Planar Chiral Dianthranilide and Dithiodianthranilide Molecules

Planar chiral dianthranilide (1) was resolved to enantiomers with use of (-)-(1S,4R)-camphanoyl chloride as a chiral derivatizing agent. The (+)-1 ena...
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Planar Chiral Dianthranilide and Dithiodianthranilide Molecules: Optical Resolution, Chiroptical Spectra, and Molecular Self-Assembly Teresa Olszewska,† Maria Gdaniec,‡ and Tadeusz Połon´ski*,† Department of Chemistry, Technical University, 80-952 Gdan´ sk, and Faculty of Chemistry, A. Mickiewicz University, 60-780 Poznan´ , Poland [email protected] Received July 16, 2003

Planar chiral dianthranilide (1) was resolved to enantiomers with use of (-)-(1S,4R)-camphanoyl chloride as a chiral derivatizing agent. The (+)-1 enantiomer was assigned the S absolute configuration from the X-ray crystal structure of its N,N′-dicamphanoyl derivative. Optical resolution of dithionodianthranilide (2) was accomplished by inclusion crystallization with (R,R)-1,2diaminocyclohexane, and the X-ray structure of the corresponding adduct revealed the (-)-2 stereoisomer has the R configuration. A slow boat-to-boat ring inversion (∆Gq ) 24.1 ( 0.1 kcal mol-1) causes racemization of (+)-1 in solution as manifested by a gradual decrease of the CD spectrum whereas, (-)-2 is configurationally stable at these conditions. The analysis of the CD spectra of the title compounds showed that the n-π* Cotton effect signs are determined by the helicity of the skewed benzamide and thiobenzamide chromophores. The solid-state structures of the racemic and homochiral forms of 1 and 2 show different self-assembly patterns: the racemate (()-1 prefers the cyclic R22(8) hydrogen bond motif, whereas the crystalline DMSO solvates of (()-1 and (+)-1 consist of 1D homochiral hydrogen-bonded assemblies generated by the C(6) motif. In the case of dithionolactams (()-2 and (-)-2 two types of 1D networks were observed: in the racemate they are generated by the centrosymmetric R22(8) and R22(12) hydrogen bond motifs, whereas the molecules in the homochiral crystals are connected solely with use of the strongly nonplanar R22(8) motif. Introduction Molecules incorporating two rigidly oriented amide functionalities are attractive building blocks for construction of ordered supramolecular aggregates.1,2 The secondary cis-amide groups can participate in strong and highly directional complementary intermolecular hydrogen bonding, facilitating formation of well-defined and stable solidstate architectures. Dilactams possessing molecular chirality in addition can serve as models for the investigation †

Technical University. A. Mickiewicz University. (1) (a) MacDonald, J. C.; Whitesides, G. M. Chem. Rev. 1994, 94, 2383. (b) Fan, E.; Yang, J.; Geib, S. J.; Stoner, T. C.; Hopkins, M. D.; Hamilton, A. D. J. Chem. Soc., Chem. Commun. 1995, 1251. (c) Lewis, F. D.; Yang, J.-S.; Stern, C. L. J. Am. Chem. Soc. 1996, 118, 12029. (d) Palacin, S.; Chin, D. N.; Simanek, E. E.; MacDonald, J. C.; Whitesides, G. M.; McBride, M. T.; Palmore, G. T. R. J. Am. Chem. Soc. 1997, 119, 11807. (e) Tichy, M.; Ridvan, L.; Holy, P.; Zavada, J.; Cisarova, I.; Podlaha, J. Tetrahedron: Asymmetry 1998, 9, 227. (f) Kostyanovsky, R. G.; El’natanov, Y. I.; Krutius, O. N.; Chervin, I. I.; Lyssenko, K. A. Mendeleev Commun. 1998, 228. (g) Okamura, T.; Sakauye, K.; Ueyama, N.; Nakamura, A. Inorg. Chem. 1998, 37, 6731. (h) Wang, Y.; Decken, A.; Deslongchamps, G. Tetrahedron 1998, 54, 9043. (i) Williams, L. J.; Jagadish, B.; Lyon, S. R.; Kloster, R. A.; Carducci, M. D.; Mash, E. A. Tetrahedron 1999, 55, 14281. (j) Williams, L. J.; Jagadish, B.; Lansdown, M. G.; Carducci, M. D.; Mash, E. A. Tetrahedron 1999, 55, 14301. (k) Kostyanovsky, R. G.; El’natanov, Y. I.; Krutius, O. N.; Lyssenko, K. A.; Strelenko, Y. A. Mendeleev Commun. 1999, 70. (l) Lighfoot, M. P.; Mair, F. S.; Pritchard, R. G.; Warren, J. E. Chem. Commun. 1999, 1945. (m) Kuduva, S. S.; Bla¨ser, D.; Boese, R.; Desiraju, G. R. J. Org. Chem. 2001, 66, 1621. ‡

of chirality-directed molecular self-assembly, and several examples of different superstructures generated from homochiral diamides and from their racemic mixtures have been reported.2 For example, the molecules of racemic 2,5-diazabicyclo[2.2.2]octane-3,3-dione self-assemble into infinite undulating tapes, whereas the enantiomeric compound forms a 2D hydrogen bond network composed of catemers and cyclic tetrameric motifs in the solid state.2a Whereas quite a lot of work has been done on the supramolecular chemistry of dilactams,1,2 no systematic studies of analogous dithionolactams have been reported. As has been shown by Allen et al.3 the directional and acceptor properties of the CdS function differ from those of the CdO group, and therefore, a selfassembly process of dilactams and their dithiono analogues may result in quite different supramolecular architectures. (2) (a) Brienne, M.-J.; Gabard, J.; Leclercq, M.; Lehn, J.-M.; Cesario, M.; Pascard, C.; Cheve, M.; Dutruc-Rosset, G. Tetrahedron Lett. 1994, 35, 8157. (b) Brienne, M.-J.; Gabard, J.; Leclercq, M.; Lehn, J.-M.; Cheve, M. Helv. Chim. Acta 1997, 80, 856. (c) Kostyanovsky, R. G.; El’natanov, Y. I.; Krutius, O. N.; Lyssenko, K. A.; Chervin, I. I.; Lenev, D. A. Mendeleev Commun. 1999, 109. (d) Kostyanovsky, R. G.; Lyssenko, K. A.; El’natanov, Y. I.; Krutius, O. N.; Bronzova, I. A.; Strelenko, Y. A.; Kostyanovsky, V. R. Mendeleev Commun. 1999, 106. (e) Kostyanovsky, R. G.; Lyssenko, K. A.; Lenev, D. A. Mendeleev Commun. 1999, 154. (e) Lyssenko, K. A.; Lenev, D. A.; Kostyanovsky, V. R. Tetrahedron 2002, 58, 8525 and references therein. (3) Allen, F. H.; Bird, C. M.; Rowland, R. S.; Raithby, P. R. Acta Crystallogr. 1997, B53, 680. 10.1021/jo035024d CCC: $27.50 © 2004 American Chemical Society

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Dianthranilide and Dithiodianthranilide Molecules SCHEME 1

Although dianthranilide {dibenzo[b,f][1,5]diazocine6,12(5H,11H)-dione} (1) has been known for a long time, its stereochemistry and structural studies have not received considerable attention.4 The most striking stereochemical feature of compound 1 and its dithiono analogue 2 is their planar chirality.5 Planar chiral

ising candidates for correlations of the structure-optical activity relationships. The spectroscopic properties of small amide molecules have been the subject of extensive experimental and theoretical investigations in recent years.12,13 The interaction between the π-π* excited states of two amide or thioamide chromophores in the optically active 1 or 2, respectively, should give rise to circular dichroism (CD) curves with split Cotton effects, i.e., the exciton-coupled CD. This method is known as a versatile and sensitive tool for determining the absolute configuration or conformation of molecules in solution.14 Furthermore, in the case of 2 a substitution of sulfur for oxygen in the amide carbonyl results in a bathochromic shift of the electronic absorption and the corresponding CD bands that facilitates the measurements and spectroscopic assignments.13,15 Herein we report the synthesis, enantiomer separation, and determination of the absolute configurations of compounds 1 and 2. Next we examine their CD spectra to correlate the observed Cotton effect signs with the molecular geometries. Finally we compare the assembly mode of homochiral and heterochiral 1 and 2 in the solid state by studying crystal structures of their racemic and optically active forms. Results and Discussion

molecules have attracted much interest for designing chiral catalysts,6 supramolecular hosts,7 and chirality sensors.8 Important examples of planar chiral interconverting enantiomers are cyclotriveratrylenes,9a calixarenes,9b cyclooctatetraenes,9c or strained porphyrins.8 Although the dilactam 1 and dithionolactam 2 are devoid of stereogenic centers, they adopt chiral boat conformations and may exist in two enantiomeric forms. The enantiomers are exchangeable due to a slow boatto-boat ring inversion (Scheme 1). This process involves a hindered rotation about the C-N bond, and therefore, the barrier to ring inversion in structurally related monolactams exceeds 21 kcal/mol.10 Thus, it seems reasonable to expect that isolation of the enantiomers of 1 should be possible at ambient temperature. In the case of 2 the corresponding energy barrier is expected to be even higher owing to the increased partial double bond character of the C-N linkage in thioamides.11 However, in view of the configurational lability and lack of additional functional groups in 1 and 2, the optical resolution and assignment of the absolute configuration of these planar chiral compounds is a challenging task. It would afford valuable models for chiroptical studies and prom(4) Hoorfar, A.; Ollis, W. D.; Price, J. A.; Stephanatou, J. S.; Stoddart, J. F. J. Chem. Soc, Perkin Trans. 1 1982, 1649. (5) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: New York, 1994; Chapter 7.2. (6) Fu, G. C. Acc. Chem. Res. 2000, 33, 412. (7) (a) Harada, N.; Soutome, T.; Nehira, T. Uda, H.; Ui, S.; Okamura, A.; Miyano, S. J. Am. Chem. Soc. 1993, 115, 7547. (b) Okada, Y.; Mizutani, M.; Ishii, F.; Nishimura, J. Tetrahedron Lett. 1997, 38, 9013. (8) Mizuno, Y.; Aida, T.; Yamaguchi, K. J. Am. Chem. Soc. 2000, 122, 5278. (9) (a) Canceill, J.; Collet, A.; Gabard, J.; Gottarelli, G.; Spada, G. P. J. Am. Chem. Soc. 1985, 107, 1299. (b) Kusano, T.; Tabatabai, M.; Okamoto, Y.; Bo¨hmer, V. J. Am. Chem. Soc. 1999, 121, 3789. (c) Paquette, L. A.; Gardlik, J. M. J. Am. Chem. Soc. 1980, 102, 5016. (10) Lindquist, A.; Sandstro¨m, J. Chem. Scr. 1974, 5, 52. (11) Oki, M. Applications of Dynamic NMR Spectroscopy to Organic Chemistry; VCH: Deerfield Beach, FL, 1985; p 61.

Synthesis and Optical Resolution. Racemic dianthranilide [(()-1] was obtained from methyl anthranilate following the literature method.4 Thionation of (()-1 with Lawesson’s reagent16 afforded the dithionolactam 2 in nearly quantitative yield. The optically active dilactam (+)-1 was prepared in two steps involving N-acylation of the racemate (()-1 with (-)-(1S,4R)-camphanoyl chloride and subsequent selective cleavage of the camphanoyl moieties with butylamine (Scheme 2). Fortunately, the acylation step afforded the crystalline product (-)-3 that appeared to be diastereomerically pure as evidenced by the corresponding 1H NMR spectrum. Apparently, due to the configurational lability of 1, the asymmetric transformation occurs during the reaction and the equilibrium between two possible diastereomers shifts to the more stable form of 3. Indeed, the molecular mechanics calculations (MM2)17 showed that the steric energy of the second diastereomer with the configuration opposite that of the dilactam moiety is 3.1 kcal/mol higher than that of (-)-3. To diminish the degree of the racemization of (+)-1 in solution, the cleavage of the camphanoyl residues in (-)-3 (12) (a) Woody, R. W. In Circular Dichroism, Principles and Applications; Nakanishi, K., Berova, N., Woody, R. W., Eds.; VCH: New York, 1994; Chapter 17. (b) Roger, A.; Norden, B. Circular Dichroism and Linear Dichroism; Oxford University Press: Oxford, 1997; Chapter 2. (c) Klyne, W.; Kirk, D. N.; Tilley, J.; Suginome, H. Tetrahedron 1980, 36, 543. (d) Jackman, L. M.; Webb, R. L.; Yick, H. C. J. Org. Chem. 1982, 47, 1824 and references therein. (13) (a) Milewska, M. J.; Gdaniec, M.; Połon´ski, T. Tetrahedron: Asymmetry. 1997, 8, 1267. (b) Połon´ski, T.; Milewska, M. J.; Konitz, A.; Gdaniec, M. Tetrahedron: Asymmetry. 1999, 10, 2591. (14) Nakanishi, K.; Berova, N. Reference 11a, Chapter 13. (15) Kajtar, M.; Kajtar, J.; Maier, Zs.; Zewdu, M.; Hollosi, M. Spectrochim. Acta 1992, 48A, 87. (16) (a) Yde, B.; Yousif, N. M.; Pedersen, V.; Thomsen, J.; Lawesson, S.-O. Tetrahedron 1984, 40, 2047. (b) For a review see: Cava, M. P.; Levinson, M. J. Tetrahedron 1985, 41, 5061. (17) (a) Allinger, N. L. J. Am. Chem. Soc. 1977, 99, 8127. (b) Allinger, N. L.; Yuh, Y. H. QCPE 1980, 395.

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Olszewska et al. SCHEME 2

was accomplished in a hydrocarbon solvent that caused a rapid crystallization of the product. The optical purity (ee 51%) of (+)-1 having [R]20D +394 was determined by HPLC analysis on a chiral column. The absolute configuration of (+)-1 follows unambiguously from the X-ray structure of the N,N′-dicamphanoyl derivative (-)-3 (Figure 1) and was assigned to be S. The optical activity of (+)-1 is also manifested by its CD spectrum in methanol (Figure 2). The magnitude of the observed Cotton effects gradually decreases at room temperature due to a slow racemization of the compound in solution. The first-order kinetics of the racemization was followed polarimetrically in ethanolic solution at various temperatures. Thus, the measured rate constants k for the ring boat-to-boat interconvesion were 1.43 × 10-5, 1.43 × 10-5, and 5.17 × 10-4 s-1 at 25, 40, and 50 °C, respectively. Arrhenius plots and the Eyring equation finally led to the following activation parameters: Ea ) 27.2 ( 0.2 kcal mol-1, ∆Hq ) 26.6 ( 0.2 kcal mol-1, ∆Sq ) 8.6 ( 0.9 cal mol-1 K-1, and ∆Gq ) 24.1 ( 0.1 kcal mol-1. Working with the racemic (()-1, we noticed that this compound easily forms inclusion complexes with a wide variety of organic substances. This is due to the geometric features of 1 (“roof-shaped” molecule18) that makes difficult its close packing in the crystal. Therefore, we tried inclusion complexation of 1 with optically active guests as an alternative method of the optical resolution. Thus, (()-1 treated with an excess of (R,R)-1,2-diaminocyclohexane (4) in toluene afforded the crystalline inclusion complex 1‚4. Unfortunately, the dilactam 1 liberated from the complex did not show any indication of optical activity. Clearly, the hydrogen bonding between the enantiomeric pairs of 1 and (R,R)-4 leads to a more effective crystal packing than that between the homochiral molecules of 1 and (R,R)-4, which explains the failure of this attempt of the optical resolution. Fortunately, the analogous hydrogen bonds between the thioamide groups are weaker,3 and therefore, we (18) Weber, E.; Czugler, M. Top. Curr. Chem. 1988, 149, 45.

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FIGURE 1. Molecular structure of (-)-3 showing the S configuration of the dianthranilide core. The hydrogen atoms were omitted for clarity.

FIGURE 2. Decay of the CD signal of the (+)-1 solution in methanol at 21 °C.

succeeded in the optical resolution of the dithionolactam (()-2 by its cocrystallization with (R,R)-4. Again upon treatment of the racemate (()-2 with an excess of the optically active amine 4 in toluene, the 1:3 crystalline complex between the enantiomerically pure 2 and (R,R)-4

Dianthranilide and Dithiodianthranilide Molecules

FIGURE 3. Crystal structure of the complex (-)-2‚43 showing the absolute configuration of the dithionolactam (-)-2.

was formed. The solid-state structure of the adduct revealed that it is composed of one conjugated anion of 2 and the conjugated cation of (R,R)-4 per two neutral amine guest molecules (Figure 3). The thioamide groups of 2 interact solely with the amino groups of (R,R)-4, and there are no hydrogen bonds between the thioamide functions. The liberation of the optically active (-)-2 requires treatment of the complex with dilute acetic acid. The absolute configuration of (-)-2 can be deduced from the crystal structures of the adduct and was found to be R. HPLC on a chiral phase revealed that only one crystallization is sufficient for isolation of the optically pure dithionolactam (-)-2 (ee > 97%) of [R]25D -1216. Compound (-)-2 appeared to be optically stable at room temperature since its optical rotation in ethanolic solution remained unchanged after it stood for a week in the dark. On the other hand, at elevated temperatures the optical rotation gradually decreases, which is apparently due to a partial decomposition of the sample. Therefore, we tried to assess the energy barrier to the ring inversion of 2 by variable-temperature measurements of its N,N′dibenzyl derivative 5 in DMSO-d6. Since the AB system due to the CH2 benzylic hydrogens did not show any coalescence up to 210 °C, the ∆Gq value for the ring inversion should be well above 26 kcal mol-1. Chiroptical Spectra. The CD spectra of (+)-1 and (-)-2 taken in methanol are presented in Figures 2 and 4, respectively. The CD of (+)-1 is characterized by three positive Cotton effects at 288, 240, and 206 nm. The first one is very weak and unequivocally can be assigned to the aromatic 1Lb transition. The much more intense second one occurs in the region of the forbidden amide n-π* excitation.12 The carboxamide group conjugated with an aryl ring constitutes a chromophore the helicity of which determines the Cotton effect sign. Analogously to other R,β-unsaturated carbonyl compounds, the P helicity of the system should lead to the positive n-π* Cotton effects whereas the M helicity to the negative one (Chart 1).19 The X-ray structure of the DMSO solvate of (+)-1 revealed that both amide groups are severely twisted with respect to the phenyl rings in the P sense (the OdCsCdC torsion angles are 52.5° and 57.4°), (19) Snatzke, G.; Snatzke, F. In Fundamental Aspects and Recent Developments in Optical Rotatory Dispersion and Circular Dichroism; Ciardelli, F., Salvadori, P., Eds.; Heyden: London, 1973; Chapter 3.2 and references therein. (b) Gdaniec, M.; Połon´ski, T. J. Am. Chem. Soc. 1998, 120, 7353.

FIGURE 4. CD and UV-vis (lower curve) spectra of (-)-2 taken in methanol.

CHART 1

which explains the positive sign of the CD at 240 nm. The nature of the extremely strong CD band at 208 nm is less clear. Since the molecule contains two rigidly oriented amide units, the exciton coupling between these chromophores, leading to two intense and oppositely signed Cotton effects, is expected in the region of the allowed π-π* transition. However, only one positive CD band was observed in this region. On the other hand, the non-Gaussian shape of the neighboring n-π* band and a minimum near 220 nm point to a contribution from an additional band that might be due to a missing negative branch of the exciton couplet. The amide π-π* transition is polarized approximately along the N-O direction (the transition moment is rotated by 9.1° toward the C-N bond according to Peterson and Simpson20a or 6° according to Clark20b). The electronic transition moments of the planar anthranilamide chromophore showing a significant mixing of the amide and aromatic π-π* excitations (20) (a) Peterson, D. L.; Simpson, W. T. J. Am. Chem. Soc. 1957, 79, 2375. (b) Clark, L. B. J. Am. Chem. Soc. 1995, 117, 7974. (c) Recker, J.; Tomcik, D. J.; Parquette, J. R. J. Am. Chem. Soc. 2000, 122, 10298.

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Olszewska et al. CHART 2

FIGURE 5. Autostereogram23 showing the hydrogen-bonded

have been discussed by Parquette and co-workers.20c The geometry of (+)-1 implies left-handed screwness (counterclockwise orientation) of the transition moments in agreement with the observed sequence of the positive CD at the longer wavelengths and the minimum at the shorter wavelengths (negative exciton coupling,14 Chart 2). The contribution from the aromatic 1La transition occurring in the same region may also lead to the exciton CD, though the reported spectra of chiral dibenzamides exhibit a much weaker magnitude of the Cotton effects.21 The CD spectrum of (-)-2 (Figure 4) shows at least seven bands with alternating signs at the visible and near UV regions. Due to a similarity of the electronic structures of the amide and thioamide chromophores, there is a close correspondence between their lowest energy transitions and also the direction of the electronic transition moments.13,15 Furthermore, a substitution of sulfur for the carbonyl oxygen results in bathochromic shifts of the absorption maxima and a better resolution of the n-π* and π-π* electronic transitions. Therefore, the spectra of thiocarbonyl compounds may be useful in the analysis of the amide spectra. The UV-vis spectrum of 2 reveals three well-resolved absorption bands at 384, 300, and 230 nm corresponding to the thioamide n-π*, π-π*, and σC-S-π* excitations, respectively. Thus, a broad negative CD band near 390 nm should be assigned to the n-π* transition. Analogously to its parent carbonyl analogue, the Cotton effect sign is determined by the helicity of the thiobenzamide unit. According to the X-ray structure of (-)-2, it is twisted in the M sense (the Sd CsCdC torsion angles are in the range -46.6° to -58.4° for the three symmetry-independent molecules), which accounts for the observed negative n-π* Cotton effect sign. In the region of the thioamide π-π* transition there are two CD bands: a positive one at 320 nm and a negative one near 290 nm. They can be attributed to the exciton coupling of the allowed π-π* transition of two thioamide units. In this case the observed sequence of the bands points to a positive exciton coupling and the right-handed screwness (clockwise orientation) of the thioamide π-π* transition moments. The nature of two exciton couplets observed at the shorter wavelengths near 230 and 210 nm is unclear; they might be due to the σC-S-π* and aromatic 1La excitations, respectively. (21) Kawai, M.; Nagai, U. Tetrahedron Lett. 1974, 1881. (b) Połon´ski, T. J. Org. Chem. 1993, 58, 258.

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2D network formed by two symmetry-independent molecules in the crystals of (()-1. The N and O atoms are indicated with larger circles. The C-H hydrogen atoms are omitted for clarity.

FIGURE 6. Autostereogram23 showing the hydrogen-bonded 2D network formed by two symmetry-independent molecules of 1 and DMSO in (()-1‚DMSO. The DMSO molecule is disordered over two positions with overlapping of the C and O atoms. The C-H hydrogen atoms are omitted for clarity.

CHART 3

Molecular Self-Assembly. Successful transformation of the racemic mixtures of (()-1 and (()-2 into the crystalline enatiomers (+)-1 and (-)-2, respectively, prompted us to take a closer look at the assembly mode of these dilactams and dithionolactams in homochiral and heterochiral systems. Diffraction-quality crystals of the racemic dilactam (()-1 were obtained from acetic acid. This compound crystallizes in the space group P1 h with two symmetry-independent molecules in the asymmetric unit. The molecules denoted as B in Figure 5 assemble through the centrosymmetric R22(8) hydrogen bond motifs22 (Chart 3) into infinite undulating tapes composed of the alternating enantiomers, whereas the molecules (22) For details of the definition, terminology, and notation in the graph set approach, see: (a) Etter, M. C. Acc. Chem. Res. 1990, 23, 120. (b) Bernstein, J.; Davis, R. E.; Shimoni, L.; Chang, N.-L. Angew. Chem., Int. Ed. Engl. 1995, 34, 1555.

Dianthranilide and Dithiodianthranilide Molecules

FIGURE 7. Autostereograms23 showing the homochiral helices of 1 generated by the C(6) hydrogen bond motif: (a) the helix formed by the R enantiomer in (()-1‚DMSO; (b) the helix formed by the S enantiomer and the solvent molecules in (()-1‚DMSO; (c) the helix formed by the component molecules in (+)-1‚DMSO.

denoted as A form centrosymmetric dimers also with use of the R22(8) motif. These two types of structural elements are connected through N-H‚‚‚O hydrogen bonds into a 2D network. Since the crystals of the optically active compound (+)-1 were not suitable for X-ray analysis, we prepared its 1:1 solvate with DMSO that gave crystals of improved quality. For a comparison we also obtained a 2:1 solvate of the racemate (()-1 with DMSO. The 2D network of the hydrogen-bonded molecules of 1 and DMSO observed in the centrosymmetric structure of (()-1‚DMSO is presented in Figure 6. It is composed of two symmetryindependent molecules of opposite chirality denoted as A and B. Contrary to (()-1, the R22(8) motifs are not generated in this case. The homochiral molecules A connected through N2A-H‚‚‚O2A hydrogen bonds that generate the C(6) motif22 are arranged into a helical structure that is further stabilized by the weak C-H‚‚‚O1A interactions (Figure 7a). A similar helix is formed by molecules B; however, the hydrogen bond donor and acceptor sites are interchanged here (Figure 7b). The DMSO molecules are joined to the helix via strong N-H‚‚‚O and weak C-H‚‚‚O interactions. These two types of parallel helical structures are linked together through N1A-H‚‚‚O2B hydrogen bonds into the 2D assembly shown in Figure 6. The helical motif observed in the racemic solvate (()-1‚DMSO is repeated in the chiral crystals of (+)-1‚DMSO; the homochiral molecules of (+)-1 with the solvent molecules connected by the NsH‚‚‚OdS hydrogen bonds are arranged into a helix characterized by intrahelix interactions similar to those observed in the crystals of the racemate (Figure 7c). The crystal structure analysis of (+)-1‚DMSO employing the anomalous dispersion method allowed additional confirmation of the absolute configuration of the dilactam (+)-1. The structures of the racemic (()-2 and homochiral dithionolactam (-)-2 are presented in Figures 8 and 9, respectively. The infinite chains observed in (()-2 (Figure

FIGURE 8. Autostereograms23 showing the crystal structure of the racemic (()-2: (a) molecules of 2 hydrogen-bonded using the R22(12) motif assembled into a close-packed layer by aromatic ring interactions; (b) heterochiral 1D network of 2 generated by the R22(8) and R22(12) hydrogen bond motifs.

8b) are composed of alternating enantiomers held together by the N-H‚‚‚S hydrogen bonds, generating two cyclic centrosymmetric motifs, R22(8) and R22(12). The R22(12) dimers of the adjacent chains form closely packed layers stabilized by the face-to-face and edge-to-face aromatic interactions (Figure 9a). Both cyclic motifs are strongly nonplanar with CdS‚‚‚H angles of 111° and 97° for the R22(8) and R22(12) motifs, respectively. Since all strong intermolecular interactions in (()-2 occur between the enantiomeric molecules, the crystal J. Org. Chem, Vol. 69, No. 4, 2004 1253

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Experimental Section

FIGURE 9. Autostereograms23 showing the crystal structure of (-)-2: (a) homochiral tape generated by the nonplanar R22(8) motif; (b) crystal packing of the three symmetry-independent chiral tapes viewed along the x axis.

packing of the homochiral crystals of (-)-2 is evidently less efficient than that of (()-2 as indicated by its lower crystal density [1.458 and 1.416 g cm-3 for (()-2 and (-)-2, respectively]. Similarly as it occurs in the racemate, the molecules of (-)-2 assemble into 1D hydrogen-bonded networks; however, they are linked solely by the strongly nonplanar self-complementary R22(8) interactions involving translation-related molecules (Figure 9a). There are three crystallographically independent molecules in the asymmetric unit cell, and therefore, the hydrogen bonds generate three parallel symmetry-independent chains directed along the x axis (Figure 9b). The CdS‚‚‚H angles of CdS‚‚‚H-N hydrogen bonds range between 94° and 100°, which results from nearly perpendicular arrangement of the cis-thioamide groups in the chiral tapes. In conclusion, a relatively high ring inversion barrier of the dianthranilide (1) and its dithiono analogue (2) makes possible optical resolution of these planar chiral compounds. Compound (+)-1 slowly racemizes in solution at room temperature, and this process can be monitored by CD spectra or polarimetrically, whereas (-)-2 is configurationally stable at these conditions. Their longwavelength n-π* Cotton effect signs are determined by the helicity of the benzamide and thiobenzamide chromophores. In the region of the allowed π-π* transition the exciton-coupled CD curves were observed, which are also useful in the assignments of the absolute configurations. The solid-state structures of the racemic and homochiral forms of 1 and 2 show a variety of self-assembly patterns. The racemic 1 prefers assembly of enantiomeric molecules through the planar R22(8) hydrogen bond motif. However, the molecules in the homochiral crystals of (+)-1‚DMSO form helical assemblies generating the C(6) hydrogen bond motif, and this pattern is also observed in the heterochiral solvate (()-1‚DMSO. On the other hand, the enantiomeric molecules in the crystals of (()-2 generate tapes via the centrosymmetric R22(8) and R22(12) hydrogen bond motifs, whereas in (-)-2 the tapes are formed only with use of the nonplanar R22(8) motif. 1254 J. Org. Chem., Vol. 69, No. 4, 2004

1 H and 13C NMR spectra were obtained at 300 and 50 MHz, respectively, and the deuterated solvents were used as an internal lock. Optical Resolution of Dibenzo[b,f][1,5]diazocine-6,12(5H,11H)-dione (1). Racemic dilactam (()-14 (1.20 g, 5 mmol) and (-)-(1S,4R)-camphanoyl chloride (2.40 g, 11 mmol) were refluxed in pyridine (20 mL) for 20 min. The solvent was evaporated at reduced pressure, and the residue was dissolved in benzene, washed with dilute hydrochloric acid and water, dried (Na2SO4), and evaporated to dryness. The residue was crystallized from toluene-hexane to obtain 1.52 g of the N,N′dicamphanoyl derivative 3: mp 204-206 °C; [R]21D -251 (c 2, CHCl3); IR (KBr) νmax 1788, 1701 cm-1; 1H NMR (CDCl3) δ 7.43 (dd, J ) 7.4 and 1.0 Hz, 2H), 7.35 (td, J ) 7.6 and 1.3 Hz, 2H), 7.29 (m, 4H), 2.64 (m, 2H), 1.91 (m, 2H), 1.48 (m, 2H), 1.13 (s, 6H), 0.97 (s, 6H), 0.95 (s, 6H); 13C NMR (CDCl3) δ 177.4, 169.6, 167.9, 132.9, 132.0, 130.3, 129.6, 92.7, 56.4, 54.1, 31.6, 29.4, 17.3, 16.5, 9.5. Anal. Calcd for C34H34NO8N2 (599): C, 68.22; H, 5.73; N, 4.68. Found: C, 68.16; H, 5.70; N, 4.60. N,N′-Dicamphanoyl derivative 3 (0.30 g, 0.5 mmol) was dissolved in toluene (10 mL), butylamine (0.5 mL) was added, and the reaction mixture was left to stand at room temperature for 30 min. Then the precipitated crystals were filtered and washed with diethyl ether to obtain 94 mg (68%) of the product (+)-1: mp 335-337 °C (lit.4 racemate mp 333 °C); [R]20D +394 (c 0.5, MeOH); ee 51% was assigned by HPLC analysis using a chiral column (Chirobiotic V); IR (KBr) νmax 3166, 1661, 1643 cm-1; 1H NMR (DMSO-d6) δ 10.23 (s, 2H), 7.37-7.20 (complex m, 6H), 7.06 (d, 2H, J ) 7.2 Hz); 13C NMR (DMSO-d6) δ 169.9, 134.9, 133.7, 131.0, 128.4, 127.7, 126.0; UV (MeOH) λmax 271 nm ( 340), 210 (32100). Dibenzo[b,f][1,5]diazocine-6,12(5H,11H)-dithione (2). Dianthranilide (1) (0.48 g, 2 mmol) and Lawesson’s reagent (0.48 g, 1.2 mmol) were refluxed in dry pyridine (8 mL) for 30 min. After cooling, the reaction mixture was diluted with chloroform, and the precipitated yellow crystals were filtered and washed with chloroform to obtain 0.49 g (91%) of the product: mp 335 °C dec; IR (KBr) νmax 3157, 1513, 1483, 1219 cm-1; 1H NMR (DMSO-d6) δ 12.41 (s, 2H), 7.42-7.20 (complex m, 6H), 7.07 (d, 2H, J ) 7.6 Hz);13C NMR (DMSO-d6) δ 200.5, 139.6, 133.8, 130.5, 129.2, 128.5, 124.7; UV (MeOH) λmax 382 nm ( 475), 300 (18000). Anal. Calcd for C14H10N2S2 (270): C, 62.19; H, 3.73; N, 10.36; S, 23.72. Found: C, 62.45; H, 3.75; N, 10.26; S, 23.75. Optical Resolution of Dibenzo[b,f][1,5]diazocine-6,12(5H,11H)-dithione (2). Racemic dithionolactam (()-2 (0.35 g, 1.3 mmol) and (R,R)-1,2-diaminocyclohexane (4) (1.15 g, 10 mmol) were dissolved with gentle heating in toluene (5 mL). After 12 h at room temperature the precipitated crystals were filtered and washed with diethyl ether to obtain 0.31 g of the complex 2‚43. The complex 2‚43 was dissolved in acetic acid (0.5 mL), and water was added (5 mL). Then the precipitated crystals were filtered, washed with water, and dried to obtain 0.12 g of the product (-)-2: mp 304-306 °C dec; [R]22D -1216 (c 0.25, MeOH); ee > 97% was assigned by HPLC analysis using a chiral column (Chiracel OD-H). 5,11-Dibenzyldibenzo[b,f][1,5]diazocine-6,12(5H,11H)dithione (5). Thionation of 1,5-dibenzyldibenzo[b,f][1,5]diazocine-6,12(5H,11H)-dione with Lawesson’s reagent in boiling toluene afforded dithionolactam 5: mp 241-242 °C (toluene); IR (KBr) νmax 1457, 1411, 1226 cm-1; 1H NMR (CDCl3) δ 7.44-7.41 (complex m, 4H), 7.35-7.31 (complex m, 8H), 7.12 (td, J ) 7.7 and 1.1 Hz, 2H), 6.97 (td, J ) 7.7 and 1.5 Hz, 2H), 6.48 (m, 2H), 6.12 (d, J ) 14.2 Hz, 2H), 4.97 (d, J ) 14.2 Hz, 2H); 13C NMR (CDCl3) δ 198.3, 141.3, 138.0, 135.4, 129.2, 129.1, 128.8, 128.6, 128.1, 124.6, 58.5. Anal. Calcd for C28H24N2S2 (452.6): C, 74.30; H, 5.34; N, 6.19; S, 14.17. Found: C, 74.31; H, 5.12; N, 6.37; S, 14.23. X-ray Structure Analyses. Diffraction studies were carried out with a Kuma Diffraction KM-4 diffractometer [(()-1, (()-2, (-)-2, and (-)-3] and Kuma CCD diffractometer

Dianthranilide and Dithiodianthranilide Molecules [(+)-1‚DMSO, (()-1‚DMSO, and (-)-2‚43]. The data were corrected for Lorentz and polarization factors. Absorption correction (ψ-scan, multiscan) was employed in the case of (()-2, (-)-2, (+)-1‚DMSO, and (-)-2‚43. The structures were solved by direct methods using SHELXS-9724 and refined by the full-matrix least-squares method on F2 using the SHELXL97 program.25 Crystal Data for C14H10N2O2 [(()-1]: triclinic, space group P1 h , a ) 8.6349(17) Å, b ) 11.2312(19) Å, c ) 12.402(2) Å, R ) 97.534(15)°, β ) 96.796(16)°, γ ) 93.056(15)°, V ) 1181.1(4) Å3, Z ) 4, λ ) 0.71073 Å, T ) 293 K, R1 ) 0.0378 and wR2 ) 0.1018 for 2957 independent reflections with I > 2σ(I). Crystal Data for C16H16N2O3S [(+)-1‚DMSO]: orthorhombic, space group P212121, a ) 8.749(1) Å, b ) 9.771(1) Å, c ) 18.104(2) Å, V ) 1547.6(3) Å3, Z ) 4, λ ) 0.71073 Å, T ) 293 K, R1 ) 0.0470 and wR2 ) 0.0882 for 1824 independent reflections with I > 2σ(I), Flack parameter26 x ) 0.07(13). The DMSO molecule is disordered over two positions with the occupancy ratio 0.86:0.14. Crystal Data for C30H26N4O5S [(()-1‚DMSO]: monoclinic, space group P21/n, a ) 17.3970(10) Å, b ) 8.5828(5) Å, c ) 18.7108(11) Å, β ) 103.073(5)°, V ) 2721.4(3) Å3, Z ) 4, λ ) 0.71073 Å, T ) 293 K, R1 ) 0.0957 and wR2 ) 0.2544 for 3650 independent reflections with I > 2σ(I). The DMSO molecule is disordered over two positions with the occupancy ratio 0.54: 0.46. The high value of the R factors is due to crystal twinning. Crystal Data for C14H10N2S2 [(()-2]: triclinic, space group P1 h , a ) 7.669(2) Å, b ) 9.014(2) Å, c ) 9.620(2) Å, R ) 83.99(23) Katrusiak, A. J. Mol. Graph. Modell. 2001, 19, 363. (24) Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467. (25) Sheldrick, G. M. SHELXL-97. Program for the Refinement of Crystal Structures; University of Go¨ttingen: Go¨ttingen, Germany, 1997. (26) Flack, H. D. Acta Crystallogr. 1983, A39, 876.

(2)°, β ) 89.72(2)°, γ ) 68.74(2)°, V ) 616.0(2) Å3, Z ) 2, λ ) 1.54178 Å, T ) 293 K, R1 ) 0.0443 and wR2 ) 0.1192 for 1901 independent reflections with I > 2σ(I). Crystal Data for C14H10N2S2 [(-)-2]: orthorhombic, space group P212121, a ) 6.656(1) Å, b ) 14.038(3) Å, c ) 40.714(8) Å, V ) 3804(1) Å3, Z ) 12, λ ) 1.54178 Å, T ) 293 K, R1 ) 0.0323 and wR2 ) 0.0845 for 6157 independent reflections with I > 2σ(I), Flack parameter26 x ) 0.006(12). Crystal Data for C20H24N4S2 [(-)-2‚43]: monoclinic, space group P21, a ) 9.6070(10) Å, b ) 12.8255(15) Å, c ) 14.2170(12), β ) 102.919(8)°, V ) 3955.2(5) Å3, Z ) 2, λ ) 0.71073 Å, T ) 293 K, R1 ) 0.0455 and wR2 ) 0.1243 for 4967 independent reflections with I > 2σ(I), Flack parameter26 x ) 0.04(7). Crystal Data for C34H34N2O8 [(-)-3]: orthorhombic, space group P212121, a ) 10.737(2) Å, b ) 14.931(3) Å, c ) 18.911(4) Å, V ) 3031.7(10) Å3, Z ) 4, λ ) 0.71073 Å, T ) 293 K, R1 ) 0.0458 and wR2 ) 0.1084 for 2128 independent reflections with I > 2σ(I).

Acknowledgment. We are indebted to Dr. J. Frelek (IChO PAN, Warsaw) for CD measurements with use of her JASCO J-715 instrument and Dr. A. Zarecki (IChO PAN, Warsaw) for HPLC analyses with use of chiral columns. Supporting Information Available: X-ray crystallographic files in CIF format for the structures (()-1, (+)-1‚DMSO, (()-1‚DMSO, (()-2, (-)-2, (-)-2‚43, and (-)-3. This material is available free of charge via the Internet at http://pubs.acs.org. JO035024D

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