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Molecular and Crystal Structure of N-(8-benzylidene-4-phenylhexahydroquinazolin-2(1H)-ylidene)Cyanamide

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Abstract

We have obtained previously known and new 4,8-C-substituted hexahydroquinazolincyanamides by two-component condensation of 2,6-diaryl(heteroaryl)methylidenecyclohexanones with the same or different terminal substituents with N-cyanoguanidine according to a modified procedure under conditions of basic catalysis. We have grown a singlecrystal of one of the representatives of the series –N-(8-benzylidene-4-phenylhexahydroquinazolin-2(1H)-ylidene)cyanamideby crystallization from a saturated solution of acetonitrile and carried out its X-ray diffraction study. The structure of N-(8-benzylidene-4-phenylhexahydroquinazolin-2(1H)-ylidene)cyanamide, C22H20N4, has orthorhombic (P212121) symmetry. The molecule is built from fused non-planar cyclohexene and tetrahydropyrimidine rings. The cyclohexene ring is in the half-chair conformation, while the tetrahydropyrimidine ring adopts the ‘C-envelope’ conformation. The crystal packing of the compound is an alternating layered structure. The mutual arrangement of molecules promotes the formation of intermolecular hydrogen bonds (IMH) between the H1 hydrogen atoms of the quinazoline ring and the N4 nitrogen atoms of the nitrile group. Non-planar C–H···π interactions are observed in the crystal as well. The compound is in the E,E-configuration. The calculation and analysis of Hirschfeld surfaces demonstrated the presence of hydrogen bonds, different in energy, and C–H···π interactions between benzene rings and protons of other benzene rings of neighbouring molecules in both the benzylidene and phenyl substituents.

Graphical Abstract

X-ray diffraction analysis of hexahydroquinazolincyanamide showed that there are intermolecular hydrogen bonds with the hydrogen atoms of the quinazoline ring and the nitrogen atoms of the nitrile and imine groups. An assessment of the intermolecular stacking interaction is given.

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Scheme 1
Fig. 1
Scheme 2
Fig. 2
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References

  1. El-Zahabi MA, Bamanie FH, Ghareeb S, Alshaeri HK, Alasmari MM, Moustafa M, Al-Marzooki Z, Zayed MF (2022) Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of quinazoline-sulfonylurea hybrids as peroxisome proliferator-activated receptor gamma (PPARγ) and sulfonylurea receptor (SUR) agonists. Int J Mol Sci 23(17):9605–9628. https://doi.org/10.3390/ijms23179605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sakr H (2022) Review on the significance of quinazolinone derivatives as potent antihyperglycemic agents. Al-Azhar J Pharm Sci 65(1):50. https://doi.org/10.21608/AJPS.2022.223768

    Article  Google Scholar 

  3. Shaik TB, Malik MS, Routhu SR, Seddigi ZS, Althagafi II, Kamal A (2020) Evaluation of anticancer and anti-mitotic properties of quinazoline and quinazolino-benzothiadiazine derivatives. Anti-Cancer Agents Med Chem 20(5):599–611. https://doi.org/10.2174/1871520620666191224122204

    Article  CAS  Google Scholar 

  4. Khelifi I, Naret T, Hamze A, Bignon J, Levaique H, Alvarez MCG, Dubois J, Provot O, Alami M (2019) N,N-bis-heteroaryl methylamines: potent anti-mitotic and highly cytotoxic agents. Eur J Med Chem 168:176–188. https://doi.org/10.1016/j.ejmech.2019.02.038

    Article  CAS  PubMed  Google Scholar 

  5. Solyanik GI (2019) Quinazoline compounds for antitumor treatment. Exp Oncol 41:3–6. https://doi.org/10.32471/exp-oncology.2312-8852.vol-41-no-1.12414

    Article  CAS  PubMed  Google Scholar 

  6. Spanò V, Montalbano A, Carbone A, Parrino B, Diana P, Cirrincione G, Castagliuolo I, Brun P, Issinger OG, Tisi S, Primac I, Vedaldi D, Salvador A, Barraja P (2014) Synthesis of a new class of pyrrolo[3,4-h]quinazolines with antimitotic activity. Eur J Med Chem 74:340–357. https://doi.org/10.1016/j.ejmech.2013.10.014

    Article  CAS  PubMed  Google Scholar 

  7. Moustafa AH, Hussein BRM (2022) A methodological approach for the synthesis of 4-aryl-8-arylidene-2-cyanoimino-1,2,3,4,5,6,7,8-octahydroquinazolines. Synth Commun 52(8):1131–1138. https://doi.org/10.1080/00397911.2022.2072747

    Article  CAS  Google Scholar 

  8. Benassi R, Bertarini C, Hilfert L, Kempter G, Kleinpeter E, Spindler J, Taddeia F, Thomas S (2000) Exocyclic push–pull conjugated compounds. Part 3. An experimental NMR and theoretical MO ab initio study of the structure, the electronic properties and barriers to rotation about the exocyclic partial double bond in 2-exo-methylene- and 2-cyanoimino-quinazolines and –benzodiazepines. J Mol Struct 520(1–3):273–294. https://doi.org/10.1016/S0022-2860(99)00346-4

    Article  CAS  Google Scholar 

  9. Sivagami S, Kavitha K, Satanathan S, Rajesh R, Narenkumar J, Parthipan P, Muthusamy K, Alfarhan A (2022) Multicomponent one-pot synthesis, characterization and antimicrobial screening of 2 cyanoimino-6-aryl-4-(6-methoxynaphthalen-2-yl)-3,4-dihydro-1H-pyrimidines. Proc Biochem 123:63–69. https://doi.org/10.1016/j.procbio.2022.10.032

    Article  CAS  Google Scholar 

  10. Hussein BRM, Moustafa AH (2019) A regioselective and convenient one-pot multicomponent synthesis of polyfunctionalized 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrido[2,3-d]pyrimidines.Synth. Commun 49(18):2401–2410. https://doi.org/10.1080/00397911.2019.1626892

    Article  CAS  Google Scholar 

  11. Swaminathan S, &Namasivayam I (2018) An efficient synthesis and in vitro antimicrobial screening of 2-cyanoimino-4-aryl-6-(1,1’-biphenyl-4-yl)-3,4-dihydro-1 h-pyrimidines. Orient J Chem 34(2):777–782. https://doi.org/10.13005/ojc/340222

    Article  CAS  Google Scholar 

  12. Amer AA, Moustafa AH (2017) New route for the synthesis of new cyanoimino- and cyanoaminopyrimidines. Mol Divers 21(4):875–880. https://doi.org/10.1007/s11030-017-9762-7

    Article  CAS  PubMed  Google Scholar 

  13. Carbajales C, Azuaje J, Oliveira A, Loza MI, Brea J, Cadavid MI, Masaguer CF, Garcia-Mera X, Gutierrez-de-Teran H, Sotelo E (2017) Enantiospecific recognition at the A2B adenosine receptor by alkyl2-cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates. J Med Chem 60(8):3372–3382. https://doi.org/10.1021/acs.jmedchem.7b00138

    Article  CAS  PubMed  Google Scholar 

  14. Prakash N, Elamaran M, &Ingarsal N (2015) A new approach to the synthesis of cyanamide: 2-cyanoimino-4-aryl-6-(naphthalen-2-yl)-3,4-dihydro1H-pyrimidines and their antimicrobial screening.Chem. Sci Trans 4(4):947–954. https://doi.org/10.7598/cst2015.1091

    Article  CAS  Google Scholar 

  15. Moustafa AH, Shestakov AS, &Shikhaliev KS (2012) One-pot synthesis of 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidines and their reactions. Chem Heterocycl Compd 48(4):613–619. https://doi.org/10.1007/s10593-012-1034-y

    Article  CAS  Google Scholar 

  16. Hulme R, Zamora ODP, Mota EJ, Pasten MA, Contreras-Rojas R, Miranda R, Valencia-Hernandez I, Correa-Basurto J, Trujillo-Ferrara J, Delgado F (2008) Cyanamide: a convenient building block to synthesize 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidine systems via a multicomponent reaction. Tetrahedron 64(15):3372–3380. https://doi.org/10.1016/j.tet.2008.01.087

    Article  CAS  Google Scholar 

  17. Salinas-Hernández A, Delgado GE, Penieres-Carrillo JG, Delgado-Reyes JF, Gómez-Pliego R, Luna-Mora R, Ríos-Guerra H (2022) Synthesis, crystal structure and Hirshfeld surface analysis of the 1-(3,6-dihydropyrimidin-2-yl)urea salt structurally related to dihydropyrimidinon-2-ylurea-type RNA-binding ligands. J Mol Struct 1254:132314. https://doi.org/10.1016/j.molstruc.2021.132314

    Article  CAS  Google Scholar 

  18. Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JAK, Puschmann H (2009) OLEX2: a complete structure solution, refinement and analysis program. J Appl Cryst 42:339–341. https://doi.org/10.1107/S0021889808042726

    Article  CAS  Google Scholar 

  19. Sheldrick GM (2008) Acta Crystallographica A-Foundation аnd advances. Acta Cryst A 64:112. https://doi.org/10.1107/S0108767307043930

    Article  CAS  Google Scholar 

  20. Sheldrick GM (2015) SHELXT - integrated space-group and crystal-structure determination. Acta Cryst А71. 3https://doi.org/10.1107/S2053273314026370

    Article  Google Scholar 

  21. Bredikhin AA, Zakharychev DV, Bredikhina ZA, Gubaidullin AT, Fayzullin RR (2012) Crystal structure and phase behavior of the tolyl glycerol ethers. From the conglomerate former to the chirality-driven nanogelator. CrystEngComm 14(1):211–222. https://doi.org/10.1039/C1CE05637A

    Article  CAS  Google Scholar 

  22. Mehta G, Sen S, Dey S (2005) S*,2S*,4S*,5S*)-Cyclo­hexane-1,2,4,5-tetrol monohydrate. Acta Cryst. C61(1):o358. https://doi.org/10.1107/S0108270105011066

    Article  CAS  Google Scholar 

  23. Perez-Garcia L, &Amabilino DB (2002) Spontaneous resolution under supramolecular control. Chem Soc Rev 31(6):342–356. https://doi.org/10.1039/B201099M

    Article  CAS  PubMed  Google Scholar 

  24. Pidcock E (2005) Achiral molecules in non-centrosymmetric space groups. Chem Commun. https://doi.org/10.1039/b505236j

    Article  Google Scholar 

  25. Mironova EV, Krivolapov DB, Litvinov IA, Mustakimova LV, Mamedov VA (2017) Structure of new derivatives of perhydropyrimidine-2-ones and intermolecular interactions in their crystals.J. Struct Chem 58:283–290. https://doi.org/10.1134/S0022476617020093

    Article  CAS  Google Scholar 

  26. Golikov A, Krivenko A, Bugaev A, Fomina Y, &Solodovnikov S (2007) Molecular and crystal structures of 3-(4-bromphenyl)-7-furfurylidene-3,3a,4,5,6,7-hexahydro(2H)indazole. J Struct Chem 48(3):589–592. https://doi.org/10.1007/s10947-007-0090-0

    Article  CAS  Google Scholar 

  27. Golikov AG, Krivenko AP, Bugaev AA, &Solodovnikov SF (2006) Molecular and crystal structure of 2-benzylidene-6-furfurylidene-cyclohexanone. J Struct Chem 47:102–105. https://doi.org/10.1007/s10947-006-0273-0

    Article  CAS  Google Scholar 

  28. Gein VL, Zamaraeva TM, Dmitriev MV (2017) Synthesis and structure of N,6-diaryl-4-methyl-2-cyanoimino-1,2,3,6-tetrahydropyrimidine-5-carboxamides.Russ. J Gen Chem 87:350–352. https://doi.org/10.1134/S1070363217020335

    Article  CAS  Google Scholar 

  29. Hirshfeld HL (1977) Bonded-atom fragments for describing molecular charge densities. Theor Chim Acta 44:129–138. https://doi.org/10.1007/BF00549096

    Article  CAS  Google Scholar 

  30. Wolff SK, Grimwood DJ, McKinnon JJ, Turner MJ, Jayatilaka D, Spackman MA (2012) CrystalExplorer. University of Western Australia, Perth. http://crystalexplorer.scb.uwa.edu.au/

    Google Scholar 

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Authors and Affiliations

  1. Saratov National Research State University, Russian Federation, Saratov, 83 Astrakhanskaya Street, 410012, Russia

    Anna E. Sklyar, Vyacheslav S. Grinev, Natalia O. Vasilkova, Daniil A. Puzanov & Adel P. Krivenko

  2. Perm State University, 15 Bukireva Street, Perm, 614068, Russian Federation

    Maksim V. Dmitriev

  3. Institute of Biochemistry and Physiology of Plants and Microorganisms RAS, 13 Prospekt Entuziastov, Saratov, 410049, Russian Federation

    Vyacheslav S. Grinev

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AP, NO and AS wrote the main manuscript text, MV and VS prepared Figs. 1, 2, 3 and 4; Tables 1 and 2. Сhemical synthesis NO and DA. All authors reviewed the manuscript.

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Correspondence to Natalia O. Vasilkova.

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Sklyar, A.E., Grinev, V.S., Dmitriev, M.V. et al. Molecular and Crystal Structure of N-(8-benzylidene-4-phenylhexahydroquinazolin-2(1H)-ylidene)Cyanamide. J Chem Crystallogr (2024). https://doi.org/10.1007/s10870-024-01010-9

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