Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Spontaneous resolution of new conglomerates in the series of 4-arenesulfonyliminocyclohex-2-en-1-ones Remir G. Kostyanovsky,*a Anatolii P. Avdeenko,b Svetlana A. Konovalova,b Gulnara K. Kadorkinaa and Alexander V. Prosyanikc a N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow, Russian Federation.Fax: +7 095 137 3227; e-mail: kost@center.chph.ras.ru b Donbass State Machinery Academy, 343913 Kramatorsk, Ukraine. Fax: +38 0626 416 676; e-mail: dgma@dgma.donetsk.ua c Ukrainian State Chemical Technology University, 320005 Dnepropetrovsk, Ukraine. Fax: +38 0562 477 478; e-mail: ugxtu@dicht.dnepropetrovsk.ua DOI: 10.1070/MC2000v010n01ABEH001208 Racemic mixtures 1a–f, 2a–e crystallise as conglomerates at room temperature and lead to spontaneous resolution; tosylimines 1e and 2c give homochiral crystals (space group P1), whereas similar benzenesulfonyloximes 3a,b give heterochiral packings (space groups P21/n and P21/c, respectively).Conglomerate formation is a necessary condition both for spontaneous resolution of enantiomers and for resolution by crystallization from optically active solvents or by an entrainment procedure.1 Conglomerate formation is of poor occurrence; up to 1979 only 250 conglomerates were reported, according to nowaday estimations the frequency of organic conglomerates does not exceed 10%,1 so that a search for conglomerates comprises an essential challenge.Some previous studies2 have shown that this proportion can fluctuate to a large extent in some particular series of organic compounds. Earlier we have found conglomerates among various classes of organic compounds using X-ray data,3,4 resolution by crystallization from optically active solvents,5,6 and engineering homochiral crystals.7,8 In this work, another intriguing instance of conglomerate formation has been found in the rather wide series of derivatives of 4-arenesulfonyliminocyclohex-2-en-1-ones 1, 2.Compounds of this class have been synthesised recently by the halogenation of corresponding N-arenesulfonyl-p-quinone imines or 4-arenesulfonylaminophenols. 9 Similar 4-arenesulfonyloximinocyclohex- 2-en-1-ones such as 3 have been obtained by the chlorination of corresponding O-arenesulfonyl-p-quinone oximes.10–12 We optimised the above methodology and thus rised the yields by 11–25% up to 75–86% (cf.ref. 12), improved the purity of 1b,c,f, 2b, 3a (the analytically pure products were obtained after single crystallizations) and synthesised 1a,c,d, 2a,d and 3b for the first time. All the products were characterised by spectroscopic data† and elemental analysis; the structures of 1e, 2c and 3a,b were also confirmed by X-ray diffraction analysis (the C(17a) C(13a) C(14a) C(15a) C(12a) C(16a) C(11a) O(3a) S(1a) O(2a) N(1a) C(4a) C(3a) Cl(1a) C(2a) Cl(2a) C(10a) C(5a) C(6a) C(7a) C(8a) C(9a) C(1a) O(1a) Figure 1 Crystal structure of 2c. Above: two independent molecules of 2c (a and b) and a molecule of the entrained CCl4, in the molecule b a statistical disorder on two positions of the C(2b)C(3b) fragment is observed; below: the molecular structure of an independent molecule a of 2c.Selected bond lengths (Å): S(1a)–N(1a) 1.672(4), Cl(1a)–C(2a) 1.800(6), Cl(2a)–C(3a) 1.843(7), O(1a)–C(1a) 1.205(7), N(1a)–C(4a) 1.287(7), C(1a)–C(9a) 1.478(8), C(1a)–C(2a) 1.517(8), C(2a)–C(3a) 1.462(9), C(3a)–C(4a) 1.513(8), C(4a)– C(10a) 1.482(7), C(9a)–C(10a) 1.390(8); selected dihedral angles (°): S(1a)–N(1a)–C(4a)–C(10a) 179.9(4), S(1a)–N(1a)–C(4a)–C(3a) 3.0(8), C(3a)–C(4a)–C(10a)–C(9a) 17.7(7), C(2a)–C(3a)–C(4a)–C(10a) 45.2(7), Cl(1a)–C(2a)–C(3a)–Cl(2a) 177.9(3).(a) (b) (a) aOptical rotation was measured on a Polamat A polarimeter. bIn MeOH. cIn Me2CO. dOptical rotation remained unchanged after 1 week at 20 °C.eIn EtOH. f2c (100 mg) was powdered, treated under a vacuum (1 Torr, 2 h) in order to remove the entrained CCl4, and then crystallised from a mixture of the solvents with the addition of deficiency of CCl4 (the ratio 2c:CCl4 = = 4:1). Table 1 Conditions of crystallization and optical activity of the obtained compounds. Compound Solvent for the crystal growth Number of crystals Weight of each crystal/ mg Optical activity of each crystala [a]20 546/° (c, CHCl3) 1a CHCl3– n-heptane (1:1) 43 3.6–13.2 9.1–29.1 +2.7–9.3 (0.6–1.1) –4.0–7.0 (0.8–2.4) 1b CHCl3 21 10.7–30.4 11.1 +2.4–5.6 (0.9–2.5) –3.2 (0.9) 1c CHCl3– n-heptane (3:2) 11 26.6 6.3 +0.8 2.2) –3.8 (0.5) 1d CHCl3– n-heptane (1:1) 12 12.4 11.5–29.0 +4.8 (1.0) –2.9–3.1 (1.0–2.4) 1e CHCl3 313 2.7–12.2 12.2 7.5–63.4 +2.1–7.8 (0.2–0.9) +2.1 (0.9)b –2.8–6.4 (0.5–5.3) 1f CHCl3– n-heptane (3:2) 111 28.2 15.2 56.1 +12.3 (2.4) +2.4 (1.3)c –7.2 (4.7) 2a CHCl3– n-heptane (1:2) 21 20.5–26.4 14.0 +2.3–2.7 (1.7–2.2) –2.6 (1.2) 2b CHCl3– CCl4 (1:1) 13 15.9 11.1–14.2 +8.7 (1.3) –7.2–9.6 (0.9–1.2)d 2c CCl4 2211 11.5–12.6 1.3–2.5 29.0 53.5 +1.9–2.1 (1.0) +8.8–21.2 (0.1–0.2)c +0.8 (2.4)e –2.2 (4.4) 2d CHCl3– n-heptane (1:1) 11 12.6 11.5 +1.0 (1.1) –1.1 (1.0) 2e CHCl3– n-heptane (2:1) 21 3.3–13.1 7.5 +3.2–5.5 (0.3–1.1) –5.1 (1.0) 2cf Me2CO– n-hexane (1:5) the entire precipitate 45.2 –1.3 (3.8)Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) data for 1e and 3a,b will be published later). Compounds 1 and 2 both in solution and in crystals exist solely in the form of E-isomers relative to the double cyclohexene bond.For compound 3 in solution Z- and E-isomers are observed, whereas only the E-isomer is detected in a crystal (cf. refs. 10–12). All the above compounds are stable and give well-formed, rather large-sized, transparent crystals. By testing the optical activity of individual crystals, (+)- and (–)-enantiomers of compounds 1 and 2 were isolated.This results in the identification of 11 new conglomerates (Table 1). Consistently, X-ray diffraction analysis performed on 1e and 2c demonstrated that single crystals contain homochiral molecules (space groups P1) (Figure 1).‡ By contrast, structurally related O-benzenesulfonyloximes 3a,b form centrosymmetric crystals and thus do not lead to any spontaneous resolution.† Characteristics and spectroscopic data. 1H and 13C NMR spectra were measured at 300 and 75 MHz, respectively, in CDCl3. 1a: yield 72%, mp 124–125 °C (AcOH). 1H NMR, d: 2.25 (s, 3H, 3-Me), 6.64 (s, 1H, 5-H), 7.62, 7.72 and 8.05 (m, 5H, Ph). IR, n/cm–1: 1725 (C=O), 1610, 1584 (C=N, C=C), 1338, 1170 (SO2). 1b:9 yield 78%, mp 137–138 °C (AcOH). 1H NMR, d: 6.69 (s, 1H, 5-H), 7.63, 7.74 and 8.07 (m, 5H, Ph). 13C NMR {1H}, d: 58.2 [C(5)], 81.2 [C(6)], 127.8, 129.4, 134.5 and 138.2 (Ph), 138.6, 143.8 [C(2), C(3)], 160.3 [C(4)], 173.4 [C(1)]. 1c: yield 86%, mp 155–156 °C (AcOH). 1H NMR, d: 2.19 (s, 3H, 6-Me), 2.28 (s, 3H, 3-Me), 6.48 (s, 1H, 5-H), 7.60, 7.70 and 8.05 (m, 5H, Ph). 13C NMR {1H}, d: 20.12 (3-Me), 25.48 (6-Me), 46.59 [C(5)], 55.58 [C(6)], 127.55, 129.18, 133.91 and 139.32 (Ph), 133.95 [C(2)], 148.22 [C(3)], 167.10 [C(4)], 181.50 [C(1)].IR, n/cm–1: 1710 (C=O), 1600 (C=N, C=C), 1320, 1169 (SO2). 1d: yield 62%, mp 142–143 °C (AcOH). 1H NMR, d: 2.24 (s, 3H, 3-Me), 2.50 (s, 3H, Me), 6.66 (s, 1H, 5-H), 7.40 and 7.92 (dd, 4H, C6H4, 3J 8.4 Hz). 13C NMR {1H}, d: 17.02 (3-Me), 21.71 (Me), 58.64 [C(5)], 81.63 [C(6)], 127.82, 129.93, 145.52, and 146.46 (C6H4), 135.83 [C(2)], 145.52 [C(3)], 164.67 [C(4)], 174.83 [C(1)].IR, n/cm–1: 1723 (C=O), 1595, 1570 (C=N, C=C), 1339, 1161 (SO2). 1e:9 yield 77%, mp 141–142 °C (AcOH). 1HNMR, d: 2.49 (s, 3H, Me), 6.71 (s, 1H, 5-H), 7.40 and 7.97 (dd, 4H, C6H4, 3J 8.3 Hz). 13C NMR {1H}, d: 21.77 (Me), 52.8 [C(5)], 81.40 [C(6)], 128.03, 130.05, 135.46, and 145.89 (C6H4), 138.70 and 143.96 [C(2), C(3)], 160.02 [C(4)], 173.52 [C(1)].IR, n/cm–1: 1724 (C=O), 1610, 1555 (C=C, C=N), 1346, 1168 (SO2). 1f:9 yield 75%, mp 141–142 °C (AcOH). 1HNMR, d: 6.63 (s, 1H, 5-H), 7.60 and 8.00 (dd, C6H4, 3J 8.7 Hz). IR, n/cm–1: 1723 (C=O), 1600, 1553 (C=C, C=N), 1350, 1170 (SO2). 2a: yield 81%, mp 130–131 °C (CCl4). 1H NMR, d: 4.76 (d, 1H, 2-H, 3J 3.9 Hz), 6.55 (d, 1H, 3-H, 3J 3.9 Hz), 7.61, 7.68 and 8.13 (m, 5H, Ph), 7.61 and 8.12 (m, 4H, 5,6,7,8-H). 2b:9 yield 82%, mp 141–142 °C (AcOH). 1HNMR, d: 6.83 (s, 1H, 3-H), 7.61, 7.70 and 8.10 (m, 5H, Ph), 7.78 and 8.14 (m, 4H, 5,6,7,8-H). IR, n/cm–1: 1719 (C=O), 1612, 1583 (C=C, C=N), 1330, 1161 (SO2). 2c:9 yield 84%, mp 136–137 °C (CCl4). 1H NMR, d: 2.48 (s, 3H, Me), 4.75 (d, 1H, 2-H, 3J 3.6 Hz), 6.57 (d, 1H, 3-H, 3J 3.6 Hz), 7.40 and 7.99 (dd, 4H, C6H4, 3J 8.1 Hz), 7.75 and 8.13 (mm, 4H, 5,6,7,8-H).IR, n/cm–1: 1705 (C=O), 1612, 1587 (C=N, C=C), 1330, 1165 (SO2). 2d: yield 86%, mp 138–139 °C (CCl4). 1H NMR, d: 4.77 (d, 1H, 2-H, 3J 3.3 Hz), 6.51 (d, 1H, 3-H, 3J 3.6 Hz), 7.58 and 8.04 (m, 4H, C6H4, 3J 8.7 Hz), 7.77 and 8.12 (m, 4H, 5,6,7,8-H). 2e:9 yield 80%, mp 167–168 °C (AcOH). 1HNMR, d: 6.78 (s, 1H, 3-H), 7.60 and 8.05 (dd, 4H, C6H4, 3J 8.7 Hz), 7.80 and 8.17 (m, 4H, 5,6,7,8-H).IR, n/cm–1: 1725 (C=O), 1620, 1589 (C=C, C=N), 1343, 1170 (SO2). 3a:12 yield 78%, mp 110 °C (AcOH); the ratio of isomers E/Z = 2.1. E-isomer: 1HNMR, d: 1.85 (s, 3H, 6-Me), 2.02 (d, 3H, 2-Me, 4J 1.5 Hz), 5.47 (d, 1H, 3-H, 4J 1.5 Hz), 6.76 (s, 1H, 5-H), 7.58, 7.71 and 8.01 (m, 5H, Ph). 13C NMR {1H}, d: 16.74 (6-Me), 22.33 (2-Me), 53.18 [C(5)], 63.35 [C(6)], 122.67, 129.05, 129.25 and 130.03 (Ph), 134.56 and 140.54 [C(2), C(3)], 157.24 [C(4)], 188.80 [C(1)].Z-isomer: 1.86 (s, 3H, 6-Me), 2.07 (d, 3H, 2-Me, 4J 1.5 Hz), 4.89 (d, 1H, 3-H, 4J 1.5 Hz), 7.27 (s, 1H, 5-H), 7.58, 7.71 and 8.01 (m, 5H, Ph). 13C NMR {1H}, d: 16.98 (6-Me), 22.75 (2-Me), 61.71 [C(5)], 65.10 [C(6)], 122.67, 129.00, 129.24 and 130.03 (Ph), 134.44 and 141.74 [C(2), C(3)], 155.75 [C(4)], 188.60 [C(1)].IR, n/cm–1: 1703 (C=O), 1630, 1590 (C=N, C=C), 1394, 1209 (SO2). 3b: yield 73%, mp 143 °C (AcOH), the ratio of isomers in CDCl3 E/Z = 4.0. E-isomer: 1H NMR, d: 1.90 (s, 3H, 6-Me), 5.49 (s, 1H, 3-H), 7.15 (s, 1H, 5-H), 7.59, 7.72 and 8.00 (m, 5H, Ph). Z-isomer: 1.90 (s, 3H, 6-Me), 5.48 (s, 1H, 3-H), 7.14 (s, 1H, 5-H), 7.59, 7.72 and 8.00 (m, 5H, Ph).Compound 2c crystallises as a CCl4 solvate with the 2:1 stoichiometry. This achiral solvent molecule could favour the crystallization in non-centrosymmetric space group and thus acts as a conglomerator.13 Therefore, a predetermined optical enrichment of compound 2c can be performed by crystallization in the presence of a half-mole quantity of CCl4.In this case, the entire precipitate possessed optical activity whereas upon crystallization from CCl4 only individual crystals were optically active, but the entire precipitate was a racemic conglomerate. This work was supported by the Russian Foundation for Basic Research (grant no. 97-03-33021) and INTAS (grant no. 157). References 1 J.Jacques, A. Collet and S. H. Wilen, Enantiomers, Racemates, and Resolutions, Krieger Publ. Co, Malabar, Florida, 1994. 2 (a) A. Collet, Enantiomer, 1999, 4, 157; (b) A. Collet, in Comprehensive Supramolecular Chemistry, ed. D. N. Reinhoudt, Pergamon Press, Oxford, 1996, vol. 10, ch. 5, p. 113; (c) G. Coquerel, M. N. Petit and F. Robert, Acta Crystallogr., 1993, C49, 824. 3 A. B. Zolotoi, Yu.I. El’natanov, I. I. Chervin, S. V. Konovalikhin, O. A. Dyachenko, L. O. Atovmyan and R. G. Kostyanovsky, Khim. Geterotsikl. Soedin., 1988, 909 [Chem. Heterocycl. Compd. (Engl. Transl.), 1988, 746]. 4 R. G. Kostyanovsky, Yu. I. El’natanov, I. I. Chervin, S. V. Konovalikhin, A. B. Zolotoi and L. O. Atovmyan, Izv. Akad. Nauk, Ser. Khim., 1996, 1796 (Russ. Chem. Bull., 1996, 45, 1707). 5 R.G. Kostyanovsky, V. F. Rudchenko and G. V. Shustov, Izv. Akad. Nauk SSSR, Ser. Khim., 1977, 1687 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1977, 26, 1560). 6 V. F. Rudchenko, O. A. Dyachenko, A. B. Zolotoi, L. O. Atovmyan, I. I. Chervin and R. G. Kostyanovsky, Tetrahedron, 1982, 38, 961. 7 R. G. Kostyanovsky, K. A. Lyssenko, G. K. Kadorkina, O. V. Lebedev, A. N. Kravchenko, I. I.Chervin and V. R. Kostyanovsky, Mendeleev Commun., 1998, 231. 8 R. G. Kostyanovsky, K. A. Lyssenko, Yu. I. El’natanov, O. N. Krutius, I. A. Bronzova, Yu. A. Strelenko and V. R. Kostyanovsky, Mendeleev Commun., 1999, 106. ‡ Crystallographic data for 2c at 20 °C: (C17H13NO3SCl2)2·CCl4, triclinic, crystal size 0.36×0.39×0.48 mm, space group P1, a = 12.959(5) Å, b = = 13.271(6) Å, c = 13.951(7) Å, a = 63.03(4)°, b = 77.56(4)°, g = 71.69(5)°, V = 2023 Å3, Z = 2, dcalc = 1.508 g cm–3, m(MoKa) = 0.706 mm–1, F(000) = = 932.The intensities of 7581 reflections were measured on an Enraf- Nonius CAD-4 diffractometer at 20 °C (lMoKa radiation, q/2q scan, 12° < q < 23°), and 6075 independent reflections were used in further calculations and refinement.The structure was solved by a direct method and refined using the full-matrix least-squares method against F2 in the anisotropic–isotropic approximation. The refinement is converged to wR2 = = 0.2148 and GOF = 0.988 for all independent reflections [R1 = 0.0789 is calculated against F for 6044 observed reflections with I > 2s(I)]. The number of refined parameters is 514.All the calculations were performed using the SHELXS and SHELXL 93 programs. Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ‘Notice to Authors’, Mendeleev Commun., 2000, Issue 1. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/60.N O H Y Y R'' R' Y O2S X N O H Cl Cl R O2S X N O H Cl Cl Me H R O2SO a X = H, R' = Me, R'' = Y = Cl b X = H, R' = R'' = Y = Cl c X = H, R' = R'' = Me, Y = Br d X = R' = Me, R'' = Y = Cl e X =Me, R' = R'' = Y = Cl f X = Cl, R' = R'' = Y = Cl 1a–f a X = H, R = H b X = H, R = Cl c X =Me, R = H d X = Cl, R = H e X = Cl, R = Cl 2a–e a R = Me b R = Cl 3a,bMendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) 9 A. P. Avdeenko and S. A. Zhukova, Zh. Org. Khim., 1999, 35, 412 (Russ. J. Org. Chem., 1999, 35, 388). 10 (a) A. P. Avdeenko, N. M. Glinanaya and V. V. Pirozhenko, Zh. Org. Khim., 1993, 29, 1402 (Russ. J. Org. Chem., 1993, 29, 1164); (b) A. P. Avdeenko, N. M. Glinanaya and V. V. Pirozhenko, Zh. Org. Khim., 1995, 31, 1523 (Russ. J. Org. Chem., 1995, 31, 1380). 11 A. P. Avdeenko and N. M. Glinanaya, Zh. Org. Khim., 1995, 31, 1679 (Russ. J. Org. Chem., 1995, 31, 1507). 12 A. P. Avdeenko, S. A. Zhukova and N. M. Glinanaya, Zh. Org. Khim., 1999, 35, 586 (Russ. J. Org. Chem., 1999, 35, 560). 13 R. G. Kostyanovsky, Proceedings of the Interdisciplinary Symposium on Biological Homochirality, Serramazzoni (Modena), Italy, 1998, OP 20, p. 41. Received: 22nd September 1999; Com. 99/1536