On intramolecular dyotropy: Primary 2H kinetic isotope effects - two contrasting cases.

oo40-4039/92 8s.00+ .oo P~&PmOrl ken Ltd

TetmhcdmnLam. Vol. 33. No. 38. pp. 5629-5632 1992 Printedin Grea Britain

On Intramolecular

Dyotropy: Primary 2H Kinetic Isotope Effects Two Contrasting Cases.

Kenneth Mackenzie*a, Edward C. Grave@, Robert J. Gregorya, Judith A.K.Howardb and John P. Maher%

aSchoolof Chcmisey. ‘Ibc Uaivcrsity.Bristol, BS8

ITS.

b ScienceLaboduics. Universityof Durham.SouthRoad, Durham,DHl3LE

: Primary deuterium kinetic isotope effect analysis in molecules exhibiting intramolecular (4cr + 2x) dyotropy reveals evidence for non-classical behaviour for pyraxolines 10; for trienes 2 the quantum tunnelling effect appears Iess Likely.

Abstract

To discover the factors which control reaction-rate in intramolecular dyotropy is a matter of contemporary interest.l We earlier disclosedta that the& irreversible (40 + 21~)dyotropy. represented in the rearrangement of trienes 1-4, and the analogous transformations of pyraxolines 9.10 is strongly kinetically retarded by Cl and OR substituents (1~2 a3 >4 u9 alO),the effect being maximisai in pyrazolines 11 and 12, which remain unchanged at s 200’. For the pyraxolines, variations in the aryl substituents (e.g. Ar = Ph , p ClC&I4, p - MeC&T4) results in only a modest kinetic effectla Reactive intermediates are therefore unlikely to play any mechanistic r81e in these uncatalysed, exothermic rearrangements; especially since with potential intermediate - stabilising N atoms and aryl groups pyraxolines 10 are kinetically sluggish by > 103 - fold e.g. with respect to e.g. triene 2. The modest kinetic effect of differing aryl substitution in the pyraxolines and the quantitative rearrangements observdta are consistent with truly pericyclic reactions proceeding via reactant li+ transition states. Similar conclusions with regard to pericyclicity of (40 + 2x) dyotropylkh are supported by other recent work, not least by the discovery of the uncatalysed 4n homologous (40 + 6x) process.*

------,s

Rld=H 2 R16=Cl 3 R*=OEt Rz-a=Cl

‘1

4 R13,R5.6,0&&

----+6 R3.4=a

9 R’6=H 10 Rt6=(=L 11 Rl=OEt

R*-a=Cl

12 Rl~=R56=Ot&

R3.4=Q

__+

g

L __,

13 14

5630

From X-ray crystallographic structural and other information we have inferred that the rate - spread observed among the groups of compounds 1 - 4,9 and 10 (5x1012, 36’, calculated from Arrhenius parametersla e.g. 1, k 36” = 4~lO-~s-l) has its origin in the internuclear distance, +R, of H atoms transferred and the receptor sp2C atoms, and by x - electronic and strain energy (Es) changes concomitant with aromatisation of the unsaturated ring appended to the donor - sites.3s Others have subsequently drawn attention to the kinetic effect of modulation of ground state Es in essentially thermoneutral examples of (40 + 21~)intramolecular dyotropy.3c From the work which has been accomplished in this area, it is clear that the detailed study of the intramolecular dyotropic process in rigid, stereochemically well - defied molecules can yield important information with regard to spatio - proximity effects4 and transition - state theory.5ac.d.e From the X-ray3a.c and neutron scattering3h crystallographic data it has been rigorously determined that @l-l in molecules analogous to 2 and 10 is within the Van der Waals radius (2.6A) at a distance predicted by theory6 appropriate to the onset of chemical interaction but the reacting centres are not ideally co-linear, as assumed in theoretical models for intermolecular dyotropy.7s.h Theory suggests7c that non-linear and thermochemically unsymmetrical transition-states for H transfer reactions correlate with attenuated deuterium primary kinetic isotope effects (PDKIE). For this and other reasons it seemed to us of interest to prepare the hexadeuterio- analogues of compounds 2 and 10 (Ar = pClCgH4-) to investigate the magnitude of their PDKIE’s. Such experiments are also invited for their potential in distinguishing synchronous from two-stage processes during 2H transfer.2*7 In addition, especially for the pyrazolines 10, the proximity of the interacting centres, with an estimated H nuclear displacement of -1.7Ain the H transfer step determined from crystallographic da&b and a likely narrow but relatively high activation barrier, raises the possibility of a significant quantum tunnelling conuibution.~~c The required deuterium labelled analogues of lH-2 and tH-10 were made as follows: freshly prepared cyclopentadiene (CPD) exposed to an excess of mixtures of NaOD/D20(99.98% isotopically pure), the diene allowed to spontaneously dimerize, the dimer isolated and thermolysed gave CPD with 70%. randomly incorporated 2H. Adduction of this product with 1,2,3.4,7,7-hexachloronorbomadiene gave isodrin 15 similarly 2H labelled at C-l/8, C-9/10, and C-12/12 with 100% 1H at C-2/7 (4OOMhzNMR and m/z). 70% ZH-labelled triene 2 and pyraxoline 10 (Ar = pClC&L+) were then prepared from *H-isodrin by methodology previously describe&la Preliminary kinetic experiments with 70% 2H-2 and -10 showed the expected behaviour for mixed isotopic species and a considerable PDKIE for each, advantageously translated into the partially selective removals of 1H from C-4/9 in 2 and C-4/8 in 10 by heating decalin solutions for co. 8 half-lives at 95’ and 207.6’ respectively, employing known kinetic data for the 100% 1H compounds.ta Preparative TIC separation of unreacted triene 2 gave a product with 98.8% 28 at each of C-4@ and similar recovery and analysis of unreacted pyrazoline 10 delivered a product with ,98% 2H at each of C-4/8,*b depletion of 4,9-lH-2 and 4.8lH-10 being close to that predicted by their kinetic parameters,ls an indication of a negligible secondary DKIE as expected from structural feature@ (torsion angle H-3/4 -90’). Table 1. Unimolecular Rate Constants, kl, for dyotropy. ‘H-2

Temp(‘C):

175.0

179.8

182.2

184.8

187.7

190.0

195.0

196.0

1.99.9

kl=,s-1x1@: 12.34

13.85

14.85

16.26

18.46

1 10.6

1 16.6

118.4

126.2

I 199.9 11.34

1205.0 12.05

1207.6 1215.0 12.39(8) 14.26

1217.0 14.92

1220.0 16.02

1224.9 18.54

Temp(‘C): kl2QlxlOS:

1195.1 IO.956

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Heating solutions of *H-2 and *H-10 over a range of temperatures and times, as for the 1H analogues.la gave the kinetic data in Table 1 which may be compared to the originalla and, additional data for the protiocompoundso’ The data for lH,*H-2 and lH,*H-10 gave excellent hrkl - K-1 Arrhenius plots, and linear regression analysis computation10 gave thermochemical parameters presented in Table 2.

Table2.Activation Palmletenforl8omerisations.

(a) k&s mol-I (b) cal mol-lK-1 converted from data in W, J (1 cal = 4.18J) (c) *H = D For trienes 2, a mean PIXIE ratio kI 2.B/kl *B = 7.74 is calculated at loo’,11 whilst for the pyraxolines 10 direct comparison at 207.6’ yields kl *B/kl *B = 4.60 (calculated 10.8 at loo’); further rate extrapolation to 25 from the Table 2 data yields, for trienes 2 kl *Bikt *B = 13.8 and for pyraxolines 10.28.6 for this ratio. The PDKIE temperature dependance [the slope for ln(kl*B/kl*D) vs K-l] is 0.859 for nienes 2 and strikingly larger, 1.420, for the pyraxolines 10. However the most revealing difference in the data for the isotopic isomer pairs of 2 and 10 lies inthevalues of the Atrhenius pre-exponential A ratios, &.1/,42B which are 0.8OOS2OO and 0.284iO.143 respectively; values of this ratio of 0.8fo.1 and a steep temperature dependance of the PDKIE5ac.d are usuau y regarded as a reliable indicator of a tunnelling contribution. For the pyraxolmes 10the size of the PDKIE, steep temperature dependance and the fractional value of A&&B (which is similar to values reported in a number of reactions where tunnelling is reasonably well establish&), together with l\~8*B - AEa*B = 2.80zt0.51 kcal mol-1, the mean value being in excess of the zero-point C2H/C2D energy difference (2x1.20 kcal mol-1) suggest non-classical behaviour for pyrazoline 10 but probably not for triene 2 (where AEa2D - AEa*H = 1.70i0.22 kcal moll). In (cautious) comparison with the highly exothermic diimide/ethene reaction by intermolecular W’transfer. and for which theoretical considerations7a indicate a synchronous pericyclic reaction with a significantly larger computed PDKIE, klm/kI*D - 11.8 at 25’. than for a step-wise process (PDKIE -9). the magnitude of kl*B/kl*B extrapolated for trienes 2 at 25’. 13.8 strongly suggests a synchronous process which is probable as the interacting cenues are so closely proximate.. If in general the ground state - transition state CH/CD zero-point energy difference is represented as it follows that AEaD = AEaH + B&o) and A&D = aH + GEa(V&*k - 8E&o)t-.58Giveniven that for a synchronous process kl*H/klDH~~tW/kl*D],*=la, a plot of hrqkIm/kl*D] vs. K-l allows calculation of the ratio A&ABB, and also of GE&o). For the uiene 2 the slope GE&)/R = 0.430 gives SE&o) = 0.852 kcal mol-1 per D, and for the pyrazolines 10. GE&)/B = 0.709 and 6E&o) = 1.40 kcal mol-1 per D. figures of the cotrect order of magnitude compared to the known ground state value 8E(vo) US/CD of 1.20 kcal mol-1.5a.C A knowledge of kI*B/kIBB also allows calculation of the ratio &H/ABB from the expression kl*B/klBB = Az?~/ADHexp[8Ea(vo)/K~ or from the intercept of In’l[k12B/k12Dlvs. K-l. For the nienes 2 A~H/ADBhas the values 0.913fo.236. but by contrast the pyraxolines 10 have A&ABB values 0.586ztO.285 - in the mean significantly below the tunnelling limit value. It is also interesting that for trienes 2 the apparent 8Ea(vo)t.~te is +O.350 kcal moll.but for the pyraxolines 10 GEa(V0)t.s~ is -0.200 kcal mol-I, perhaps also an indication of non-classical behaviour. We intend computer analysis of the PDKJE data described hen (and other data in course of acquisition) using a computer programme enabling experimental data to be fittedsa to the Bell equatio& relating the tunnelliigll frequency to tunnelling correction coefficients t&B, Qp. It may then be possible to obtain a value &(Vo)

5632

for the activation barrier half-width, a,for comparison with X-ray (neutron) crystallographic parameters for 2H10 (and 2H-2). This is an important objective, since most information about tunnelling effects refers to intermolecular reactions for which barrier parameters cannot be so directly correlated with experimental structural data. There is also relatively little information about barrier parameters,t2 certainly none to our knowledge for instances of intramolecular dyotropy, other than measured values of AE,.laJ Acknowledgements : We thank the SERC for a Postgraduate Studentship for E.C.G.. and for financial support (J.A.K.H. and K.M.). We also thank Dr. John S. Littler for an original suggestion which prompted this work, and Dr. Peter Cox for information on the preparation of ZH-labelled CPD. We also thank Prof. W. H. Saunders for helpful comments and for a copy of a computer programme. References and Notes 1. (a) K. Mackenzie, G. Proctor and D. J. Woodnut, Tetrahedron, 1987, a.5981and references cited. (b) L. A. Paquette, M. A. Kessehneyer and R. D. Rogers, J. Am. Chem. Sot., 1990, J_Q,284. (c) A. P. Marchland, P. Annapuma, W. H., Watson and A. Nagl, J. Chem. Sot. Chem. Comm., 1989,281; T. J. Chow and M.-F. Ding, Angew. Chem. Internat. Ed. English, 19&a, 1121; S.-P. Hagenbuch, B. Starnpfli and P. Vogel, J. Am. Gem. Sot., 1981,~. 3934; D. Ginsberg, Tetrahedron, 1974.2, 1483; R. Srinivasen, Tetrahedron Letters. 1973,4029. 2. H. Geich, W. Grimme and K. Proske, J. Am. Chem. Sot.. 1992.114.1492. (@, note 11 below). (a) J. A. K. Howard, K. Mackenzie, R. E. Johnson and K. B. Astin, Tetrahedron Letters. 1989, JQ,5005. 3. (b) J. A. K. Howard, K. Mackenzie, T. Preiss and C. Wilson, unpublished work. (c) L. A. Paquette, G. A. O’Doherty and R. D. Rogers, J. Am. Gem. Sot., 1991, m, 7761, and private communication. 4. F. M. Menger. Accounts Chem. Res., 1985. .l&128. (a) L. Melander and W. H. Saunders, Reuction Rates of isotopic Molecules, J. Wiley and Sons, New 5. York, 1980. (b) ibid., p.97 Fig 4.1. (c) R. P. Bell, The Proton in Chemistry, Chapman and Hall, London, 1973. (d) M. A. Amin, R. C. Price and W. H. Saunders, J. Am. Chem. Sot.. 1990, u 4467.: (e) A. E. Dorigo and K. N. Houk. J. Am. Chem. Sot.. 1987,lQ& 3698; cf. M. Sherrod and F. M. Menger, 6. 7.

8.

9. 10. 11. 12

Tetrahedron Letters, 1990,31459. J. Gerratt. D. L. Cooper and M. Raimondi, Advances in Gem. Physics, 1987, LX& 319. (a) D. K. Agrafiotis and H. S. Rzepa, J. Gem. Sot. Perk 2.1989.475. (b) D. F. Feller, M. W. Schmidt and K. Ruedenberg, J. Am.Gem. Sot., 1982, m 960.(c) A. E. Pain and I. H. Williams, J. Chem. Sot. Gem. Comm., 1991.1417; R. A. More CYFerrall,J. Chem. Sot. (B), 1970,785; F. H. Westheimer, Chem. Rev., 1%1,$&265.

(a) 2H-2, m.p. 293-294’ (concomitant 2H-)ta m/z: 550(M+’ isotopic ion cluster). 2H, %: 2H3 0.82,2H4 3.41, as 23.12, *& 72.6. 1H NMR 4OOMHz, tH, 8: H-3,10 6.7; H-16.16’ 7.7. 2H NMR 67MHz. ppm: 1.62,2.02 (16,16’ ); 3.04 (3,lO); 3.11 (4,9). (b) 2H-10, m.p., crystals turn opaque 170-180’, m. 274-276’ (concomitant 2H-)lao m/z: 624(M+’ isotopic ion cluster). 2H, %: 2H3 3.79.2H4 6.31.2H5 16.9,2b 61.5. tH NMR 4OOMHz, tH, 96: H-3.9 6.95; H-15,15’ 9.6. 2H NMR 67MHz, ppm: 1.51, 1.74 (15.15’); 2.94 (3,9); 3.88,4.36 (8.4). Both 2H-2 and 2H-10 had the expected UV absorbtionta Compounds 2 and 10,their analoguesta and 2H analogues exhibit particularly clean kinetic behaviour; from the m.p. behaviour, the dyotropy observed has been shown to be quantitative Computer programme devised by J. P. Maher and G. Mrotxek. For comparision with the PDKIE evaluated for a 4n homologous system2 at 160.7’, kt2H/k12D, at this temperature is calculated to be 5.60. E. F. Caldin and G. Tomalin, Trans. Fur&y Sot.. 1968. f&,2814; 2823.

(Received in UK 30 June 1992)