Synthesis and Conformational Analysis of Sterically Congested (4R)-(？)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone: X-Ray Crystallography and Semiempirical Calculations
The crystal structure of (4R)-(？)-1-(2,4,6-trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3) was determined by single-crystal X-ray diffraction. Compound 3 crystallizes in triclinic system in space group P1 (≠ 1). The crystal data are ？？, ？？, ？？, , , , ？？3, , ？g/cm3, ？cm？1, , °C, and . The crystal structure confirmed the occurrence of three molecules of 3A, 3B, and 3C in which the n-butyryl moiety adopted the s-transoid conformation. Crystal structure also revealed that the conformation of 2,4,6-trimethylbenzenesulfonyl groups was in anti-position relative to tert-butyl group. The crystal packing showed that three molecules of compound 3 are stacked as a result of intermolecular π-π interactions between the phenyl ring of one molecule and the phenyl ring of the other molecule by approaching each other to an interplanar separation of 5.034？？. Interestingly, these stacked molecules are also connected by intermolecular CH-π interaction. The conformational analysis of the s-transoid？？3A, 3B, and 3C was separately performed by molecular mechanic MM+ force field. Additionally, computational investigation using semiempirical AM1 and PM3 methods was performed to find a correlation between experimental and calculated geometrical parameters. The data obtained suggest that the structural data furnished by the AM1 method is in better agreement with those experimentally determined for the above compound. It has been found that the lowest energetic conformer computed gives approximate correspondence with experimental solid state data. 1. Introduction The energy based conformational searching technique is a considerable computational request and is still an active area of research. When the property of interest is energy, the following methodology is indicated: full conformational search using molecular mechanics, followed by geometry optimization using semiempirical model for selected conformers, and finally single-point calculation using ab initio models for selected conformers [1]. On the other hand, steric bulkiness of chiral 2-imidazolidinones [2] plays an effective role in greatly enhancing stereoselectivity, and so sterically congested chiral 2-imidazolidinones [3–5] represent promising auxiliaries for providing excellent diastereocontrol. We reported the synthesis and chiral application of 4-tert-butyl-2-imidazolidinone which were greatly enhanced by the occurrence of N-arylsulfonyl fragments [4]. Moreover, several 2-imidazolidinone derivatives containing diarylsulfonylurea pharmacophore have been synthesized and screened for antitumor
References
[1]
W. J. Hehre, Dealing with Conformationally Flexible Molecules, Practical Strategies for Electronic Structure Calculations, Wavefunction, chapter 6, 1995.
[2]
H. Matsunaga, T. Ishizuka, and T. Kunieda, “Synthetic utility of five-membered heterocycles—chiral functionalization and applications,” Tetrahedron, vol. 61, no. 34, pp. 8073–8094, 2005.
[3]
N. Hashimoto, T. Ishizuka, and T. Kunieda, “Highly efficient chiral 2-oxazolidinone auxiliaries derived from methylcyclopentadienes and 2-oxazolone,” Tetrahedron Letters, vol. 35, no. 5, pp. 721–724, 1994.
[4]
A. A.-M. Abdel-Aziz, J. Okuno, S. Tanaka, T. Ishizuka, H. Matsunaga, and T. Kunieda, “An unusual enhancement of chiral induction by chiral 2-imidazolidinone auxiliaries,” Tetrahedron Letters, vol. 41, no. 44, pp. 8533–8537, 2000.
[5]
A. A.-M. Abdel-Aziz, H. Matsunaga, and T. Kunieda, “Unusual N-acylation of sterically congested trans-4,5-disubstituted 2-imidazolidinones: remarkably facile C–C bond formation,” Tetrahedron Letters, vol. 42, no. 37, pp. 6565–6567, 2001.
[6]
H.-Y. P. Choo, S. Choi, S. H. Jung, H. Y. Koh, and A. N. Pae, “The 3D-QSAR study of antitumor arylsulfonylimidazolidinone derivatives by CoMFA and CoMSIA,” Bioorganic & Medicinal Chemistry, vol. 11, no. 21, pp. 4585–4589, 2003.
[7]
S. H. Jung, J. S. Song, H. S. Lee, S. U. Choi, and C. O. Lee, “Synthesis and evaluation of cytotoxic activity of novel arylsulfonylimidazolidinones,” Bioorganic & Medicinal Chemistry Letters, vol. 6, no. 21, pp. 2553–2558, 1996.
[8]
S. H. Jung, J. S. Song, H. S. Lee, S. U. Choi, and C. O. Lee, “Synthesis and evaluation of cytotoxicity of novel arylsulfonylimidazolidinones containing sulfonylurea pharmacophore,” Archives of Pharmacal Research, vol. 19, no. 6, pp. 570–580, 1996.
[9]
S. H. Jung and S. J. Kwak, “Planar structural requirement at 4-position of 1-arylsulfonyl-4-phenyl-4,5-dihydro-2-imidazolones for their cytotoxicity,” Archives of Pharmacal Research, vol. 20, no. 3, pp. 283–287, 1997.
[10]
S. Jung, H. Lee, J. Song et al., “Synthesis and antitumor activity of 4-phenyl-1-arylsulfonyl imidazolidinones,” Bioorganic and Medicinal Chemistry Letters, vol. 8, no. 12, pp. 1547–1550, 1998.
[11]
E. Y. Moon, S. K. Seong, S. H. Jung et al., “Antitumor activity of 4-phenyl-1-arylsulfonylimidazolidinone, DW2143,” Cancer Letters, vol. 140, no. 1-2, pp. 177–187, 1999.
[12]
E. Y. Moon, H. S. Hwang, C. H. Choi, S. H. Jung, and S. J. Yoon, “Effect of DW2282 on the induction of methemoglobinemia, hypoglycemia or WBC count and hematological changes,” Archives of Pharmacal Research, vol. 22, no. 6, pp. 565–570, 1999.
[13]
H. S. Hwang, E. Y. Moon, S. K. Seong et al., “Characterization of the anticancer activity of DW2282, a new anticancer agent,” Anticancer Research B, vol. 19, no. 6, pp. 5087–5093, 1999.
[14]
S. H. Jung, S. J. Kwak, N. D. Kim, S. U. Lee, and C. O. Lee, “Stereochemical requirement at 4-position of 4-phenyl-1-arylsulfonylimidazolidinones for their cytotoxicities,” Archives of Pharmacal Research, vol. 23, no. 1, pp. 35–41, 2000.
[15]
S. H. Lee, K. L. Park, S. U. Choi, C. O. Lee, and S. H. Jung, “Effect of substituents on benzenesulfonyl motif of 4-phenyl-1-arylsulfonylimidazolidinones for their cytotoxicity,” Archives of Pharmacal Research, vol. 23, no. 6, pp. 579–584, 2000.
[16]
I. W. Kim and S. H. Jung, “Recognition of the importance of imidazolidinone motif for cytotoxicity of 4-phenyl-1-arylsulfonylimidazolidinones using thiadiazolidine-1,1 -dioxide analogs,” Archives of Pharmacal Research, vol. 25, no. 4, pp. 421–427, 2002.
[17]
I. Kim, C. Lee, H. Kim, and S. Jung, “Importance of sulfonylimidazolidinone motif of 4-phenyl-1-arylsulfonylimidazolidinones for their cytotoxicity: synthesis of 2-benzoyl-4-phenyl[1,2,5]thiazolidine-1,1-dioxides and their cytotoxcity,” Archives of Pharmacal Research, vol. 26, no. 1, pp. 9–14, 2003.
[18]
A. Guirado, R. Andreu, B. Martiz, D. Bautista, C. Ramírez de Arellano, and P. G. Jones, “The reaction of 4-amino-2-oxazolines with isocyanates and isothiocyanates. Synthesis and X-ray structures of polysubstituted 2-imidazolidinones, 1,3-oxazolidines and 1,3-thiazolidines,” Tetrahedron, vol. 62, no. 26, pp. 6172–6181, 2006.
[19]
K.-L. Park, B.-G. Moon, S.-H. Jung, J.-G. Kim, and I.-H. Suh, “Multicentre hydrogen bonds in a 2:1 arylsulfonylimidazolone hydrochloride salt,” Acta Crystallographica C, vol. 56, pp. 1247–1250, 2000.
[20]
A. A.-M. Abdel-Aziz, M. A. Al-Omar, A. S. El-Azab, and T. Kunieda, “Conformational preferences of sterically congested 2-imidazolidinone using X-ray analysis and computational studies. Part 1: trans-1-acetyl-4,5-di-tert-butyl-2-imidazolidinone,” Journal of Molecular Structure, vol. 969, no. 1–3, pp. 145–154, 2010.
[21]
I. A. Al-Swaidan, A. M. Alanazi, A. S. El-Azab, and A. A. -M. Abdel-Aziz, “An alternative route for synthesis of chiral 4-substituted 1-arenesulfonyl-2-imidazolidinones: unusual Utility of (4S,5S)- and (4R,5R)-4,5-dimethoxy-2-imidazolidinones and X-ray crystallography,” Journal of Chemistry, vol. 2013, Article ID 349519, 5 pages, 2013.
[22]
A. Altomare, M. C. Burla, M. Camalli et al., “SIR92-a program for automatic solution of crystal structures by direct methods,” Journal of Applied Crystallography, vol. 27, p. 435, 1994.
[23]
P. T. Beurskens, G. Admiraal, G. Beurskens et al., “DIRDIF 94: the DIRDIF-94 program system,” Technical Report of the Crystallogtaphy Laboratory, University of Nijmegen, Nijmegen, The Netherlands, 1994.
[24]
D. T. Cromer and J. T. Waber, "International Tables for X-Ray Crystallography, vol. 4, Table 2. 2 A, The Kynoch press, Birmingham, UK, 1974.
[25]
J. A. Ibers and W. C. Hamilton, “Dispersion corrections and crystal structure refinements,” Acta Crystallographica, vol. 17, pp. 781–782, 1964.
[26]
D. C. Creagh and W. J. McAuley, International Tables for Crystallography, Vol. C, (A.J.C.Wilson, Ed.), Table 4.2.6.8, Kluwer Academic, Boston, Mass, USA, 1992.
S. Profeta Jr. and N. L. Allinger, “Molecular mechanics calculations on aliphatic amines,” Journal of the American Chemical Society, vol. 107, no. 7, pp. 1907–1918, 1985.
[30]
M. Lipton and W. C. Still, “The multiple minimum problem in molecular modeling. Tree searching internal coordinate conformational space,” Journal of Computational Chemistry, vol. 9, no. 4, pp. 345–355, 1988.
[31]
A. A.-M. Abdel-Aziz, “Novel and versatile methodology for synthesis of cyclic imides and evaluation of their cytotoxic, DNA binding, apoptotic inducing activities and molecular modeling study,” European Journal of Medicinal Chemistry, vol. 42, no. 5, pp. 614–626, 2007.
[32]
M. J. S. Dewar, E. G. Zoebisch, E. F. Healey, and J. J. P. Stewart, “Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular model,” Journal of the American Chemical Society, vol. 107, no. 13, pp. 3902–3909, 1985.
[33]
J. J. P. Stewart, “Optimization of parameters for semiempirical methods I. Method,” Journal of Computational Chemistry, vol. 10, no. 2, pp. 209–220, 1989.
[34]
http://openmopac.net/home.html.
[35]
J. W. Steed, “Should solid-state molecular packing have to obey the rules of crystallographic symmetry?” Crystal Engineering Communications, vol. 5, pp. 169–179, 2003.
J. L. Flippen, “The crystal and molecular structures of reaction products from -irradiation of thymine and cytosine: cis-thymine glycol, C5H8N2O4, and trans-1-carbamoylimidazolidone-4,5-diol, C4H7N3O4,” Acta Crystallographica B, vol. 29, pp. 1756–1762, 1973.
[38]
H. Ueda, H. Onishi, and T. Nagai, “Structure of p-aminobenzoic acidi-1,3-dimethyl-2-imidazolidinone (1/1),” Acta Crystallographica C, vol. 42, pp. 462–464, 1986.
[39]
M. Kapon and G. M. Reisner, “Structure of 2-imidazolidinone hemihydrate,” Acta Crystallographica C, vol. 45, pp. 780–782, 1989.
[40]
O. M. Peeters, N. M. Blaton, and C. J. De Ranter, “Structure of 1-(5-nitro-1,3-thiazol-2-yl)-2-imidazolidinone (niridazole), C6H6N4O3S,” Acta Crystallographica C, vol. 40, pp. 1748–1750, 1984.
[41]
F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen, and R. Taylor, “Tables of bond lengths determined by x-ray and neutron diffraction. Part 1. Bond lengths in organic compounds,” Journal of the Chemical Society, no. 12, pp. S1–S19, 1987.
[42]
A. Caron, “Redetermination of thermal motion and interatomic distances in urea,” Acta Crystallographica B, vol. 25, p. 404, 1969.
[43]
P. Vaughan and J. Donohue, “The structure of urea. Interatomic distances and resonance in urea and related compounds,” Acta Crystallographica, vol. 5, pp. 530–535, 1952.
[44]
A. Caron and J. Donohue, “Three-dimensional refinement of urea,” Acta Crystallographica, vol. 17, pp. 544–546, 1964.
[45]
Y. Umezawa, S. Tsuboyama, H. Takahashi, J. Uzawa, and M. Nishio, “CH/π interaction in the conformation of organic compounds. A database study,” Tetrahedron, vol. 55, no. 33, pp. 10047–10056, 1999.
[46]
U. El-Ayaan, A. A.-M. Abdel-Aziz, and S. Al-Shihry, “Solvatochromism, DNA binding, antitumor activity and molecular modeling study of mixed-ligand copper(II) complexes containing the bulky ligand: bis[N-(p-tolyl)imino]acenaphthene,” European Journal of Medicinal Chemistry, vol. 42, no. 11-12, pp. 1325–1333, 2007.
[47]
U. El-Ayaan and A. A.-M. Abdel-Aziz, “Synthesis, antimicrobial activity and molecular modeling of cobalt and nickel complexes containing the bulky ligand: bis[N-(2,6-diisopropylphenyl)imino] acenaphthene,” European Journal of Medicinal Chemistry, vol. 40, no. 12, pp. 1214–1221, 2005.
[48]
G. R. Desiraju, J. A. R. P. Sarma, and T. S. R. Krishna, “Dipole-dipole interactions and the inversion motif in the crystal structures of planar chloro aromatics: the unusual packings of 1,2,3-trichlorobenzene and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin,” Chemical Physics Letters, vol. 131, no. 1-2, pp. 124–128, 1986.
[49]
J. C. Burley, R. Gilmour, T. J. Prior, and G. M. Day, “Structural diversity in imidazolidinone organocatalysts: a synchrotron and computational study,” Acta Crystallographica C, vol. 64, pp. o10–o14, 2008.
[50]
A. G. Santos, S. X. Candeias, C. A. M. Afonso et al., “Rationalising diastereoselection in the dynamic kinetic resolution of α-haloacyl imidazolidinones: a theoretical approach,” Tetrahedron, vol. 57, no. 30, pp. 6607–6614, 2001.
