1978 1421 Conformational Behaviour of Medium-sized Rings. Part 8. 6H,12H,-18H-Tribenzob,f,jJl,5,9trithiacyclododecin and its 5,5,11,11,17,17-Hexaoxide By W. David Ollis,' Julia Stephanidou Stephanatou, and J. Fraser Stoddart, Department of Chemistry, The University, Sheffield S3 7HF Michael N6grhdi. institute of Organic Chemistry, Technical University, Budapest XI, Gellert t6r 4, Hungary The temperature-dependences of the lH n.m.r. spectra of 6H,12H.18H-tribenzob,f.j 1,5,9trithiacyclododecin (7) and its 5.5.1 1.1 1.1 7,17-hexaoxide (8) have been interpreted in terms of ring inversions between enantiomeric helical conformations. The free energy of activation for conformational inversion in the cyclic trisulphide (7) is compared with that previously obtained for the ring inversion of the enantiomeric C, conformations of the parent hydrocarbon, 5,6,11,12,17,18-hexahydrotribenzo a,e,icyclododecene (1 ).OURearlier interest in the conformational behaviour of twelve-membered ring systems encouraged us to investi- gate the conformational properties of the hexahydro- tribenzocyclododecene (1) and its 2,3,8,9,14,15- (2) and 1,4,7,10,13,16- (3) hexamethyl derivatives by 394 dynamic 13C and lH n.m.r. spectroscopy and strain energy calculations. Although the hydrocarbons (1)-(3) are conformationally mobile in solution, they all exist 3 preferentially in ground state conformations with C, symmetry. The ternperature-dependences of their n.m.r. spectra have been interpreted3 in terms of ring inversion between enantiomeric C, conformations and the barrier heights for this conformational change were found 394 to depend on the nature of the substituent atoms or groups at the ortho-positions of the aromatic rings.A comparison between the activation parameters for the hexahydrotribenzocyclododecene (1) and its 2,3,8,9,14,15-(2) and 1,4,7,10,13,16- (3) hexamethyl derivatives shows that approximately the same barrier (AGI 9.9-10.1 kcal mol-l) is associated with ring inversion in compounds (1) and (2) whereas a much higher barrier (17.4 kcal mol-l) is associated with the same ring inversion process in compound (3). The activation parameters for the conformational changes experienced by the trisalicylides (4)-(6) in solution were also found to correlate in a predictable manner with the Part 7, F.E. Elhadi, W. D. Ollis, and J. F. Stoddart, preceding paper. W. D. Ollis and I. 0. Sutherland, Chem. Comm., 1966, 402; A. P. Downing, W. D. Ollis, and I. 0. Sutherland, ibid., 1967, 171; A. P. Downing, W. D. Ollis, I. 0. Sutherland, J. Mason, and S. F. Mason, ibid., 1968,329; A. P. Downing, W. D. Ollis, and I. 0. Sutherland, J. Chem. SOC.(B),1970, 24. steric bulk of the various alkyl substituents occupying the ortho-positions of the aromatic rings. Thus, the free energies of activation for ring inversion and inter- conversion processes are considerably less for tri-3,6- dimethylsalicylide (4) than they are for tri-o-thymotide (5) or tri-o-carvocrotide (6). However, whereas the hydrocarbons (1)-(3) adopt 394 only one conformation with C, symmetry in solution, both helical (C, symmetry) and propeller (C, symmetry) conformations are present at equilibrium in solutions of the trisalicylides (a)-( 6) with the more symmetrical propeller always preferred.In the light of these results it was of interest to discover the effect on the conformational behaviour of the twelve- membered ring when single methylene groups in the three dimethylene bridges of the hexahydrotribenzocyclo-dodecene (1) are replaced by heteroatoms in a con-stitutionally symmetrical manner. The first com-pounds of this type we chose to study were the readily available trithia-analogue (7) of the hydrocarbon (1) and the easily derived cyclic tris-sulphone (8). The cyclic trisulphide (7) is obtained, together with the dithiocin (9) and higher oligomers including the cyclic tetra- and penta-sulphides, when o-mercaptobenzyl chloride (10) reacts with sodium hydroxide in ethanol.Oxidation of the cyclic trisulphide (7) with hydrogen peroxide in glacial acetic acid afforded the cyclic tris-sulphone (8). In this paper, we report the results of our investigations Part 6, D. J. Brickwood, W. D. Ollis, J. S. Stephanatou,and J. F. Stoddart, J.C.S. Perkin I, 1398. D. J. Brickwood, W. D. Ollis, and J. F. Stoddart, J.C.S. Chem. Comm., 1973, 638. G. W. Stacey, F. W. Villaescusa, and T. E. Wollner. J. Org.Chem., 1965, 50, 4074. on the conformational behaviour of the cyclic trisulphide (7) and tris-sulphone (8)in solution by dynamic lH n.m.r.spectroscopy. Part of this investigation has been the R2 (1) XmCH,, R'=R2=H (4)R'= R2= Me (2) XeCH,, R1=H ,RMe (5 1 R'* Me, R2=CHMc2 (3) X=CH,, R'mMe, RXH (6) R1=CHMe2, R2=H (7) x=s , R'.R~=H (8) X SO,, R'=R2= H 0'"CHZCl (10) subject of a preliminary communication and has also been discussed briefly in a recent review 7 on the con- formational behaviour of some medium-sized ring systems. In addition, one of us has described the X-ray crystal structure of the cyclic trisulphide (7). EXPERIMENTAL The general methods have been discussed in Parts 3 and 6.3 Reaction of o-MercuptobenzyZ Chloride (10) with Sodium Hydroxide in EthanoZ.6-A solution of o-mercaptobenzyl chloride (10) (10.1g) in ethanol (1 1)was added during 4 h to a solution of sodium hydroxide (25 g) in ethanol (1.5 1).Evaporation of the solvent was followed by repeated extraction with chloroform. The chloroform solution was evaporated and the residue was subjected to column chromatography on silica gel using benzene-light petroleum (b.p. 60-80 "C) (1 : 4) as eluant. Fraction 1 corresponded to the cyclic disulphide, 6H, 12H-dibenzob,fJ 1,5dithiocin (9)(2.1g, 27), m.p. 170-173" (lit.,5 17P-176"). Fraction 2 corresponded to the cyclic trisulphide, 6H, 12H, 18H- tribenzob,f,j1,5,9trithiucycZododecin(7) (0.5g, 6.4y0), m.p. 197-198" Found: C, 68.6; H, 5.9; M (mass spec.), 366. C21H18S3 requires C, 68.8; H, 4.95; M, 3661, r(CS,) 2.30-2.96 (12 H, m, aromatic) and 5.51 (6 H, s, 3 x CH,).However, t.1.c. of the original reaction mixture * The program numbers (viz. I-V) have been established in Parts 3,9 6,3, and 7 and this present program (i.e.VI) represents the latest addition to the series; programs I-VI will form the basis of a collection for reference in future Parts of this series. 6 W. D. Ollis, J. F. Stoddart, and M. NbgrAdi, Angew. Chem. Internat. Edn., 1975, 14, 168. 7 W. D. Ollis, J. F. Stoddart, and I. 0. Sutherland, Tetra-hedron, 1974, 30, 1903. J.C.S. Perkin I on silica gel using benzene-light petroleum (b.p. 60-80 "C) (2 : 3) as eluant indicated the presence of two slower moving components in addition. These were separated by pre- parative t.1.c.on silica gel using this solvent system as eluant to give (i) the cyclic tetrasulphide, 6H, 12H, 18H,- 24H-tetrabenzob,f,j,n1,5,9,13tetrathiacyclohexadecin, obtained pure after recrystallisation from chloroform-ether-light petroleum (b.p. 60-80 "C) (210 mg, 2.8), m.p. 195-196" Found: M (mass spec.), 488.076 3. C28H24S4requires M, 488.076 11, r(CDC1,) 2.46-2.90 (16 H, m, aromatic) and 5.84 (8 H, s, 4 x CH,), and (ii) the cyclic pentasulphide, 6H,12H, 18H,24H,30H-pentabenzo- b,f,j,n,r1,5,9,13,17pentathiacycloeicosin,which was re-crystallised from light petroleum (b.p. 60-80 "C) (120 mg, 1.5), m.p. 120-122" Found: M (mass spec.), 610.094 9. C3,H3,S5requires M, 610.095 13, r(CDC1,) 2.54-3.00 (20 H, m, aromatic) and 5.83 (10 H, s, 5 x CH,).6H, 12H, 18H-Tribenzob,f,j 1,5,9trithiacyclododecin 5,5,11,11,17,17-Hexaoxide(8).-Acetic acid (10 ml) and 30 hydrogen peroxide (5ml) were added to a solution of the cyclic trisulphide (7) (60 mg) in chloroform (10 ml) and the mixture was refluxed for 3 days. On cooling, the cyclic tris-sulphone (8) separated as a crystalline compound (55mg, 73Y0), m.p. 305" Found: C, 54.7; H, 4.25; S, 20.6 ; M (mass spec.), 462. C,lHl,O,S, requires C, 54.5; H, 4.05; S, 20.8; M, 4621, T(CD,C~,-CF,CO,H) 1.56-2.38 (12 H, m, aromatic) and 4.62 (6 H, s, 3 x CH,). Determination of Rates of Conformational Changes by Dynamic 1H N.m.r. Spectroscopy.-A program VI * for exchange of nuclei between all six sites of three AB systems, AlB1, A2B2, and A3B3 was written (coded in FORTRAN IV) using simultaneous equations obtained from a density matrix approach.1deg;-12 This program was used to simulate the 1H n.m.r.spectral line-shapes associated with (i) the methylene protons of the cyclic trisulphide (7) between -36 and -106 "C and (ii)the methylene protons of the cyclic tris-sulphone (8) between -77 and +6 "C. The problem in relation to the spectral line-shapes for compounds (7) and (8) can be stated as follows. The con- formational itinerary (see Results and Discussion section) dictates (i) that each of the six sites is visited by each of the six methylene protons Hc, HD, HE, HF, HG, and HH, and (ii) that the site visits can be represented by two cyclic permutations.It transpires that a clockwise sequence of site visits on the conformational itinerary leads to one cyclic permutation (CFHDEG) (read: C is replaced by F, F is replaced by H, . . ., G is replaced by C). The other cyclic permutation (CGEDHF) is the inverse of the first and cor- responds to an anticlockwise sequence of site visits on the conformational itinerary. It is now necessary to enumerate all cyclic permutations of six spins which can be made to correspond with these two cyclic permutations of protons given the restriction that the six spins consist of three paired systems. Each spin system will be designated by a numeral (1, 2, or 3) and each spin in. a pair by a letter (A and B). By definition, C is paired with D, E with F, and G with H.Reference to the two cyclic permutations of protons shows 8 L. PArkAnyi, A. KAlmAn, and M. NbgrAdi, Acta Cryst., 1975, B31, 2716. 9 Part 3, W. D. Ollis and J. F. Stoddart, J.C.S. Perkin I, 1976, 926. 10 J. I. Kaplan, J. Chem. Phys., 1958, 28, 278; 1958, 29, 462. l1 S. Alexander, J. Chem. Phys., 1962, 37, 967, 974; 1963, 88, 1787; 1964, 40, 2741. l2 C. S. Johnson, J. Chem. Phys., 1964,41,3277; Adv. MagneticResonance, 1965, 1, 33; J. Magnetic Resonance, 1969,1, 98. that the paired spins are separated antipodally in the cycle. It follows that there are two and only two cycles of numerals, (123123) and its inverse (132132), and two and only two cycles of letters, (AAABBB) and (ABABAB). There is one and only one combination of (123123) and its inverse with (ABABAB); there are three and only three combinations of (1231 23) and its inverse with (AAABBB) .Consequently, there are four and only four combinations which can be expressed by the following mappings: 123123 123123 123123 123123 LABAB) {AAABBBI LAABB) LBAAABl and the inverses. The situation can be visualised easily in terms of the pairwise superposition of hexagons : 1 1 1 1 1 1 1 1 A A B B B B A A from which the four site exchange schemes: (ii) (ii i) (ivl can be written down. Figure 1 shows the density matrix elements associated with each transition and the rate constants associated with each site exchange of nuclei between the six sites Al, B1, A2, B2, A3, and B3 of the three AB systems corresponding to the site exchange schemes (i)-(iv).The density matrix approach was used to examine all four site exchange schemes. Attempts to perform line-shape analysis on the temperature-dependen- dent lH n.m.r. spectra (Figure 2) of the cyclic trisulphide (7) indicated that only the computer program constructed on the basis of site exchange scheme (iv) provides good matches between computed and experimental spectra. The temperature-dependent lH n.m.r. spectra of the cyclic tris-sulphone (8) were amenable to line-shape analysis using site exchange schemes (ii)-(iv). The method of comput- ation will now be illustrated for site exchange scheme (iv). k21P132 f h31P133 -'12p13' -'13P13' -P131/t2A1 -2nip131(vAl -v f QJ1) + ip121nJ1 + pli c = 0 (l) '12P13' + '32P123 -h21P132 -'23P1 -P132/t2A2 -2nip132 (vA2 -v + +J2) + zp122nJ2 + p2ic = 0 (2) '13P13' + -k31p133 -'32plq -P1S3/j3A3 -2nip13~(VA3 -v f amp;J3) + zPi!z3XJ3 + p3ic = 0 (3) k21p122 f k3iPi23 -h12p121 -ki3pi21 -p112/t2B1 -2nip12' (VBl -v f amp;J1) f + p1ic = 0 (4) k12p121 + h32Pi33 -K21P122 -K23pi22 -6'122/t2B2 --2xip12~(VA2 -v + amp;J2) + ip132XJ2 + p2ic = 0 (5) '13p12' + '23P132 -K31P123 -k32P123 --2nipi23(vB3 -v f *J3) + ip133nJ3 + p3ic = 0 (6) For three AB systems undergoing the exchange of nuclei between the sites illustrated in scheme (iv) in Figure 1 the FIGURE The site exchange schemes (i)-(iv) for exchange of1 nuclei between six sites (Al, B1, A2, B2, A3, and B3) of three AB systems.The density matrix element corresponding to each transition is indicated. The double-headed arrows represent site exchanges with the appropriate rate constant given alongside each arrow density matrix approach lWl2gives two sets of six simultane-ous equations in the density matrix elements for the twelve allowed transitions corresponding to the twelve lines observed in three AB systems. The first set of six simultaneous equations involves the density matrix elements p121, p122, pI23, p131, p132, and p1a3. The subscripts have their usual significance in referring to spin states ; the superscripts 1, 2, and 3 refer to the three different AB system in scheme (iv) in Figure 1. By considering the effects of the site exchanges shown in scheme (iv) in Figure 1 upon the basis functions, the simultaneous equations (1)-(6) in p para-meters may be obtained for ' steady-state ' conditions (8p121/i3t = 0, etc.).A second set of six simultaneous equations may be obtained in the density matrix elements ~1~ ~~242, P2d3, , p341, p342, and p343 which differ from the first set (1)-(6) only in the sign of the J parameters. These twelve complex simultaneous equations were solved for the p parameters at each input value of the frequency v by use of a MASTER SIX SITE computer program. Values for the site frequencies Val,VA2, vA3, VB1, 52, and vB3, the popul- ations pl, p2, and p3 and relaxation times t2A1, t2A2, t2A3, t2132,and t2B3 were obtained initially from chemical -36OC -50 "C -61"C A1 A2 tI I II I jL I /I L ~4.43 4.61 5.53 5.99 6.02 6.10 2FIGURE Observed (full line) and computed (broken line) spectra of the methylene protons of 6H,12H,18H-tribenzo-b,f,jl,5,9trithiacyclododecin (7) using program VI for ex- change of nuclei between six equally-populated sites Al, euro;31, A2, B2, A3, and B3 (the input values for all the rate constants, k,,, etc., were the same so they will be referred to collectivelyas k): (a) at -106 "C, k 5.5 s-l; (bi at -92 "C, k 17.5 s-l; (c) at -87 "C, k 47.2 s-l; (d) at -82 C, k 75.2 0;(e) at -77 "C, k 173 s-l; (f) at -71 "C, k 345 s-l; (g) at -61 "C, k 1 318 s-l; (h)at -50 "C, k 3 630 s-'; (i) at -36 "C,k 19 500 s-l shifts, relative intensities, and half-peak widths for the individual signals of the three AB systems in the low temperature spectra.The absorption intensity at frequency v is proportional to the imaginary part of Cprgn for all the twelve allowed transitions. Solutions to the simultaneous equations for a range of values for v which cover the appropriate region of the spectrum give line shapes for selected input values of the rate constants k12, K2,, K13, J.C.S. Perkin I KS1, K23, and k32. Since the input values for all these rate constants were the same in the present instances, they will be referred to collectively as k. A spectrum consisting of the absorption intensities at 500 values of v required a computing time of only 46 s on an I.C.L. 1907 computer. The density matrix approach can be applied to schemes (i)-(iii) in Figure 1 in analogous fashion to that described for scheme (iv).RESULTS AND DISCUSSION The lH n.m.r. spectrum of the cyclic trisulphide (7) in carbon disulphide showed temperature-dependence (see TABLE1 Temperature-dependent lH n.m.r. spectral parameters (LOO MHz) for compounds (7) and (8) Com-pound X Solvent Temp.("C) Group T (J/Hz) 0 (7) (8) S SO, CSa CDaCIa-CFSCOZH -106 -36 -77 C,H4 Camp;4 CHa CH, C,H4 2.30-2.96 (m) 4.61 (A2), 6.18 5.53 (A3), 6.99 2.30-2.96 (m) 4.43 (Al), 6.02 (Bl) (J 9.0) (B2) (J9-01 (B3) (J 9.0) 5.51 (AB123) 1.52-2.40 (br,m) (10: 1) +30 CHa Camp;4 CH, 3.64 (Al), 5.24 (Bl) (J 16.0) C 3.86 (A2), 6.36 (B2) (J 16.0)4.12 (A3). 5.37 (B3) (J 16.0)1.56-2.38 (m)4.62 (AB123) 0 Sites are designated Al, B1, A2, B2, A3, and B3 for six-site systems where there is coupling in the form of three AB systems. Sites that represent six time-averaged signals are designated AB123.b The three AB systems were identified unambiguously by homonuclear INDOR spectroscopy (seetext). c The assignment of the pairing of these three AB systems is arbitrary. Table 1). Three AB systems for the six methylene protons were identified (see Figures 2 and 4) at -106 "C and the pairing of each AB system was established by homonuclear INDOR spectroscopy (Figure 4). The three AB systems coalesced to give a sharp singlet at -36 "C and above. This observation indicates that the ground-state conformation of the cyclic trisulphide (7) has C, symmetry.Temperature-dependence was also observed (see Table 1) when the lH n.m.r. spectrum of the cyclic tris-sulphone (8) was examined in dichloro- dideuteriomethane containing a few drops of trifluoro-acetic acid. At +30 "C, a singlet was observed for the six methylene protons. On cooling to -77 "C, the singlet was resolved into three AB systems. Thus, the ground-state conformation of the cyclic tris-sulphone (8) must also have C, symmetry. The pairing of the three AB systems given in Table 1 is arbitrary since all attempts to unravel the coupling pattern by (i) spin-spin decoupling and (ii) homonuclear INDOR spectroscopy were unsuccessful on account of the insoluble nature of the sample at low temperatures. However, because of the relatively large chemical shift differences between the A and B protons in all cases, the theoretical line-shapes (see later and Figure 3) are in fact quite insensitive to the actual assignment of AB systems to chemical shifts.Acceptance of the requirement for ground-state conformations with C, symmetry and examination of molecular models suggest that the molecules (7) and (8) both adopt helical conformations (cj. ref. 2) in solution. There are two enantiomeric conformations of this type (lla and b) and they will be referred to by the des- criptors H and H*. These conformations are analogous to the C, and C2*conformation3s4 of the hydrocarbons (b) consideration of the H H* inversion process. The itinerary of H +H* inversion processes which are required to exchange the six methylene protons of (7) and (8) with the six different sites conveniently labelled 1-OUT, 1-IN, 2-OUT, 2-IN, 3-OUT, and 3-IN is shown in Figure 5.The sites occupied by the three pairs of diastereotopic methylene groups have been labelled by the numbers 1,2, and 3 in an arbitrary fashion. Further-more, the protons are considered to occupy IN or OUT sites depending on whether they are oriented inside or outside the diagrams in Figure 5. This notation is -55OC I I5.24 5.35 5.37 FIGURE Observed (full line) and computed (broken line) spectra of the methylene protons of 6H.12H,18H-tribenzob,f,j1,5,9-3 trithiacyclododecin 5,5,11,11,17,17-hexaoxide(8) using program VI for exchange of nuclei between six equally-populated sites Al, B1, A2, B2, A3, and B3 (the input values for all the rate constants, k,,, etc., were the same so they will be referred to collectively as k): (a) at --77 "C, k 3.7s-l; (b) at -55 "C, k 44.6 s-l; (c) at -6 "C, k 2 488 s-l; (d) at +6 "C, k 3 558s-1 (1)-(3).In common with these hydrocarbon molecules where none of the more symmetrical D,and D,* con-formations were detected in solution, the molecules (7) and (8) do not appear to populate the more symmetrical propeller conformations with C, symmetry to any extent in solution. Formally, there are two enantio- meric conformations of this type (12a and b) which can be recognised with molecular models and they can be de- noted by the descriptors P and P*.The conformational inversion and interconversion processes involving these enantiomeric and diastereoisomeric conformations are represented by the equilibria P +H H* wP* in a manner reminiscent of the case of the trisalicylides (4)-(6).2 However, in order not to complicate unneces- sarily the problem involving the site exchanges between the six sites and the protons of the three pairs of diastereo- topic methylene groups in the H and H* conformations (lla and b), the discussion will now be limited to a necessary because a unique assignment of protons to the sites Al, B1, A2, B2, A3, and B3 is not possible and an arbitrary assignment could be misleading (see Experi- mental section). If the identity of the protons in Figure 5 is established using subscripts C, D, E, F, G, and H, then the six diastereotopic protons Hc, HD,HE,HF, HG;, and HHcan be associated with the six different options corresponding to three degenerate H conformations (lla)-I, (1la)-11, and (1la)-1111 and three degener- ate H* conformations (lib)-I, (1lb)-11, and (1lb)- 1111in Figure 5.Simultaneous torsion about a carbon- sulphur (e.g. 4a,5) and a carbon-carbon (e.g. 6,6a) bond linking a particular X-CH, group to two aromatic rings (e.g.those defined by atoms 1, 2, 3, 4, 4a, 18a and 6a, 7, 8, 9, 10, 10a) can formally lead to H T-H* inversion. Previously, we have likened this synchronous torsional change to a pedalling motion. Pedalling of the X-CH, bridges I1 or I11 of H-I, I or I11 of H-11, I or I1 of H-I11 1426 J.C.S.Perkin I effects H @H* inversion such that H-I is inverted to either H*-I11 or H*-11, H-I1 to either H*-I11 or H*-I, of activation for the H +H* inversion process were determined at different temperatures. Table 2 records 6 5 H*conforrnation (llbl P conformation Wa) P*conformation (12b) and H-I11 to either H*-I1 or euro;euro;*-I. From a consider-ation of Figure 5 it is obvious that each one of the six protons visits a particular site in the order: This cyclic array determines (see Experimental section) the two cyclic permutations (CFHDEG) and its inverse (CGEDHF) which lead to the four possible site exchange schemes (i)-(iv) involving sites Al, B1, A2, B2, A3, and B3 observable in the low temperature lH n.m.r.spectra (see Figures 2 and 3) of compounds (7) and (8). Inspection of Figure 5 in relation to the site exchange schemes (i)-(iv) shows that the H +H* inversion process is associated with a first-order rate constant k which in turn may be related directly to the site exchange rate constants kl2, k,,, k13, k3r, k,, and k32. The rate constants for H H* inversion at different temper- atures were determined (see Figures 2 and 3) for com- pounds (7) and (8) by comparing lH n.m.r. spectra for the methylene protons in each case with theoretical spectra generated by the line-shape procedure outlined in the Experimental section. Values of the free energies B1A3 A2 82ii II I I I'4.43 4.61 5.53 5.99 6.026.18 FIGURE Assignment of the three AB systems, AlB1, A2B2, 4 and A3B3 of 6H,12H, 18H-tribenzob,f,j 1,5,9 trithiacyclo- dodecin (7) by liomonuclear INDOR spectroscopy.An observing frequency v0b. monitors a single spectral line while a second irradiating frequency qrr.sweeps the spectrum. When virr. crosses a spectral line which has an energy level in common with the observed spectral line, a positive (+)or negative (-) intensity change occurs depending upon the sign of the general- ised Overhauser effect. The following information can be gleaned from the INDOR spectra (a)-@) : Line Lines exhibiting Spectrum observed intensity change (a) 6 7(+); 8(-) (b) 5 7 (-1; 8 (+)(4 4 9 (+); 10 (-1(4 3 9(-); lo(+) (el 2 7(+); 8(-) (f) 1 7(-); a(+) the average values of AGI (H ==== H*) for compounds (7) and (8).TABLE2 Thermodynamic parameters associated with H +H* inversion in compounds (7) and (8) Com-'H N.m.r. AGt/kcalpound X Solvent probe a~* mol-l (7) s csz CH2 9.3 f0.2 (8) SO, CD2Clz-CF,C02H (10 : 1) CH2 11.3 f0.4 0 Details of the 1H n.m.r. chemical shifts are given in Table 1. b The site exchanges involving sites Al, Bl, A2, B2, A3, and B3 are described in the text with reference to Figures 1 and 4. Line-shape analyses were carried out using program VI. e Value obtained from lH n.m.r. line-shape analysis (see Figure 2).. d Value obtained from lH n.m.r. line-shape analysis (see Figure 3). 1978 1427 111 H-I11 (1la)-111 1II Ht 11 (11 b)-lI I I11 H-I1 .(lla)-II III Ht III (1T b) -111 Sites 1-OUT 1-IN 2-OUT 2-IN 3-OUT 3-INrsquo; H-I11 HC HD HE HF Hci HH HF HE Ha HH Ha HD HH HO HC HD HF HE HD HC HF HE HR HQ H*-I1 HE HQ HF HH HH HD HQ HC HD HE HC HF FIGURE The itinerary of H =+?= H* inversion processes required to exchange the sixdifferent methylene protons Hc, HD, HE, Hp, 5 Ha, and HR with the six different sites 1-OUT, 1-IN, 2-OUT, 2-IN, 3-OUT, and 3-IN in the cyclic trisulphide (7) and the cyclic tris-sulphone (8) Molecular models of the cyclic trisulphide (7) and the cyclic tris-sulphone (8) reveal that two diastereoiso-meric transition states to H =a= H* inversion need to be considered in each case.These are the TS1 (13) and TS2 (14) conformations which differ as a result of pedalling of an appropriate CH,X group in an H (1la) or H* (llb) conformation in opposite directions.In the TS1 conformation (13) the methylene group passes through the interior of the ring whereas in the TS2 conformation (14) a sulphur atom or sulphone grouping experiences this transformation. In the diagrams (13) and (14) the portions of the molecule indicated by thickened bonds are coplanar in each case. Attempts to manipulate CPK space-filling molecular models demon- strate that the passage of either a sulphur atom or a sulphone grouping through the interior of the ring is a highly unattractive proposition compared with an internal passage of a methylene group.Thus, only the TS1 conformation (13) in each case is worthy of further consideration. The fact that the free energy of activ- ation for H eH* inversion in the cyclic trisulphide is not much smaller (indeed only by 0.8 kcal mol-l) than the barrier of 10.1 kcal mol-l for C, lsquo;~iCz*ring inver- sion in the analogous hydrocarbon (1) is of particular interest. If the transition state conformation for H H* inversion in the cyclic trisulphide (7) is indeed of the TS1 type (13) then any conjugative stabilisation of the TS1 conformation (13) as a result of electron delocalisation between the lone pairs on sulphur and the x-system of the aromatic rings is rather small in energy terms. J.C.S. Perkin I Finally, it should be noted that the asymmetrical helix conformation (lla and b) which has been estab- lished as the only observable ground-state conformation TS1 conformation (13) TS2 conformation (14) ax H of the cyclic trisulphide (7) in solution also corresponds * to the solid-state conformation of the molecule (7). We thank Professor K. Mislow for criticism and discus- sions on the interpretation and presentation of the results, and Dr. A. G. Ferrige (Wellcome Research Laboratories) for recording homonuclear INDOR spectra. We gratefully acknowledge financial support (to J. S. S.) from the State Scholarship Foundation of the Government of Greece. 7/1694 Received, 26th September, 19771
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