Structural Studies of Enantiomers, Racemates, and Quasiracemates. N-(2-Chlorobenzoyl)methylbenzylamine and N-(2-Bromobenzoyl)methylbenzylamine Shella L. Fomulu,† Mukta S. Hendi,† Raymond E. Davis,‡ and Kraig A. Wheeler*,†
CRYSTAL GROWTH & DESIGN 2002 VOL. 2, NO. 6 645-651
Department of Chemistry, Delaware State University, Dover, Delaware 19901-2202, and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712-1167 Received August 1, 2002;
Revised Manuscript Received September 6, 2002
W This paper contains enhanced objects available on the Internet at http://pubs.acs.org/crystal. ABSTRACT: Recrystallization of equimolar quantities of (R)-N-(2-chlorobenzoyl)methylbenzylamine (1) and (S)N-(2-bromobenzoyl)methylbenzylamine (2) forms quasiracemic crystals (3) with approximately centrosymmetric molecular frameworks. The molecular recognition behavior observed for the principal quasiracemate diarylamide components follows a best-fit scenario controlled by topological influences. The relation of molecular shape to crystalline architectures is supported by a systematic structural study of the complete family of quasiracemate, racemate, and enantiomer structures, including two polymorphic forms of enantiomeric 1. Each of the enantiomeric, racemic, and quasiracemic compounds crystallizes to form molecular scaffolds linked by C(4) N-H‚‚‚O interactions. Although this typical hydrogen bond motif of the trans amide moiety provides a common structural theme for these diarylamides, significant variations in crystal packing arise due to the orientation of molecules within the catemeric hydrogen bond motif and the alignment of neighboring C(4) chains. Introduction Understanding the organization of molecular crystals continues to receive significant attention because of potential applications to materials design and processes. Over the years, the details from individual investigations have contributed to a growing body of information used to codify the influence of specific structural features to crystal packing. Use of this extant information has facilitated many elegant exercises in the construction of crystalline architectures with predetermined frameworks.1-6 In contrast to the bulk of these studies that exploit electrostatic interactions to organize molecular assemblies, relatively few reports in the current literature cite molecular topology as a design strategy for alignment of multimolecular arrays. Although the contribution of molecular shape to crystal packing is widely recognized in the field, the lack of studies in this area is not surprising due to the difficulty in quantifying topological influences. Motivated by our recent successes in constructing molecular assemblies based on shape mimicry methods,7-10 we have recently explored the synthesis and crystal structures of a homologous family of chloro- and bromo-substituted diarylamides (1-3). We use molecular shape as an approach to organizing crystal packing by constructing sets of isosteric molecules that are chemically unique and opposite in handedness.7-11 We have shown that cocrystallization of such compounds produces crystals, termed quasiracemates,12 in which the isosteric molecules have an approximately centrosymmetric arrangement. Crystal* To whom correspondence should be addressed. Fax: (302)8576539. E-mail:
[email protected]. † Delaware State University. ‡ University of Texas at Austin.
lographic evidence from our previous studies of chloronitrophenoxy (4)7 and trichloroaryl (5)10 quasiracemates suggests that the alignment of quasiracemate components originates from the complementary features of molecular topology and the overwhelming tendency of organics to crystallize with centrosymmetric alignments. As a means to extend the current collection of known quasiracemates and structural preferences, we have synthesized and determined the crystal structures of a new quasiracemic system based on diarylamide molecular frameworks (1-3). In addition to quasiracemate 3, structures of the principal components (i.e., racemates and enantiomers of 1 and 2) were determined to provide a comparative view of the structural features that influence the specificity and transferability of individual structural motifs as they relate to quasiracemate formation. In addition, this study reports the crystal structures of two polymorphic forms of enantiomeric 1.
10.1021/cg025564o CCC: $22.00 © 2002 American Chemical Society Published on Web 10/11/2002
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Experimental Section General Considerations. All chemicals and solvents were purchased from the Aldrich Chemical Co. or Acros Chemicals and used as received without further purification. 1H NMR spectral data were recorded using a JEOL FX90Q spectrometer equipped with the TECMAG computer interface. Melting point data were determined using a Melt-Temp apparatus and are uncorrected. Recrystallization experiments were conducted at room temperature using spectroscopic grade solvents. Standard organic synthetic methods, as described for (R)-1, were used to produce the homologous series of diarylamides 1-3 with yields in excess of 80%. (R)-N-(2-Chlorobenzoyl)-r-methylbenzylamine, (R)-1a. 2-Chlorobenzoyl chloride (3.5 g, 20 mmol) and 30 mL of methylene chloride were added to a 100 mL round-bottomed flask and stirred at 0 °C for 20 min. A solution of (R)-(+)-Rmethylbenzylamine (4.85 g, 40 mmol) in 5 mL of methylene chloride was added to the reaction mixture and stirred for an additional 30 min. The homogeneous solution was placed into a separatory funnel and washed with 50-60 mL of water. The resulting organic layer was extracted with a succession of water, saturated sodium bicarbonate, 4 M HCl, and water and finally dried with anhydrous magnesium sulfate. Reduction of the organic layer under vacuo gave a colorless oil. Addition of hexane afforded a white solid (4.3 g, 83%) that was isolated by vacuum filtration. A series of slow evaporations, first from a 1:1 solution in chloroform and hexane and then from a solution in methanol, yielded X-ray quality crystals of (R)-1a as transparent needles. MP 108-110 °C. 1H NMR (CDCl3): δ 7.70 (br s, N-H), 7.60-7.20 (m, 9H), 5.40 (dq, J ) 6.84, 7.08, 1H), 1.62 (d, J ) 6.84, 3H). (R)-N-(2-Chlorobenzoyl)-r-methylbenzylamine, (R)-1b. Transparent needles of (R)-1b were obtained by slow evaporation of (R)-1a in a 1:1 mixture of methylene chloride and hexane. MP 108-110 °C. 1H NMR (CDCl3): δ 7.70 (br s, N-H), 7.60-7.20 (m, 9H), 5.40 (dq, J ) 6.84, 7.08, 1H), 1.62 (d, J ) 6.84, 3H). (()-N-(2-Chlorobenzoyl)-r-methylbenzylamine, (()-1. Compound (S)-1 was prepared using a similar procedure as described for (R)-1a. Recrystallization of a 1:1 mixture of (R)-1 and (S)-1 from a 1:1 mixture of methanol and chloroform at room temperature resulted in (()-1 as transparent colorless plates. MP 103-105 °C. 1H NMR (CDCl3): δ 7.88 (br s, N-H), 7.60-7.10 (m, 9H), 5.27 (dq, J ) 7.02, 7.02, 1H), 1.55 (d, J ) 7.02, 3H). (S)-N-(2-Bromobenzoyl)-r-methylbenzylamine, (S)-2. Compound (S)-2 was prepared using a similar procedure as described for (R)-1a. Recrystallization by slow evaporation of (S)-2 from a 1:1:1 mixture of chloroform, methanol, and hexane yielded transparent plates. MP 108-110 °C. 1H NMR (CDCl3): δ 7.68-7.00 (m, 9H), 6.23 (br s, N-H), 5.33 (dq, J ) 6.84, 7.08, 1H), 1.60 (d, CH3, J ) 6.84, 3H). (()-N-(2-Bromobenzoyl)-r-methylbenzylamine, (()-2. Compound (R)-2 was prepared using a similar procedure as described for (R)-1a. Recrystallization of a 1:1 mixture of (R)-2 and (S)-2 from a 1:1:1 mixture of methanol, methylene chloride, and hexane at room temperature resulted in (()-2
Fomulu et al. as colorless transparent plates. MP 111-113 °C. 1H NMR (CDCl3): δ 7.65-6.85 (m, 9H), 6.23 (br s, N-H), 5.33 (dq, J ) 6.84, 7.08, 1H), 1.62 (d, CH3, J ) 6.84, 3H). Quasiracemate 3. Transparent needles of the quasiracemate were obtained from slow evaporation of an equimolar mixture of (R)-1 (0.235 g, 0.906 mmol) and (S)-2 (0.275 g, 0.906 mmol) in a 1:1 mixture of methanol and acetone. MP 105108 °C. 1H NMR (CDCl3): δ 7.70-7.09 (m, 9H), 6.42 (br s, N-H), 5.38 (dq, J ) 6.83, 7.08, 1H), 1.62 (d, CH3, J ) 6.84, 3H). Crystallography. The X-ray data for compounds 1-3 were collected on a Siemens P4 diffractometer at 25 °C using graphite monochromatic Mo KR radiation (λ ) 0.71073 Å) and XSCANS software package.13 The data were corrected for Lorentz and polarization effects. No absorption corrections were applied to (R)-1a, (R)-1b, and (()-1 because the absorption coefficient, µ, was low and crystal geometry was favorable in each case. Absorption corrections were applied to (S)-2, (()2, and 3. The crystal data, details of the diffracted intensity measurements, and refinement conditions are summarized in Table 1. Crystal stabilities were monitored by measuring three standard reflections every 97 reflections with no significant variations (
