Synthesis and solid-state characterisation of 4-substituted methylidene oxindoles
Tóm tắt
4-substituted methylidene oxindoles are pharmacologically important. Detailed analysis and comparison of all the interactions present in crystal structures is necessary to understand how these structures arise. The XPac procedure allows comparison of complete crystal structures of related families of compounds to identify assemblies that are mainly the result of close-packing as well as networks of directed interactions. Five 4-substituted methylidene oxindoles have been synthesized by the Knoevenagel condensation of oxindole with para-substituted aromatic aldehydes and were characterized in the solid state by x-ray crystallography. Hence, the structures of (3E)-3-(4-Bromobenzylidene)-1,3-dihydro-2H-indol-2-one, 3a, (3E)-3-(4-Chlorobenzylidene)-1,3-dihydro-2H-indol-2-one, 3b, (3E)-3-(4-Methoxybenzylidene)-1,3-dihydro-2H-indol-2-one, 3c, (3E)-3-(4-Methylbenzylidene)-1,3-dihydro-2H-indol-2-one, 3d and (3E)-3-(4-Nitrobenzylidene)-1,3-dihydro-2H-indol-2-one, 3e, were elucidated using single crystal X-ray crystallography. A hydrogen bonded dimer molecular assembly or supramolecular construct was identified in all the crystal structures examined along with a further four 1D supramolecular constructs which were common to at least two of the family of structures studied. The 1D supramolecular constructs indicate that once the obvious strong interaction is satisfied to form hydrogen bonded dimer it is the conventionally weaker interactions, such as steric bulk and edge-to-face interactions which compete to influence the final structure formation.
Tài liệu tham khảo
Spencer J, Mendham AP, Kotha AK, Richardson SCW, Hillard EA, Louise M, Hursthouse MB: Structural and biological investigation of ferrocene-substituted 3-methylidene-1-3-dihydro-2H-indol-2-one. Dalton Transactions. 2009, 6: 918-921. doi:[10.1039/B816249B]
Huber K, Schemies J, Uciechowska U, Wagner JM, Rumpf T, Lewrick F, Suss R, Sippl W, Jung M, Bracher F: Novel 3-Arylideneindolin-2-ones as Inhibitors of NAD+-Dependent Histone Deacetylases (Sirtuins). J. Med. Chem. 2010, 53 (3): 1383-1386. 10.1021/jm901055u. doi:10.1021/jm901055u
Tripathy R, Reiboldt A, Messina PA, Iqbal M, Singh J, Bacon ER, Angeles TS, Yang SX, Albom MS, Robinson C, Chang H, Ruggeri BA, Mallamo JP: Structure guided identification of novel VEGFR-2 kinase inhibitors via solution parallel synthesis. Bioorg. Med. Chem. Lett. 2006, 16 (8): 2158-2162. 10.1016/j.bmcl.2006.01.063. doi:10.1016/j.bmcl.2006.01.063
Kin-Chun L, Mary Ellen S, Andy S, Karen R, Thelma T, Yi C, Ursula K, Wanda DP, Pete D, Apos D, Apos D: A new series of potent oxindole inhibitors of CDK2. Bioorg. Med. Chem. Lett. 2004, 14 (4): 913-917. 10.1016/j.bmcl.2003.12.009. doi:[10.1016/j.bmcl.2003.12.009]
Ashwini N, Gautam Radhakrishna D: Design of Organic Solids. Edited by: Weber E. 1998, Berlin: ringer-Verlag, 87-
Schneider TR: A genetic algorithm for the identification of conformationally invariant regions in protein molecules. Acta Cryst. 2002, D58: 195-208. doi:[10.1107/S0907444901019291]
Etter MC, MacDonald JC, Bernstein J: Graph-set analysis of hydrogen-bond patterns in organic crystals. Acta Cryst. 1990, B46: 256-262. doi:[10.1107/S0108768189012929]
Blatov VA: A method for hierarchical comparative analysis of crystal structures. Acta Cryst. 2006, A62: 356-364. doi:[10.1107/S0108767306025591]
Zabrodsky H, Peleg S, Avnir D: Continuous symmetry measures. J. Am. Chem. Soc. 1992, 114: 7843-7851. 10.1021/ja00046a033. doi:10.1021/ja00046a033
Spackman MA, Byrom PG: A novel definition of a molecule in a crystal. Chem. Phys. Lett. 1997, 267: 215-220. 10.1016/S0009-2614(97)00100-0. doi:10.1016/S0009-2614(97)00100-0
McKinnon JJ, Mitchell AS, Spackman MA: Hirshfeld surfaces: a new tool for visualising and exploring molecular crystals chem. Chem.–Eur. J. 1998, 4 (11): 2136-2141. 10.1002/(SICI)1521-3765(19981102)4:11<2136::AID-CHEM2136>3.0.CO;2-G. doi:10.1002/(SICI)1521-3765(19981102)4:11<2136::AID-CHEM2136>3.0.CO;2-G
Gelbrich T, Hursthouse MB: A versatile procedure for the identification, description and quantification of structural similarity in molecular crystals. CrystEngComm. 2005, 7 (53): 324-336. 10.1039/b502484f. doi:10.1039/B502484F
Gelbrich T, Hursthouse MB: Systematic investigation of the relationships between 25 crystal structures containing the carbamazepine molecule or a close analogue: a case study of the XPac method. CrystEngComm. 2006, 8 (6): 448-460. 10.1039/b600753h. doi:10.1039/B600753H
Zhang W, Go M-L: Functionalized 3-benzylidene-indolin-2-ones: Inducers of NAD(P)H-quinone oxidoreductase 1 (NQO1) with antiproliferative activity. Bioorg. Med. Chem. 2009, 17 (5): 2077-2090. 10.1016/j.bmc.2008.12.052. doi:10.1016/j.bmc.2008.12.052
Milanesio M, Viterbo D, Albini A, Fasani E, Bianchi R, Barzaghi M: Structural Study of the Solid-State Photoaddition Reaction of Arylidenoxindoles. J. Org. Chem. 2000, 65 (11): 3416-3425. 10.1021/jo991873i. doi:10.1021/jo991873i
Tian-Tu X, Shun-Yi W, Shun-Jun J: Facile Synthesis of Z/E-3-Arylmethylidene-2,3-dihydroindol-2-one under Solvent-Free Conditions. Chin. J. Org. Chem. 2006, 26 (10): 1414-1417.
Allen FH: The Cambridge Structural Database: a quarter of a million crystal structures and rising. Acta Cryst. 2002, B58: 380-388. doi:10.1107/S0108768102003890