Generic placeholder image

Current Chinese Chemistry

Editor-in-Chief

ISSN (Print): 2666-0016
ISSN (Online): 2666-0008

Research Article

Geometric Isomerism and DFT Theoretical Explanation of the Unexpected Formation of N, N-disubstituted Formamidines from 2-amino-3-cyano-4.6- diarylpyridines

Author(s): El-sayed M. Abdelrehim* and Doaa S. El-Sayed

Volume 1, Issue 1, 2021

Published on: 23 January, 2020

Page: [21 - 29] Pages: 9

DOI: 10.2174/2666001601666200123150220

Abstract

Introduction: Unexpected series of N,N-disubstituted formamidines were obtained upon the reaction of 2-amino-3-cyano-4.6-diarylpyridines with triflouroroacetic anhydride (TFAA) in dimethyl formamide (DMF).

Methods: The syn/anti ratio of N,N-disubstituted formamidines was calculated by applying the 1H-NMR additivy increment rule. The mechanism of formamidine formation is suggested using the experimental results, 1H NMR and 13C NMR spectroscopy and successfully computed with DFT calculations using the B3LYP functional and 6-311G (p,d) basis set.

Results: The reaction mechanism classified as unexpected nucleophilic attack reaction of the solvent (DMF) on the carbonyl group leaving a positively charged intermediate which was attacked with nitrogen atom of the amine form N,N-disubstituted formamidines. Bond lengths and Mulliken atomic charges were calculated to support the reliability of the predicted reaction mechanism. The activation energy of each species appears in the reaction pathway was calculated.

Conclusion: HOMO-LUMO analysis showed that the reaction pathway is preferred to proceed through the suggested mechanism. It is clear that DMF is not the appropriate solvent in the case of preparation of triflouroacetamide.

Keywords: Formamidines, Triflouroroacetic anhydride, syn/anti ratio, DFT calculations, HOMO-LUMO, geometric isomerism.

Graphical Abstract
[1]
Donetti, A.; Cereda, E.; Bellora, E.; Gallazzi, A.; Bazzano, C.; Vanoni, P.; Del Soldato, P.; Micheletti, R.; Pagani, F.; Giachetti, A. (Imidazolylphenyl)formamidines. A structurally novel class of potent histamine H2 receptor antagonists. J. Med. Chem., 1984, 27(3), 380-386.
[http://dx.doi.org/10.1021/jm00369a025] [PMID: 6142117]
[2]
Furth, P.S.; Reitman, M.S.; Gentles, R.; Cook, A.F. Solid-phase synthesis of novel amino-ether derivatives‏. Tetrahedron Lett., 1997, 38, 6643.
[http://dx.doi.org/10.1016/S0040-4039(97)01579-7]
[3]
Goto, T.; Sakashita, H.; Murakami, K.; Sugiura, M.; Kondo, T.; Fukaya, C. Novel histamine H3 receptor antagonists: synthesis and evaluation of formamidine and S-methylisothiourea derivatives. Chem. Pharm. Bull. (Tokyo), 1997, 45(2), 305-311.
[http://dx.doi.org/10.1248/cpb.45.305] [PMID: 9118445]
[4]
(a)Bohme, F.; Kunert, C.; Klinger, C.; Komber, H. Structural influences on the properties of aromatic polyamidines. Macromol. Symp., 1998, 128, 183.
[http://dx.doi.org/10.1002/masy.19981280118]
(b)Bohme, F.; Klinger, C.; Komber, H.; Haussler, L.; Jehnichen, D. Synthesis and properties of polyamidine. J. Polym. Sci. A Polym. Chem., 1998, 36, 929.
[http://dx.doi.org/10.1002/(SICI)1099-0518(19980430)36:6<929:AID-POLA8>3.0.CO;2-B]
[5]
Rudyk, H.; Knaggs, M.H.; Vasiljevic, S.; Hope, J.; Birkett, C.; Gilbert, I.H. Synthesis and evaluation of analogues of Congo red as potential compounds against transmissible spongiform encephalopathies. Eur. J. Med. Chem., 2003, 38(6), 567-579.
[http://dx.doi.org/10.1016/S0223-5234(03)00081-3] [PMID: 12832128]
[6]
Mehdi, S.; Mohsen, M.; Akbar, H. A new and green synthesis of formamidines by γ-Fe2O3@ SiO2–HBF4 nanoparticles as a robust and magnetically recoverable catalyst. J. Mol. Structure, 2012, 1027, 156-161.
[7]
Marchildon, L.; Daneault, C.; Leduc, C.; Sain, M.M. Deinking conditions for yellow directory using formamidine sulfinic acid as a repulping chemical. Cellul. Chem. Technol., 1996, 30, 473.
[8]
Norihiko, T.; Okiko, M.; Takeaki, N. Efficient synthesis of benzofurans utilizing [3,3]- sigmatropic rearrangement triggered by N‐trifluoroacetylation of oxime ethers: short synthesis of Natural 2‐Arylbenzofurans. Eur. JOC, 2007, 9, 1491.
[http://dx.doi.org/10.1002/ejoc.200601001]
[9]
Delarue, S.; Girault, S.; Ali, F.D.; Maes, L.; Grellier, P. Sergheraert, one-pot synthesis and antimalarial activity of formamidine derivatives of 4-aminoquinolie. C. Chem. Pharm. Bull. (Tokyo), 2001, 49, 933.
[http://dx.doi.org/10.1248/cpb.49.933] [PMID: 11515580]
[10]
Watkins, W.M.; Sixsmith, D.G.; Spencer, H.C.; Boriga, D.A.; Kariuki, D.M.; Kipingor, T.; Koech, D.K. Effectiveness of amodiaquine as treatment for chloroquine-resistant Plasmodium falciparum infections in Kenya. Lancet, 1984, 1(8373), 357-359.
[http://dx.doi.org/10.1016/S0140-6736(84)90410-0] [PMID: 6141423]
[11]
Meesala, R.; Arshad, A.S.M.; Mordi, M.N.; Mansor, S.M. A facile synthesis of (carbazolyl) formamidines. Tetrahedron Lett., 2014, 10, 123.
[12]
Delarue, S.; Sergheraert, C. A convenient activator for the synthesis of formamidines‏. Tetrahedron Lett., 1999, 40, 5487.
[http://dx.doi.org/10.1016/S0040-4039(99)01054-0]
[13]
Boulton, L.T.; Fox, M.E.; Hodgson, P.B.; Lennon, I.C. Zinc-mediated intramolecular acyl and imino transfer reactions of aryl iodides. Tetrahedron Lett., 2005, 46, 983.
[http://dx.doi.org/10.1016/j.tetlet.2004.12.034]
[14]
Bredereck, H.; Gomper, R.; Klen, H.; Kempfer, M. Formamid‐Reaktionen, XIV. Reaktionen von Säureamid‐Acylhalogenid‐Addukten: Darstellung substituierter Amidine und Amidrazon. Chem. Ber., 1959, 92, 837.
[http://dx.doi.org/10.1002/cber.19590920411]
[15]
Cai, L.; Han, Y.; Ren, S.; Huang, L.; Dication, C. R1)–N (R2) 2 Synthons and their use in the synthesis of Formamidines, Amidines, and α-Aminonitriles. Tetrahedron, 2000, 56, 8253.
[http://dx.doi.org/10.1016/S0040-4020(00)00785-7]
[16]
Taylor, E.C.; Ehrhart, W.A. A convenient synthesis of N,N-disubstituted formamidines and acetamidines. J. Org. Chem., 1962, 27, 1108.
[17]
Mekhalifia, A.; Mutter, R.; Heal, W.; Chen, B. Unexpected formation of N, N-disubstituted formamidines from aromatic amines, formamides and trifluoroacetic anhydride. Tetrahedron B, 2006, 62(24), 5617-5625.
[http://dx.doi.org/10.1016/j.tet.2006.03.099]
[18]
Elsaedany, S.K.; Zein, M.A.; Abdelrehim, E.M.; Keshk, R.M. Synthesis, anti-microbial, and cytotoxic activities evaluation of some new pyrido[2,3-d]pyrimidines. J. Heterocyclic. Chem., 2016, 53, 1534.
[19]
Abdelrehim, E.M.; Zein, M.A. Synthesis of some novel Pyrido[2,3‐d]pyrimidine and Pyrido[3,2‐e][1,3,4]triazolo and Tetrazolo[1,5‐c]pyrimidine derivatives as potential antimicrobial and anticancer agents. J. Heterocyclic. Chem., 2018, 55, 419.
[20]
Abdelrehim, E.M.; Zein, M.A. Aminolysis of Z-4-Furylidene Oxazolin-5-One derivatives-configuration and kinetics. Eur. Sci. J., 2014, 3, 39.
[21]
Odame, F. DFT study of the reaction mechanism of N-(Carbomylcarbamothioyl) benzamide. Acta Chim. Slov., 2018, 65(2), 328-332.
[http://dx.doi.org/10.17344/acsi.2017.4001] [PMID: 29993105]
[22]
Frisch, M.J. Gaussian 09, Revision A.02; Gaussian, Inc.: Wallingford, CT, 2016.
[23]
(a)Wei, D.; Fang, L.; Tang, M.; Zhan, C.G. Fundamental reaction pathway for peptide metabolism by proteasome: insights from first-principles quantum mechanical/molecular mechanical free energy calculations. J. Phys. Chem. B, 2013, 117(43), 13418-13434.
[http://dx.doi.org/10.1021/jp405337v] [PMID: 24111489]
(b)Lee, R.; Zhong, F.; Zheng, B.; Meng, Y.; Lu, Y.; Huang, K.W. The origin of enantioselectivity in the L-threonine-derived phosphine-sulfonamide catalyzed aza-Morita-Baylis-Hillman reaction: effects of the intramolecular hydrogen bonding. Org. Biomol. Chem., 2013, 11(29), 4818-4824.
[http://dx.doi.org/10.1039/c3ob40144h] [PMID: 23774825]
[24]
Krenske, E.H. Aromatic interactions in asymmetric catalysis: control of enantioselectivity in Diels-Alder reactions catalysed by camphor-derived hydrazides. Org. Biomol. Chem., 2013, 11(32), 5226-5232.
[http://dx.doi.org/10.1039/c3ob40850g] [PMID: 23800726]
[25]
(a)Barone, V.; Cossi, M.; Mennucci, B.; Tomasi, J. Ab initio study of ionic solutions by a polarizable continuum dielectric model. J. Phys. Chem. A, 1998, 102, 1995.
[26]
Zhu, Y.; Chen, Z.F.; Guo, Z.J.; Wang, Y.; Chen, G.J. Systematic characterization on electronic structures and spectra for a series of complexes: a theoretical study. J. Mol. Model., 2009, 15, 469-479.
[http://dx.doi.org/10.1007/s00894-008-0432-7] [PMID: 19083029]
[27]
Fukui, K. The path of chemical reactions - the IRC approach. Acc. Chem. Res., 1981, 14, 363-368.
[http://dx.doi.org/10.1021/ar00072a001]
[28]
Gonzalez, C.; Schlegel, H.B. An improved algorithm for reaction path following. J. Chem. Phys., 1989, 90, 2154-2161.
[http://dx.doi.org/10.1063/1.456010]
[29]
Zhurko, G.; Zhurko, D. Chemcraft: Lite Version Build 08; Freeware, 2005.

© 2024 Bentham Science Publishers | Privacy Policy