3. Bond lengths and angles for compound 3. Atom-Atom Bond length (Å) Atom-Atom Bond length (Å) O1-C7 1.238(3) C3-C4 1.391(5) C8-C9 1.360(5) C3-C13 1.487(6) C8-C7 1.428(4) C5-C4 1.380(5) C2-C1 1.390(5) C5-C12 1.496(5) C2-C3 1.380(5) F4-C12 1.315(5) C9-N1 1.330(4) F5-C12 1.310(5) C7-C1 1.507(4) C12-F6 1.329(5) C1-C6 1.389(4) C13-F1 1.283(5) C6-C5 1.391(4) C13-F2 1.293(5) N1-C11 1.450(5) C13-F3 1.304(6) N1-C10 1.456(5) Atom-Atom-Atom Bond angles (°) Atom-Atom-Atom Bond angles (°) C9-C8-C7 119.8(3) C6-C5-C12 120.2(3) C3-C2-C1 120.4(3) C4-C5-C6 120.5(3) N1-C9-C8 128.2(3) C4-C5-C12 119.3(3) O1-C7-C8 124.1(3) C5-C4-C3 119.0(3) O1-C7-C1 117.5(3) F4-C12-C5 114.3(3) C8-C7-C1 118.4(3) F4-C12-F6 104.2(4) C2-C1-C7 118.3(3) F5-C12-C5 113.3(4) C6-C1-C2 119.0(3) F5-C12-F4 106.8(4) C6-C1-C7 122.7(3) F5-C12-F6 105.4(4) C1-C6-C5 120.3(3) F6-C12-C5 112.0(4) C9-N1-C11 121.2(3) F1-C13-C3 115.2(4) C9-N1-C10 120.9(3) F1-C13-F2 106.4(4) C11-N1-C10 117.8(4) F1-C13-F3 104.7(4) C2-C3-C4 120.7(3) F2-C13-C3 113.6(4) C2-C3-C13 119.3(4) F2-C13-F3 102.9(5) C4-C3-C13 120.0(3) F3-C13-C3 112.8(4) Acknowledgements The authors would like to thank Rev. Fr. Dr. Stephen Mavely, Vice Chancellor, Assam Don Bosco University for providing infrastructure for the execution of this work. The authors also express their heart-full gratitude to Mr. Tridib Ranjan Nath and Mr. Biraj Jyoti Borah, SAIC, Tezpur University, Napaam for recording the XRD spectra. The authors are very much grateful to Mr. Farlando Diengdoh, Department of Chemistry, St. Anthony’s College, Shillong for his generous help extended for solving the XRD spectra. Supporting information CCDC-194391 contains the supplementary crystallo- graphic data for this paper. These data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/, or by e- mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have adhered to. Sample availability: Samples of the compounds are available from the author. Funding This investigation was funded by the Department of Biotechnology, Government of India, India. ORCID Stability Nongrum http://orcid.org/0000-0002-2427-6007 Susma Das http://orcid.org/0000-0002-2391-8792 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.381-385.1922 https://www.ccdc.cam.ac.uk/structures/ mailto:data_request@ccdc.cam.ac.uk http://orcid.org/0000-0002-2427-6007 http://orcid.org/0000-0002-2391-8792 Nongrum et al. / European Journal of Chemistry 10 (4) (2019) 381-385 385 Shikpika Khanikar http://orcid.org/0000-0001-9845-2002 Jai Narain Vishwakarma http://orcid.org/0000-0001-9068-4554 References [1]. Musumeci, D.; Irace, C.; Santamaria, R.; Montesarchio, D. Med. Chem. Commun. 2013, 4, 1405-1410. [2]. Wang, J.; Sanchez-Rosello, M.; Acena, L. 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SHELXS-97 and SHELXL-97, Program for Crystal Structure Solution and Refinement, University of Gottingen, Gottingen, 1997 [13]. Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837-838. Copyright © 2019 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.381-385.1922 http://orcid.org/0000-0001-9845-2002 http://orcid.org/0000-0001-9068-4554 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Instrumentation 2.2. Synthesis 2.3. Crystallographic details 3. Results and discussion 3.1. Spectral analysis 3.2. Crystal structure 4. Conclusion Acknowledgements Supporting information Disclosure statement Funding ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: