Conformational behaviour of medium-sized rings. Part 4. Heterocyclic analogues of 7,8,13,14-tetrahydrobenzo6,7cyclonona1,2,3-denaphthalene and 7,8,15,16-tetrahydrocyclodeca1,2,3-de:6,7,8-dprime;eprime;dinaphthalene

摘要

1978 1385 Conformational Behaviour of Medium-sized Rings. Part 4.l Hetero-cyclic Analogues of 7,8,13,14-Tetrahydrobenzo[6,7jcyclonona{1,2,3-de]-naphthalene and 7,8,15,16-Tetrahydrocyclodeca[l,2,3-de:6,7,8-d'e8]di-naphthalene By David J. Brickwood, W. David Ollis," and J. Fraser Stoddart, Department of Chemistry, The University, Sheffield S3 7HF The temperature dependences of the lH n.m.r. spectra of 8N.15H-dinaphtho[l,8-bc : 1',8'-gh] [1,5]dioxecin (4) and of heterocyclic analogues (Za, b, e, and f) of 7.8.1 3.1 4-tetrahydrobenzo[6,7]cyclonona[l,2,3-de]naphthalene have been interpreted in terms of ring inversion between enantiomeric twist-boat conformations. The temperature dependences of the lH n.m.r. spectra of the dithionins (2c and d) have been interpreted in terms of interconversions between chair and twist-boat conformations. A comparison of activation parameters shows that when peri-annelated naphthalene rings replace ortho-annelated benzene rings in ' 6.8.6 ' systems (1).chair-like conformations are destablised relative to boat-like conformations and the energy barriers to ring inversions involving pseudo- rotational processes are considerably higher. THE recognition that 5,6,11,12-tetrahydrodibenzo[a,e-j-3,4-dihydroxytoluene (8b), benzene-l,2-dithiol (8c), to- cyclo-octene (1; W = X = Y = 2 = CH2)2-5and many heterocyclic analogues 2p39677 of this '6,8,6 ' system (1) exist in diastereoisomeric conformations in solution has encouraged us to examine the nine- and ten-membered ring systems (2)-(4) in which ortho-annelated benzene rings of (1) are replaced partially or wholly by peri-anne- lated naphthalene rings.Although the stereochemistry and transannular reactions of the seven-and eight- membered ring systems, exemplified by the 7,12-di- hydropleiadenes (5)and by derivatives (6) of 7H,14H- cyclo-octa[ 1,2,3-& :5,6,7-d'e']dinaphthalene, have at-tracted * attention in recent years, the conformational behaviour of higher-membered ring homologues such as (2)-(4) had not been discussed in the literature prior to publication of our preliminary communication 9 in 1974. Base-promoted condensations between 1,8-bisbromo-methylnaphthalene (7) and 1,e-dihydroxybenzene (Sa) , Part 3, W. D. Ollis and J. F. Stoddart, J.C.S.Perkin I, 1976, 926. Part 1, R. Crossley, A. P. Downing, M. NbgrAdi, A. Bragade Oliveira, W. D. Ollis, and I. 0. Sutherland, J.C.S. Perkin I, 1973, 205. W. D. Ollis, J. F. Stoddart, and I. 0. Sutherland, Tetra-hedron, 1974, 30, 1903. D. Montecalvo, M. St.- Jacques, and R. Wasylishen, J.Amev. Chem. Soc., 1973, 95, 2023. ti F. Sauriol-Lord and M. St.- Jacques, Canad. J. Chem., 1975,63,3768. luene-3,4-dithiol(Sd),"'-dimethyl-o-phenylenediamine (Se), and NN'-ditosyl-o-phenylenediamine (Sf) afforded compounds (2a-f). Compounds (3) and (4) were obtained by base-promoted condensations of 1,&dihydroxynaph-thalene (9) with o-xylylene dibromide (10) and 1,S-bis-bromomethylnaphthalene (7),respectively. In the prep- aration of the dioxecin (4), C-alkylation also occurred, affordinga spiro-dienone with either structure (11)or (12). Evidence for structure (11)was forthcoming from the lH n.m.r.spectrum of the diacetate [i.e. either (13) or (14)] obtained on (i) borohydride reduction of the spiro- dienone to give a diol followed by (ii) acetylation of the diol. The absence of (i)vicinal coupling between Ha and Hb, and (ii) allylic coupling between Ha and H, is ex-cellent evidence for assigning structure (13) to the diace- tate and hence structure (11)to the spiro-dienone. In this paper we discuss the results of our studies on A. Saunders and J. M. Sprake, J.C.S. Perkin I, 1972, 1964; J.C.S. Perkin 11, 1972, 1660. H. L. Yale, F. Sowinski, and E. R. Spitzmiller, J. Hetero-cyclic Chem., 1972, 9, 899; H.L. Yale and E. R. Spitzmiller, ibid., p. 911; M. S. Paur, H. L. Yale, and A. I. Cohen, Org. MagneticResonance, 1974, 6, 106.* W. C Agosta, J. Amer. Chem. SOC.,1967, 89, 3505, 3926; C. R. Johnson and D. C. Vegh, Chem. Comm., 1969, 557; P. T. Lansbury, Accounts Chem. Res., 1969, 2, 210. D. J. Brickwood, W. D. Ollis, and J. F. Stoddart, Angew.Chem. Internat. Edn., 1974, 13, 731. 1386 J.C.S. Perkin I the conformational behaviour of the nine- and ten-T (CDC1,) 2.04-3.12 (10 H, m, aromatic) and 4.59 (4 H, s, membered ring systems (2)-(4) lH n .m.r. spectroscopy.1° ay-zDx-w 8 CH2 CH2 15 in solution by dynamic R Y3 6/&, 5\ /2 43 2 x CH,). 1 O-MethyZ-7H, 14H-benzo[b]nuphtho[ 1,8-fg] [1,4]dioxonin (2b).-1,8-Bisbromomethylnaphthalene (7)-(5 g) dissolved in dimethyl sulphoxide (60 ml) was added dropwise during 1 h under nitrogen to a stirred mixture of 3,4-dihydroxytol- uene (8b) (3 g) and sodium hydride (1 g) in dimethyl sul- phoxide (20 ml).The mixture was stirred for 10 h and then poured into water (1 1). Extraction with chloroform (3 x 200 ml), followed by washing of the combined extracts with water (3 x 100 ml), afforded the crude product after re- moval of the solvent under diminished pressure. This product was subjected to column chromatography on silica gel using chloroform-light petroleum (b.p. 60-80 "C) as eluant to give a crystalline compound. Recrystallisation from chloroform-light petroleum (b.p.60-80 "C) gave the II (2) a; R = b; R = '; d; R = 43 e; R = f; R = (3) R = H, X = 0,y = Me, X = 0, Y H~ = '* = Me, x = s , y H, X = NMe, Y H, x = NT~,y H, X = CH2, Y CH~ dioxonin (2b) (0.93 g, 21%), m.p. 120-121" (Found: C, 82.5; H, 5.85%; M (mass spec.), 276.1144. C1,H,,O2 re- = CH~quires C, 82.6; H, 5.85%; M, 276.11501, T (CDC1,-CS,)CH2 2.12-3.36 (9 H, m, aromatic), 4.68 and 4.72 (4 H, 2 x s, = CHz 2 x CH,), and 7.74 (3 H, s, CH,). = CH2 7H,14H-Benzo[b]nafihtho[1,8-fg][l,4]dithionin(2c).-1,8-= CH2Bisbromomethylnaphthalene (7) (5.0 g) in dimethyl sulph- = 0 oxide (50 ml) was added dropwise during 1h under nitrogen to a stirred mixture of benzene-1,2-dithiol (8c) l2 (2.3 g) and sodium hydride (1 g) in dimethyl sulphoxide (50 ml).The RQ Xqw/xx (8) a; R = H, X = OH b; R= Me, X = OH C; R= H, X= SH d; R= Me, X = SH e; R= H, X = NHMe f; R = H, X = NHTs YY (10) R = H, X = CH2Br EXPERIMENTAL The general methods are described in Part 3.' 7HJ14H-Benzo(b]nufihtho[l,8-fg][l,4]~io~o~in(2a).-lJ8-Bisbromomethylnaphthalene (7) l1 (1.0 g) dissolved in di- methyl sulphoxide (20 ml) was added dropwise under nitro- gen to a stirred mixture of 1,2-dihydroxybenzene (8a) (0.35 g) and sodium hydride (0.35 g) in dimethyl sulphoxide (20 ml) . The mixture was stirred for 5 h and then poured into water (500 ml). Extraction with chloroform (3 x 100 ml), followed by washing of the combined extracts with water (3 x 100 ml), afforded a crude product after removal of the solvent under diminished pressure.This product was purified by (a)preparative t.1.c. on silica gel (chloroform as eluant) and then by (b) sublimation at 135" (10 mmHg) to give the dioxonin (2a) (0.1 g, 12%), m.p. 125-127" [Found: M (mass spec.), 262.0994. C,,H,,O, requires M, 262.09941, 10 For reviews see: G. Binsch, Topics Steveochem., 1968, 8, 97; I. 0.Sutherland,Ann. Reports N.M.R. Spectroscopy, 1971, 4, 71. mixture was stirred for 16 h and then poured into water (11). The organic material was extracted with chloroform (3 x 200 ml) and the extracts were washed with water (3 x 100 ml) and dried (MgSO,). Removal of the solvent under diminished pressure gave an oil which was subjected to column chromatography on silica gel using chloroform- light petroleum (b.p.60-80 "C) (1 : 1)as eluant to afford the dithionin (2c) (0.12 g, 3%), m.p. 195-197 " [Found : M (mass (11) (12) AcO Ha Hc (13) (14) spec.), 294.0935. C,,H,,S, requires M,294.09371, T (CDCl,) 2.44--3.28(10H,m,aromatic) and5.12(4H, brs, 2 x CH,). lO-Methyl-'IH, 14H-benzo[b]nuphtho[ 1,8-fg] [1,4]dithioniw 11 R. H. Mitchell and F. Sondheimer, Tetrahedron, 1968, 24, 1397. 12 A. Ferretti, Org. Synth., 1962, 42,54. 1978 (2d).-1,8-Bisbromomethylnaphthalene (7) (10 g) in dimethyl sulphoxide (100 ml) was added dropwise during 1 h to a stirred mixture of toluene-3,4-dithiol (8d) (5 g) and sodium hydride (3 g) in dimethyl sulphoxide (40 ml) under a stream of dry nitrogen.The mixture was stirred for 16 h and then poured into water (1.5 1). The organic material was ex- tracted with chloroform (3 x 250 ml) and the extracts were washed with water (3 x 150 ml) and dried (MgSO,). Re-moval of the solvent under diminished pressure gave an oil which was subjected to column chromatography on silica gel using chloroform-light petroleum (b.p. 60-80 "C) (1: 1) as eluant to afford a crystalline compound. Recrystallis-ation from chloroform-light petroleum (b.p. 60-80 "C) gave the dithionin (2d) (1.0 g, lo%), m.p. 272-274" (Found: C, 74.2; HI 5.35; S, 20.9%. C1,Hl,S2 requires C, 74.0; H, 5.25; S, 20.8%), z(CDCl,) 2.38-3.46 (9 H, m, aromatic), 5.08(4 H, br s, 2 x CH,), and 8.00 (3 HI s, CH,). 7,8,13,14-Tetrahydr0-8,13-dimethyZbenzo[b]naphtho[1,8-fg]-[1,4]diazonine (2e).-1,8-Bisbromomethylnaphthalene (7) (2.8 g) in dry tetrahydrofuran (50 ml) was added dropwise during 2 h under a stream of dry nitrogen to a stirred mixture of NN'-dimethyl-o-phenylenediamine (8e) l3 (1.24 g) and sodium hydride (0.5 g) in dry tetrahydrofuran (50 ml).The mixture was stirred for 16 h and then poured into water (300 ml). The organic material was extracted with chloro- form (2 x 200 ml) and the extracts were dried (MgSO,). Removal of the solvent under diminished pressure gave an oil which was purified by preparative t.1.c. on silica gel using chloroform-light petroleum (b.p. 60-80 "C) as eluant to afford the diazonine (2e) (80mg, 3%), m.p. 100-102", z (CDC1,) 2.19 and 2.62 (2 H and 4H, t and d, J 5 Hz, naphtho- protons), 3.05 (4 H, s, benzo-protons), 5.46 (4 H, br s, 2 x CH,), and 7.14 (6 H, s, 2 x CH,).7,8,13,14-Tetrahydro-8,13-bis-p-tolylsulphonylbenzo[b]-naphtha[ 1,8-fg][1,4]diazonine (2f) .-NN'-Ditosyl-o-phenyl- enediamine (8f) l4 (1.94 g) was suspended in water (15 ml) and potassium hydroxide (0.56 g) was added. 1,8-Bisbromo-methylnaphthalene (7) ( 1.56g) in benzene (30 ml) was added with stirring to the aqueous suspension and the mixture was stirred under reflux for 16 h. Benzene was removed under diminished pressure and the suspension was filtered and washed with water. The crude product was recrystallised from chloroform to afford the diazonine (2f) (2.34 g, 88%), m.p. 320" (sublimes at 300-302") (Found: C, 67.3; HI 5.15; N, 4.6; S, 11.5.C,,H,,N,S,O, requires C, 67.6; H, 4.95; N, 4.9; S, 11.3y0),z (CDCl,) 1.95-2.90 (14 H, m, aromatic naphtho- and tosyl protons), 3.24 (4 H, s, benzo-protons), 4.24 and 5.11 (4 H, two superimposed AB systems, JAB 13.0 Hz, 2 x CH,), and 7.50 (6 HI s, 2 x CH,). 8,13-Dihydrobenzo[g]na~htho[l,8-b~][1,5]dioxonin(3).-o-Xylylene dibromide (10) (3.14 g) in dimethyl sulphoxide. (25 ml) was added dropwise during 0.5 h under a stream of dry nitrogen to a stirred mixture of 1,8-dihydroxynaphtha- lene (9) (2.0 g) and sodium hydride (1.0 g) in dimethyl sulphoxide (50 ml). The mixture was stirred for 10 h and then it was poured into water (500 ml). The organic material was extracted with chloroform (3 x 100 ml) and the extracts were washed with water (3 x 100 ml) and dried (MgSO,). Removal of the solvent under diminished pres- sure gave an oil which was subjected to column chroma- tography on silica gel using chloroform-light petroleum (b.p.60-80 "C) as eluant to afford the dioxonin (3) (0.1 g, 5%), * The program numbers (viz.I and 111) established in Part 3 will be adhered to in this paper; these programs will form the basis of a collection for reference in future Parts of this series. m.p. 125-126", T (CDCl,CS,) 2.65-3.25 (10 H, m, aro- matic) and 5.04 (4 HI s, 2 x CH,). 8H,15H-Dinaphtho[1,8-bc : 1',8'-gh][l,5]dioxecin (4).-1,8-Bisbromomethylnaphthalene(7) (5 g) in dimethyl sul- phoxide (50 ml) was added dropwise during 1 h under a stream of nitrogen to a stirred mixture of 1,8-dihydroxyna-phthalene (9) (2 g) and sodium hydride (0.75 g) in dimethyl sulphoxide (50 ml).The mixture was stirred for 16 h then poured into water (1.5 1). The organic material was ex- tracted with chloroform (3 x 200 mi) and the extracts were washed with water (3 x 100 ml) and dried (MgSO,). Re-moval of the solvent under diminished pressure gave an oily residue which was subjected to column chromatography on silica gel using chloroform-light petroleum (b.p. 60-80 "C) (1: 1)as eluant to afford two crystalline constitutionally iso- meric products. The isomer eluted second was the dioxecin (4) (0.25 g, 5%), m.p. 214-215" (from light petroleum, b.p. 60-80 "C) [Found: C, 84.3; H, 5.25%; M (mass spec.), 312.1137. C,,H,,O, requires C, 84.6; H, 5.15%; M, 312.11501,v,, (Nujol) 1260, 1050, and 825 cm-l, A,,,.(CHC1,) 198 nm (log E 4.2), z(CDC1,-CS,) 2.0A2.83 (12 H, m, aromatic) and 4.46 (4 H, s, 2 x CH,). The isomer eluted first was 8-hydroxyspiro[naphthalene-2(1H) ,2'(3'H)- l'H-phenalen]-l-one (11) (0.20 g, 4%), m.p. 178-180 "C)] (from chloroform-light petroleum (b.p. 60-80 "C) [Found : C, 84.8; H, 5.35%; M (mass spec.), 312.1137. C,,H,,O, requires C, 84.6; HI 5.15%; M, 312.11501, vmx, (Nujol) 1 600, 1340, and 1 160 cm-l, Amx. (CHCl,) 293 (log E 4.13) and 373 nm (4.01), T(CDC1,) 2.24-3.72 (10 H, m, aromatic and OH), 3.77 and 4.17 (2 H, AB system, JAB 10 Hz, ole-fink), and 6.29 and 7.10 (4 H, 2 AB systems, 16 Hz, 2 x CH,).A portion (20 mg) of this isomer was reduced with sodium borohydride (10 mg) in methanol (5 ml) and tetrahydrofuran (5 ml). After 15 min at room temperature, the mixture was acidified with 5~-hydrochloric acid (0.1 ml) and then diluted with water (20 ml). The organic material was extracted into ether (2 x 20 ml) and dried (MgSO,). Evaporation afforded an oil which was acetylated with acetic anhydride (2 ml) in pyridine (10 ml) to give the diacetate (13) (21 mg, 82%), m.p. 184-187" [Found: M (mass spec.), 398. C,,H,,O4 requires M, 3981, z(CDC1,) 2.25-3.13 (9 H, m, aromatic), 3.51 and 4.24 (2 H, AB system, JAB 10 Hz, olefinic), 6.01 (1 HI s, CHOAc), 6.52 and 6.64 (2 H, AB system, JAB 16 Hz, CH,), 6.92 (3 H, s, aromatic OAc), 7.11 and 7.23 (2 H, AB system, JAB 15 Hz, CH,), and 8.08 (3 H, s, YHOAC).Determination of Rates of Conformational Changes by Dynamic 1H N.m.r.Spectroscopy.-The methods used have been described in Parts 1,, 2,15 and 3.l The computer pro- grams (coded in Fortran IV) used to generate the theoretical line-shapes are now described for the general methods 1-111. Method I. A program (I)* for exchange of nuclei be- tween two equally populated sites A and B, with no mutual coupling. The aromatic methyl group of compound (2d) gave two singlet signals of unequal intensities at low tem- peratures and so spectral line shapes were simulated between -33 and -3 "C by using this program. Calculated and observed spectra are shown in Figure 1. Method 11.A program (111)* for exchange of nuclei between the pairs of sites A1 and B1, A2 and B2, A1 and A2, and B1 and B2 in two AB systems. This program was used l3 G. W. H. Cheeseman, J. Chem. SOC.,1955, 3309. l4 H. Stetter, Chem. Ber., 1953, 86, 161. 15 Part 2, R. P. Gellatly, W. D. Ollis, and I. 0. Sutherland, J.C.S. Perkin I,1976, 913. to simulate the lH n.m.r. spectral line shapes associated with the C-7and C-14 methylene protons of compound (2c) be- tween -51 and +lo "C. At low temperatures, this com- pound exhibits (Figure 2 and Table 1)two AB systems (AlBl AB A T 7.62 8.08 FIGURE Observed (full line) and computed (broken line) 1 spectra of the aromatic methyl protons of lO-methyl-'jrH, 14H-benzo[b]naphtho[l,8-fgl[1,4]dithionin(2d) : (a) at -3 "C, kAB =628 S-', PA = 0.20, PB = 0.80; (b) at -15 "c,kAB = 82 S-l,PA = 0.20, PB = 0.80; (C) at -21 "c,kAB = 63 S-',~A = 0.20,PB = 0.80; (d) at -29 "c,kAB = 37 S-l, PA = 0.20,PB = 0.80; (e) at -33 "C, ka = 29 S-', PA = 0.20, PB = 0.80 and A2B2) characteristic of the presence of two diastereoiso- meric conformations in solution.Calculated and observed spectra are shown in Figure 2. Method III. For compounds (2a, e, and f), (3), and (4) site exchange rate constants, K,, were calculated (see Table 2) KO = x[(vA -VB)' + 6 JAB']*/2* (i) at coalescence temperatures, T,,by using the approximate relationship (i), which is suitable for exchange of nuclei J.C.S. Perkin I between two sites A and B with equal populations and chemical shifts, VA and YB, respectively, and a mutual coup- ling constant, JAB.RESULTS AND DISCUSSION At low temperature, a single AB system is observed in the lH n.m.r. spectra of compounds (2a, e, and f), (3), and (4) for their ring methylene protons. In all cases, the AB system coalesces to a singlet at higher tempera- tures. This means (i) that the single AB system must be associated with either enantiotopic or homotofiic ring methylene groups and (ii) that only one conformation is present in solution in the case of all of these compounds. The spectral changes associated with the signals for their ring methylene protons are summarised in Tables 1 and 2. Table 1 gives chemical shifts and coupling constants of the high- and low-temperature spectra.Table 2 records the spectral data which permit calculation by method I11 (see Experimental section) of the rate con- stants at the coalescence temperatures and the associated free energies of activation for the ring inversion pro- cesses. The temperature dependent lH n.m.r. spectra of the compounds (2c and d) demonstrate that two diastereoiso- meric conformations are populated in solution. At low temperatures, the ring methylene protons of compound (2c) give rise to two AB systems of unequal intensities which may be assigned to a major and a minor conform- ation. The signals coalesce to a singlet as the tempera- ture is increased. Three exchange processes were identi- fied by line-shape analyses (Figure 2) and these may be associated with conformational interconversion of the two diastereoisomeric conformations and slow inversion of each of the diastereoisomers with its enantiomer.In the low temperature spectra of compound (2d), two signals of unequal intensities are observed (Figure 1) for the aromatic methyl protons. Their coalescence be- haviour permits independent line-shape analysis of the interconversion process involving the two diastereoiso- meric conformations. The spectral changes associated with the signals for the ring methylene protons and the aromatic methyl protons are sumniarised in Tables 1 and 3. Table 1 gives the chemical shifts and coupling con- stants of the high- and low-temperature spectra. Table 3 gives details of the site exchanges affecting the signal line-shapes and some thermodynamic parameters asso- ciated with the conformational changes.These are derived by comparison (see Figures I and 2) of observed and calculated spectra over a range of temperatures by methods I and I1 (see Experimental section). Good agreement is attained for the thermodynamic parameters associated with the interconversion process involving two diastereoisomeric conformations of compounds (2c and d) by using methods I and I1 on signals arising from two different 1H n.m.r. probes. However, line-shape analysis (Figure 2) was relatively insensitive to the value of the rate constants employed to simulate the ex-change process associated with the signals arising from the minor conformation. Accordingly, some uncertainty 1978 1389 surrounds the thermodynamic parameters for this ring conformations as participants in possible ring inversion inversion.processes. With the TB conformation (17a), however, The observation of isochronous ring methylene groups ring inversion would have to involve the enantiomeric A 12 B 12 L---c--c -----(c) -29OC I I 1 I T 4.51 5-15 5-53 5.72 FIGURE Observed (full line) and computed (broken line) spectra of the C-7 and C-14 methyl protons of 7H,14H-benzo[b]naphtho-2 [1,8-fg][1,4]dithionin (2d); (a) at +10 OC, k, = 125s-l, k, = 125s-l. k,, = 250 s-l, p1 = 0.86, p, = 0.14; (b) at -5 "C, k, = 25 s-l, k, = 25 s-1, k,, = 50 s-1, p1 = 0.86, p, = 0.14; (c) at -29 "C,k, = 2.5 s-', k, = 2.5 s-l, k,, = 5.0 s-l, p, = 0.86, pz = 0.14; (d) at -33 "C, k, = 1.5s-l, k, = 1.5 s-l, k,, = 3.0 s-1, p, = 0.86, p, = 0.14; (e) at -51 OC, k, = 0.05 s-l, k, = 0.05 s-l, k,, = 0.1 s-l, p1 = 0.86, p, = 0.14 in compounds (2) and (3) at low temperatures requires TB* conformation (17b).These conformations are that the observable ground state conformation must have conveniently 1-3915 described by using the usual + and -either C, or C, symmetry. The chair C (15a) and boat B notation l6 for torsional angles and referring in turn to (16a) conformations both have C, symmetry whereas the the bonds 6a-7, 7-8, 8-8a, 12a-13, 13-14, and 14-14a. twist-boat TB conformation (17aj has C, symmetry. l6 W. Klyne and V. Prelog, Experientia, 1960, 16,521; J. B.In the Of the (Isa) and (Isa) it is Hendrickson, J.Amer.Chem. Soc., 1961,83,4537; 1962,84,3355; necessary to consider degenerate C* (15b)and B* (16b) 1964, 86, 4854; 1967, 89, 7036,7043, 7047. 1390 J.C.S. Perkin I TABLE1 Temperature-dependent lH n.m.r. spectral parameters (100 MHz) for compounds (2a-f), (3), and (4) Temp.X Solvent ("C) Group T (Jin Hz) 0 0 CDCl,-CS, -97 OCH, 4.56(A1), 4.86(Bl) (J11.1)(1 : 4) -50 4.72(s) (AB1) 0 CDCl,-CS, -90 OCHZb 4.52(Al), 4.86(B1) (J12)(1: 2) 4.58(Cl), 4.86(D1) (J 12)ArCH, 7.74(s)+ 30 OCHZb 4.68(s) (ABl) 4.72(s) (CDl) ArCH, 7.64(s)S CDC1,-CS, -51 SCH, 4.51(Al), 5.72(B1) (J 12) efd (2: 1) 5.15(A2), 5.53(B2) (J14) d -33 SCH, 4.50(A12), 5.73(B12) (J 12)+ 37 SCH, 5.12(s) (AB12) S CDCl, -45 SCHZb 4.32(A1), 5.62(Bl) (J12) 5.10(A2), 5.44(B2) (J 14)f4.5O(Cl), 5.66(D1) (J12) Cpe 5.10(C2), 5.47(D2) (J14)f ArCH, 7.62(s) (A) 8.08(s) (B)+ 44 SCHZb 5.08(br s) (ABCD12)ArCH, 8.01(s) (AB) NMe CDCl, -20 NCH, 4.25(Al), 6.64(Bl) (J 14)NCH, 7.10(s)+ 30 NCH, 5.46(br s) (AB1)NCH, 7.14(s)NTs CDC1, NCH, 4.24(Al), 5.10(B1) (J13)30 70 NCH, 4.66(br s) (ABl) CH, CDCl,-CS, -85 OCH, 4.81(Al), 5.13(B1) (J10.7)(1: 2) -30 OCH, 5.02(s) (AB1) CDCl,-CS, -80 OCH, 4.26(Al), 4.54(B1) (J 10)(2: 1) -20 OCH, 4.33(s) (AB1) 0 The designations Al, B1, etc., correspond to the site exchanges cited in Tables 2 and 3 (see note a in Table 2). Sites are desig- nated A and B for uncoupled two-site systems.Sites that represent two time-averaged signals are designated AB.Sites are designated A1 and B1 for coupled AB systems. Sites are designated Al, B1, A2, and B2 for four-site systems where there is coupling in the form of two AB systems. Sites that represent two time-averaged signals are designated AB1 (average of A1 and Bl), A12 (average of A1 and A2), etc. The C-7 and C-14 methylene groups are constitutionally heterotopic. c The signal(s) for the major conformation. The chemical shift differences VA~-VB~and VA, -VB2 equal 121 and 38 Hz, respectively. The chemical shift assignments to AB systems AlBl and ClDl are arbitrary. .f The chemical shift assignments to AB systems A2B2 and C2D2 are arbitrary. TABLE2 Free energies of activation for ring inversion (TB TB *) in compounds (2a, e, and f), (3), and (4) Prochiral AGt (at Tc)/ Compound Solvent group (VA -VB)/HZa JAR/HZ TCIK kCb/s-' kcal mol-I (24 CDCl,-CS, (1: 4) OCH, 33.0 11.1 194 95 9.5 (24 CDC1, NCH, 241.0 14.0 303 541 14.0 ( 2f) CDC1, NCH, 87.0 13.0 330 216 15.9 (3) CDCl,-CS, (1 : 2) OCH, 32.0 10.7 199 93 9.7 (4) CDCl,-CS, (2 : 1) OCH, 28.0 10.0 212 26 10.4 a Details of chemical shifts are given in Table 1 where the AB system is denoted as AlBl. b Calculated by method 111 (see Ex-perimental section).The singlet for the aromatic methyl group in the 10-methyl derivative (2b) remains sharp down to -100 "C, thus indicating the absence of exchange between diastereoisomeric conformations. The singlet for the N-methyl group remains sharp down to -50 "C, thus indicating the absence of exchange between diastereoisomeric conformations. TABLE3 Site exchanges and thermodynamic parameters associated with conformational changes in compounds (2c and d) Site AGO/ AGt/Compound Solvent Program exchanges a fil or fi~ p, or PB kcal mol-l li kcal mol-1 Process ( 24 CDCl,-CS, 111 A1 -+A2 0.86 0.14 0.80 13.3 TB-C (2: 1) B1 --.f B2 (-51 "C) A1 B1 13.7 TB+TB* A2 B2 13.7e C*C* (24 CDCl, I A-B 0.20 0.80 0.63 12.6 C-TB B-A (-45 "C) 13.2 TB+C 6 Details of chemical shifts and coupling constants are given in Table 1.In compound (2c), the AB system AlBl refers to the C-7 and C-14 methylene protons of the twist-boat (major) conformation (17) and the AB system A2B2 refers to the C-7 and C-14 methylene protons of the chair (minor) conformation (15).In compound (2d), the singlet A refers to the aromatic methyl protons of the chair (minor) conformation (15) and the singlet B refers to the aromatic protons of the twist-boat (major) conformation (17). b The AGO values are for the process TB C. Some uncertainty surrounds this value for C +C * ring inversion (see text). Molecular models indicate that the per;-interaction and boat (16) conformations (2a-f) is particularly large. between methylene groups of the ring in the chair (15) This transannular steric interaction is relieved partially 1978 1391 in the twist-boat conformation (17) where the principal NMe) of the chemical shift of differences [(vA -vg) in non-bonded interactions are between the ring methylene Tables 2 and 31 for the ring methylene protons is found groups and the heteroatoms (X = 0, S, NMe, or NTs).7yX8&Ra \ (15a) C'(+-4-+) (15b) C* (-44-4) (16a) B (+--44-) (16b) 8ap37~3 'yl4 We therefore propose that the twist-boat conformation (17) is the ground state conformation and that ring inversion involves a TB TB* pseudorotational process (see Figure 3). Four observations support this \ Cf---TS--JT B TB*+TS*-c* \ .=f FB2\ B* YFB' FIGURE Conformational changes in heterocyclic analogues of3 7,8,13,14-tetrahydrobenzo[6,7]cyclonona[1,2,3-de]naphthalene proposal. (i) The magnitudes (33 Hz for X = 0,87Hz for X = NTs, 121 Hz for X = S, and 241 Hz for X = l7 S. Winstein, P. Carter, F. A. L. Anet, and A. J. R. Bourn, J. Amer.Chem. SOC.,1965, 87, 5239; T. Sat0 and K. Uno, J.C.S. Perkin I, 1973, 895. to depend significantly upon the nature of the ring hetero- atoms. There are a number of examples 8917 where van der Waals interactions between heteroatoms and proxi- mate protons lead to deshielding of the proton involved. The expectation l8 that the deshielding influence of heteroatoms will be related to their polarisabilities also appears to be fulfilled by the data recorded in Tables 2 and 3, (ii) The fact that the free energies of activation (AG$ 13.7-15.9 kcal mol-l) for TB+TB* ring in- version in the dithionins (2c and d) and diazonines (2e, and f) are larger than those (9.5kcal mol-l) for the dioxon- ins (2a and b) is consistent with the pseudorotational process shown in Figure 3 where the FB1 (18a and b) and (18~) FB1 (o+-o+-) (18b) FB1* (O-+O-+) (19~)F62 (-+o-+o) (19b) FB2* (+-'ot-o) (20a) TS (+-oo+-) (20b) TS* (-too-+) FB2 (19a and b) conformations correspond to the transi- tion state conformations.The main component of strain in these folded boat transition states (18) and (19) arises from non-bonded interactions between the ring L. M. Jackman and S. Sternhell, ' Applications of Nuclear Magnetic Resonance Spectroscopy to Organic Chemistry,' Perga- mon, London, 1969, p. 71. methylene (Y = CH,) groups and the heteroatoms (X = 0,S, NMe, or NTs). (in) The fact that the free energies of activation (AGJ 9.5-9.7 kcal mol-l) for the dioxonins (2a and b) and (3) are almost identical is compatible with twist-boat (17) ground state conformations and folded boat [( 18) and (19)] transition state conformations with very similar energy contents.Molecular models reveal that this is the case whether X = 0 and Y = CH, as in dioxonin (2a) or X = CH, and Y = 0 as in dioxonin (3). (iv)When the heteroatoms are both sulphur (X = S)as in the dithionins (2c and d), then transannular nonbonded interactions with the ring methylene groups (Y = CH,) destabilise the twist-boat conformation (17) sufficiently to permit the observation of ca. 20% of a second conform- ation at low temperatures. The minor conformation * is presumably the chair conformation (15). Molecular models indicated that the most probable transition state conformation for ring interconversion is the TS conform- ation (20a and b) with C, symmetry on the pathway be- tween the chair (15) and boat (16) conformations (see Figure 3).The chair conformation (15) can therefore be regarded as a detectable intermediate in the TB +TB* ring inversion of the dithionins (2c and d). In principle, the free energy of activation for TB C interconver-sion should be reduced by RTln 2 relative to that for TB T-TB* inversion since ~TB*TB* = 0.5 kTR-C if the inversion process involves intermediate chair con- formations (15). Qualitatively, this feature is evident (see Table 3) in the dithionins (2c and d) where the only +criteria exercised in the determination of kTB ~ T B and kTB+c by line-shape analysis using two different n.m.r. probes were the matches between observed and calculated spectra (see Figures 1 and 2).It is noteworthy that when a peri-annelated naphtha- lene ring replaces an ortho-annelated benzene ring in ‘ 6,8,6 ’ systems (l),chair-like conformations are de-stabilised relative to boat-like conformations. Also, the * We assign as the major conformation the twist-boat conform- ation (17) because the more intense AB system (AlB1) has a larger chemical shift difference (vAl -vB1) of 121 Hz associated with it [see observation (i)] than has the less intense AB system(A2B2) where the chemical shift difference (VA~-VB~)is only 38 Hz. J.C.S. Perkin I increase in transannular non-bonded interactions asso- ciated with the peri-positions of the naphthalene nngs leads to much higher barriers to ring inversions involving pseudorotational processes.At low temperatures, the dioxecin (4) exhibits an AB system for the ring methylene protons in its IH n.m.r. spectra. Since chair and boat conformations would both be even more unstable relative to a twist-boat conform- ation (21) in a ten-membered ring containing two per& interactions, we proposed that the ground state con-formation is once again of this type. The notation (21a) TB (-+--+-) (21b) TB*(+-++:+) for torsional angles in the TB (21a) and TB* (21b) con- formations refers in turn to the bonds 6a-7, 7-8, .8-8a, 14a-15, 15-16, and 16-16a. Two observations support the proposal that the observable ground state conform- ation is a twist-boat conformation (21). (i) The magni- tude (28 Hz) of the chemical shift difference [(va -vB) in Table 21 for the ring methylene protons is very similar to those of 33 and 32 Hz observed for the dioxonins (2a) and (3). (ii) The value of 10.4 kcal mol-l for the free energy of activation to TB-TB* ring inversion is very similar to those of 9.5 and 9.7 kcal mol-l observed for this process in the dioxonins (2a) and (3), and is entirely in accord with a pseudorotational process. We acknowledge the award of an S.R.C. Research Studentship (to D. J. B.). [711690 Received,26th September, 19771