Synthesis and X-Ray Crystal Structure of New Substituted 3-4'-Bipyrazole Derivatives. Hirshfeld Analysis, DFT and NBO Studie

Synthesis and X-Ray Crystal Structure of New Substituted 3-4'-Bipyrazole Derivatives. Hirshfeld Analysis, DFT and NBO Studie

crystals Article Synthesis and X-ray Crystal Structure of New Substituted 3-40-Bipyrazole Derivatives. Hirshfeld Analysis, DFT and NBO Studies Ahmed T. A. Boraei 1,*, Matti Haukka 2 , Ahmed A. M. Sarhan 3, Saied M. Soliman 4 , Abdullah Mohammed Al-Majid 5 and Assem Barakat 5,* 1 Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt 2 Department of Chemistry, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, Finland; matti.o.haukka@jyu.fi 3 Chemistry Department, Faculty of Science, Arish University, Al-Arish 45511, Egypt; [email protected] 4 Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt; [email protected] 5 Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; [email protected] * Correspondence: [email protected] (A.T.A.B.); [email protected] (A.B.); Tel.: +966-11467-5901 (A.T.A.B.); Fax: +966-11467-5992 (A.B.) Abstract: A new compounds named 3-40-bipyrazoles 2 and 3 were synthesized in high chemical yield from a reaction of pyran-2,4-diketone 1 with aryl hydrazines under thermal conditions in MeOH. Compound 2 was unambiguously confirmed by single-crystal X-ray analysis. It crystalizes in a triclinic crystal system and space group P-1. Its crystal structure was found to be in good agreement Citation: Boraei, A.T.A.; Haukka, M.; with the spectral characterizations. With the aid of Hirshfeld calculations, the H ... H (54.8–55.3%) Sarhan, A.A.M.; Soliman, S.M.; and H ... C (28.3–29.2%) intermolecular contacts are the most dominant, while the O ... H (5.8–6.5%), Al-Majid, A.M.; Barakat, A. Synthesis N ... H (3.8–4.6%) and C ... C (3.0–4.9%) are less dominant. The compound has a polar nature and X-ray Crystal Structure of New with a net dipole moment of 6.388 Debye. The BD(2)C31-C32!BD*(2)N4-C34 (27.10 kcal/mol), Substituted 3-40-Bipyrazole ! ! Derivatives. Hirshfeld Analysis, DFT LP(1)N5 BD*(2)C31-C32 (36.90 kcal/mol), BD(1)C32-C34 BD*(1)C18-C31 (6.78 kcal/mol) and and NBO Studies. Crystals 2021, 11, LP(1)N4!BD*(1)N5-C31 (7.25 kcal/mol) are the strongest π!π*, n!π*, σ-σ* and n!σ* intramolec- 953. https://doi.org/10.3390/ ular charge transfer processes, respectively. cryst11080953 Keywords: pyran-2,4-dione; bipyrazole; Hirshfeld analysis; NBO; DFT Academic Editor: Paul R. Raithby Received: 10 July 2021 Accepted: 13 August 2021 1. Introduction Published: 15 August 2021 Pyranones are examples of ester-functional heterocyclic molecules which have been employed as a synthon for several targeted organic compounds [1]. These synthetic Publisher’s Note: MDPI stays neutral pyranones have been reported to have several applications related to medicine, including with regard to jurisdictional claims in HIV protease inhibitors [2], anticonvulsants [3], antitumor [4,5], antifungal [3], and anti- published maps and institutional affil- microbial [6] agents, and as plant-growth regulators [2,7]. On the other hand, some other iations. naturally occurring pyranones were reported to have interesting actions against bacteria, and also have cytotoxic effects (e.g., Marin natural product, Pectinatone) [8]. Another representative example works against inflammation and rheumatism (e.g., Bufalin) [9], and many others such as Pentylpyran-2-one [10] and Griseulin [11,12] exhibited antibiotic Copyright: © 2021 by the authors. and mosquitocidal effects, respectively. These substituted pyranones scaffold have been Licensee MDPI, Basel, Switzerland. studied extensively in the literature [13–15]. This article is an open access article Heterocycles comprising five-membered rings with two adjacent nitrogen atoms are distributed under the terms and called pyrazoles, and these pharmacophore-containing heterocycles have been shown to conditions of the Creative Commons have several therapeutic applications. They were reported to have interesting actions Attribution (CC BY) license (https:// against different diseases, including cancer, inflammation, and bacterial infection, and creativecommons.org/licenses/by/ 4.0/). can also be used as analgesic and antidepressant agents [16–18]. Pyrazolines are also Crystals 2021, 11, 953. https://doi.org/10.3390/cryst11080953 https://www.mdpi.com/journal/crystals Crystals 2021, 11, 953 2 of 13 widely distributed in nature in the cells of animals and plants, and also exist in alkaloids, pigments, and vitamins [19]. Many approaches have been reported for the synthesis of pyrazoline scaffolds [20–26]. One representative common approach is a reaction of carbonyl compounds with hydrazines under thermal conditions [27], in addition to other reported methods for the synthesis of pyrazolines scaffold, such as the metal catalyzed approach [28]. In this context and continuation of our research program [29,30] here, we are reporting a facile and direct straightforward approach for the synthesis of substituted 3-40-bipyrazoles in a catalyst free one-pot reaction, from pyran-2,4-dione and arylhydrazines. The structure of the newly synthesized 3-40-bipyrazoles was confirmed by using different spectral charac- terizations. The X-ray structure of the bipyrazole 2 was further confirmed by single-crystal X-ray structure. Additionally, DFT calculations were used to predict its electronic parame- ters and calculate the different intramolecular charge transfer processes which stabilize the structure of 2. 2. Materials and Methods 2.1. General Melting points were measured using a melting-point apparatus (SMP10) in open capillaries and are uncorrected. The progress of the reaction was observed by thin-layer chromatography (TLC), and detection was achieved by UV light. Nuclear magnetic res- 1 13 onance ( H- and C-NMR) spectra were determined in DMSO-d6 and were recorded on a Bruker AC 400 MHz spectrometer using tetramethylsilane as an internal standard. Chemical shifts are described in d (ppm) and coupling constants are given in Hz. Ele- mental analysis was performed on a Flash EA-1112 instrument. X-ray crystallographic analysis was collected on a Rigaku Oxford Diffraction Supernova diffractometer using Cu Kα radiation. The UV-Vis electronic spectra were recorded in EtOH using a T90+UV/VIS spectrometer. 2.2. Synthesis of 2 and 3 A methanolic solution of pyran-2,4-dione 1 (1.0 mmol) was mixed with phenylhy- drazine or 4-chlorophenylhydrazine HCl (2.2 mmol) in methanol (10 mL), then the mixture was refluxed for 4 h. The resulting solutions were cooled to room temperature. The formed precipitates were collected by filtration and dried. Purifications were performed by re- crystallization from EtOH in case of 2 and DCM/MeOH in case of 3. Only good quality single crystals were obtained for 2, which were found to be suitable for single-crystal X-ray diffraction analysis. 2.2.1. 2,20,5,50-Tetraphenyl-10,20-Dihydro-2H,30H-[3,40-Bipyrazol]-30-One (2) ◦ 1 Yield: 88%, m.p. 270–271 C. H-NMR (400 MHz, DMSO-d6) δ 12.01 (s, 1H), 7.99 (d, J = 7.6 Hz, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.53 (t, J = 7.6 Hz, 2H), 7.48 (t, J = 7.6 Hz, 13 2H),7.40–7.23 (m, 12H), 7.16 (s, 1H); C-NMR (101 MHz, DMSO-d6) δ 151.31, 140.28, 135.72, 133.33, 129.55, 129.30, 129.12, 128.79, 128.47, 127.57, 126.79, 126.59, 125.75, 124.21, 122.07, 108.40 (Figures S1 and S2 (Supplementary data)); CHN analysis for [C30H22N4O] C, 79.27; H, 4.88; N, 12.33; O, 3.52 found C, 79.38; H, 4.99; N, 12.21. UV-Vis (EtOH): 264 nm (Figure S7 (Supplementary data)). 2.2.2. 2,20-Bis(4-Chlorophenyl)-5,50-Diphenyl-10,20-Dihydro-2H,30H-[3,40- Bipyrazol]-30-One (3) ◦ 1 Yield: 61%, m.p. 227–228 C. H-NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.97 (d, J = 7.6 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H), 7.48(t, J = 7.6 Hz, 2H), 13 7.41–7.27 (m, 10H), 7.16 (s, 1H); C-NMR (101 MHz, DMSO-d6) δ 151.68, 138.97, 135.66, 133.04, 131.88, 130.34, 129.54, 129.33, 129.16, 129.04, 128.91, 128.83, 128.65, 126.67, 126.36, 125.80, 125.65, 123.35, 108.53 (Figures S3 and S4 (Supplementary data)); CHN analysis for Crystals 2021, 11, 953 3 of 13 [C30H20Cl2N4O] C, 68.84; H, 3.85; Cl, 13.55; N, 10.70 found C, 68.99; H, 3.86; Cl, 13.67; N, 10.62. UV-Vis (EtOH): 269 nm and 320 nm (Sh); (Figure S7 (Supplementary data)). 2.3. Crystal Structure Determination The collecting experimental data for compound 2 are provided in the Supplementary Information. 2.4. Computational Study Protocols All software and protocols employed for Hirshfeld surface analysis and DFT calcula- tions are provided in the Supplementary Information. 3. Results and Discussion 3.1. Synthesis of 2 and 3 In our recent publication [29], we reported that the pyran-2,4-diketone 1 could react with different amines and also amino acid esters to afford b-enaminones in a region- selective conversion. Interestingly, when pyran-2,4-dione 1 was reacted with aromatic hydrazines (phenylhydrazine and 4-chlorophenylhydrazine HCl) in MeOH under reflux conditions, the 3,40-bipyrazol-30-ones 2 and 3 were obtained. We assumed that the reaction occurred under a set of chemical transformations, including keto-enol tautomerism, aryl hydrazone formation, ring opening–closure, then keto-enol tautomerism, followed by aryl hydrazone formation with the second molecule of aryl hydrazine, and finally, ring closure upon the dehydration process (Scheme1).

View Full Text

Details

  • File Type
    pdf
  • Upload Time
    -
  • Content Languages
    English
  • Upload User
    Anonymous/Not logged-in
  • File Pages
    13 Page
  • File Size
    -

Download

Channel Download Status
Express Download Enable

Copyright

We respect the copyrights and intellectual property rights of all users. All uploaded documents are either original works of the uploader or authorized works of the rightful owners.

  • Not to be reproduced or distributed without explicit permission.
  • Not used for commercial purposes outside of approved use cases.
  • Not used to infringe on the rights of the original creators.
  • If you believe any content infringes your copyright, please contact us immediately.

Support

For help with questions, suggestions, or problems, please contact us