摘要:

428 QUARTERLY REVIEWS Transformations related and photo- chemical rearrangements 15 393 Transformations thermal in solids 11 246 Transition metals cyanide complexes of the. 16 188 Transition-metal compounds crystal- line electron resistance in 14 427 Transitions in solids and liquids 3 65 Transport control in heterogeneous reactions 6 157 Transport properties of liquids in relation to their structure 14 236 Triplet state 12 205 Triterpenes tetracyclic 9 328 Tropolones 5 99 Tryptophan biological degradation of 5 227 Ultrasonic analysis of molecular relaxation processes in liquids 11 134 Ultrasonic waves effects of on electrolytes and electrolytic pro- cesses 7 84 Veratrum alkaloids 12 34 Vibrational spectra of ionic melts 17 Wittig reaction 17 406 Wool wax constitution of 5 390 X-Ray crystal analysis modern methods of determination of mole- cular structure by and their ac- curacy 7,335 p-Xylylene chemistry of and of its analogues and polymers 12 301 225 428 QUARTERLY REVIEWS Transformations related and photo- chemical rearrangements 15 393 Transformations thermal in solids 11 246 Transition metals cyanide complexes of the.16 188 Transition-metal compounds crystal- line electron resistance in 14 427 Transitions in solids and liquids 3 65 Transport control in heterogeneous reactions 6 157 Transport properties of liquids in relation to their structure 14 236 Triplet state 12 205 Triterpenes tetracyclic 9 328 Tropolones 5 99 Tryptophan biological degradation of 5 227 Ultrasonic analysis of molecular relaxation processes in liquids 11 134 Ultrasonic waves effects of on electrolytes and electrolytic pro- cesses 7 84 Veratrum alkaloids 12 34 Vibrational spectra of ionic melts 17 Wittig reaction 17 406 Wool wax constitution of 5 390 X-Ray crystal analysis modern methods of determination of mole- cular structure by and their ac- curacy 7,335 p-Xylylene chemistry of and of its analogues and polymers 12 301 225

ISSN:0009-2681    

DOI:10.1039/QR96418FP001

出版商:RSC    

年代:1964

数据来源: RSC

摘要:

THE ABSOLUTE INTENSITIES OF INFRARED ABSORPTION BANDS By D. STEELE (DEPARTMENT OF CHEMISTRY ROYAL HOLLOWAY COLLEGE ENGLEFIELD GREEN SURREY) THE intensity of absorption of infrared radiation by a given system is intimately related to the electronic charge movements during the associated vibrational quantum transition. Molecular deformations must involve bond deformations and are very unlikely to affect any but the valence-shell electrons. Consequently in principle absorption intensities could yield not only information on charge distributions in molecules but also infor- mation on the manner in which the valence electrons redistribute them- selves during molecular deformations. Since chemical reactions of neces- sity involve specific bond deformations such information could lead to a deeper understanding of reaction mechanisms.The equilibrium charge distributions can lead to a better understanding of the bonding. During recent years a large number of publications on the theory measurement and interpretation of the absolute intensities of infrared absorption bands has appeared in the literature. Many serious difficulties still beset the spectroscopist in the interpretation of the results but the information gleaned has reached the state where a survey of the gains the difficulties and the prospects can be usefully made. Experimental Techniques.-It has proved to be extremely difficult to make accurate absolute measurements of absorption intensities. The intensities are usually defined as (1) where c is the absorbent concentration I is the path length of the beam through the absorbing material (Io)y and (Iv) are the initial and final intensities of the beam of frequency v (expressed in cm.-l in all subsequent equations) and the integration is over the complete band.Such a definition follows readily from the usual exponential low of absorption. The ex- perimental difficulties were first made apparent by the early measurements of Bourginl and Bartholomk2 Independently they measured the intensity of the vibration-rotation band of hydrogen chloride in the gas phase and obtained results which differed by a factor of four. The major reason for this was that for finite slit-widths the beam is not monochromatic and consequently the measured fractional absorption of the sample [(TO-T)/TO], at a given frequency setting Y generally differs from the true transmission in such a way that the measured absorption value is too low.B~urgin,~ Bartholomt5,2 Penner and we be^-,^ Wilson and Wells,5 and others Gc = 1 /cl Sin [(I O ) l m v Id 1nv D. G. Bourgin Phys. Rev. 1927 29 794; ibid. 1928,32,237. E. BartholomC 2. phys. Chem. 1933 b23 131. D. G. Bourgin Phys. Rev. 1928,31 503. S . S. Penner and D. Weber J. Chem. Phys. 1951 19 801 817 974 ibid. 1953 21 E. B. Wilson and A. J. Wells J. Chem. Phys. 1946 14 578. 649. 21 22 QUARTERLY REVIEWS have investigated the conditions under which these two values approach one another and how the true absorption can be evaluated with an instru- ment of limited resolving power. In the procedure of Wilson and Wells the measured integrated optical density Jlog, (TOIT) d In V divided by the concentration is graphed against the concentration and the plot extra- polated to zero concentration.It was shown that the limiting value of the integral for zero concentration is equal to Jlog, (Io/I)>y d In v if (a) the incident intensity I, does not vary over the slit-width and (b) the resolving power is high compared with the variations in the absorption coefficient. In Bourgin’s method [ f(T,/T) dv]/c is graphed against c and the ratio extrapolated as in the Wilson-Wells technique to zero concentration. However the curvature of the plot is far greater and the extrapolation consequently less accurate. Since the aim of absorption intensity measurements is usually to study intramolecular properties it is necessary to carry out studies on the gaseous phase where intermolecular interactions are reduced to a minimum.Unfortunately the removal of intramolecular interactions results in sharp vibrational-rotational absorption lines. As a consequence condition (b) is difficult to attain. In order that this condition should be satisfied the rotational bands must be collision-broadened by adding a high pressure of a chemically inert non-absorbing gas or for the study of weak absorp- tion bands by self-broadening at high pressures. The pressure-broadening is considered to be sufficient when an increase of total pressure produces no further change in the molecular extinction coefficient E = l/cZ loglo(lo/l),ax. However even when the individual rotational lines are sufficiently broadened to yield an overall smooth absorption curve the band contour may still have sufficiently steep gradients to result in low measured values of the absorbance.This is particularly the case with bands having strong sharp Q branches (corresponding to no change in the rotational quantum number J ) such as the out-of-plane deformation bands in aromatic sys- tems. The pressure required to produce broad Q branches may be exces- sively high and it is to be noted that in such cases the extrapolation pro- cedure still may not be strictly valid if condition (b) has not been fully met. Consequently the use of instruments of high resolving power is really required in such cases. At very high pressures the molecule is being subjected to excessive col- lisional perturbations which are often undesirable. Thus it has been shown that absorption by the infrared-inactive a, mode of methane can be induced in this manner,6 and many examples are now known of simultane- ous transitions in mixed gases at high pressures.‘ In a simultaneous transi- tion absorption occurs at a frequency v & vb where v and Vb are transi- tion frequencies for two different molecules and can be for two different R.Coulon B. Oksengorn J. Robin and B. Vodar J. Phys. Radium 1953 14 63. H. L. Welsh M. F. Crawford J. C. F. McDonald and D. A. Chisholm Phys. Rev. 1951 83 1264; J. Fahrenfort and J. A. A. Ketelaar J . Chem. Phys. 1954 22 1631. STEELE INFRARED INTENSITIES 23 chemical species. Such evidence indicates that pressure-broadening must be treated cautiously especially when dealing with weak bands and easily polarisable molecules. The sources of error in the Wilson-Wells and Bourgin procedures are so serious that efforts have been made to find alternative techniques.The dispersion of infrared rays has proved to be a very valuable tool in this connection since a vibrating electric moment in a molecule gives a con- tribution to the refractive index. Molecular vibrations are separable into normal modes each of which makes a contribution to the refractive index n of A i ( n - 1) =- where N is the number of molecules per ml. p is the molecular dipole moment,Qi is the ith normal co-ordinate vi is the frequency of the cor- responding vibration and v is that of the incident light (in cm.-l). (This formula known as the Kramers-Heisenberg formula assumes that the absorption line is infinitely narrow and has to be modified slightly for finite line widths). The infrared absorption intensity of a given fundamental band has been shown to be equal to (This formula is derived neglecting rotational quantisation.An exact summation of intensity over the rotational components of a parallel band of a symmetric rotor molecule* leads to a correction factor equivalent to multiplying the right-hand side of (3) by 2 B c [l + exp (- hv,/kT)] v [I - exp (- h v o / k ~ ) r + B the rotational constant is equal to h/8n2c IB where IB is the moment of inertia perpendicular to the axis of the top and c is the velocity of light. This factor is unlikely to lead to an error exceeding 5% in (ap/8Q)2 and is usually neglected on the excuse that the experimental uncertainty is generally of the same order of magnitude.) Thus the vibrational contribution to the refractive index is intimately related to the infrared absorption intensity and in fact these two pheno- mena are manifestations of the same property.Consequently absolute infrared absorption intensities can be deduced from dispersion studies. The particular advantage of the dispersion method as can be seen from equation (2) is that even for infinitely narrow absorption lines the change of the refraction with frequency is quite gradual. A typical refraction spectrum due to the R2-0 bands of H35Cl and H3'Cl is shown in Fig. 1,9 B. L. Crawford and H. L. Dinsmore J. Chern. Phys. 1950,18 1682. F. Legay Rev. Opt. (theor. instrum.) 1958 37 11. 24 QUARTERLY REVIEWS 2 I ‘ 0 0 9 x c P t - I - 2 -3 5 7 3 0 5725 5720 5715 FIG. 1. The vibration-rotation contribution to the refractive index by the R(2) bands of the 2-0 vibrationaL transitions of H35Cl and H3’Cl.The vertical lines indicated as R(2) represent the relative intensities of the corresponding absorption lines. and is compared with the corresponding absorption curve. It can be seen that the distance between opposite branches of the refraction curve is a function of the absorption intensity. The technique is only suitable at present for simple molecules with well-separated strong absorption bands. This is a very severe restriction but fortunately it is for such molecules that the Wilson-Wells procedure is most unsuitable. The results of the dispersion measurements generally compare quite favourably with those of the best absorption measurements and are usually though by no means always higher than their Wilson-Wells counterparts.An excellent sum- mary of measurements up to 1960 is given in ref. 10. Another recent technique capable of giving relatively accurate results is the curve-of-growth method.ll This involves making measurements at different path-lengths and allows the error due to finite slits to be eliminated if the band shape is known. It can be applied only if the individual rota- tional lines can be resolved which seriously restricts its applicability. Where it can be applied it is usual to assume that the lines can be des- lo J. H. Jaffe “Advances in Spectroscopy,” Interscience New York 1961 Vol. 2 p. 263. l1 S. S. Penner and €I. Aroeste J. Chem. Phys. 1955 23 2244. STEELE INFRARED INTENSITIES 25 cribed by the Lorentzian function. In such cases the technique would be expected to be of superior accuracy to the Wilson-Wells procedure.Consequently there was a great deal of consternation when the intensity of the 670 cm.-l band of carbon dioxide was measured in this way and a result obtained which was 50% higher than previous results.12 As pointed out by Kaplan and Eggers,12 this 670 cm.-l band is an extremely difficult band to study as far as the Wilson-Wells procedure is concerned since (a) it has a great deal of its intensity concentrated in a sharp Q branch (half-width ca. 0.35 cm.-l); (b) to measure it it is necessary to remove absorption due to atmospheric carbon dioxide; and ( c ) it lies in a range of the spectrum where sodium chloride prisms begin to absorb appreciably and where the dispersion of potassium bromide prisms is low. This means that all the serious problems characteristic of this technique are in force for this case.Crawford and his co-workers13 have remeasured the intens- ity by the Wilson-Wells procedure exercising great care to overcome these problems and have obtained a result very close to that of the curve-of-growth method (see Table 1). Also they pointed out that cakcula- TABLE 1. Measured intensities of 15p band of carbon dioxidc. Ref. 15 16 17 18 12 13 Intensity (103cm.2/mole) 7.40 6.28 5.41 6.02 8.07 8-09 Method C-0-G W-W W-W D C-0-G W-W C-o-G curve-of-growth. W-W Wilson-Wells. D dispersion. tions made by Kostkowski and B a d 4 on the functional dependence of the errors in measuring intensities of individual rotational lines should be applicable to measurements on sharp Q branches. Using Kostkowski and Bass’s results and estimating the pressure-broadened line-widths from collision theory they showed that the pressure-broadening in previous determinations of the intensity (at total pressures of up to 5 atm.) had been inadequate.At the pressures of about 68 atm. that they had employed the error resulting from slit-widths should be negligible. Also they had failed to observe any induced absorption. These careful measurements indicate that the Wilson-Wells procedure is capable of reasonable accuracy (within 2-3 %) if sufficient care is exercised. Interpretation of Results.-The interpretation of the measured intensities in terms of bond properties is best appreciated by considering what can be deduced with and without assumptions from the intensity measurements. Equation (3) is derived on the assumption that the dipole moment p can l2 L.D. Kaplan and D. F. Eggers J. Chem. Phys. 1956,25 876. l3 J. Overend M. J. Youngquist E. C . Curtis and B. Crawford J . Chem. Phys. 1959 l4 H. J. Kostkowski and A. M. Bass J. Opt. Soc. Amer. 1956 46 1060. l5 L. D. Kaplan J. Chem. Phys. 1947 15 809. l6 A. M. Thorndike J. Chem. Phys. 1947 15 868. l7 D. F. Eggers and B. L. Crawford J. Chem. Phys. 1951 19 1554. 30 532. Values reviewed by 0. Fuchs 2. Physik 1927,46 519. 26 QUARTERLY REVIEWS be expanded as a Taylor series in terms of displacements from the equilibrium positions and all but the first derivatives can be neglected. That is p = po -I- 2 ( a ~ / a Q ~ ) ~ Q k -/- higher terms (negligible). k Q k represents the molecular distortion in the vibration k (i.e. normal co- ordinate for k).This is the assumption of electrical harmonicity which is true only to a first approximation. The intensity of infrared combination bands ought to be zero in this approximation. This is certainly not so but the intensities are usually far less than those of fundamentals unless a combination band gains intensity from a fundamental of the same sym- metry by resonance. This confirms the validity of the assumption. The error involved is certainly much less than the present experimental errors and those which are to be discussed later arising from the uncertainty in the normal co-ordinate Q. If the molecule has any symmetry the vibrations can be separated into independent groups each group being characterised by the behaviour of its constituents towards the symmetry elements.This means that the normal co-ordinates Qk separate according to this behaviour. For example in carbon dioxide there are two non-degenerate vibrations and one doubly degenerate vibration. The linear molecule has three planes of symmetry mutually perpendicular and passing through the carbon nucleus. This also implies a centre of symmetry and rotation axes but a consideration of the symmetry of the vibrations with respect to the planes suffices for our present purpose. Each vibration must be symmetric or antisymmetric with respect to a particular plane. If a vibration is sym- metric with respect to the XZ and YZ planes (axes defined in Fig. 2) then i 0-2 Y FIG. 2. The vibrational modes of carbon dioxide and the definition of the Cartesian axes. clearly this cannot involve movements of the nuclei in the 2 direction.Consequently only CO stretching motions belong to the symmetry classes involving these symmetry characteristics. In addition the CO stretching STEELE INFRARED INTENSITIES 27 vibrations must be symmetric or antisymmetric with respect to the X Y plane. This means that the CO bonds must vibrate either in phase (sym- metric stretch) or out of phase (antisymmetric stretch). Similar reasoning shows that the only deformation which can be antisymmetric with respect to either the XZ or the YZ plane is that of the 0-C-0 angle. Thus in this simple case the normal co-ordinates are apart from normalisation factors dr + 4 r 2 dr - dr2 and da. In general the symmetry of Qk and hence of ap/aQk is known but in solving for the dipole gradients from the measured intensities using equation (3) there are sign ambiguities arising from taking the square root of the intensities.Furthermore the exact form of the vibrations Qk must be determined before any further inter- pretation of the gradients is possible. That is it is necessary to obtain a relationship between the normal co-ordinates Q and a set of co-ordinates such as Cartesians which are defined with respect to the molecular axes. Provided that the potential energy can be expressed as a function of all possible distortions of the molecule molecular-vibration theory will yield the required relationship as well as the vibration frequencies. In order to know the potential energy it is sufficient to know the force field i.e.,the force constants connecting all atoms in the molecule. Unfortunately these are known with precision for very few molecules.A simple example is that for the harmonic oscillator for which the vibrational frequency v is given by 1 2 n v = - J ( k / p ) and V = &q2 (4) where k is the force constant for the distortion q and p is the reduced mass of the system. Such equations describe to a first approximation the vibrational motions of a diatomic molecule. Purely theoretical approaches to evaluating the force constants of the system are impossible at present except for the simplest of molecules. Force constants have been calculated for a number of simple systems such as LiHI9 C-H,20 CH4 (C-H stretch),21 and 0,22. Except for diatomic molecules there are more quadratic force constants than fundamental vibrational frequencies. Thus for the non- linear triatomic system XYX a complete description of the potential energy arising from molecular deformations requires a knowledge of four force constants-those for the X-Y stretch the XYX deformation the interaction between the X-Y stretches and between the stretch and angle motions-whereas there are only three fundamental vibrational frequencies.(The number of vibrational frequencies is 3N - 6 for a non- linear molecule or 3N - 5 for a linear molecule). For molecules with a high degree of symmetry certain of the fundamental vibrations have the l9 A. M. Karo and A. R. Olsen J. Chem. Phys. 1959 30 1232. 2o J. Higuchi J. Chem. Phys. 1954 22 1339. 21 R. G. Parr and A. F. Saturno unpublished data; I. M. Mills Mol. Phys. 1958 22 A. Meckler J. Chem. Phys. 1953 21 1750. 1 99 107. 28 QUARTERLY REVIEWS same frequencies i.e.they are degenerate. As the number of atoms in- creases and the molecular symmetry decreases the situation becomes rapidly more unfavourable. Clearly additional sources of experimental data are needed in order to deduce the force field. By means of isotopic substitution the harmonic vibrational frequencies are altered without affecting the electronic binding. By this expediency it is possible to obtain further sets of experimental data from which to deter- mine the force constants. At first it would appear that M isotopic sub- stitutions would yield Mx sets of data where x is the number of funda- mental frequencies. In practice this is not so. There are several reasons for this. First whilst the molecular vibrational frequencies are properties of the molecule as a whole it is well known that many bonds vibrate almost independently of the remainder of the molecule.Thus >X-H stretching modes interact only very weakly with other modes. This clearly means that isotopic substitution of such atoms will not give significant data on the interaction terms which do not involve the X-H stretching motion. Secondly whilst all the vibrational frequencies may change on isotopic substitution it may be found that all changes are not independent. Vibra- tional theory shows that the product of the vibrational frequencies of any symmetry class are related by the geometry of the molecule and the masses of the atoms to the product of the equivalent vibrations of an isotopically substituted Such internal relationships reduce the number of independent equations relating frequencies to force constants.A third limitation arises from the extremely small changes in the majority of the vibrational frequencies which result from isotopic mass changes of atoms other than hydrogen. This insensitivity of the vibrational frequencies to the isotopic masses drastically restricts the usefulness of the observed data. Frequently all the vibrational frequencies may prove quite insensitive to a particular interaction force constant thus making the uncertainty in the value of that constant large compared with its actual magnitude. An inter- esting case of this type has been discussed by Li~~nett.~* The two stretching vibrations of HCN belong to the C symmetry class and may be considered independently of the angular deformation frequency of the 7~ class.Writing the stretching part of the potential energy as 2v = k + k2(drC$ + 2k, (&d @rcN) and using the values of k and k as determined from HCN and DCN it may be shown that a change in the interaction constant kI2 from 0 to 1 x lo5 dynes/cm. results in a change in the calculated stretching frequencies of HC14N and HC15N of only 1.7 and 1-1 cm.-l whilst for DCN the corresponding changes are 100 and 74 cm.-l. The actual value of k12 is near -0.4 x lo5 dynes/cm. Clearly the constant k12 contributes little to 23 0. Redlich 2. phys. Chem. 1935 b28 371; see also W. R. Angus C. R. Bailey J. B. Hale C . K. Ingold A. H. Leckie C. G. Raisin J. W. Thompson and C. L. Wilson. f. 1936 971. 24 J . W. Linnett A m . Reports 1952 49 8. STEELE INFRARED INTENSITIES 29 the potential energy of HC14N and HC15N and would be difficult to estimate from the vibrational frequencies of those systems.The reason why the frequencies of DCN are so much more sensitive to k12 is that the CD stretching frequency near 2320 cm.-l is much closer to the stretching frequency of the CN group (at 2089 cm.-l in HCN) than is the CH frequency of 3310 cm.-l. If we are to arrive generally at a realistic force field and hence at a good description of the vibrational distortions we must seek additional sources of information about the force constants. Such information can be ob- tained in principle from the magnitudes of vibration-rotation interactions and centrifugal distortions from mean-square vibrational amplitudes as determined by electron diffraction and in certain circumstances from absorption intensity studies.According to the Born-Oppenheimer approxi- mation electronic vibrational and rotational motions are independent of one another for non-degenerate vibrational states. For example the rotational energy levels of a spherical rotor (e.g. CH, SF,) can be written as ( 5 ) where Erot. is the rotational energy h is Planck’s constant and B is the moment of inertia about any axis. Hence since AJ = 1 for the P and R branches of a vibrational band we have Erot./h = BJ (J t I) A Erot.lh = 2 BJ (6) which is independent of the vibrational and electronic states. In the case of a degenerate vibrational band the rotational spacings in the R (AJ = + 1) and the P (AJ = - 1) branches are different as a result of vibration- rotation interaction. The rotational spacings are now 2B (J + Ci) and 2 4 (J - Ci) respectively.ti is the magnitude of the angular momentum arising from the interaction and may be expressed in terms of the potential constants and the masses. This has been done in algebraic form for many of the more important types of vibration of simple molecules.25 Clearly each ti value gives an extra relationship between the force constants and the result of an observation. Unfortunately Coriolis constants which is the name given to the vibration-rotation coupling parameters can only be determined with reasonable precision for small molecules. In a similar manner the change in rotational spacing with changes in the rotational parameter J can be related to the force constants and molecular para- meters. This effect of Centrifugal distortion has proved of little value owing to the rather large uncertainties in the observed values.In principle it is possible to determine from the electron-diffraction patterns of gases the mean-square amplitudes of bond and angle vibrations as well as the bond and angle values themselves.26 These amplitudes are 23 G. Herzberg “Infrared and Raman Spectra of Polyatomic Molecules,” Van Nostrand New York 1945. 26 J. L. Karle and J. Karle J. Chem. Phys. 1949 17 1052. 30 QUARTERLY REVIEWS readily evaluated from the force field and have been used to test assumed field^.^'^^^ The precision of the experimental data is again low. Even so such calculations have served to show inadequacies of assumed fields. The mathematical difficulties involved in determining the set of force constants which give the most satisfactory fit between observed and cal- culated frequencies distortion constants etc.are very formidable for all but the very simplest of molecules. Electronic computers have been pro- grammed by several groups of research workers to derive optimum sets of force constant^.^^-^^ Early optimism in obtaining good fields in this way was rapidly dispelled when it was discovered that further mathematical problems were of prime importance. The major problem arises from the fact that the solution of a vibrational problem involving n vibrational frequencies involves the solution of an equation of order n to which there are generally n solutions. In the computing procedure a guessed set of constants is used to derive a calculated set of frequencies distortion con- stants etc.The difference between the calculated and observed sets are then used to derive an improved set of force constants by a perturbation tech- nique. It was expected that if a reasonable set of force constants was chosen initially from previous experience with simpler molecules then the pertur- bation would lead to convergence on a unique set of improved constants which would yield a description of the vibrational distortions close to the truth. In practice it was found that the perturbation problem was often unstable and the perturbed constants diverged to impossible values. This usually arises from the differences between the calculated and observed frequencies being too large for a perturbation treatment and can some- times be overcome by taking small fractional improvements i.e.iffi is a typical input constant and J3. is its “improved” value then using fi + (f3 - fi)x where x < 1 in the next cycle may remove the divergence of the constants. Occasionally the cause of the divergence is more deep-seated and arises from an unstable situation in the perturbation solution due to a special case of ill-conditioned beha~iour.~~ Another frequent occurrence is that the convergence of the force constants terminates at a stage of oscillation. This behaviour has been shown to correspond to a set of com- plex solutions. Such complex solutions may arise as a result of simplifying assumptions made in the force field to make the problem tractable. It has been shown however that the oscillations occur about the real compo- nents of the converged set. Finally and perhaps most disturbing of all it has been found that in certain cases slightly different initial guesses lead to a different set of converged solutions.32 Various criteria have been de- scribed to test the validity of the final answers but the uncertainty in the 27 D.A. Long and E. A. Seibold Trans. Faraday. Soc. 1960,56 1105. 28 D. E. Mann T. Shimanouchi J. H. Meal and L. Fano J. Chem. Phys. 1957,27 29 J. Overend and J. R. Scherer J. Chem. Phys. 1960,32,1289. 30 D. A. Long R. B. Gravenor and M. Woodger Spectrochim. Acta 1963 19 937. 31 D. A. Long and R. B. Gravenor Spectrochim. Acta 1963 19 961. 32 Joan Aldous and I. M. Mills Spectrochim. Acta 1962,18 1073. 43. STEELE INFRARED INTENSITIES 31 reliability of the distortional co-ordinates remains a major obstacle to progress in the interpretation of absorption intensities.Once the force field has been deduced and hence the form of the normal co-ordinates determined or approximated the next step is to visualise what the resulting ap/aQj mean. The molecular dipole gradient will generally be difficult to visualise and to utilise. Since physical chemists almost invariably find life a great deal easier if they can translate molecular properties into comparatively simple directed and more-localised pro- perties the next step is to find a suitable set of assumptions that will yield the desired simplifications. The obvious assumptions are those that will decompose the molecular properties into the sum of a set of bond pro- perties and are generally chosen as (a) the stretching of a bond by dr produces a change of dipole moment along the bond of (aplar) dr; (b) the deformation of a bond through an angle dB produces a dipole change (ap/aB)dB perpendicular to the bond and in the plane of movement ; (c) changes in one bond do not result in changes in another bond except when this is geometrically necessary.The test of the validity and usefulness of these assumptions is whether any or all of the following criteria are found to hold and if not whether anything positive can be deduced from the discrepancies. (i) Values of the deduced bond moments and gradients in different molecules are comparable. (ii) Values of given gradients and moments derived from different sym- metry classes of the same molecule are equal. (iii) The perpendicular gradients to any bond are negligible. (iv) Values of the bond dipoles derived are comparable with the static dipoles as measured by other methods.TABLE 2. Efective bond dipole moments and derivatives for C-H bonds. Compound Symmetry Dipole- Effective Measure- Ref. Class moment bond dipole ment derivative moment @/A) (D) CH4 f 2 50.83 'f 0.37 w-w 33 CzH* C2H2Dz b2u 50.26 0-42 w-w 35 } a1,e -0.61 0.33 w-w 34 CHSD CHZD CD3H C2D4 b3U 0.23 =F 0.60 bl u 0.67 33 I. M. Mills Mol. Phys. 1958 1 107. 34 R. E. Hiller and J. W. Straley J. Mol. Spectroscopy 1960 5 24. 35 R. C. Golike I. M. Mills W. B. Person and B. L. Crawford J. Chern. Phys. 1956 25 1266. 32 QUARTERLY REVIEWS TABLE 2.-continued. Compound C2H2 C2D2 C2H2 C2HD C2H6 c6H6 CH,CI CH,Br CH,I NH3* PH3 SiH, SiD Symmetry Class C U + ZU+ n u c u + n u F) a2u e u e1u a2u a1 e a1 e a1 e 01 e a1 e f2 f2 Dipole- moment derivative 0.8 0.78 0.87 0*79(H) 0*78(D) +1-24 &0*75 + 0.45 + 1.00 + 0-24 + 0.98 +0.19 + 0.73 0.61 0.16 1.2 0-8 31-23 5 1-44 4-0.13 Effective bond dipole moment 1 -05 0.89 I -05 0.9qH) 0*92(D) F 0.23 F 0.26 - 0.3 1 - 0.61 +0.17 + 0.27 - 0.48 + 0.42 - 0.46 1-04 0.52 - 0.45 1-58 Me as u r e - ment D w-w w-w w-w w-w w-w w-w w-w W-W w-w w-w w-w w-w Ref.36 37 37 37 40 38 39 39 39 41 41 42 43 W-W Wilson-Wells method. D dispersion method. * Introduction of apu.,,./2a and assumption of complete bond following leads to a, P ~ . ~ . = 0 . 7 4 ~ and ~ N H = -0.650; e ptl.Il. = 0 . 7 0 ~ and ~ N H = - 0 . 6 8 ~ . It can be seen from Tables 2 and 3 that criteria (i) (ii) and hence (iv) certainly do not hold though there is a certain amount of consistency between the gradients and dipoles for similar molecules and some trends are apparent.The situation is particularly bad for carbon-hydrogen bonds. It is from an analysis of these inconsistencies that a great deal of useful information and knowledge of molecular structure has been gleaned. The first step in such an analysis must be a consideration of the four major reasons for the failure of the model. 36 R. L. Kelly R. Rollefson and B. S. Schurin J . Chem. Phys. 1951,19 1595. 37 D. F. Eggers I. C. Hisatsune and I. Van AIten J . Phys. Chem. 1955 59 1124. 38 H. Spedding and D. H. Whiffen Proc. Roy. Soc. 1956 A 238,245. 39 A. D. Dickson I. M. Mills and B. L. Crawford J . Chem. Phys. 1957 27 445. 40 I. M. Nyquist I. M. Mills W. B. Person and B. L. Crawford J . Chem. Phys. 1957 41 D.C. McKean and P. N. Schatz J . Chem. Phys. 1956k 24 316. 42 D. F. Ball and D. C . McKean Spectrochim Acta 1962 18 1019. 43 I. W. Levin and W. T. King J . Chem. Phys. 1962 37 1375. 26 552. STEELE INFRARED INTENSITIES 33 TABLE 3. Eflective bond dipole moments and derivatives for X-F bonds. Compound CF CH3F CF3Br C2F6 C6F6 ;:::: } p-C6H2F4 BF3 NF3* SF6 SiF Symmetry class fi a1 a1 e a2 u eU el U 4 U bl u ef az" a1 e flu f 2 Dipole moment derivative 5.99 or 3.71 4.9 or 3.4 4.0 + 8.1 +4*1 + 3-4 + 3.8 + 5.0 + 6.5 + 5.2 h4.0 or 76.1 + 1.5 to +2-0 or 3.3 ca. $4.7 3.85 3.3 or 7-5 Effective bond dipole moment (4 1.11 or 2.98 1.1 or 2.4 + 2-8 +0*5 ( ~ 5 ) + 2.2 $1.6 + 0.7 1.6 1-3 + 1 * 1 (v6) 12.6 or ~ 0 . 9 1.7 + 0.9 to +1.2 0 to 0-3 2.65 3.3 2.3 Measure- ment D w-w w-w w-w w-w w-w w-w w-w w-w w-w w-w w-w Ref.44 45 46 47 48 49 50 50 51 52 53 53 D dispersion method. W-W Wilson-Wells method. * Introduction of apU.Jaa and assumption of complete bond following for the u1 class leads to pU.p.- 1.7 or 1 . 2 ~ ; p ~ - 1 . 1 ~ . (a) In criterion (i) it is implicitly assumed that the charge distribution in the bond XY is always the same and always alters in the same manner. It is common experience that all XY bonds do not have the same chemical reactivity apart from steric effects and since chemical reactivity is inti- mately related to the valence-shell electronic structure of the bonds this contradicts the above assumption. Furthermore all XY bonds do not have 44 B. Schurin J. Chem. Phys. 1959 30 1. 45 P. N. Schatz and D. F. Hornig J . Chem. Phys. 1953 21 1516. 46 G.M. Barrow and D. C. McKean Proc. Roy. SOC. 1952 A 213,27. 47 W. €3. Person and S. R. Polo Spectrochim. Acta 1961 17 101. 48 1. M. Mills W. €3. Person J. R. Scherer and B. Crawford J. Chem. Phys. 1958,28 49 D. Steele and D. H. Whiffen J. Chem. Phys. 1958 29 1 194. 50 D. Steele and D. H. Whiffen Trans. Furaday SOC. 1960 56 177. 51 D. C. McKean J. Chem. Phys. 1956,24 1002. j2 P. N. Schatz and I. W. Levin J. Chem. Phys. 1958 29 475. 53 P. N. Schatz and D. F. Hornig J. Chem. Phys. 1953 21 1516. 851. L 34 QUARTERLY REVIEWS the same bond length but this in turn depends on the environment of X and Y. Thus the CH bond decreases in length as the local hybridisation at the carbon atoms takes on less p and more s character. Thus this is a further manifestation of the variation of the electronic structure of the bond between two given atoms.(b) The effect of lone-pair electrons on the dipole change during a vibration is ignored. As the molecule vibrates the hydridisation of the orbitals will generally change and consequently affect the infrared ab- sorption. Burnelle and Coulson62 have shown using wave-mechanical TABLE 4. Efective bond dipole moments and derivativesfor various bonds. Com- Symmetry Bond pound class C6H6 el u c160180 c ClCN c n BrCN c n CH3CN a e HC1 c c 17 SO2 b a1 c-c c=o c=o c=o c=o c=o C r N CEN 12CrN 13CrN C r N C=N C r N CGN C-N H-Cl C=N C f N s=o s=o Dipole- moment derivative 0.0 5.79 6.0 5.85 (D/& 0.585 0-595 0.605 0-3 to 0.7 0.5 to 0.8 1.21 0.66 4.17 f 2.0 or &4.3 Effective Measure- moment bond dipole ment ( D ) w-w w-w w-w w-w 1 *33 w-w 1.33 C-O-G w-w 1.2 w-w w-w 1.4 1.3 W-W w-w w-w w-w w-w 1.3 1.8 1.3 f l .2 W-W Wilson-Wells method. C-o-G curve-of-growth method. 54 D. F. Eggers and C. B. Arends J. Chem. Phys. 1957 27 1405. 55 T. Miyazawa J. Chem. Phys. 1958,29 421. 56 J. W. Schultz and D. F. Eggers J. Mol. Spectroscopy 1958 2 113. 57 R. W. Hendricks and D. F. Hornig see ref. 58. 58 D. F. Hornig and D. C. McKean J . Phys. Chem. 1955 59 1133. 59 A. V. Golton D.Phi1. Thesis Oxford 1953. 6 o S. S. Penner and D. Weber J. Chem. Phys. 1953 21 649. 61 G. E. Hyde and D. F. Hornig J. Chem. Phys. 1952,20 647. 62 L. Burnelle and C. A. Coulson Trans. Furaduy SOC. 1957 53,403. Ref. 38 54 16 17 13 12 55 56 57 58 59 60 61 33 STEELE INFRARED INTENSITIES 35 calculations of Ellison and Shu1P3 and Higu~hi,~* that the lone-pair contribution to the molecular-dipole change associated with the bending vibrations of H,O and NH3 is nearly as large as the contribution resulting from the bond deformations.Thus for HzO apL/aa - 1 . 4 1 ~ and apB/aa - -2.13~ where pL and pB are the lone-pair and bonding con- tributions respectively to the molecular dipole. That this must be the case can be seen from the fact that the lone-pair contribution to the molecular dipole is calculated to be 1.69~ for H,O. In the deformed state where the oxygen and hydrogen atoms are collinear the lone-pair contribution must be zero by symmetry. Several of the discrepancies between the effective bond moments given in Tables 2 3 and 4 can be explained by similar reasoning to the above. Thus in boron trifluoride which in its equilibrium position is planar there is a vacant p orbital associated with the boron atom and perpendicular to the plane of the molecule.During the symmetrical out-of-plane bending vibration rehybridisation of the B-F bonding electrons at the boron atom I -\ I \ ‘ I ‘ - - I FIG. 3. Electron rehybridisations in the p a orbitals during the transitions of symmetry (a) aN2 of boron trifluoride; (b) a21 of benzene. results in electron-flow into an orbital on the opposite side of the original atomic plane to the fluorine atoms [see Fig. 3(a)]. This makes the fluorine atoms appear to carry less negative charge than they actually do. In the e’ class the F-B-F angular deformation cannot result in electron flow into the vacant p z orbital. In agreement with this reasoning the effective BF dipole as deduced from the a,” class is only 1 .7 ~ compared with 2 . 6 ~ as deduced from the e’ class. In the out-of-plane CH deformation of benzene a similar effect occurs in the a, out-of-plane deformation. The p z orbital is fully occupied in this case but rehybridisation at the carbon atom takes place in the form of s character being introduced in the p z orbital (Fig. 3(b)]. That this must be so is readily apparent from the fact that when the HCH angles are deformed to 108” the carbon hybridisation must be sp3 compared with sp2 for the planar configuration. The effect 6s F. 0. Ellison and H. Shull J . Chem. Phys. 1953 23,2348. 64 J. Higuchi J. Chem. 1956 24 535. 36 QUARTERLY REVIEWS once again is to make the substituent appear less negative. Since the hydrogen atoms in benzene are known to be at the positive end of the CH dipole,65 the numerical value of the effective dipole should be greater for the a 2 class than for the in-plane el class.The observed values are 0 . 6 1 ~ and 0 - 3 1 ~ respectively. Clearly an adequate theory of infrared intensities must incorporate terms of the nature of 8pPz/&. Coulson and Stephen66 have shown that the variations in the deduced effective dipoles in benzene acetylene and ethylene are compatible with reasonable degrees of rehybridisation and bond following (see below). However they were unable to deduce the relative contributions of the two effects. (c) Hybridisation changes can also occur as a bond stretch. If we con- sider the CH stretching in methane and assume that in the extreme case we have a CH radical and an H atom then it can be seen that rehybridisa- tion of the orbitals around the carbon atom must have occurred.The configuration of the CH radical is still uncertain but it seems probable that it is planar. In this case the hybridisation at the carbon atom will be sp2 as compared with sp3 in CH,. Though in both the extreme cases i.e. those of the unperturbed CH molecule and of a CH radical and an H atom there is no total dipole moment it seems necessary to assume that there is a dipole gradient during the vibrational motion. This gradient can be expected on the above grounds to be different from that in say the vibrational motion in which the stretching of one CH bond is out of phase with the remaining two (v of symmetry classf,). (d) A bond is usually thought of as being directed along the line con- necting the bonded atoms.This is frequently a false picture particularly for vibrationally distorted configurations. Wave-functions are not usually localised in one bond. Indeed the orthogonality of the wave-functions generally forbids this. By their delocalisation these wave-functions are not directly related to the usual conception of chemical bonds. Burnelle and Cou1son62 transformed the accurate SCF-LCAO wave-functions for H20 and NH so that the resulting wave-functions satisfied the following conditions (a) that they were orthogonal; (b) that the orbitals associated with identical bonds should be equivalent; and (c) that the lone-pair orbitals should contain only orbitals of the central atom. The resulting picture of the molecular orbitals showed that the hybrid orbitals at the central atom are not in general directed along the bond direction.This means that the bonds may be considered to be bent and to have dipole gradients perpendicular to the internuclear axis. The individual contributions to the dipole moment of H,O are for an inter- bond angle of 105" pL = 1 . 6 9 ~ pB = 0.20D and pBy = - 0 - 3 7 ~ where pL pB and pBY are the contributions due to the lone-pair electrons the 65 (a) R. P. Bell H. W. Thomspon and E. E. Vago Proc. Roy. SOC. A 192 498; (6) A. R. H. Cole and H. W. Thompson Proc. Roy. Suc. 1951 A 208,341. 66 C. A. Coulson and M. J. Stephen Trans. Furuduy SOC. 1957,53 272. STEELE INFRARED INTENSITIES 37 bond electrons in the direction of the internuclear axis and the bond electrons in a direction perpendicular to the internuclear axis respectively.If the HOH angle is deformed the resulting molecular dipole gradient of -@72~/radian is derived from the following contributions = 1-41 D/Radian; apBZ/aa = -0.20 D/Radian; and apBy/&t = 1-93 D/Radian. The transverse moment is very sensitive to the inter-bond angle and its derivative is the major contributing term to the absorption in- tensity. An analysis of the absolute absorption intensities of the infrared bands of 1 ,2,4,5-tetrafluorobenzene50 showed that the dipole gradient ap/ar,, lies along the internuclear axis within the experimental error. However the asymmetry of the CF bond in this compound is not very pronounced and it is not unreasonable to expect the above result. The Polarity of the Dipole Gradients.-According to equation (3) the absorption intensity is proportional to the square of the dipole gradient.In the preceding section it has been assumed that in solving for the gradient the sign of the square root of the intensity is known. In fact the question of these signs introduces what is frequently a serious uncertainty into the interpretations. The seriousness of this problem can be ap- preciated from the fact that if there are n fundamental vibrations in a given symmetry class then there are 2" possible ways of choosing the sign combinations leading to 2" distinct solutions for the bond parameters. Isotopic substitution should leave the dipole gradients unchanged whilst changing the form of the vibrational modes. The sets of dipole gradients with respect to bond co-ordinates-or with respect to combinations of the co-ordinates in the form of symmetry co-ordinates-will not all be con- sistent with the observed intensities of the other isotopic system.Generally there are rarely more than three sets which yield acceptable values for the intensities of the other isotopic system. A choice between sets acceptable by the above criterion is usually made on the basis of lack of credulity of the authors to certain of the derived gradients. When no isotopic data existed sign choices have often been made on the basis of one set giving bond gradients and dipoles which were in line with values for similar molecules. Clearly this is not an acceptable criterion especially as the aim has usually been to discover if the gradients and dipoles were indeed com- parable for bonds of a given type in similar molecules.Blatant cases of this practice have been excluded from the Tables. As an example of the above technique the CN dipole gradient for cyanogen derived from the infrared-active CEN stretching vibration of 12CN12CN is compared in Table 5 with those derived from the ''almost symmetric" CN and CC stretching vibrations of 13CN12CN.56 Owing to the presence of normal cyanogen in the heavy-isotopic system the intensity of the antisymmetric mode was not measured. In this case it is very clear that the ap/aQ values must have the same sign. Occasionally the sign of the square root in equation (3) can be deter- 38 QUARTERLY REVIEWS TABLE 5. Dipole-moment derivatives for cyanogen D/A Dipole-moment (12CN) Relative signs for 12CN13CN derivative ap/aQ values aplar(cN)l &0.585 same k0.595 different 0-41 6 aPlar,c,l ‘f 0.585 same ‘f 0.607 different &0*718 aPlar(c-,) zero by symmetry same ~ 0 4 0 0 3 different TO-107 mined from vibration-rotation interaction studies.Thus Hermann and WalW7 were able to show that for a diatomic molecule the ratio of intensities of corresponding rotational absorption lines in P and R branches is proportional to (1 + 4y8J)J where y = 2B,/ve 8 = [po/((?p/ar)]l/re and J is the rotational quantum number of the initial state. B is the rota- tional constant for the equilibrium bond length re; po is the molecular dipole; and ap/& is the dynamic dipole gradient. If the sign of p0 is known then the sign of the dipole gradient can be deduced. In this way they were able to show that ap/ar for HCl has the same sign as po.Clearly it is also possible to use the above technique to evaluate the ratio of the magnitude of the gradient to the static dipole. Thus p/(+/ar)r for LiH has been determined as -1.8 & 0 . 3 ~ . ~ * Clearly a prerequisite of this tech- nique is the existence of an equilibrium molecular dipole. The Hermann- Wallis theory has been extended to the case of linear polyatomic mole- c u l e ~ ~ ~ (group C,,) but no application to intensity interpretation has yet been made. that the intensities of the out-of-plane deformations in various alkyl- and halogen-substituted benzenes indicate that the effective CH dipole is of opposite sign to the effective halogen dipole. As it is reasonably certain that the halogen atom is at the negative end then this implies that the hydrogen atom is at the positive end of the CH dipole in benzenes in the out-of-plane deformations.Since out-of-plane deformations have the effect of making the dipoles appear less positive the hydrogen atom must also be at the positive pole of the static bond. Interaction between two vibration-rotation bands can occur if the sym- metry of the vibrations and of a principal rotation axis bear a certain simple relationship to one another. Specifically the Coriolis force on each atom is of magnitude 2ma Va w sin + where YlZa is the mass of the atom w is the angular velocity of the co-ordinate system with respect to a fixed co-ordinate system Va is the velocity of atom “a” and+ is the angle between the axis of rotation and the direction of Va. The force is directed at right- angles to the direction of Va and to the axis of rotation.If the forces on the T. C. James W. G. Norris and W. Klemperer J. Chem. Phys. 1960,32,728. Bell Thompson and Vago and Cole and Thompson have 67 R. Hermann and R. F. Wallis J. Chem. Phys. 1955 23 637. 69 G. A. Gallup J. Chem. Phys. 1957 27 1338. STEELE INFRARED INTENSITIES 39 atoms constituting the molecule which arise from a vibration j and from rotation about a specific axis m have the same symmetry as a second vibration k which is not too far removed in frequency fromj then the two vibrations will interact. The effect of this interaction on the vibrational frequencies is to make the P and R rotational band spacings different from one another (apart from the small effect arising from centrifugal distor- tion). This Coriolis interaction has been mentioned previously in connec- tion with the dependence of the 5 constants on the potential constants.In addition to the frequency effect the intensities are also altered. In the approximation of no vibration-rotation interaction the lines in the P and R branches arising from transitions from the same initial state have equal strengths. The effect of the Coriolis interaction is to increase (or decrease) the R-line intensities of the higher-frequency band and also the P-line intensities of the lower band whilst decreasing (or increasing) the intensi- ties of the other AJ = &- 1 lines. Which in fact occurs depends on the sing of Cjkz (ap/aQj)z(ap/aQk)g where the j and k subscripts specify the two vibrations. The sign of cjk is generally determinable and hence from the intensity asymmetry of the bands the relative signs of the two dipole transitions can be deduced.70 This new technique has considerable promise.The Effect of Change of State on Intensities.-Recently there has been a renewed interest in the intensities of absorption bands in condensed phases. Until the last two or three years it was believed that intensity changes arising from intermolecular interactions would be small except where structural changes took place or where definite bonds were formed be- tween molecules. Examples of these special cases are the crystallisation of trans-dichloroethane from a mixture of the trdnS- and gauche-forms and the formation of intermolecular hydrogen bonds in hydroxyl-containing compounds. Considerable theoretical work has been carried out to evaluate the magnitude of the intensity changes in the absence of ap- preciable intermolecular interaction~.~l-~~ The basic theory is encompassed in the e q ~ a t i o n ~ ~ y ~ ~ (7) rliq (n2 + 2)2 r g a s 9rr ' which is derived for an oscillating dipole in a spherical cavity in a medium of refractive index n.This equation implies that the intensities ought always to be greater in a condensed phase than in the gaseous phase. Experi- mental work until very recently was restricted to isolated absorption bands-isolated in the sense of a single band of a certain molecule. Equation (7) and its refined forms have met with very limited success. - - - 7 0 I. M. Mills unpublished work. 71 N. Q. Chako f. Chem. Phys. 1934,2 644. 72 S. R. Polo and M. K. Wilson f. Chem. Phys. 1955 23 2376. 73 J. van Kranendonk Physica 1957 23 825.74 A. D. Buckingham Proc. Roy. Sac. 1960 A 255 32. 75 L. Onsager f. Amer. Chem. Soc. 1936 58 1486. 40 QUARTERLY REVIEWS Intensity data now exist for all infrared active bands of in vapour liquid and solid phases. The results are very disturbing. The in- tensity changes are far greater than can be accounted for by dielectric changes or by the expected magnitudes of intermolecular perturbations. Similar results have been reported for ethylene.79 The results for benzene are shown in Table 6. These results pose a fascinating theoretical problem TABLE 6. Absolute intensities of benzene trdnSitiOnS in various phuses ( 103cm2/mole). Band (crn.-l) r.cl rt r s 3060 1 -95 1 *45 0.65 1480 0.878 1 -29 2.56 1036 0.850 1 . 1 1 1 *69 673 12.95 14.1 13.6 on which no headway has been made at the present time and which is certain to attract considerable attention from theoretical chemists and physicists in the future.Applications of Absolute Intensity Measurements to Determination of Chemical Structure.-The intensities of some absorption bands character- istic of certain groupings such as those generally associated with the stretching of -C= N -C = 0 -C-H ( in hydrocarbons) and -OH bonds have been correlated in an empirical manner with the structure of the attached group. In many cases it is possible to deduce the number of absorbing centres in an unknown molecule. This aspect of intensity measurement has been thoroughly reviewed by T. L. Brown.80 It is inter- esting that such empirical correlations actually do exist. The so-called characteristic group vibrations are rarely confined to one bond and the mode may change quite drastically for small structure changes without the frequency being much affected.It is likely that the main reason for the success of these empirical correlations is that the groups studied usually have very large dipole gradients associated with their stretching motions so that participation in the vibration by other parts of the molecule is relatively unimportant. Even so these correlations imply that the stretching gradients of these groups are reasonably constant. Very few detailed studies of molecules involving these groupings have been carried out at present. As a consequence of the interpretational difficulties of intensity measure- ments absorption intensities have been little used in elucidating molecular structure apart from the empirical approach mentioned above.The following examples show that in special circumstances absolute in- tensity measurements can be used in structure determinations. 76 D. A. Dows and A. L. Pratt Spectrochim. Acta 1962 18 433. 77 I. S. Hisatsune and E. S. Jayadevappa J. Chem. Phys. 1960 32 565. 78 J. L. Hollenberg and D. A. Dows J. Chem. Phys. 1962 37 1300. 7 9 G. M. Wieder and D. A. Dows J. Chem. Phys. 1962,37 2990. 8o T. L. Brown Chem. Rev. 1958,58 581. STEELE XNFRARED INTENSITIES 41 Until recently magnesium dicyclopentadienyl was believed to be an ionic salt. However its solubility in benzene was inconsistent with this belief. An analysis of its vibrational spectrum indicated a marked simil- arity in its vibrational modes to ferrocene.81 If it is principally ionic then the absorption intensity of the antisymmetric ring-metal stretching vibra- tion ought to be well represented by the ionic model Fig.4 where the rings + 2E - € - € CP M9 C P FIG. 4. An ionic model for the antisymmetric stretching vibration of magnesium di- and the metal atom are represented by point charges. The absolute in- tensity calculated for this model was approximately seventy times as large as the observed value.81 This can only be explained on the basis of princip- ally covalent bonding. Magnesium dicyclopentadienyl or magnacene is the first established covalently bonded sandwich compound of a non-transition element. The vibrational stretching frequencies of cyanide bonds are outstanding in their insensitivity to the presence of other groups.Furthermore there is little coupling between the stretching vibrations of cyanide groups attached to a common atom. Thus in maleonitrile only one C N stretching frequency is observed in the infrared and Raman spectra,82 and in sulphur dicyanide the symmetric and antisymmetric modes are at 2184 and 2179 cm.-l respectively only 5 cm.-l apart.83 This indicates that the electronic wave-functions are highly localised in the bonds themselves. The stretching gradients for cyanides are all of the same order of magnitude. The only reported absolute intensity measurements on a dicyanide are those on ~ y a n o g e n . ~ ~ Rather surprisingly the stretching gradients derived from the symmetric stretching modes of 12CN13CN and from the antisymmetric mode of 12CN12CN are in excellent agreement.These facts have been used as the basis for a determination of the angle between the cyanide groups in the dicyanamide ion N(CN)2-.84 Assuming that the bond-moment hypothesis holds for this ion then it is easy to show that the ratio of the intensities of the antisymmetric to the symmetric stretching modes is given by ras sin28/2 where 8 is the inter-bond angle. A fortuitous splitting of the antisymmetric E. R. Lippincott J. Xavier and D. Steele J. Amer. Chem. SOC. 1961 83 2262. 82 F. Halverson and R. J. Francel J. Chem. Phys. 1948 17 694; K. W. F. Kohl- 83 D. A. Long and D. Steele Spectrochim. Acta 1963 19 1731. 84 D. A. Long J. Y. H. Chau and D. Steele unpublished results. cyclopentadienyl (MgCp,) - rs cos2e/2’ rausch and G. P. Ypsilanti Z . phys. Chem. 1934 b29 274. 42 QUARTERLY REVIEWS mode occurs as a result of Fermi resonance.This allowed the relative intensities of the two cyanide bands to be measured with reasonable precision. The value derived for the inter-bond angle was 145". The original measurements were made in potassium bromide media. Accord- ing to the dielectric theories of the effects of phase on intensities the rela- tive intensities should be unaffected by phase changes. However in view of the previously noted influences on the bands of benzene and ethylene the measurements have been repeated in aqueous The two results agree well. Other Aspects and Present Trends.-A certain amount of research has been devoted towards the evaluation of higher-order derivatives of the dipole moment in suitable systems-generally diatomic ~ y s t e m s .~ ~ - ~ ~ An interesting special case was the interpretation of the intensities of certain combination bands of benzene arising from the out-of-plane motions of the C-H These bands which are characteristic of benzene and sub- stituted benzenes occur in the region 2000-1500 cm.-l. It was shown that the intensities of these bands of C6H6 C6D6 and p-C6H,D2 could be interpreted satisfactorily using only one parameter. This parameter which is the second derivative of the dipole moment with respect to the out-of- plane deformation of thejth bond 82p/ay2j has the value 1.10~. Several important theorems concerning the vibrational frequencies and intensities of isotopically related systems have been advanced by B. Craw- f0rd.9~9~3 The most important of these shows that the function ;I'/va is invariant to isotopic substitution when the summation is over all vibra- tional bands in a given symmetry class.ra is the absorption intensity of the band centred at a frequency va. This theorem when applicable provides a very useful test on measured intensities. A typical set of results is shown below for C2H6 and C2DG40 C2H6 C2D6 class 2.810 0.024 class 0-737 & 0.008 2.942 0.140 ~rn.~/mole. 0.775 r f i 0.037 ~m.~/mole. Le Fkvre and Rao,94995 Whiffen,96 and Illinger and SmythS7 have shown 85 D. Stele unpublished results. 86 W. S. Benedict R. Hermann G. E. Moore and S. Silvermann J. Chem. Phys. 88 S . S . Penner and D. Weber J. Chem. Phys. 1953 21 649. 89 B. Schurin and R. Rollefson J. Chem. Phys. 1957 26 1089. 91 F. E. Dunstan and D. H. Whiffen J. 1960 5221. 92 B. Crawford J.Chem. Phys. 1952 20 977. 93 I. M. Mills and D. H. Whiffen J. Chem. Phys. 1959,30 1619. 94 D. A. A. S. N. Rao Trans. Faraday SOC. 1963 59 43. 95 R. J. W. Le Fkvre and D. A. A. S. N. Rao Austral. J. Chem. 1955 8 39. 96 D. H. Whiffen Trans. Faraday Soc. 1958,54 327. g7 K. H. Illinger and C. P. Smyth J. Chem. Phys. 1960 32 787. 1957,26. 1671. G. A. Kuipers J . Mol. Spectroscopy 1958 2 75. E. K. Plyler W. S. Benedict and S. Silvermann J. Chem. Phys. 1952 20 175. STEELE INFRARED INTENSITIES 43 that the atomic polarisation of a molecule is related to its infrared absorp- tion by the relationship p * = - - p . Nc 3T2 j vj The significance of the atomic polarisation can be understood by con- sidering the effect of an applied oscillating electric field on a molecular gas. The induced and the permanent dipole moments align as far as permitted by the thermal motions against the applied field thus reducing the effective field.The molecular polarisation is defined as the total dipole moment per unit volume parallel to the field arising from the above contributions. As the field frequency is decreased the total molecular polarisation de- creases in certain frequency ranges. At very high oscillating frequencies only the electrons are mobile enough to follow the field changes. In the infrared frequency range the nuclei become able to follow the field and finally at still lower frequencies the molecular dipoles are able to align with the field (see Fig. 5). Clearly it is reasonable to consider the molecular FIG. 5. polarisation as I I lnfro U l t r o - -red vlolot Y- The variation of molecular polarisability with frequency.consisting of three parts the electron and the atomic induced polarisations and that arising from the permanent dipoles. Values for the atomic polarisation of non-polar molecules as deter- mined from refractive-index and dielectric-constant studies (see e.g. ref. 94) agree very well with those deduced from intensity measurements. Some typical results are shown in Table 7. In the case of polar molecules the discrepancies are generally much greater but it is very likely that these discrepancies arise from difficulties in determining the total polarisability at frequencies such that only Po is measured. It is clear from preceding sections that any successful theory of absorp- tion intensities must incorporate terms involving derivatives of the dipole (PE P A and Po).44 QUARTERLY REVIEWS Compound PA Infrared studies ( ~ m . ~ ) BF3 2.19 CF4 2-89 C2H2 1 -28 CH4 0.1 1 TABLE 7. PA Compound Dielectric studies ( ~ m . ~ ) 0.08 SiF4 1 a27 SF6 2.8 1 C2H6 2-86 C6H6 p* 1 nfrared studies ( ~ r n . ~ ) 0.12 0.73 4-82 5.07 PA Dielectric studies ( c ~ I . ~ ) 0.09 0.80 5.46 5.20 contribution of lone-pair electrons rehybridisable orbitals conjugated systems etc. with respect to bond deformations. McKean and Schatz41 and Hornig and M ~ K e a n ~ ~ have utilised terms involving the lone-pair electrons. Sverdlovg8 has developed a complete second-order bond- moment theory which incorporates terms such as api/aRj where the i and j subscripts refer to different bonds. In this way instead of single terms being determinable only combinations of terms such as (ap/aO,),,) - (ap/M,) (4) can be evaluated.An appreciation of these results necessitates a judicious assessment of the relative importance of the additional terms. Much of the present experimental data cannot be satisfactorily treated owing to the sensitivity of the modes to uncertainties in the force fields. Further developments in gas-phase intensities must come through the deduction of satisfactory force fields and the use of treatments such as those of Hornig and McKean and of Sverdlov. It is usually the unexpected results which prove to be the most fascinating and the most rewarding. The changes of intensities with phase changes are certainly the most surprising results during recent years of the field re- viewed. It is too early to even surmise the importance of an interpretation but it must modify the present concepts of condensed phases. In conclusion much has been achieved in the interpretation of infrared intensities but many important problems remain to be solved. I sincerely thank Dr. I. M. Mills for describing his work on the determination of the sign of dipole gradients from Coriolis interaction studies prior to its publication. 98 L. M. Sverdlov Optics and Spectroscopy 1959 6 477; 1959 7 1 1 ; 1960 8 316; 1960 8,96.

ISSN:0009-2681    

DOI:10.1039/QR9641800021

出版商:RSC    

年代:1964

数据来源: RSC

摘要:

NEIGHBOURING GROUP PARTICIPATION By BRIAN CAPON (CHEMISTRY DEPARTMENT BIRKBECK COLLEGE MALET STREET LONDON W.C. 1) THE most widely investigated effects of a substituent in an organic molecule on the reactions of that molecule are electronic effects transmitted through the carbon skeleton and steric effects. In addition however some sub- stituents may influence a reaction by stabilising a transition state or inter- mediate by becoming bonded or partially bonded to the reaction centre. This behaviour is called neighbouring group participation,l or sometimes if an increased reaction rate results intramolecular catalysis,2 and as with intermolecular catalysis nucleophilic electrophilic and basic catalysis or participation are possible. If the transition state of a rate- determining step is stabilised in this way an increased reaction rate results and the neighbouring group is then said to provide anchimeric assistance.Many examples of nucleophilic participation in displacement reactions at saturated carbon centres [cf. (I)-(III)] have been described mainly by Winstein and his co-workers. One of the steps of all these reactions is an CH,OAc (I) AcO A c c c - AcO OAC OAc intramolecular nucleophilic displacement. Sometimes the resultant inter- mediate reacts to yield a product which differs from that which would be expected in the absence of participation. This may be a product with retained configuration [e.g. (l)] a ring-closed product [e.g. (2)] or a product in which the participating ‘group has migrated [e.g. (3)J Jn some reactions [e.g. (IV)6] participation occurs after a rate-determining ionisation; the structure of the product may then be affected but there is no anchimeric assistance.When describing nucleophilic participation it is frequently convenient to use the symbol “G-n” where G is the participating Winstein and Buckles J . Amer. Chem. SOC. 1942 64 2780. Bender J . Amer. Chern. SOC. 1957 79 1258. Lemieux and Brice Canad. J. Chem. 1955 33 109. Heine Miller Barton and Greiner J . Amer. Chem. SOC. 1953 75 4778. Heck and Winstein J. Amer. Chem. SOC. 1957 79 3432. Collins and Bonner J . Amer. Chem. SOC. 1955 77 92. 45 46 QUARTERLY REVIEWS AcOH + Y (IV) Ph,CH-&-iPh*OTs - Ph,CH-?Ph PhCH-CHPh P h$H-?H Ph 1 1 P~,cH-~HP~ OAc OAc group and n the size of the ring formed in the transition state.’ Reactions (1)-(111) are then examples of Ac0-5 €30-5 and Ph-3 participation respectively.Examples of displacement reactions at unsaturated carbon involving nucleophilic participation are also known [e.g. (V)8]. J ( y 2 H - @+ NH3 The number of reactions in which a neighbouring group is known to act as an electrophile or as a general-base is much smaller. In nearly all the known examples of electrophilic participation the neighbouring group acts as a general-acid catalyst [e.g. (VI)9]. An example of participa- “;wo C%W0 (VI) H ; ~ a . w c 4 0 c_t H ! -t -0,c “0 C t - F w o I H m H OH tion by a neighbouring group acting as a general-base is found in the coupling reaction of diazonium ions at the ortho-position of phenoxide ions which is thought to proceed as shown in Scheme (VII).l0 The Measurement of Anchimeric Assistance To measure anchimeric assistance it is of course necessary to be able to estimate what the reaction rate would be in the absence of neighbouring (a) Heck and Winstein J.Amer. Chem. Soc. 1957 79 3105; (6) Winstein Allred Heck and Glick Tetrahedron 1958 3 1. Zurn Annalen 1960 631 56; Martin Hendrick and Parcell J. Org. Chem. 1964 29 158. Capon Tetrahedron Letters 1963 911. lo Stamm and Zollinger Helv. Chim. Acta 1957 40 1955; see also Zollinger “Azo and Diazo Chemistry,” Interscience New York 1961 p. 254. CAPON NEIGHBOURING GROUP PARTICIPATION 47 group participation. In cyclic compounds the molecular geometry fre- quently restricts the possibility of nucleophilic participation to trans- isomers and hence the unassisted rate approximates to that of the cor- responding cis-isomer.This approximation neglects any conformational effects on the reactivities of the cis- and trans-isomers. These are probably not very large but correction for them is not easy. In acylic compounds in which neighbouring group and reaction centre are at adjacent carbon atoms the separation of anchimeric assistance from polar and steric effects is more difficult. The most satisfactory procedure for the separation of polar effects is that of Streitwieser,ll using Taft’s equation. Taft’s equation log kfk = p*o* is a linear free-energy relation- ship correlating reaction rates and equilibria of aliphatic compounds. o* is the polar substituent constant derived from the relative rates of the acid and alkaline hydrolysis of aliphatic esters and p* is a constant giving the susceptibility of a given reaction series to polar substituents.12 Reac- tions in which a substituent provides anchimeric assistance i.e.stabilises the transition state through bonding to the reaction centre will therefore show positive deviations from this relationship. However reactions in which there is a release of non-bonding compression on going to the transi- tion state will also show enhanced rates i.e. they will be sterically ac- celerated. Separation of these two effects is largely a matter of chemical intuition and different chemists may give different assessments of their importance. As an example consider the solvolyses of 2,2,2-triphenylethyl chloride13 arid toluene-p-~ulphonate~~ which are accelerated to a far greater extent than can be accounted for by the inductive effects of the phenyl groups and are accompanied by phenyl migration.The reactions therefore probably pass through transition states such as (4). The problem is to decide how much of the enhanced rate results from stabilisation of this transition state by bonding of the phenyl group to C-1 and how much results from release of non-bonding compression on going to this or some other intermediate state. The answers that have been given range from 100 % anchimeric assistance13 to 100 % steric a~ce1eration.l~ When the neighbouring group and the reaction centre are separated by a several-membered carbon chain as in e.g. HO-CH2-CH2CH2-CH,Cl l1 Streitwieser Chem. Rev. 1956 56 694. l2 Taft in “Steric Effects in Organic Chemistry,” ed. Newman Wiley New York l3 Unpublished results reported by Ingold “Structure and Mechanism in Organic Chemistry,” Cornell University Press Ithaca N.Y.1953 p. 514. l4 Winstein Morse Grunwald Schreiber and Corse J . Arner. Chem. SOC. 1952 74 1113. l5 Brown in “The Transition State,” Chem. SOC. Special Publ. No. 16 1962 p. 152. 1956 p. 586. 48 QUARTERLY REVIEWS the polar and steric effects of a neighbouring group are generally small and the unassistsd rate is often taken to be that of the compound in which the neighbouring group is replaced by hydrogen although a better estimate can be made more laboriously by making use of Taft’s equation. With re- actions of substituted benzene derivatives in which there is participation by an ortho-substituent the rate with the corresponding para-compound is of course a good approximation to the unassisted rate.Some workers prefer to improve this approximation a little by multiplying by the ratio of the rates with the ortho- and para-compounds found with similar non- participating substituents.lG When a substituent such as hydroxyl is providing assistance by acting as an intramolecular acid catalyst the rate of the corresponding methylated derivative is frequently used to give the unassisted rate. This of course neglects the different steric and electronic effects of H and CH3. It is seen from the foregoing account that it is not possible to estimate very accurately what reaction rates would be in the absence of neighbouring group participation. For this reason an increase in rate at least five-fold and preferably more than fifty-fold is necessary for the identification of neighbouring group participation through the recognition of anchimeric assistance.Sometimes when comparing the rates of reactions involving neighbour- ing group participation it is frequently convenient to use three different symbols :7 kd the rate constant for the anchimerically assisted reaction; k, the rate constant for the reaction not anchimerically assisted but assisted by solvent (the relative importance of kd and k of course depends upon the solvent. For instance with a reaction involving nucleophilic participation there will be more successful competition from the solvent when it is say water than when it is the much less nucleophilic formic acid) ;kc is sometimes used with reactions involving nucleophilic participa- tion; it is the rate constant for the idealised ionisation to the open ion (5)’ formed without neighbouring group or solvent participation.This will generally be less than ks and Winstein et uZ.17 have given a method for its approximate calculation. The quantity L = RTln (kA/kc) termed the driving force is then the free-energy difference between the open and closed carbonium ions ( 5 ) and (6). Participation by Methoxyl Groups Displacement Reactions at Saturated Carbon.-Many of the results described in this section are due to Winstein and his co-workers who have Cf. Bender and Silver J. Amer. Chem. SOC. 1962,84,4589. l7 Winstein Grunwald and Ingraham J. Amer. Chem. SOC. 1948,70 821. CAPON NEIGHBOURING GROUP PARTICIPATION 49 summarised7 their outstanding contribution. Unfortunately most of the experimental details have not yet been published.The absence of a steady trend in the rates of solvolysis of a series of w-methoxyalkyl p-bromobenzenesulphonates (see Table 1) indicates the TABLE 1. The relative rates of solvolyses of w-methoxyalkyl p-bromo- benzenes~lphonates.~~ Compound Relative rate EtOH AcOH HCO (75") (25") (75") MeO.[CH,],-OBs (8) 0.25 0.28 0.10 MeO. [CH2I3.OBs (9) 0.67 0-63 0.33 MeO- [CH,],.OBs (10) 20.4 657.0 461.0 MeO. [CH,],.OBs (1 1) 2.8 123.0 32.6 MeO-[CH,],.OBs (12) 1-19 1.16 1.13 Me.[CH,I3-OBs (7) 1.00 1.00 1-00 Calc. k/ks at 75" EtOH AcOH HC02H 0.93 0.81 1.07 1.33 1.51 0.85 1-14 1.20 0.84 22.2 425.0 610.0 2.42 47.2 30.6 0.87 0.71 0.85 importance of an effect by the methoxyl groups other than the inductive effect. In particular the high rates for the 4-methoxybutyl and 5-methoxy- pentyl compounds [(lo) and (1 l)] suggest nucleophilic participation and Winstein and his co-workers have formulated these reactions as proceed- ing through the cyclic oxonium ions (13) (Me0-5) and (14) (Me0-6 parti~ipation).~ Hence the primary methoxyl group provides assistance when a five- or six-membered cyclic oxonium ion is possible but not when this intermediate would have seven three or four members.The increase in rate due to Me0-5 participation in the acetolysis of secondary p-bromobenzenesulphonates [cf. compounds (1 7) and (21) in Table 21 is about twenty-fold less than for the analogous primary com- TABLE 2. The relative rates of acetolysis of some methyl-substituted butyl p-bromobenzenesulphonates at 25°.7b Compound Me. [CH,],-OBs (1 5) MeO. [CH,],.OBs (16) MeO. [CH,],CHMe.OBs (17) MeOCHMe.[CH,],.OBs (1 8) Relative rate 657 1.00 - 4140 6-29 30 41 10 6.26 - - - 1 _ _ evythro (19) 9450 14.4 67 Me0'CHMe*[CH212'CHMe*0Bs (three (20) 2.28 x 104 34.7 163 MeCH,CHMe.OBs (21) 140 - 1-0 pounds [cf. compounds (1 5 ) and (16)]. The a-methyl group in the second- ary compound helps to disperse the positive charge in the transition state and hence the need for assistance from the neighbouring methoxyl group 50 QUARTERLY REVIEWS to do this is less. The compound (18) with a secondary methoxyl group reacts faster than the corresponding compound (16) with a primary methoxyl group. This accelerating effect of alkyl substituents on ring- closure reactions is frequently encountered and is discussed on p. 109. The slightly greater rate of acetolysis of threo-5-methoxy-1-methylpentyl p-bromobenzenesulphonate (20) than its erythro-isomer (1 9) probably results from steric retardation in the formation of the cyclic oxonium ion from the erythro-isomer.In the ion (22) from the threo-isomer the three methyl substituents may all be staggered but in that (23) from the erythro-isomer two must be eclipsed. 4-Methoxypentyl (1 8) and 4-methoxy- 1 -methylbutyl p-bromobenzene- sulphonate (17) should yield the same cyclic oxonium ion (24) and hence the products of their acetolyses should be identical. Winstein and his co-workers report7b (without details) that this is so. The cyclic oxonium ion (24) undergoes ring cleavage but there is the possibility of methyl- oxygen cleavage as well. According to Winstein et al. Me-0 cleavage is un- important in Me0-5 participation but significant in Me0-6 participation ; the acetolysis of 5-methoxypentyl p-bromobenzenesulphonate yields tetrahydropyran methyl acetate methyl p-bromobenzenesulphonate and 5-me thoxypent y 1 acetate .Although the primary methoxyl group in 2-methoxyethyl p-bromoben- zenesulphonate provides no anchimeric assistance7 the absence of partici- pation in a step after the rate-determining one cannot be entirely dis- counted. Me0-3 participation by secondary and tertiary methoxyl groups however quite definitely occurs. Examples of participation by secondary methoxyl groups are found in the reactions of compounds (25) (26) and (27) with silver acetate in acetic acid which yield methoxy-acetates of retained configuration.l* The tertiary methoxyl group in 2-bromo-3- methoxy-3-methylbutane (28) participates in the hydrolysis since it Winstein and Henderson J.Amer. Chem. SOC. 1943 65 2196. CAPON NEIGHBOURING GROUP PARTICIPATION 51 Y H-$-Br Ye H-$-Br Ma-5- H H-$-OMe Me tvk (27) Br (25) (26) migrates and the product is 3-methoxy-2-methylbutan-2-01 (29).19 Me0-3 Me O+ Me / \ ,Me Y (XIe tv?~O H - Me-?-?-Me 4 ‘ (2 8) (29) Me-C-C-Me - /c-c\H HO H & 2 Me participation by tertiary methoxyl groups can provide considerable anchimeric assistance ; k/ks for the acetolysis of 2-methoxy-2-methylpropyl p-bromobenzenesulphonate (30) is about 1500 and when the solvent is aqueous dioxan the major product is isobutyraldehyde (3 1).20 - I Me’” -‘H Me’+ A A very thorough and illuminating investigation of Me0-5 participation in the acetolysis of trans-4-methoxycyclohexyl toluene-p-sulphonate (32) (32) (33) (334) has been made by Noyce and his co-workers.21 By comparing the reaction rate with that of the cis-isomer and making a small allowance for the amount of cis-isomer in a conformation with the toluenesulphonyl- group in a more reactive axial position they estimated that k/k8 for the trans-compound is about 5-6.Hence a large amount of the product must result from a reaction involving participation by the methoxyl group. The products are 4-methoxycyclohexene (67-7 %) cis-4-methoxycyclo- hexyl acetate (8-7 %) and trans4methoxycyclohexyl acetate (23-6 %). l9 Winstein and Ingraham J. Amer. Chem. Soc. 1952 74 1160. 2o Winstein Lindegren and Ingraham J. Amer. Chem. SOC. 1953,75,155. 21 (a) Noyce Thomas and Bastian J. Amer. Chem. Suc. 1960,82,885; (b) Noyce and Bastian ibid.p. 1246. 52 QUARTERLY REVIEWS It seems likely therefore that much of the 4-methoxycyclohexene results from a reaction involving participation. The products of acetolysis of trans-4-methoxy [ 1 -3H]cyclohexyl toluene-p-sulphonate are given in Table 3. Any products derived from the bicyclic oxonium ion (33) should have TABLE 3. Products of acetoljsis of trans-4-inethoxy [ 1 -3H]cycluhexyZ toluene-p-sulphonate.21 4-Methoxy [l-3H]cyclohexene 66.4 % cis-4-Methoxy [ l-3H]cyclohexyl acetate 9.6 % trans-4-Methoxy [ 1 -3H]cyclohexyl acetate 13.8% the tritium scrambled equally between the I- and the 4-position or possibly have a slight excess in the 4-position owing to a secondary isotope effect. The trans-4-methoxycyclohexyl acetate has 35 % more tritium in the 1-position than in the 4-position and hence some of it cannot have been formed by way of the oxonium ion (33).Also the 4-methoxy- cyclohexene contains all its tritium in the 1-position but nevertheless as argued above from the rate data much of it probably came from an assisted reaction. These observations led Noyce and Bastian21 to suggest that participation by the methoxyl group first involves partial bonding to the reaction centre to give an internally solvated ion-pair intermediate (34) the anchimeric assistance being associated with the formation of this trans-4- Methoxy [4-3H]cyclohexyl acetate 10.2 species. This ion-pair may then react with acetic acid to give trms-acetate Me0 &OTs normal 1 /assisted T (T= tritium ; Ts= toluene-p- sulphonyi) CHART 1. collapse to give a bicyclic oxonium ion or undergo elimination the coni- plete reaction scheme being as shown in Chart 1.The driving force for participation in the acetolysis of 4-methoxycyclohexyl toluene-p-sulphon- CAPON NEIGHBOURING GROUP PARTICIPATION 53 ate is much less than in the acetolysis of a similar acyclic compound 5-methoxy-2-methylpentyl p-bromobenzenesulphonate for which k/ks= 163 (See Table 2). This is because much of the energy gained from partici- pation in the 4-methoxycyclohexyl compound is lost in non-bonded interactions on going over to the unfavourable boat conformation. The work of Noyce et al. must throw some doubt on the details of Winstein's interpretation of methoxyl-group participation presented in the first part of this Section. Obviously more experimental work is needed to determine the exact proportions of methoxyl-assisted reactions which involve cyclic oxonium ions.Participation by methoxyl groups attached to benzene rings as shown in (35) sometimes occurs. The nucleophilicity of such groups is reduced by the mesomeric interaction with the benzene ring but this is at least partly counterbalanced by the increased rigidity of the system. In compounds where this kind of participation is possible there is also the possibility of aryl participation [see (36)] and competition between MeO-n and Ar- (n-2) participation may occur. The rates of solvolyses (Table 4) of 2-(o-methoxyphenyl)-2-methylpropyl toluene-p-sulphonate (38) are smaller than those of the p-methoxy-isomer (37) but the occurrence of o-MeO-5 participation is clearly shown by the reaction products (Table 5 ) which in TABLE 4.Relative rates of solvolysis of methoxyphenylalkyl toluene-p- sulphonates.22 HCOZH AcOH (25 ") (75 ") 2-Methyl-2-phenylpropyl 1.0 1.0 2-(o-Methoxyphenyl)-2-methylpropyl (38) 6.47 5.5 240- Methoxyp heny1)e thy1 (3 9) 0.66 0.99 2-(p-Methoxyphenyl)-2-methylpropyl (37) 72.0 88.0 2-(p-Methoxyphenyl)ethyl (40) 0.67 1.3 TABLE 5. Products of solvolysis of 2-(o-methoxyphenyl)-2-methylpropyl toluene-p-sulphondte.zz Solvent Temp. Added base Total Olefin Tert. Prim. Furan Alcohol (41) + (43) (44) (45) AcOH 25" NaOAc 0.0301~ 96 8 15 4 73 HC02H 25" NaOCHO 0.0515~ 92 32 42 - 26 22 Heck Corse Grunwald and Winstein J. Amer. Chem. SOC. 1957 79 3278. (42) 54 QUARTERLY REVIEWS OH (42) CHART 2. acetolysis formolysis and ethanolysis all contain some of the benzo- furan (45).22 The solvolyses therefore proceed as shown in Chart 2.The ethanolysis and formolysis reactions obey the first-order rate law and give the theoretical infinity titres but the acetolysis reaction gives infinity titres (presumably after 10 half-lives) corresponding to 63 % reaction. This is due to the formation of methyl toluene-p-sulphonate which undergoes aceto- lysis 500 times more slowly. In the presence of sodium acetate or lithium perchlorate fairly good infinity titres are obtained. This is not due to reaction between methyl toluene-p-sulphonate and sodium acetate because this is too slow. The sodium acetate or lithium perchlorate must prevent the methyl toluene-p-sulphonate from being formed. The following very reasonable explanation has been given by Winstein et aZ.7b Ionisation is thought to occur first to an ion-pair (46) which may collapse through nucleophilic attack of the toluenesulphonate ion on the methyl group to yield methyl toluene-p-sulphonate (Chart 2 path B); this is referred to as ion-pair return.In the presence of lithium perchlorate or sodium acetate rapid exchange of partners between ion-pairs occurs and hence the oxonium ion is paired with perchlorate or acetate and cannot yield methyl toluene-p-sulphonate by ion-pair return. The rates of solvolysis in ethanol formic acid and acetic acid of 2-(0- methoxypheny1)ethyl toluene-p-sulphonate (39) are approximately the same as those of its para-isomer (40).23 Although no product analyses were reported it therefore seems likely that 0-MeO-5 participation is not im- portant in the reactions of this compound.However 0-MeO-6 participa- tion occurs extensively in the acetolysis and formolysis of the analogous 3-(o-methoxyphenyl)-propyl p-bromobenzenesulphonate (47) and 3-(0- 23 Winstein Lindegren Marshall and Ingraham J. Arner. Chem. SOC. 1953,75,147. CAPON NEIGHBOURING GROUP PARTICIPATION 55 methoxyphenyl)-3-methylbutyl toluene-p-sulphonate (48) (see Table 6).7 Any competing aryl participation would be Ar,-4 participation and as TABLE 6. Rates and products for the formolyses of 3-(o-methoxyphenyl)- propyl p-bromobenzenesulphonate (47) and 3-(o-methoxyphenyl)-3-methyl- butyl toluene-p-sulphonate (48) at 25°.7b Compound 105k 105k for Products (47) 0.2 0.01 46 % 49 % (48) 22.0 -0 4% >95 % para-isomer Alcohol Pyran shown by the reaction rates for the para-isomers is unimportant.The reaction products (Table 6) contain large amounts of the pyran derivatives (49) and (50) and of the methyl arenesulphonates and the reactions may therefore be formulated as shown in Charts 3 and 4. The infinity titres for the acetolysis of 3-(o-methoxyphenyl~-3-methylbutyl toluene-p-sulphonate correspond to 34 % reaction at 75 O and this value is decreased by the addi- 4% - HOBs Eo Eo Qo,Me c,H2 CH,- CH,OS (49) (49) -t MeOBs + MeOS (SOH= solvent ; Bs=p-bromobanzene sulphonyl) CHART 3. + MeOS + MeOTs (SOH=solvent ; Ts = toluene-p-sulphonyl) CHART 4. 56 QUARTERLY REVIEWS tion of lithium toluene-p-sulphonate a result which indicates that forma- tion of methyl toluene-p-sulphonate involves more than just ion-pair return. Reactions at Carbonyl Carbon.-When heated to 100-150" y- and 6- (but not E) alkoxyacyl chlorides rearrange to give the alkyl y- and 6- chloro-esters re~pectively.~~,~~ cis- 3- and -4-Methoxycyclohexanecarbonyl chloride undergo this rearrangement but their trans-isomers do not,26 a result which excludes an intermolecular reaction between the acyl chloride group of one molecule and the ether group of another.The cis-3- and -4-methoxycyclohexanecarbonyl chlorides26 and (+)-4-methoxyvaleryl chloride2' yield chloro-esters with inverted configuration. All these results support a mechanism involving intramolecular nucleophilic attack by the alkoxyl group as in Scheme (VIII). 4-Ethoxybutyryl chloride rearranges about forty times faster than 5- ethoxyvalerlyl and so if return to the acyl chloride occurs to the same extent for both compounds the assistance for Et0-5 participation is greater than for Et0-6.No example of alkoxyl cleavage of the oxonium intermediate in this type of reaction has been reported. cis-3- and -4-Methoxycyclohexanecarboxylic acid undergo a similar re- arrangement when heated in acetic anhydride containing sulphuric acid.28 Participation by Hydroxyl Groups Displacement Reactions at Saturated Carbon.-The rates of hydrolysis in water of a series of co-hydroxyalkyl halides (Table 7 ) 2 9 9 3 0 indicate that TABLE 7. The rates of hydrolysis of some halohydrins Cl.[CH,];OH in water at 70-5°.29130 n 2 3 4 5 105k (min.-l) 1-82 7.79 1710 70 and Robertson Cunad. J. Chem. 1959 37 1491) is-15. The value of 105k for n-propyl chloride extrapolated from the value at 100" (Laughton neighbouring group participation is probably occurring with 4-hydroxy- 24 Blicke Wright and Zienty J.Amer. Chem. SOC. 1941 63 2488 for a similar but not completely analogous reaction of alkylmercaptoacyl chlorides see Truce and Abra- ham J. Org. Chem. 1963 28 964. 25 Prelog and Heimback-Juhasz Ber. 1941 74 1702. 26 Noyce and Weingarten J. Amer. Chem. SOC. 1957 79 3093. 27 Wiberg J. Amer. Chem. SOC. 1952 74 3957. 28 Noyce and Weingarten J. Amer. Chem. SOC. 1957 79 3098. 2 9 Heine Miller Barton and Greiner J. Amer. Chem. SOC. 1953 75 4778. 30 Capon and Farazmand unpublished observations. CAPON NEIGHBOURING GROUP PARTICIPATION 57 butyl and 5-hydroxypentyl chloride an interpretation which is supported by the isolation of tetrahydrofuran and tetrahydropyran from the reactions of these compounds.The increase in rate associated with this participation is not very great because the solvent water is itself fairly highly basic and nucleophilic and hence the rate in the absence of neighbouring group participation is already quite high. In alkaline solution hydroxyl groups (pKa 14-18) are appreciably ionised and participation by RO- can occur (see Table 8).30931 Under these TABLE 8. The rates of ring-closure of some halohydrins in aqueous sodium hydroxide at 30°.30,31 k (1. mole-'min.-') C1. [CH,],*OH 0.13 C1. [CH,&.OH 0.172 C1. [CH,],.OH 0*0007* * Extrapolated from results at higher temperatures. conditions the most reactive of the w-hydroxyalkyl chlorides is 2-hydroxy- ethyl chloride. However this is because there is a higher standing con- centration of the conjugate base owing to the acid strengthening effect of chlorine on a carbon atom adjacent to an alcohol group.It is claimed that the solvent deuterium isotope effect for the reaction of 2-hydroxyethyl chloride is consistent with a two-stage mechanism as /O ClCHiCH,;O- - CH,-CH + Sl' shown but not with a mechanism in which removal of the proton and ring- closure occur synchron~usly.~~ 1,4-Epoxycyclohexane is the main product of the alkaline hydrolysis of trans-4-chlorocyclohexanol.33 The rate of reaction is however 1 100 times less than the rate of formation of tetrahydrofuran from 4-chlorobutanol under the same conditions. 0-4 participation occurs with compounds of suitable configuration but is frequently accompanied by fragmentation. [see Scheme (IX)] 5a- Hydroxycholestan-3/3-yl toluene-p-sulphonate (51) reacts with potassium t-butoxide in t-butyl alcohol to yield 3a,5a-epoxycholestene (52) (55 x) 31 Heine and Siegfried J.Amer. Chem. SOC. 1954 76 489. 32 Swain Ketley and Bader J . Amer. Chem. SOC. 1959 81 2353; see also Ballinger 33 Heine J. Amer. Chem. SOC. 1957 79 6268. and Long ibid. p. 2347. 58 QUARTERLY REVIEWS \ / \ /c\ / /v /=\ \ x-+>c=c< + >c=o 0 I l l I I l l Ox) x-L-c-c-OH - X-$-$-FO- and 4,5-secocholest-3-en-5-one (54) (37 %) at a rate much faster than that with which cholestan-3/3-yl toluene-p-sulphonate reacts under the same conditions. 34 5 /3-H y dr oxycopros tan-3 a-yl t oluene-p-sulphona te (5 5) reacts at approximately the same rate as 5a-hydroxycholestan-3/3-yl toluene-p- sulphonate but yields only the seco-ketone (54).34 no& - & (52) -O (51) \ E- +(541 OTs Other examples of 0-4 participation are shown in Schemes (X)- (XII).35 >=b K O B ~ in B ~ H HO I~LJ Bu ‘9 P (XI I) HOCH,.~-CH~OBS - H C< >CH2 Bu 0 Reactions of Carboxylic Acids and their Derivatives.-Neighbouring hydroxyl-group participation in the alkaline hydrolysis of esters has frequently been reported,36 an example3’ being the hydrolysis of 3c~- acetoxycholestan-5~~-01(56~ which proceeds faster than that of 3P-acetoxy- 34 Clayton Henbest and Smith J. 1957 1982. 36 Henbest and Millward J. 1960 3575; see also Lindegren and Winstein Abstracts 36 See Kupchan Slade Young and Milne Tetrahedron 1962 18 499 and papers 37 Henbest and Lovell J. 1957 1965. of Papers 123rd American Chemical Society Meeting 1953 30M. cited therein.CAPON NEIGHBOURING GROUP PARTICIPATION 59 ik0& Ho (56) Ho (57) cholestan-5a-01 (57) the usual rate order that equatorial esters are more readily hydrolysed than axial ones,38 being reversed. Possible mechanisms include nucleophilic participation as (a) or (b) in Chart 5 (shown for an > c-05 Hf'OH >C-0 ,R )C-0-C-R :c-OH (a) ,C-R - f lC\ - i d - + RCO,' >c-0 +n >c-0 0- >C-OH >C-OH (59)" H0-3 H-O-C- b) Yf-+ -$-0-CR d bOH I (5 8) I C- -$-OH HO-C- - 03-+ RCO; - 1 1 >c-oy X - O H >C-O-$R k - O H :c-0 )C-OH >C-O'- F-R >C-OH 0- - f + RCO; OH f J-e- - f t RCO,' OH CHART 5. ester with the hydroxyl substituent in the alkyl portion) or electrophilic participation as (c) or (d) as well as several mechanism involving intra- molecular general- base cat a1 y sis.Participation of type (a) in Chart 5 will only result in an increase in rate if ester (58) is more reactive than ester (59). In type (b) the ester group is merely the leaving group for an intramolecular displacement at saturated carbon. In type (c) the hydroxyl group facilitates the reaction by hydrogen bonding to the carbonyl oxygen and in type (d) by hydrogen bonding to the ether oxygen of the ester. Generally it is easy to exclude mechanisms (a) and (b) but to distinguish between (c) and (d) is much more difficult. If the mechanism of ester hydrolysis is written :39 38 See Eliel "Stereochemistry of Carbon Compounds," McGraw-Hill New York 39 Bender Chern. Rev. 1960,60,61. 1962 p. 222. 60 QUARTERLY REVIEWS the measured rate constant km is given by k = k,(l + k,/k,).Participa- tion by the hydroxyl group as in (c) would result in an increased value of k, and as in (d) with an increased value of k3 and k, although the effect on k would be expected to be much less than with (c). Also any effect on k3 would not significantly affect the overall rate (see ref. 117) since for the alkaline hydrolysis of esters k2/k is never greater than about 0 ~ 2 . ~ ~ There- fore a large increase in rate must be ascribed to a mechanism such as (c) but a small increase is consistent with both (c) and (d). Unfortunately the rate increases that are observed are frequently small. Henbest and Love113’ originally tried to distinguish between mechanisms (c) and (d) by examining the infrared spectra of the esters to find whether the hydroxyl group was bonded to the carbonyl or ether oxygen of the ester.However the value of this approach is limited since the infrared spectra were always measured in aprotic solvents such as carbon tetra- chloride and quite different state of affairs may prevail in the hydroxylic solvents used in the solvolyses (generally hydrolyses). More seriously however since the rates of reactions depend on the free-energy differences between initial and transition states the point of interest is the relative strengths of the hydrogen bonding in these two states,*l and hence a knowledge of the nature of the hydrogen bonding in the initial state alone in a different solvent is only partly relevant. Bruice and Fife4 attempted to distinguish between the two possibilities by considering the rates of hydrolyses of the esters given in Table 9 and TABLE 9.The rates of hydrolysis of some esters at 78”.42 Esters Cyclopentyl (61; (60) (61; (62) (63; (63; k (1. mole-’sec.-l) 9.3 31.6 174 309 85.1 5.0 79-4 acetate R = Me) R=H) R=H) R=OH) came to the conclusion that the rate acceleration found with esters (60) (61; R=H) (62) and (63; R=OH) and with esters previously studied resulted from a mechanism “in which a neighbouring hydroxyl group solvates the transition state for nucleophilic attack of the hydroxyl ion on the ester carbonyl group” i.e. of type (c). However they assumed that the OAr AcO hydroxyl group participates in the same way in all these reactions but as pointed out by Kupchan and his co-worker~,~~ this may not be so and might well vary with the geometry of the molecule. Sometimes geometrical con- siderations exclude one of the possible mechanism for particular com- 4 0 Bender and Thomas J .Amer. Chem. SOC. 1961 83 4189. 41 West Korst and Johnson J. Org. Chem. 1960 25 1976. 42 Bruice and Fife J . Arner. Chem. SOC. 1962 84 1973. 4R Kupchan Eriksen and Friedman J. Amer. Chem. Soc. 1962,84,4159. CAPON NEIGHBOURING GROUP PARTICIPATION 61 pounds as with esters (60) and (62) in which hydrogen bonding to the ether oxygen of the ester grouping is not possible and has been shown not to occur in carbon tetrachloride solution. For their compounds Bruice and Fife’s conclusion is therefore probably correct but it should clearly not be generalised particularly when the rate differences are small. Some other examples of intramolecular electrophilic participation by hydroxyl groups are found in the reactions of salicylic and 1’-a- hydroxylbenzylferrocenecarboxylic acid45a with diphenyldiazomethane.The alkaline hydrolysis of p-nitrophenyl 5-nitrosalicylate occurs much faster than expected and the pH-rate profile is consistent with either a reaction of the un-ionised ester with hydroxide ion or of the ionised ester with water.45b The reactions of this ester with other nucleophiles are not however abnormally fast which would be surprising if the fast hydrolysis involved attack of hydroxide ion on the unionised ester the phenolic group providing intramolecular general acid catalysis. Bender Kezdy and Zerner,45b therefore prefer a mechanism involving the intramolecularly general base-catalysed attack of water on the ionised ester. This interesting conclusion must of course raise the question as to whether some of the examples of intramolecular catalysis by alcoholic hydroxyl groups do not involve general base catalysis.Nucleophilic participation by hydroxyl groups has been shown to occur in the hydrolyses of 4-hydroxybutyramide 5-hydroxy~aleramide,~~~~~ and several aldonamide~,~~ and in the esterification of o-hydroxyphenoxyacetic acid. 47 The nucleophilicity of the mono-anion of catechol is abnormally high in reactions with several ary148 and phosphoryl fluorides,49 and with phenyl chlor~acetate.~~ Probably the un-ionised hydroxyl group is providing assist- ance as signified by (64) or (65) and (66). It is interesting to note that the (6 5) R reaction of p-nitrophenyl acetate with several hydroxyl substituted irnidazoles is not similarly f a ~ i l i t a t e d .~ ~ Other Reactions.-An example where an ionised hydroxyl group parti- cipates in a reaction by acting as a general-base rather than as a nucleo- 44 Norris and Strain J. Amer. Chem. Suc. 1935 57 187. 45 (a) Little and Eisenthal J. Amer. Chem. Suc. 1961 83 4936; (6) Bender Kezdy 46 (a) Bruice and Marquardt J. Amer. Chern. Soc. 1962 84 365; (6) Wolfrom 4i Kupchan and Saettone Tetrahedron 1962 18 1403. 48 Churchill Lapkin Martinez and Zaslowsky J. Amer. Chem. Sue. 1958,80 1944. 45 Epstein Rosenblatt and Demek J. Amer. Chem. Suc. 1956 78 341. 51 Bruice and Schmir J. Amer. Chem. SOC. 1958 80 148. and Zerner J. Amer. Chem. SOC. 1963 85 3017. Bennett and Crum J. Amer. Chem. Sue. 1958,80,944. Fuller,J. Amer. Chem. Suc. 1963 85 1777. 62 QUARTERLY REVIEWS phile is found in the coupling reaction between the o-nitrodiazonium ion and 1-hydroxynaphthalene-3-sulphonic acid.1° The reactions at both the ortho- and the para-positions of the phenol are general-base catalysed by external bases but extrapolation to zero buffer concentration shows that the “water”-catalysed reaction for ortho-coupling is considerably faster than that for para-coupling.Stamm and ZollingerlO explained this as being due to the fact that proton loss from the a-complex for ortho-coupling is catalysed intramolecularly by the phenoxide ion acting through a water molecule [see (VII) on p. 461. The reaction of cyclohex-2-en01 with perbenzoic acid yields the cis- epoxide exclusively probably because of intramolecular electrophilic participation the transition state being as (67).52 Participation by Amino-groups Many examples of nucleophilic participation by amino-groups are known and large rate acceleration have been observed with the formation of 3- 4- 5- and 6- membered The pattern of behaviour found for the ring-closure reactions of w-aminoalkyl halides (Table 10) is similar Br.[CH,];NH, in water at 25°.53 TABLE 10. The rates of ring-closure of o-aminoalkyl halides n 2 3 4 5 6 k (min.-l) 0.036 0.0005 30 0.5 0-00 1 TABLE 11. The efect of chain-branching on the rates of ring-closure of o-aminoalkyl halides. Rates of solvolysis* in 80% ethanol at 56°.54 Me,NCH,CH,CH,Cl 10.5 Me,N.CH,CMe,CH,Cl 98.0 1 05k (sec.-l) klkKClt 6 x lo3 5 x 1 0 6 Relative rates of solvolysis in acetate buffer at 30°.55 kEl. H,NCH,CH2CH,CH,Br 1 H,NCH,CEt,CH,CH,Br 594 H,NCH,-CMe,CH,CH,Br 158 H,NCH,CPri,CH,CH,Br 9790 corresponding compound in which the Me,N group is replaced by H.* Ring-closure occurs exclusively with these compounds. ?Rate constant for the 52 Henbest and Wilson J. 1957 1958. 53 Freundlich and Kroepelin 2. phys. Chem. 1926 122 39. 54 Grob and Jenny Tetrahedron Letters 1960 No. 23 p. 25. 55 Brown and van Gulick J. Org. Chem. 1956,21 1046. CAPON NEIGHBOURING GROUP PARTICIPATION 63 to that found with the analogous o-hydroxy- and w-methoxy-compounds (see previous Sections). Branching at the non-terminal positions of the alkyl chain increases the rate of formation of the 4- and 5-membered rings. (Table 1 1 ) 5 4 y 5 5 (see p. 109 for a discussion of this effect). Examples of a similar participation with more complex molecules are found in the solvolysis of tropan-3a-yl [Scheme (XIII)] and in the racemisa- tion of L-( +)-tropan-2a-ol by boiling acetic anhydride5' [Scheme (XIV)].Nucleophilic participation by amino-groups in reactions of carboxylic acid derivatives is found in the hydrolysis of aryl 4-(NN-dimethylamino)- butyrates and 5-(NN-dimethylamino)valerate~,~~ e.g. (68)+(70) and in the hydroxyl-ion catalysed lactamisation of methyl m-amino-a-(toluene-p- su1phonamido)-butyrates and -valerate~,~~ e.g. (71)+(72). Considerable rate accelerations result and in the former series the rate of formation for a 5-membered ring is slightly greater than for a 6-membered ring but with the latter compounds 6-membered-ring formation is faster. 6 0 + MeOH OMe p/ (72) Reactions in which amino-groups participate by acting as general-bases are rare.A recently discovered example is the methanolysis of cevadine orthoacetate diacetate which is thought to proceed as shown in (73).60 56 Archer Bell Lewis Schulenberg and Unser J. Amer. Chem. Soc. 1957 79 6337; Grob I.U.P.A.C. Kekule Symposium Butterworths London 1959 p. 121. 67 Archer Lewis Bell and Schulenberg J. Arner. Chern. Soc. 1961 83 2386. 5 8 Bruice and Benkovic J. Arner. Chern. Soc. 1963 85 1. 60 Curragh and Elmore J. 1962 2948. 6 o Kupchan Eriksen and Yun-Teh Shen J. Arner. Chern. Soc. 1963 85 350. 64 QUARTERLY REVIEWS The protonated amino-group is a particularly effective intramolecular acid catalyst in the hydrolysis of 2-NN-dimethylaminoethyl thioacetate in acid solutions [see (74)] the rate being about 240 times greater than that for the ester (75) which lacks the acidic proton.61 A similarly caused but smaller (about 20-fold) rate accelerating effect is found in the hydrolysis of 2-NN-dimethylaminoethyl benzoate.62 There is some evidence that the positively charged trimethylamino-group can stabilise the transition state in the alkaline hydrolysis of esters through "electrostatic bonding" as shown in (76).63 The ester Me3N+-CH,CH2-OAc is hydrolysed more slowly than ethyl acetate in acidic solutions but about 10 times faster in alkaline solutions.Use is made of amino-group participation in a stepwise degradation of peptides devised by Holley and H ~ l l e y ~ ~ of which several modifications have been reported.65 The original procedure involved reaction of the free amino-groups with methyl 4-fluoro-3-nitrobenzoate and reduction to yield an N-aminophenylpeptide which reacts as shown A similar reaction sequence is employed in the use of o-nitrophenoxyacetyl chloride as a protective group in peptide synthesis.66 This may be removed by reduction and hydrolysis with participation by the resulting amino- group [(77)+(78)1.61 Hansen Acta Chem. Scatid. 1958 12 324. 62 Agren Hedsten and Jonsson Acta. Chem. S c a d . 1961 15 1532. 63 Davis and Ross J. 1950 3056; Butterworth Eley and Stone Bioclrent. J. 1953 64 Holley and Holley J. Atner. Chem. SOC. 1952 74 5445. 65 Jutisz and Ritschard Biochem. Biophys. Acta 1955 17 548; Scoffone Vianello Holley and Holley J. Amer. Chem. Soc. 1952 74 3069. 53 30. and Lorenzini Gazzetta 1957 87 354. CAPON NEIGHBOURING GROUP PARTICIPATION 65 Many examples of neighbouring amino-group participation are found in the reactions of the nitrogen mustard^.^^,^^ Participation by Thioether Groups* trans-2- Chlor ocycl o hex y 1 and trans- 2-chl or oc y clo pen t y 1 phen y 1 sulphide undergo solvolysis in 80 % aqueous ethanol 106-106-fold faster than their cis-i~omers.~~ Electron-releasing substituents in the para-position of the phenyl ring increase? and electron-withdrawing substituents decrease? the rates for the trans-compounds (p values are -1.431 and -1.388 at 30") but have no effect on the rates of the cis-isomers.The trans-isomers there- fore react with nucleophilic participation of the thioether group I 5 1 / \ >c-c - >c,-c,< c1- A A" A trans-configuration is however not a sufficient condition for participa- tion; it is also necessary that the molecule be sufficiently flexible to allow the thioether group a- and /3-carbon atoms and the leaving group to be in one plane in the transition state.Thus the rigid trans-chloro-sulphide (79) undergoes solvolysis only four times as fast as its cis-i~omer.~~ It therefore seems likely that the cyclohexyl and cyclopentyl compounds would have to react by way of the conformations (80) and (81). Participation of a thioether group to yield 5- and 6-membered cyclic sulphonium ions may also occur (see results in Table 12).71 The anchimeric assistance decreases with ring size in the order 3 > 5 > 6. The ethylthio-group provides more anchimeric assistance than the * For a recent review see Gundermann Angew. Chem. Internat. Edn. 1963,2,599. 67 See papers cited by Streitwieser Chem.Rev. 1956,56,678. See Chapman and Triggle J. 1963 1385 and earlier papers. 6* Goering and Howe J. Amer. Chem. SOC. 1957 79 6542. 'O Cristol and Arganbright J. Arner. Chem. Soc. 1957 79 3441. 71 Bohme and Sell Chem. Ber. 1948 81 123. 66 QUARTERLY REVIEWS TABLE 12. The rates of solvolysis of some w-chloroalkyt phenyl sutphides. 50% Aqueous acetone 20 mole % Aqueous dioxan at 80O.71 at 100°.72 102k (min.-l) 10% (min.-l) 5.5 PhS. [CH,]g*Cl - PhS. [CH,]*Cl 6.5 1 - 1 PhS. [CH2]5*CI 0.085 - C,H1&1 - 0053 phenylthio-group ; 2-chloroethyl ethyl sulphide for example undergoes solvolysis about forty times faster than 2-chloroethyl phenyl ~ulphide.~' This may be ascribed to a decreased nucleophilicity of the phenylthio- groups because of delocalisation of the electrons on the sulphur throughout the phenyl ring as represented by resonance between structures (82)-(85).PhS. [CH,],.Cl - 0.029 (82) (83) 034) (85) Probably the most thoroughly studied reactions involving participation by a thioether group are those of 2,2'-bischloroethyl sulphide (mustard gas) (86) which readily undergoes cyclisation to the ion (87). Competition factors of a large number of nucleophiles for the ion (87) have been m e a s ~ r e d . ~ ~ ~ ~ Participation by Halogeno-groups Evidence for nucleophilic participation by halogeno-groups comes both from kinetic measurements and from the configuration of certain reaction products. The rate of formation of titratable acid in acetic acid solutions of trans-2-bromocyclohexyl p-brom~benzenesulphonate~~ is appreciably faster than would be expected for its unassisted acetolysis as estimated by the rate for the cis-isomer7* and from the p*o* correlation for other cyclohexyl p-brornobenzenesulphonates.ll trans-2-Iodocyclohexyl toluene p-sulphonate is unstable and liberates titratable acid about 1000 times faster than cyclohexyl toluene-p-sulphonate when dissolved in acetic acid.17 Unfortunately the products of these reactions have not been determined Ogston Holiday Philpot and Stocken Trans.Faraday SOC. 1948,44,45; see 7 2 Bennett Heathcoat and Mosses J. 1929 2567. 74 Grunwald J. Amer. Chem. SOC. 1951 73 5458. Bartlett and Swain J. Amer. Chem. Soc. 1949 71 1406. CAPON NEIGHBOURING GROUP PARTICIPATION 67 but the results at least suggest the occurrence of participation by the bromo- and iodo-groups to yield the bromonium and iodonium ions (88) and (89).(Bromonium ions have of course also been postulated as intermediates in the addition reaction of bromine with 01efins.~~) trans-2-Chlorocyclo- hexyl p-bromobenzenesulphonate does not react abnormally fast in acetic Among reactions whose products suggest the incursion of bromonium ions are those of dl-erythro- and d2-threo-3-bromobutano1 (90) and (9 l) with concentrated hydrobromic acid.?g These yield meso- and dl-2,3-dibro- mobutane (92) and (93) respectively and the racemic product is also (88 obtained from the optically active threo-bromobutanol. Hence these reac- tions proceed with retention of configuration by way of symmetrical inter- mediates which are most likely the bromonium ions (94) and (95). Similar results indicate the incursion of the corresponding iodonium ions in the reaction of the 3-iodobutan-2-01s with concentrated hydrochloric and hydrobromic acid.77 The corresponding chloronium ions are however formed much less readily but there is some evidence for their incursion in the reactions of the 3-chlorobutan-2-01s with thionyl chloride.7s Br Me Me.../+ 0r \ ...*Me - ;c-c - H 'H 1.951 That nucleophilic participation by halogeno-groups increases in the order Cl<Br<I is of course to be expected from the known ease with which these elements increase their valency. The conformational requirements for nucleophilic participation by a bromo-group were investigated by Alt and Barton.79 They found that whereas the diaxial 2~-bromocholestan-3a-ol readily underwent reactions (e.g. with PBr and PCl,) which appeared to involve participation by the bromo-group the di-equatorial isomer 2a-bromocholestan-3~-01 did 75 Roberts and Kimball J.Amer. Chem. SOC. 1937 59 947; see also Traynham J. Chem. Educ. 1963,40,392. 76 Winstein and Lucas J. Amer. Chem. SOC. 1939 61 1576 2845. 77 Lucas and Garner J. Amer. Chem. SOC. 1950,72,2145. '* Lucas and Gould J. Amer. Chem. SOC. 1941 63,2541. 70 Alt and Barton J. 1954,4284. 68 QUARTERLY REVIEWS not. It thus appears that as found with participation by a thioether group (see p. 65) a trans-planar arrangement of participating and leaving groups is highly favourable for participation. Interesting examples of bromine and iodine participation occur in the acid-catalysed addition of hypochlorous acid to allyl bromideSo and iodide,s1 which yield besides the normal addition products 28% of 2- bromo-3-chloropropene and 45 % of 3-chloro-2-iodopropene formed by the rearrangement shown in Scheme (XV).The corresponding reaction of allyl chloride with hypobromous acid yields very little rearranged product because of the much smaller tendency of chlorine to participate. Participa- tion by the hydroxyl and acetoxy-groups in the addition of chlorine and bromine to the double bonds of allyl alcohol and acetate also does not occur.s2 CI CI OH I (XV) C Hz =C H - C HaX+ C I0 H +C La-C H-C Ha +C H p - C H - 2 H p I (X=Br or I) \x+/ X Evidence of nucleophilic participation by a more remote iodo-group [see Scheme (XVI)] is provided by the ob~ervation~~ that treatment with mercuric chloride in chloroform replaces one of the iodo-groups of several 1,4-di-iodoalkanes with chloride but that the second iodo-group is inert.Neighbouring Ester Groups The acetoxy-group MeCO.0 is electron-withdrawing and has a strong retarding effect on reactions in which a carbonium ion is generated at an adjacent atom. Thus the rate of acetolysis of cis-2-acetoxycyclohexyl toluene-p-sulphonate is about one two-thousandth that of cyclohexyl toluene-p-sulph~nate.~~ The acetolysis of the isomeric trans- toluene-p- sulphonate (96) proceeds however almost as fast as that of cyclohexyl toluene-p-~ulphonate,~~ and yields in the presence of potassium acetate the tram- diacetate formed with retention of configuration ; when optically active material is used it yields a racemic The symmetrical ion (97) is therefore an intermediate. Solvolyses in wet acetic acid in absolute so de la Mare Naylor and Williams J.1962,443. 8B Summerbell and Forrester J. Org. Chem. 1961 26,4834. 86 Winstein Hew and Buckles J. Amer. Chem. SOC. 1942 64 2796. de la Mare Naylor and Williams J. 1963 3429. Winstein and Goodman J. Amer. Chem. Soc. 1954 76 4368. Winstein Grunwald Buckles and Hanson J. Amer. Chem. Soc. 1948 70 816. CAPON NEIGHBOURING GROUP PARTICIPATION 69 alcohol or in dry acetic acid in the absence of potassium acetate yield mainly products with a &configuration formed probably by way of derivatives of the ortho acid [e.g. (98)].85 Similar behaviour is observed with the acyclic compounds erythro- and threo-2-a~etoxy-3-bromobutane,~ and erythro- and threo-3-acetoxybut-2-yl toluene-p-sulphonate.88 The carbohydrate field is particularly rich in examples of neighbouring acetoxy-group participation.Two recently reported examples occur in the Q &ay) - a o.Ic"o __t Ace- Q __c @ (96) OTS (97) OAc AcO AcOH formation with retention of configuration of an a-linked disaccharide from the reaction of tetra-0-acetyl-am-mannopyranosyl bromide with 1,2,3,4-tetra-O-acetyl-/3-~-glucose [Scheme (XVII)],87 and in the opening of the epoxide ring of methyl 2-0-acetyl-3,4-anhydro-a-~-altroside in aqueous acetic acid [Scheme (XVIII)]88 to yield a mannose derivative almost exclusively. In the absence of participation predominant formation of the idose derivative (99) would be expected through diaxial ring- opening similar to that found with the unacetylated epoxide.88 (XVI I) Br I Minor OAC reaction CH;Ok OR - -4- b.0 we f An interesting example of ionisation proceeding concurrently with and without neighbouring group participation occurs in the sulphuric acid Lucas Mitchell and Garner J.Arner. Chem. SOC. 1950,72,2138. Gorin and Perlin Canad. J. Chem. 1959 37 1930. Buchanan and Schwarz J. 1962,4770. 70 QUARTERLY REVIEWS catalysed anomerisation of glucose penta-acetates in acetic acid.89 The rates of anomerisation and acetate-exchange of the a-anomer are identical but the /3-anomer undergoes acetate exchange about 15 times faster than it undergoes anomerisation. Hence in addition to the reactions in which the a- and /I-anomers are interconverted which by the principle of micro- scopic reversibility must involve the same transition state [as (loo)] the /I-anomer must have a pathway for undergoing acetate exchange without anomerisation by way of the ion (101) formed by neighbouring group participation.An example of Ac0-6 participation has recently been re- ported.g0a OAC it " (101) An interesting speculation has been madeg0 that an intramolecular SN2' mechanism occurs in the second stage of the reaction of trans-3,5- dibromocyclopentene with tetramethylammonium acetate in acetone.91 It is known that a cis-arrangement of entering and leaving groups is favourable for this mechani~rn,~~ and hence it is not unreasonable to sup- pose that the postulated intermediate (102) would react as shown to yield cis-3,5-diacetoxycyclopentene. Up to now only reactions involving intramolecular nucleophilic dis- placement of a group in the alcohol portion of esters have been considered but reactions in which the displaced group is in the acid portion are also Lemieux Brice and Huber Canad.J. Chem. 1955 33 134; see Capon and Over- end Adv. Carbohydrate Chem. 1960 15 42 for a mechanistic interpretation. O0 (a) Kovics Schneider and LAng Proc. Chem. Suc. 1963 374; (h) Saegebarth J. Org. Chem. 1960,25 2212. s1 Owen and Smith J. 1952 4042. O2 Stork and White J. Amer. Chem. SOC. 1953 75,4119; 1956 78,4609. CAPON NEIGHBOURING GROUP PARTICIPATION 71 possible. An example of such a reaction is the solvolysis of 2-phenoxycar- bonyldiphenylmethyl bromide (102a) in aqueous acetone which is 60-80 times faster than that of its LGisomer and yields 3-phenylphthalide (103).93 The corresponding o-methoxy-carbonyl compound is so reactive that attempts to prepare it yield only 3-phen~lphthalide.~~ Participation does not occur in the solvolysis of the fluorene ester ( 104),94 presumably because the geometry of the molecule does not allow rearside attack by the ester group at position 9.Me Ph. H& a P &?-m-R@m-pg ~ I 1 (1 02a) (103) \i 04) A similar intramolecular nucleophilic attack by an ester group on iodine occurs in the dissociation of the dichloride of methyl 2-iodobenzoate in acetic acid as shown in Scheme (XIXhg5 Participation by Amide Groups Amides are ambident nucleophiles and examples of nuclesphilic partici- pation involving attack by both the nitrogen and oxygen atoms of amide groups are known. When rings of the same size would result from either 0- or N-attack 0-attack is generally favoured with un-ionised amide groups but N-attack is favoured with their conjugate bases.Thus when fused with alkali 4-bromo-N-cyclohexylbutyramide (105) yields the pyrrolidone (106) but when fused alone it yields the tetrahydrofuran derivative (107).06 The relative importance of N- and U-attack may however be governed by the sizes of the resulting rings when these are different. For example 005) (107) 93 Singh Andrews and Keefer J. Amer. Chem. Soc. 1962,84 1179. 94 Lovins Andrews and Keefer J. Amer. Chem. SOC. 1962 94 3959. 96 Andrews and Keefer J Amer. Chem. SOC. 1959 81,4218 5329. Stirling J. 1960 255. 72 QUARTERLY REVIEWS N-(2-bromoethyl)-4-chlorobenzamide (1 OS) on reaction with sodium methoxide in methanol yields the oxazoline (109) by 0-5 participation rather than the aziridine (1 10) by N-3 parti~ipation.~~" trans-2-Benz- amidocyclohexyl toluene-p-sulphonate with sodium ethoxide in ethanol however yields a mixture of the corresponding aziridine and oxa~oline.~~ The ethanolysis of trans-2-benzamidocyclohexyl toluene-p-sulphonate in the presence of potassium acetate which yields an oxazolinium ion is about 1000 times faster than that of the cis-isomer and about 200 times faster than that of trans-2-acetoxycyclohexyl toluene-p-sulphonate.g8~gg In the presence of strong bases participation by amide groups becomes much more effective owing to conversion into the more highly nucleophilic con- jugate bases (see Table 13).loo The measured second order rate constant km is then equal to the product of the equilibrium constant for the forma- tion of the conjugate base and the rate constant for its ring-closure km=Kk.The rate-accelerating effect of an ionised amide group may be judged by comparing the value of km for the reaction of 4-bromo-N- phenylbutyramide with sodium methoxide in methanol at 22-90' (3 x TABLE 13.Participation by ureido- and urethano-groups.lOO Fi'h yaph. yaph F t-JH YH Y SJ" ?h TCO /co HVC0 ,co HY Compound aiCH2Br CH2CH2Br C\CH,Br &U-$Br CHiCHsCli@ ( I l l ) (112) (I 13) (114) (I 15) Solvolysis in 80% ethanol at 50" lo% (sec.-l) 110 45.4 2.56 3.36 0.18 Type of participation 0-5 0 - 5 0 - 5 0 - 5 0 - 6 Solvolysis in absolute ethanol containing sodium ethoxide. at 25". 1 05k (1. mole'-lsec.-l) 13000 1360 1.5 x lo5 1-2 x 10' >lo5 Type of participation 0-5 N-5 N-5 N-5 N-6 O7 (a) Heine J. Amer. Chem. Soc. 1956 78 3708; (6) Taguchi and Kojima ibid. O8 Winstein Goodman and Boschan J.Amer. Chem. Soc. 1950 72,2311. loo Scott Glick and Winstein Experientza 1957 13 183. 1959 81 4316; see also Buss Hough and Richardson J. 1963 5295. Winstein and Boschan J. Amer. Chem. Soc. 1950,72,4669. CAPON NEIGHBOURING GROUP PARTICIPATION 73 1. mole-lsec.-l)lol with the second-order constant for the displacement reaction of propyl bromide with sodium ethoxide in ethanol at 55" (5.5 X lo-* 1. mo1e-1sec.-1).102 A preliminary report of an investigation on the participation of ureido- and urethano-groups appeared in 195710O but at the time of writing (June 1963) full details are still awaited. In neutral solution both thesegroups provide less anchimeric assistance than the amido-group [cf. compounds (1 1 l) (1 12) and (1 13) in Table 131 and 0-attack predominates.In basic solution N-attack occurs and the values of km decrease in the order urethano > amido > ureido. Comparison of the results for compounds (114) and (115) (Table 13) shows that 0-5 is more effective than 0-6 urethano-participation. Sicher and his co-workers have made an interesting investigation on the neutral ethanolysis of some 2-benzamidocyclohexy1 methanesulphonates in which conformational movements were restricted by a t-butyl group in the 4-position (Table 14).lo3 The high rate for the di-axial compound (1 17) TABLE 14. Rates of ethanolysis of some 2-benzamidocyclohexyl methane- sulphonates in the presence of potassium acetate.lo3 O.Mes ==; Bu' 4 ~ U t ~ I k S (1 16) (117) NH-COPh (I 18) 10% (sec.-l) 352 628n 76-2 OMes & ,.t&l-lCOf% NH-m 10% (s~c.-') 0.687 0.692 2.95 shows that such an arrangement is highly favourable for participation but the only slightly slower rate for compound (1 18) compared to compound (I 16) indicates that in these di-equatorial compounds participation can occur without inversion to the other chair conformation.Examples of participation of amido-groups in addition reactions to olefinic double bonds are also k n o ~ n . ~ ~ J ~ [See e.g. Scheme (XX)]. ooo p B r + - ca" - 01" HN OH bh H'yC '@ HN C y o Ph ;yn" OH lol Heine Love and Bore J. Amer. Chem. SOC. 1955 77 5420. loe Dhar Hughes Ingold and Masterman J. 1948 2055. loS Sicher Tichy SipoS and PafikovA Proc. Chem. Soc. 1960 384; Coll. Czech. lo6 Goodman and Winstein J. Amer. Chem. SOC. 1957 79 4788. Chem. Comm. 1961 26 2418. 74 QUARTERLY REVIEWS The importance of amide participation in the reactions of peptides and their derivatives is becoming increasingly recognised.lo5 A striking example is afforded by the hydrolyses of the /3-benzyl esters of N-benzyloxy- carbonyl-~-aspartyl amide and methylamide (1 19) which occur in alkaline solutions with nucleophilic participation by the amide groups (N-attack).loB The hydrolyses of the resulting imides (120) are the slow steps and the imides have been isolated from the reaction solutions.Nucleophilic parti- cipation by an amide group with O-attack occurs in the acid-catalysed hydrolysis of O-benzamido-NN-dicyclohexylbenzamide [see Scheme (XXI) for the probable mechani~rn1.l~~ The rate of hydrolysis of this corn- pound is at least lo4 times greater than that for NN-dicyclohexylbenza- mide but part of this increase in rate may be due to steric acceleration.Other examples of amide participation in peptide chemistry are found in the specific cleavage of the peptide linkage adjacent to an S-alkylated methionine residuelo8 [see Scheme (XXII)] and in the Edman procedure for the removal of terminal amino-acid residues.log In this procedure the free amino-groups of the peptide are allowed to react with phenyl isothio- lo5 See Cohen and Witkop Angew. Chem. 1961 73 253. lo6 Bernhard Berger Carter Katchalski Sela and Shalitin J . Amer. Chem. SOC. lo' Cohen and Lipowitz J. Amer. Chem. Sx. 1961 83 4866; see also Shafer and lo* Lawson Gross Foltz and Witkop J . Arnev. Chem. SOC. 1962,84 1716. log Edman Ada. Chem. Scand. 1950 4 283. 1962,84 2421. Morawetz J. Org. Chem. 1963 28 1899.CAPON NEIGHBOURING GROUP PARTICIPATION 75 v I' S*CH&O.NH v 'I ;!ji-CI-$CO-NY R$H*NH=C-$H o'/c-$H a 2 H N H d NH-COR' + RCH(NH&H cyanate and the resulting thiourea derivative is allowed to hydrolyse with N-participation [See Scheme (XXIII) 1. (XXIII) FI-NCS + YNCHRCONHR' - P~NHG-NHCHRCONHR' I An interesting example of amide participation occurs in the Diels-Alder reaction between N-isobutylsorbamide (1 21) and maleic anhydride which yields compound ( 122).Ilo It is not known whether the amide participation occurs concurrently with or subsequent to the Diels-Alder addition. Neighbouring Carboxyl and Carboxylate Groups Reactions at Saturated Carbon Centres.-There appears to be no clear evidence for participation by the un-ionised carboxyl group in substitution reactions at saturated carbon.The ionised carboxyl group however provides considerable anchimeric assistance as is seen from the high rates of hydrolysis of 5-chlorovaleric and 4-chlorobutyric acid in sodium hydrox- ide solution and the independence of these rates on the concentration of sodium hydroxide (Table 1 5).30 If this participation were nucleophilic the initially formed products would be the corresponding lactones [see Scheme (XXIV)] and this is almost certainly so since it has been shown that in neutral solution sodium 4bromobutyrate yields the lacfone,lll but of course in alkaline solutions the lactones are rapidly saponified. n Crombie and Manzoor-I-Khuda J. 1957 2767. ll1 Caldin and Wolfenden J. 1936 1239. 76 QUARTEaLY REVIEWS The occurrence of CO,-4 participation is shown by the isolation of several /3-lactones from the hydrolysis of salts of the corresponding bromo- acids.112 The anchimeric assistance however is not large; sodium 3- bromobutyrate for instance is hydrolysed about five-fold faster than isopropyl bromide (see Table 1 5).l13 TABLE 15.The kinetics of solvolysis of halogeno-acids. First-order rate constants (set.?) Solvent 4-Chlorobutyric acid 5-Chlorovaleric Propyl chloride in 0. SM-NaOH 3-96 x 10-5 1.70 x 10-4 - at 3i'.So3O acid30 at 50-0" water at lW"t O-~M-N~OH 4-05 x 10-5 1-73 X 10"' 6.81 x 10-5 3-Bromobutyrate 2-Bromopropionate Isopropyl ionlls bromide 3.0 x 10-5* H20 at 38" 1.5 x 1W - H20 at 25" - 4.2 x 10-7 7.0 x 5-12 x 10-5 2.3 x MeOH at 64" - *Extrapolated from results at higher temperatures; Leffek Robertson and Sugamori Canad.J. Chem. 1961 39 1989. t Laughton and Robertson Canad. J. Chem. 1959 37 1491. The solvolyses of the anions of a-halogeno-carboxylic acids in slightly alkaline solutions yield products of retained and hence C02-3 participation is occurring [Scheme (XXV)]. The intermediate a-lactones have however never been isolated. The rate of methanolysis of the 2-bromopropionate ion is about twenty times greater than that expected for isopropyl bromide115 (see Table 15). For hydrolysis in water however these reactivities are reversed because the solvolysis of isopropyl bromide is sensitive to solvent effects but that of the 2-bromopropionate ion is not.115 This insensitivity to solvent effects and to salt effects and the high rate in methanol are good evidence that the rate-determining step of the solvolyses of the a-bromopropionate ion involves a direct intramole- cular displacement by the carboxylate group.If the reaction involved a prior ionisation followed by ring-closure the typical high dependance of S,l reactions on solvent effects would be expected. Reactions of Carboxylic Acid Derivatives.-Examples of intramolecular participation by the carboxylate ion in displacement reactions at carboxyl lla Johansson Ber. 1915 48 1262; Johansson and Hagman ibid. 1922 55 647. 113 Lane and Heine J. Amer. Chem. Soc. 1951 73 1348; Heine Becker and Lane 114 Cowdrey Hughes and Ingold J. 1937,1208,1243 and references cited by Cowdrey ibid. 1953 75 4514. Hughes Ingold Masterman and Scott ibid. p. 1262. Grunwald and Winstein J. Amer. Chem. Soc. 1948 70 841. CAPON NEIGHBOURING GROUP PARTICIPATION 77 carbon are also known.The hydrolyses of phenyl hydrogen succinate and glutarate are particularly fast at pHs at which the carboxyl group is ionised (see Table 16).l16 The rate for phenyl hydrogen succinate is almost TABLE Phenyl Phenyl 16. The kinetics of the hydrolyses of phenyl hydrogen succinate and glutarate.lI6 lo4k (sec.-l) at 25.3" pH 5.0 pH 7.0 hydrogen succinate 11 14-2 hydrogen glutarate - 0.1 k for phenyl acetate in O-OShi-acetate buffer at pH 5-27 and 60.8" = 1.25 x lo-6sec.-1 independent of pH in the region 5-10 and decreases at lower pH's where the carboxyl group becomes protonated. Hence intramolecular participa- tion by the carboxylate-ion group is occurring. Although no definite evidence has been provided for these reactions there is evidence for nucleo- philic participation in the hydrolyses of two closely analogous esters.These are acetylsalicylic acid discussed below and the mono-p-methoxyphenyl ester of 7-oxabicyclo [2,2,1 ]hept-2-ene-5,6-exo-dicarboxylic acid. The hydrolysis of the latter has been S~OWIP~ to yield phenol and a neutral (123) 8 intermediate which is itself hydrolysed at rates identical with those of the anhydride (123) and hence is presumably the anhydride. The hydrolysis of the succinate and glutarate may therefore be formulated similarly as in Scheme (XXVI) but with these the subsequent hydrolyses of the an- hydrides are fast compared to the ring closures. Participation by the carboxylate ion also occurs in the hydrolysis of acetylsalicylic acid118JlD and probably in that of methyl hydrogen phtha- late.llD The pH-rate profiles between 2.5 and 7.0 for these reactions follow the ionisation curves for the carboxylic acid groups; the rates being pro- portional to the concentration of the ionised forms.(The results for methyl 116 Gaetjens and Morawetz J. Amer. Chem. SOC. 1960 82 5328. 11' Bruice and Pandit J. Amer. Chem. SOC. 1960,82 5858. "*Edwards Trans. Farahy SOC. 1950 46 723; 1952 48 696; Garrett J. Amer. llS Bender Chloupek and Neveu J. Amer. Chem. SOC. 1958,80 5384. Chem. SOC. 1957 79 3401. 78 QUARTERLY REVIEWS hydrogen phthalate119 have been questioneds2 on the grounds that similar results were not obtained with ethyl hydrogen phthalate.) At pH 6.0 acetylsalicylic acid is hydrolysed about eighty times faster than p-acetoxy- benzoic acid,120 and at pH 5-5 methyl hydrogen phthalate is hydrolysed about ten times faster than methyl benzoate.ll9 Hydrolysis of acetyl- salicylic acid in water enriched in oxygen-1 8 yields salicylic acid enriched in oxygen-18 approximately to the (small) extent that would be expected if acetylsalicylic anhydride were an intermediate.'19 The hydrolysis there- fore probably proceeds as shown in Scheme (XXVII).+ MeC0,'- The hydrolysis of phthalamic acid differs from those of the esters just discussed in being more rapid at pH's at which the carboxyl group is un-ionised than at those where it is ionised;121 in 10-3~-hydrochloric acid the rate is 75,800 times greater than that for benzamide. The reaction in- volves intramolecular nucleophilic participation with phthalic anhydride as an intermediate since when phthalamic acid in which the amide carboxyl group is specifically enriched in carbon-13 is allowed to hydro- lyse in water enriched in oxygen-1 8 the oxygen- 18-enriched carbon dioxide obtained from the resulting phthalic acid comes from both carbon- 13- enriched and non-enriched carboxyl groups [see Scheme (XXVIII)].121 The rate law may be written CO*NH2 where Ka= [ C6H czkf""B The reaction cannot involve a simple intramolecular displacement by the carboxyl group since if' this were so the carboxylate group would be expected to be more effective.Bender et prefer a mechanism [Scheme (XXIX)] involving simultaneous nucleophilic attack and proton transfer to the amide nitrogen ("intramolecular nucleophilic-electrophilic cata- lysis'') but the results are equally consistent with an intramolecular dis- placement by the carboxylate group on the protonated amide [Scheme (XXX) I* 120 Schmir and Bruice J.Amer. Chem. SOC. 1958,80 1173. 181 Bender Yuan-Lang Chow and Chloupek J. Amer. Chem. SOC. 1958 80 5380. CAPON NEIGHBOURING GROUP PARTICIPATION 79 0 0 The Carboxyl-group as an Intramolecular Acid Catalyst.-The possibility of participation by a carboxyl group acting as an intramolecular general- acid catalyst seems to have been first considered by Ingold for the re- arrangement of substituted alkyl hydrogen phthalates [as in Scheme (Xxxl)] but the suggestion was not pursued.122 More recently Morawetz and his co-workers have demonstrated that such participation occurs RCH=CH-rR’ ?3HO 5 a$/ R-FH -G= CH R’ q*B (XXXI) =& - \ / concurrently with nucleophilic participation by an ionised carboxyl group in the hydrolysis of the ester (124)123 and the amide (125)12* (intramole- cular bifunctional catalysis).The pH-rate profiles for both of these reactions are bell-shaped curves indicating that the half-ionised forms are more reactive than either the un-ionised or the fully ionised. At the rate maximum at pH 3.8 the ester (124) is hydrolysed 24,000 times more rapidly than acetylsalicyclic acid and 66 times more rapidly than the di-ester (126). The high reactivity of the half-ionised form could result from reaction by way of either of two pathways (see Scheme (XXXII)] differing in which group acts as nucleophile and which as general acid. Kinetically these pathways are equivalent and hence additional information such as the trapping of an intermediate is required to distinguish between them.Similar pathways are available for the hydrolysis of the amide (125). However what is probably the most striking example occurs in the hydrolysis of o-carboxyphenyl /?-~-glucopyranoside.~~~ This reaction shows la2 Ingold “Structure and Mechanism in Organic Chemistry,” Cornell University Press Ithaca N.Y. 1953 p. 596. 123 Morawetz and Oreskes J. Amer. Chem. SOC. 1958 80 2591. la‘ Morawetz and Shafer J. Amer. Chem. SOC. 1962 84 3783. lZ6 Capon Tetrahedron Letters 1963 91 1. 80 QUARTERLY REVIEWS L 0 a sigmoid pH-rate profile indicating a dependence of rate on the con- centration of the un-ionised species and at pH 3-5 the rate is about 104 times faster than that for p-carboxyphenyl 6-D-glucopyranoside. As in the hydrolysis of phthalamic acid the rate law is consistent with the reactive species being the un-ionised form or with a specific acid-catalysed reaction of the ionised form.In view of the known susceptibility of glycoside hydro- lysis to acid catalysis and the lack of reactivity of glucopyranose derivatives to nucleophilic attack at C, it seems reasonable to ascribe the high reac- tivity to general-acid catalysis operating as shown in Scheme (XXXIII). Addition Reactions.-Neighbouring group participation by a carboxyl group in the addition of halogens to olefinic double bonds has been ob- served by several ~orkers.1~~,~2~ The addition of iodine in the presence of sodium iodide and sodium hydrogen carbonate is probably the most systematically studied of these reactions and the results obtained (Table 17) indicate that the formation of y-iodo-lactone occurs most readily.la7 TABLE 17.Carboxylate participation in the addition of iodine to otefinic double bonds.127 Reactant Product CH,.CH =CH.C02H No iodo-lactone CHa= CHCHaC02-H CH,-CH = CHCH,*COBH CHa=CH*CHa.CHa.COaH CHa=CH*CHlCHa*CHa*C02H No iodo-lactone l-0-1 CHMe.CHI.CH,-CO ,-0- CH(CH,I)CH,CH,-kO kH(CH,I)*CH,-CH,CH,.CO* 0 I Arnold de Moura Campos and Lindsay J . Amer. Chem. SOC. 1953 75 1044; Arnold and Lmdsay ibid. p. 1048; de Moura Campos ibid. 1954 76 4480; Tarbell and Bartlett ibid. 1937,59,407. la' van Tamelen and Shamma J. Amer. Chem. SOC. 1954,76 2315. CAPON NEIGHBOURING GROUP PARTICIPATION 81 The mechanism is probably as shown in Scheme (XXXIV). The pH-rate profile for the hydration of fumaric to malic acid is a bell- shaped curve indicating that the mono-anion is especially reactive.It has been suggestedlZ8 that both the carboxylic acid and carboxylate groups participate the reaction proceeding through the lactonic acid (1 27) as shown R - H ,Cb 0 H\ H4F-F”0 __c $qco2H c-0 Y L S J - 0 - 4 c %,C’ co2- 6 b (127) Participation by Imidazole Groups Several examples of neighbouring group participation by an imidazole nucleus in ester and amide hydrolyses have been investigated by Brrice and his co-workers. Interest in these reactions has been stimulated by the likely possibility of participation by an imidazole group of histidine in reactions catalysed by several esterases and proteinases. Aryl esters (129) but not the methyl ester of 4-4’-imidazolylbutyric acid are hydrolysed at greatly enhanced rates in neutral solution the rate increase for the p- nitrophenyl ester being approximately 3 x 104.129a The pH-rate profiles for the hydrolyses of the aryl esters show that the rates are approximately proportional to the concentration of the unprotonated forms of the imi- dazoles but they do not follow exactly the expected ionisation curve (as determined for the methyl ester) and the apparent pKa’s vary with the substituents in the aryl residue.Since these substituents would not be expected to influence the true PKa of the imidazoyl group these results suggest that there is an additional substituent-dependent equilibrium and Bruice and Sturtevant have that this is the formation of the tetrahedral intermediate (1 30). Kinetic analysis of the reaction series (128)+(131) then shows that Kapp.= K,(K + 1). In this mechanism the imidazole group participates by acting as a nucleophile but a kinetically a m r & 22 Q&LQ0 Nz,) + ArOH H N < + ~ 0 H N 4 0 N V (1 28) (1 29) (130) 12* Bender and Connors J. Amer. Chem. Suc. 1962,84,1980. lZ9 (a) Bruice and Sturtevant J. Amer. Chem. Soc. 1959 81 2860; (b) See Bender Chem. Rev. 1960,60,78. 4 82 QUARTERLY REVIEWS equivalent scheme in which it acts as a general base is formally possible although unlikely in view of the known tendency of imidazole itself to act as an intermolecular nucleophilic catalyst in the reactions of aryl esters.129 In the hydrolysis of the analogous thiol ester (132) however nucleophilic participation has been demonstrated unequivocally by following the forma- tion and decomposition of the intermediate lactam (1 3 l ) spectrophoto- metri~ally.l3~ This ester hydrolyses at a rate 3 x lo6 times that expected in the absence of imidazole participation.The pH-rate profile for the hydrolysis of the amide of 4-4'-imidazolyl- butyric acid differs from that for the aryl ester and n-propyl thiol-ester in showing a rate-dependence on the concentration of the protonated form.129a This behaviour is analogous to that found in participation by the carboxyl group (see p. 78) and in the amide hydrolysis the imidazole group possibly acts as an intramolecular nucleophilic-electrophilic catalyst [see (134)l. Examples of imidazole participation in ester hydrolysis when the irni- dazole group is in the phenol portion of the ester are also known. The rate of hydrolysis of 4-(2-acetoxyphenyl~imidazole depends on the con- centration of the unprotonated i m i d a z ~ l e .~ ~ ~ ~ ~ ~ At pH 6 at 30" the rate of hydrolysis is slightly faster than that for acetylsalicylic acid (Table 18) TABLE 18. A comparison of imidazole and carboxyl group participation in ester CO2H 104k (rnh-l) at pH 6 and 30" 15 40 0.05 and the hydrolysis probably involves intramolecular nucleophilic partici- pation as shown in Scheme (XXXV). lS0 Bruice J. Amer. Chem. SOC. 1959 81 5444. 131 Pandit and Bruice J. Amer. Chem. Soc. 1960 82 3386. CAPON NEIGHBOURING GROUP PARTICIPATION 83 Intramolecular imidazole participation occurs in the hydrolysis of the alkyl ester 4-(2- acetoxyethyl)imidazolelzga [see Scheme (XXXVI)]. Com- parison of Im-6 participation observed with this ester and Im-5 participa- tion which might be expected to occur in the hydrolysis of 4-(acetoxy- methyl)-imidazole is precluded because the latter undergoes hydrolysis with alkyl-oxygen fission132 [see Scheme (XXXVII)].Although methyl 4-4’-imidazolylbutyrate apparently does not undergo hydrolysis with participation of the un-ionised imidazole group like the phenyl esters since a plot of kobs. against uoH- goes through the origin the second-order rate constant for hydrolysis by OH- is about 20 times greater than that for methyl butyrate. This may be due to participation by the ionised imidazole group as shown in Scheme (XXXVIII).129a Neighbouring Aldehydo- and Keto-groups Nucleophilic participation by an aldehydo- or keto-group can occur in several ways. First by direct displacement=by the oxygen as in the solvo- lysis of the bromo-ketone (135) which is anchimerically assisted and yields the vinyl ether (136) as one of the Alternatively participation by the enol form may occur as in the ethanolysis of 6-0x0-cyclodecyl Me,+ 0 -& H2C+ -0 (135) ( 1 36) toluene-p-sulphonate (1 37) which yields a mixture of cis- and trans- bicyclo [5,3,0]decan-2-one ( 138).134 The rate of this reaction depends 132 Bruice and Fife J.Amer. Chem. SOC. 1961 83 1124. 133 Baddeley Baylis Heaton and Rasburn Proc. Chem. Soc. 1961 451. 13* Goering Olson and Espy J. Amer. Chem. Soc. 1956 78 5371. 84 QUARTERLY REVIEWS partly on the rate of enolisation and hence the reaction is acid-catalysed. n 0 (138) In the presence of bases ionisation to an ambient enolate ion can occur and intramolecular displacement by both the carbon and oxygen ends of this ion is possible.The ion (139) formed by reaction of acetoacetic ester with up-dihalides undergoes cyclisation at carbon when n = 2 4 or 5 to yield a 3- 5- or 6-membered ring but at oxygen if n = 3 when the alternative product of carbon participation would be a four-membered ring.135 MeC-C- C02Et 8 $ C G Participation in a completely different way can occur through the addition products with nucleophiles. The most striking example to date is the hydroxyl-ion catalysed hydrolysis of methyl 2-formylbenzoate which proceeds lo5 times faster than would be expected from the electronic and steric effects of a formyl ~ubstituent.~~~ Probably the mechanism shown in Scheme (XXXIX) is followed. + MeOH The hydrolysis is also catalysed by morpholine and here the incursion of an intermediate has been demonstrated spectrophotometrically.136 Similar participation occurs in the hydrolysis of certain methyl substituted o-benzoylbenzoate~~~~ and of dimethylpho~phoacetoin.~~~ Participation by the ketone-carbonyl group frequently occurs in reac- tions at the acid-carbonyl group of keto-acids.Examples are found in the hydrolysis of ethyl acetoacetate which probably owes its high rate139 to 135 See Perkin J. 1929 1347. 136 Bender and Silver J. Amer. Chem. SOC. 1962 84 4589. 13' Newman and Shinzaburo Hishida J. Amer. Chem. SOC. 1962 84 3582. 13* Ramirez Hansen and Desai J . Amer. Chem. SOC. 1962 84 4588. 139 Goodhue and Dunlap J. Amer. Chem. SOC. 1928 50 1920. CAPON NEIGHBOURING GROUP PARTICIPATION 85 stabilisation of the transition state as shown in (140),140 and in the de- carboxylation of acetoacetic acid in which the ketone group is thought to act as a general base as shown in Scheme (‘XL).141 Participation by Oxime Groups Intramolecular displacement reactions by the ionised oxime group are an important synthetic method for isoxazoles [see Schemes (XLI) and (XLII)].142 A kinetic investigation of the reactions shown in Scheme (XLII) has been made by Bunnett and Yih.143 (X=F,Cl.Br.or 1) Participation by Neighbouring Carbon The subject of nucleophilic participation by carbon in reactions occur- ring at saturated carbon centres is intimately bound up with the roles played by classical and non-classical or bridged carbonium ions.144 The question to be answered for any reaction in which carbon migrates or is thought to participate is “does ionisation to the bridged ion occur directly [as in Scheme (XLIII)] or is a classical ion formed first followed by interconversion with another classical ion the bridged ion though possibly being the transition state [as Scheme (XLIV)] ?” Direct formation of a non-classical ion would mean that it is of lower free energy than the alternative classical ion and hence its formation should be associated with an increased rate.Hence reactions of this type which show enhanced rates are frequently written as involving direct ionisation to a bridged ion. The difficulty is however to decide what is an enhanced rate and to exclude 140 Bender Chem. Rev. 1960 60 70. 141 See Gould “Mechanism and Structure in Organic Chemistry,” H. Holt and Company New York 1959 346.14% See Quilico Speroni Behr and McKee “Five and Six-Membered Compounds with Nitrogen and Oxygen,” Interscience New York 1962; Scott Riordan and Hegarty Tetrahedron Letters 1963 537. 143 Bunnett and Yih J. Amer. Chem. Soc. 1961 83 3805. IQ4 See Bethell and Gold Quart. Rev. 1958 12 173. 86 QUARTERLY REVIEWS other causes for it especially steric acceleration. Product formation by nucleophilic attack on a bridged ion must be stereospecific [e.g. (141)+ (142) and (143) only] but nucleophilic attack on classical ions can be non- stereospecific [e.g. (144)+(145) and (146); (147)+(148) and (149)l. t 111 t Y x-q + A-c r;l (142) r;J (143) 111 $ + Y ? ;c-c< + :c-cc Neighbowing Aryl Groups.-(a) Ar-participation. Participation by neighbouring aryl groups occurs in the solvolysis of the conjugate bases of 2-(phydroxyphenyl)ethyl bromide (1 50)145 and 4-(p-hydroxyphenyl)bu tyl p-bromobenzenesulphonate (1 5 l).146 In favourable instances the inter- mediate dienones (152) and (153) have been isolated and the formation and decomposition of the dienone (1 52) has been followed spectrophoto- The anchimeric assistance for Ar,-3 participation is con- siderably greater than that for Arl-5 participation (see Table 19).The TABLE 19. A compdrison of A r l - 3 and Arl-5 p a r t i ~ i p a t i o n . ~ ~ ~ ~ ~ ~ -OCGH4CH2CH2Br MeO.C,H,-CH,.CH,Br Methanolysis 103k at 25" 0.86 - Ethanolysis 103k at 25" 1.3 2 x -OC6H4. [CH,],.OBs MeOC6H4. [CH,],.OBs Methanolysis 105k at 50" 8.9 1-08 analogous six-membered spirodienone is formed much less readily but has been prepared by heating the potassium salt of 5-(p-hydroxyphenyl)- pentyl bromide to 170" in t-butyl (b) Ar-3 participation in reactions at primary carbon centres.Participation by uncharged aryl rings also occurs but the anchimeric assistance is much lo5 Baird and Winstein J. Amer. Chem. Soc. 1963 85 567. 146 Baird and Winstein J. Amer. Chern. Soc. 1962 84 788. 14' Dreiding Helv. Chim. Acta 1957 40 1812. CAPON NEIGHBOURING GROUP PARTICIPATION 87 Iess. A well investigated example occurs in the acetolysis of 2-methyl-2- phenypropyl (neophyl) p-bromobenzenesulphonate (1 54) which proceeds about 80 times faster than that of isobutyl p-bromobenzenesulphonate to yield 33.4 % of the rearranged acetate (1 56) and 66.3 % of the rearranged olefin (1 57).14* The rate is increased by electron-releasing substituents in the p-position of the phenyl ring and decreased by electron-withdrawing substituents the rates being correlated by the a+ constants and the p constant being -2~96.l~~ Thus the rate-determining step involves an electrophilic attack on the aryl ring the ring acting as a nucleophile to give the phenonium ion (155).The two methyl groups in the neophyl compounds facilitate aryl participation (see p. 109 for a discussion of this - Q *-‘ 0 I + ) Q * . - Me,C-CH,F)h t Me,C=CHPh .I -. H CI--’CH 2 AAC Me & -CH,.OBs M e,C’-CH2 (154) (I 55) (1 56) (1 57) (I 58) effect) which occurs much less in the reactions of 2-phenylethyl com- pounds. The toluene-p-sulphonate for instance undergoes ethanolysis and acetolysis more slowly than ethyl toluene-p-~ulphonate,~~~ and experiments with the 14C-labelled compound show that little phenyl migration occurs (Table 20).15* In formolysis however the 2-phenylethyl TABLE 20.Rates of solvolysis of 2-phenylethyl and ethyl toluene-p- sulphonates at 75°.14991509151 Ethyl toluene-p-sulphonate 2-Phenylethyl toluene-p-sulphonate Solvent k A S k A S % Phenyl migration EtOH 2.95 x - 17.5 7.08 x -220.2 0.2 A~OH 7.7 x 10-7 - 16.7 2.88 x -17.3 4.6 compound reacts and there is considerable phenyl migration.150 Direct ionisation to the phenonium ion (158) therefore only occurs in the formolysis reaction and the ethanolysis and acetolysis probably proceed mainly by the SN2 mechanism. Unreacted 14C-labelled 2-phenylethyl toluene-p-sulphonate from the formolysis reaction is also partly re- arranged,152 and in the presence of 35S-labelled sodium toluene-p-sulphon- ate there is partial incorporation of the label into the rearranged 2-phenyl- ethyl toluene-p-sulphonate.This result indicates that the rearrangement probably proceeds partly through an intimate ion-pair and partly through 148 Heck and Winstein J. Amer. Chem. SOC. 1957 79 3432. 148 (a) Winstein Lindegren Marshall and Ingraham J. Amer. Chem. SOC. 1953 75 I5O Lee Slater and Spinks Canad. J. Chern. 1957 35 1417; see also Saunders 151 Winstein and Heck J. Amer. Chem. SOC. 1956 78 4801; see also Cram and 152 Lee Tkachuk and Slater Tetrahedron 1959,7,206. HCO,H 1-85 x 10-5 - 16.5 3.94 x 10-5 - 9.5 43.3 147; (b) Winstein and Marshall J. Amer. Chem. SOC. 1952 74 1120. Asperger Edison J. Amer. Chem. SOC. 1958 80,2421. Singer ibid. 1963,85 1075.88 QUARTERLY REVIEWS solvent-separated ion-pairs or free ions [see Scheme (XLV) 3. The entropy of activation for the formolysis of 2-phenylethyl toluene-p-sulphonate (Table 20) is more positive than that for acetolysis and ethanolysis and also than that for the solvolysis of the ethyl there being less loss of randomness on going to the transition state for the intramolecu- lar than for the intermolecular displacements. Further p-phenyl substitution in ethyl arenesulphonates and halides results in increased solvolysis rates (see Table 2l).l39l4 This probably TABLE 21. The efect of P-phenyl substituents on the rate of acetolysis of ethyl toluene-p-sulphonate at 75”. CH3*CH2*OTs PhCH,.CH,*OTs Ph2CHCH2*OTs Ph,C*CH,.OTs 107k (sec.-l) 7-7 2.9 27 3200 Ref. 149b 23 14 14 results from both an increased stability of the bridge ion (i.e.decreased transition-state free-energy) and from release of steric strain on going to this ion (i.e. increased initial-state free-energy). CH -CH 2-OTs in tima te * ,.**‘ ?h.,* CH2-CH Ph &; CH20Ts -0Ts -0Ts x Ph CHiCHiO -C HO PhZHi CHiO CHO t (c) Ar-3 participation in reactions at secondary carbon centres. Solvoly- sis studies on secondary arylalkyl arenesulphonates enable the steric course of reactions for which aryl participation is suspected to be studied. The first proposal for the incursion of a phenoniumion came in fact from such studies by Cram on the acetolysis of optically active erythro-l- methyl-2-phenylpropyl toluene-p-sulphonate (1 59) which yields the optically active erythro-acetate (160) with about 94 % retention of con- figuration and of the optically active threo-isomer (1 6 l) which yields CAPON NEIGHBOURING GROUP PARTICIPATION 89 almost racemic threo-acetate ( 162).153 These results may be explained by postulating the incursion of the intermediate phenonium ions (163) and ( 164),153 but are however also consistent with a rapidly equilibrating pair of classical ions [e.g.(1 65a) and (1 65b)] if their rate of interconversion were considerably faster than the rate of rotation about the C2-C3 bond and ( I 65a) (165b) if attack from the phenyl sides of the ions were prevented sterically. It has been that this might be so by analogy with the results obtained in the acetolysis of 1,2,2-triphenylethyl toluene-p-sulphonate which almost certainly reacts through a pair of classical ions (see below p.90) and which also yields acetate with some retention of configuration. The amount of retention observed155 (55 %) is however considerably less than that found with the 1-methyl-2-phenylpropyl compounds. The rates of acetolysis of the 1-methyl-2-phenylpropyl p-bromobenzenesulphonates are less than that of 1-methylpropyl p-bromobenzenesulphonate although when allowance is made for the rate decelerating effect of the phenyl group they are probably greater than would be expected if the reactions involved a direct ionisation to classical ions.14 The balance of evidence would therefore seem to support weakly anchimerically assisted ionisations to the phenonium ions (163) and (164). The acetolysis of one of the 2-(p- methoxypheny1)-1-methylpropyl toluene-p-sulphonates (1 66a) proceeds about 45 times faster than 1-methylpropyl toluene-p-sulphonate and hence almost certainly involves ionisation to the p-methoxyphenonium ion ( 166b).156 OMe 6 / -0 ,’ ..- @ M&J-$H.Me MeeCH-CHeMe Me. CH- FH-Me ( I66a) ( I 66b) OTs 0% In a very interesting investigation Collins and Bonner showed that the rate constants for the equilibration of the carbon-14 labels in 172,2-tri- phen yl [ 1 - 14C]ethyl acetate (1 67) and 1- [14C]phenyl-2,2-diphenylethyl acetate (168) to the randomly labelled mixtures of 50% (169) and 50% (170) and of 66.7 % (172) and 33.3 % (171) respectively and the rate constant for acetate exchange of 172,2-triphenylethyl [carb~nyZ-~~C]acetate (173) in acetic acid in the presence of toluene-p-sulphonic acid are 153 Cram J. Amer. Chem. SOC. 1949 71 3863.154 Brown in “The Transition State,” Chem. SOC. Special Publ. No. 16 1962 p. 152. 155 Collins Bonner and Lester J. Amer. Chem. SOC. 1959 81 466. lK6 Winstein Brown Schreiber and Schlesinger J. Amer. Chem. SOC. 1952 74 1140. 90 QUARTERLY REVIEWS identi~a1.l~’ Hence “statistical equilibration of each label occurs each time an acetoxyl group is removed from the discretely labelled starting material”. (1 67) (169) 50% (170) 50% (1 68) (171) 33.3% (172) 66.7% P hzC H-C* H P h .OAc -+ P h,CH-C * H P h.OAc + P h zC* H-CH P h.OAc PhzCH-CHPh*.OAc -+ Ph,CH-CHPh*.OAc + Ph,*CH-CHPh.OAc P hzC H-CH P h .OAc* -+ P h2CH-C H P h*OAc (173) The reaction cannot therefore proceed by way of the phenonium ion (1 74) since this would yield a 5050 mixture of the phenyl-labelled acetates. However incursion of a rapidly equilibrating pair of classical ions (175) and (176) would allow complete randomisation of each label before the product-forming step.A similar mechanism also probably operates in the acetolysis of 1,2,2-triphenylethyl t~luene-p-sulphonate,~~~ for which the chain-labelled compound yields 40 % and the ring-labelled 47 % of the re- arranged acetates. These results were shown to be mutually consistent if the reaction proceeded through a pair of rapidly equilibrating classical ions in which either phenyl group had an equal chance of migrating. The results are only consistent with the incursion of non-classical ions in the unlikely event that the acetolysis were preceded by a rapid equilibra- tion of the toluene-p-sulphonates by internal return involving the cis- and the trans-ion (177) and (178) equally.This elegant demonstration of the H .. .zh. ... Ph ph+.c- H (178) non-incursion of bridged ions should however not be generalised to other systems; undoubtedly the high degree of phenyl substitution strongly favours the formation of classical ions. (d) Participation by more remote aryl rings. The rates of acetolysis and formolysis of 3-phenylpropyl 4-phenylbutyl and 5-phenylpentyl p-bromo- benzenesulphonate are similar to those of propyl and butyl p-bromo- benzenesulphonate indicating that for these reactions Ar,-4 Ar,-5 and Ar,-6 participation are not very important.159 In an attempt to observe such participation Winstein studied the effect of introducing methoxyl substituents into the phenyl ring (Table 22).159 This would be expected IK7 Bonner and Collins J.Amer. Chem. SOC. 1955 77 99. lK8 Collins and Bonner J. Amer. Chem. Soc. 1955 77 92. lKD Heck and Winstein J. Amer. Chem. SOC. 1957 79 3105. CAPON NEIGHBOURING GROUP PARTICIPATION 91 TABLE 22. The eflects of methoxyl substituents on the rates of solvolysis of some o-phenylalkyl p-bromobenzenesulphonates.159 Relative rates Relative rates Solvent Ph- [CH,],.OBs Ph. [CH,]~*OBS H 4-Me0 2,4-(MeO) H 4-Me0 2,4-(MeO) &OH 1-00 81 1590 1-00 1.07 3.69* HC0,H 1-00 53 672 Ph. [CH,],*OBs Ph. [CH,],*OBs H 4-Me0 2,4-(MeO) H 2,4-(MeO) AcOH 1-00 1-31 4.32 1-00 1 *05 HC0,H 1.00 1.77 9.9 1 1.00 1 -07 * Reaction involves o-MeO-6 participation. to increase the rate of the aryl-assisted reaction by increasing the nucleo- philicity of the ring but not greatly to affect the rate of the bimolecular reaction with solvent.It is seen that Ar,-3 participation occurs most readily and then Ar1-5 participation but that Ar,-4 and Ar,-6 Participation are unimportant. The products of formolysis of the 2,4-dimethoxyphenyl p-methoxy- phenyl and unsubstituted 4-phenylbutyl p-bromobenzenesulphonate contain 76 % 51 % and 16.5 % of the corresponding tetralins [e.g. (179)] which are thought to arise from the spirocarbonium ion [e.g. (lSO)] by ring-expansion as shown in Scheme (XLVI).159 The spirocarbonium ion (1 8 1) from 4-phenylbutyl p-bromobenzenesulphonate and the correspond- ing six-membered-ring ion (1 82) have also been generated by solvolysis of the p-nitrobenzoates (1 83) (1 84) and (1 85) in aqueous acetone.160 The five-membered-ring ion (1 8 1) rearranges exclusively to the decalin (1 86) but the six-membered-ring ion (182) yields only 40 % of the benzocyclo- heptene (187) the expansion of a five-membered to a six-membered ring occurring much more readily than that of a six-membered to a seven- membered one.5,7-Dimethoxytetralin also results from the formolysis of 4-(3,5- dimethoxypheny1)butyl p-bromobenzenesulphonate (1 88) which proceeds about 6 times faster than that of the 4-phenylbutyl compound.lsl These results have been attributed to intramolecular nucleophilic attack by the 2-position of the aryl ring (Ar2-6 participation) [see (1 88)+(190)]. Similar 160 Friedrich and Winstein Tetrahedron Letters 1962 475. 161 Heck and Winstein J. Amer. Chem. SOC. 1957 79 3114. 92 QUARTERLY REVIEWS (PNB = p-nitrobenzoyl) experiments with the analogous w-aryl-propyl and -pentyl compounds show that Ar,-5 and Ar,-7 participation are unimportan t.lsl (188) (189) (190) An interesting example of Ar,-6 participation occurs in the acetolysis of [9]paracyclophen-4-y1 toluene-p-sulphonate (1 9 1) which has a high rate and yields besides the olefins (192) and (193) the tricyclic hydrocarbon (195) and the acetate (194) with retention of configuration.162 The ana- logous 5-toluene-p-sulphonate also yields these products but in different proportions and probably reacts with simultaneous participation of hydrogen and the benzene ring [see (196)l.+ + (191) @f OTs (1%) 162 Cram and Goldstein J. Amer. Chem. SOC. 1963 85 1063. CAPON NEIGHBOURING GROUP PARTICIPATION 93 Neighbouring Olefinic Double Bonds.-Acetolysis of 4-methylpent-3- enyl toluene-p-sulphonate (197) proceeds 1200 times faster than that of ethyl toluene-p-sulphonate and yields 2-cyclopropylpropene (200) and 4-methylpent-3-enyl acetate ( 199).163 The reaction therefore proceeds with participation by the double bond the homoallylic cation (198) being an intermediate.The entropy of activation -7.8 cal. deg-l also supports this interpretation being similar to that found for reactions which involve plienyl participation (see p. 88). The ion (198) has also been considered as an intermediate in the reaction of 4-methylpent-3-enyl chloride with phenol,16* but since chloride which is specifically deuterated in the l-posi- tion yields a product in which the deuterium is scrambled the sym- metrical structure (201) is probably a better representation.The two terminal methyl groups must lend considerable stability to this ion since the analogous allylcarbinyl chloride and benzenesulphonate do not under- go solvolyses at enhanced rates. Among the first reactions in which homoallylic participation was thought to occur are those of cholester-3/3-yP5 and e~o-norborn-5-en-2-yl~~~9~~~ derivatives (see Table 23). With these compounds however the amount of anchimeric assistance which results is more difficult to assess. Acetolysis of both endo- and exo-norborn-5-en-2-yl p-bromobenzenesulphonates (202) and (205) yields 3-acetoxytricyclo [2,2,1 ,O]heptane (207)167 and exo- norborn-5-en-2-yl acetate (206) slightly more of the latter resulting from the endo-isomer probably from a direct displacement reacfion.l6* The em-isomer reacts about 8000 times more rapidly,169 a result which it is difficult to explain without invoking anchimeric assistance due to the formation of the bridged ion (204) but it reacts more slowly than the ana- logous saturated compound em-norborn-2-yl p-bromobenzenesulphon- 163 Rogan J.Org. Chem. 1962 27 3910. 164 Corbin Hart and Wagner J. Amer. Chem. SOC. 1962 84 1741. 165 See Fieser and Fieser “Steroids,” Reinhold New York 1959 p. 314. 166 Roberts Bennett and Armstrong J. Amer. Chem. SOC. 1950 72 3329. 167 Winstein Walborsky and Schreiber J. Amer. Chem. SOC. 1950 72 5795. 16* Roberts Lee and Saunders J. Amer. Chem. SOC. 1955 77 3034. 169 Unpublished work of H. J. Schmid and K. C. Schreiber reported by Winstein and Shatavsky J. Amer. Chem. SOC. 1956 78 595. v P TABLE 23. The acetolysis of norborn-5-en-2-yl and cholester-3-yl derivatives.exo-norborn-5-en-2-yl endo-norborn-5-en-2-yl exo-norborn-2-yl endo-norborn-2-yl p-bromobenzenesulphonate (205) p-bromobenzenesulphonate (202) p-bromobenzene- p-bromo benzene- 0 c k at 25" 4.5 x (ref. 169) 5.7 x (ref. 169) 8-82 x (ref 170) 2.5 x lO-'(ref. 170) W sulphonate P (sec.-l) 3 ? sulphonate Product 3-acetoxytricyclo [2,2,1 ,O]heptane and exo-norborn-5-en-2-yl exo-norborn-2-yl acetate (1 88 189) E E acetate (ref. 167 168) 5 cholester-3P-yl cholester-3cc-yl cholestan-3P-yl cholestan-3cc-yl toluene-p-sulphonate (209) toluene-p-sulphonate toluene-p-sulphonate toluene-p-sulphonate k at 50" 1.32 x (ref. 171") 2.55 x (ref. 173) 1.1 x (ref. 171b) 7.3 x (ref. 171b) (sec.-l) cholester-3-P-yl acetate (ref. 172) cholesta-2,5-diene (ref.173) - - CAPON NEIGHBOURING GROUP PARTICIPATION 95 ate.170 This is because acetolysis of the latter is itself considerably assisted through formation of the bridged ion (233) (see p. 98). The acetolysis of the (202) 6Bs (203) / endo-isomer probably proceeds with ionisation to the classical ion (203) followed by rearrangement to the bridged ion (204) since (rearranged acetate is formed.16' Acetolysis of both the endo- and exo-p-bromobenzene- sulphonates labelled at C-2 and C-3 with carbon- 14 yields exo-acetate which has lost about one third of the label at these positions and formoly- sis of the exo-isomer results in about 50% loss.168 These results were ex- plained as resulting from rearrangement of ion (204) to its enantiomorph (208) but since the exact locations of the label in the products were not determined the occurrence of hydride-ion shifts as well like those found in the reactions of exo-norbornyl compounds (seep.99) cannot be excluded. Evidence for participation by the double bond in the acetolysis of cholester-3P-yl toluene-p-sulphonate [see (209)+(211) J is provided by ihe increased rate,171a compared with that for cholester-3 P-yl toluene-p- sulphonate,171 and the cholester-3P-yl acetate which is formed with retention of configuration (see Table 23). The rate is however only about five times greater than that for cholester-3a-yl toluene-p- sulphonate which undergoes a particularly facile elimination of the axially disposed toluene-p-sulphonate and hydrogen groups at C-2 and C-3 to yield chole~ta-2,5-diene.l'~ Solvolyses of cholester-3P-yl compounds in buffered media frequently yield derivatives of 3,5-cyclocholestan-6/3-01.~~5 Ts - cIc>- -,co& (209) (2 10) (21 I) Thus methanolysis of cholester-3#?-yl toluene-p-sulphonate in the presence of potassium acetate yields 90 % of the methyl ether of 3,5-cyclocholestan- 6p-01 and 10% of that of cholester-3P-01.The same mixture is obtained 170 Winstein Morse Grunwald Jones Corse Trifan and Marshall J. Amer. Chem. Soc. 1952 74 1127. 171 (a) Winstein and Adams J. Amer. Chem. Soc. 1948,70,838; (b) Winstein personal communication to Shoppee and Johnston J. 1961 3265. 172 Shoppee and Summers J. 1952 3361. 173 Shoppee and Williams J. 1955 686. 96 QUARTERLY REVIEWS from 3,5-cyclocholestan-6cu- and -6P-yl trichloroacetate (21 3) and (212),l74 and a similar mixture of the corresponding alcohols is obtained from the hydrolysis of the toluene-p-sulphonate of 3/3-hydroxymethyl-~-norcholest- Sene (214).175 These four compounds must therefore react by way of a rapidly equilibrating set of ions or through a symmetrical ion (215).The 3,5-cyclocholestanyl chlorides undergo solvolysis 107-10s times faster than cholester-3/3-yl chloride owing to their higher initial-state free- energies.l 76 A pair of structurally related homoallylic ions which are not inter- converted are those formed in the acetolyses of exo- and endo-7-isopro- pylidenenorborn-5-en-2-yl toluene-p-sulphonate (2 19) and (2 1 6).177 These Ts u)- 2xJ$YJ3 0 (214) \\ ;?1;6;/ (212) O*cO.CCL (213) OCOCL ....-.+ .... reactions are anchimercially assisted and yield different products (22 1) and (218).Hence ions (220) and (217) formed by participation of the 5,6- and 7,8-double bonds respectively are completely independent. (21 6) (2 I 7) (2 18) AOTS __c $:. - - - - - - - - __c & (2 19) (220) (22 0 A striking example of homoallylic participation is found in the acetolysis of anti-norborn-2-en-7-yl toluene-p-sulphonate (222)17* which proceeds 1011 times faster than that of the analogous saturated compound norborn- 7-yl toluene-p-sulph~nate.~~~ The v-electron cloud of the double bond in this compound is particularly well placed to interact with the developing 174 Kosower and Winstein J. Amer. Chem. SOC. 1956 78 4347. 175 Whitham Proc. Chem. SOC. 1961 422. 176 Winstein and Kosower J. Amer. Chem. SOC. 1959 81 4399. 17' De Puy Ogawa and McDaniel J. Amer. Chem. SOC.1961 83 1668. 17* Winstein Shatavsky Norton and Woodward J. Amer. Chem. SOC. 1955 77 4183; see also Brown and Bell ibid. 1963 85 2324; Winstein Lewin and Pande ibid. 1963 85 2324. 179 Winstein and Shatavsky J. Amer. Chem. SOC. 1956,78,592; Winstein and Stafford ibid. 1957 79 505. CAPON NEIGHBOURING GROUP PARTICIPATION 97 carbonium ion at position 7 to yield the ion (223) the intervention of which is also indicated by the reaction product mti-norborn-2-en-7-yl acetate (224) obtained with retention of ~0nfiguration.l~~ Norbornadien-7-yl (222) (223) (224) derivatives undergo solvolysis even more readily than anti-norborn-2-en- 7-yl ones the hydrolysis of the chloride (225) in aqueous acetone to yield norborndien-7-01 (227) being faster by a factor of about 750.lS0 The intermediate carbonium ion written as (226) forms a stable fluoroborate whose structure has been investigated by nuclear magnetic resonance 1225) (226) (227) spectroscopy.181 The results obtained support an unsymmetrical non- classical structure the lack of symmetry possibly resulting from the com- pound being an ion-pair.Participation by more remote double bonds is also possible and has been shown to occur in the solvolyses of compounds (228)-(232).lS2-ls7 2-(Cyclopen t-3-enyllethyl p-nitrobenzenesulphonate for example under- goes acetolysis 95 times faster than the analogous saturated compound and yields exo-norbornyl acetate.lS4 It is difficult to see any explanation of this result other than that the reaction is anchimerically assisted through formation of a bridged ion as (233). This ion has also been postulated as an I8O Winstein and Ordronneau J.Amer. Chem. SOC. 1960 82 2084. lS1 Story and Saunders J. Amer. Chem. SOC. 1962,84,4876; Story Snyder Douglass lS2 Bruck Thompson and Winstein Chem. and Ind. 1960 590. lE3 Winstein and Hansen Tetrahedron Letters 1960 No. 25 4. lE4 Lawton J. Amer. Chem. SOC. 1961 83 2399; Bartlett and Bank ibid. p. 2591. lE5 Le Ny Compt. rend. 1960 251 1526. 186 Winstein and Carter J. Amer. Chem. SOC. 1961 83 4485. Anderson and Kornegay ibid. 1963,85,3680. See also Bartlett Annalen 1962 653 45; Allred and Schreiber Tetrahedron Letters 1963 949 98 QUARTERLY REVIEWS intermediate in the acetolysis of em-norbornyl p-bromobenzenesulphon- ate,188 which proceeds 350 times faster than that of its endo-isomerls9 and which yields the exo-acetate.Winstein has designated these two routes to the same bridged ion the n-route and o-route respectively.ls6 The bicyclo [2,2,2]oct-2-~1(234) trans-bicyclo [3,2,1 ]oct-2-y1(235) and 2-(cyclo- hex-4-enyl)ethyl(236) systems and the cis-bicyclo [3,2,1 ]oct-2-y1(237) and cyclohept-4-enylmethyl(238) systems are similarly related.186 ,& n-route c- 6-route ::I--$ 1'2% (233) __c 0 ArSo2O Additional information about the mechanism of the acetolysis of exo- norbornyl p-bromobenzenesulphonate comes from an investigation188 using the optically active compound which yields racemic acetate as would be expected if the symmetrical ion (233) were an intermediate. The rate of loss of optical activity is however about 3 times faster than the rate of formation of p-bromobenzenesulphonic acid.Racemisation of the p - bromobenzenesulphonate probably by ion-pair return is therefore occurring concurrently with the acetolysis [see Scheme (XLVII)]. Hydride- ion shifts also occur since the product obtained from the p-bromo- benzenesulphonate labelled specifically in the 2- and 3-positions with 1 AcOH lS8 Winstein and Trifan J. Amer. Chem. Soc. 1952 74 1154. lSs Winstein and Trifan J. Amer. Chem. Soc. 1952 74 1147. CAPON NEIGHBOURING GROUP PARTICIPATION 99 carbon-14 contains radioactivity in the 1- 2- 3- 5- 6- and 7-positions as shown in (240) whereas in the absence of hydride shifts the ion (233) would be expected to yield acetate labelled only in the 1- 2- 3- and 7- positions as (239).lgo 2590 22% A very elegant experiment by Corey and his co-workers supports the formation of the symmetrical ion (233) as the initially formed intermediate in the solvolyses of exo-norbornyl arenes~lphonates.~~~ The optically active compound (241) with a nucleophilic rneta-carboxylate-ion group was used so that the product the carboxylic ester (243) would be formed with only the slightest molecular movement after ionisation.Hence if an initially formed unsymmetrical intermediate [e.g. (242)] of an appreciable lifetime were formed it should react to yield active product but the product was in fact wholly racemic. Neighbouring Small Rings.-The solvolyses of cyclopropylmethyl chloride and benzenesulphonate proceed at high rates for primary com- p o u n d ~ ~ ~ ~ ~ ~ ~ ~ the ethanolysis of the benzenesulphonate for instance pro- ceeding 500 times faster than that of ethyl benzene~u1phonate.l~~ The acetolysis of the chloride yields cyclopropylniethyl and cyclobutyl acetate in the ratio 2.6:1 a small amount of but-3-enyl acetate and a 1.7:l mixture of cyclobutyl and but-3-enyl chloride which do not undergo acetolysis under the conditions used and could not therefore have been precursors of the corresponding acetates.lg2 Cyclobutyl toluene-p-sulphon- ate behaves similarly yielding 65 % of cyclopropylmethyl acetate 22 % of cyclobutyl acetate and 13 % of but-3-enyl toluene-p-sulph~nate.~~~ An experiment with specifically deuterated cyclopropylmethyl chloride in- dicated considerable skeletal rearrangement in the cyclopropylmethyl chloride isolated from a partly solvolysed reaction mixture.lg5 These results suggest that ionisation of the cyclopropylmethyl and cyclobutyl compounds yield the same ion or readily interconvertible ions which may either react with solvent or may re-form chloride or toluene-p-sulphonate lg0 Roberts Lee and Saunders J.Amer. Chem. SOC. 1954 76 4501. lgl Corey Casanova Vatakencherry and Winter J. Amer. Chem. SOC. 1963 85 169. lg2 Roberts and Mazur J. Amer. Chem. SOC. 1951 73 2509. lQ3 Bergstrom and Siegel J. Amer. Chem. SOC. 1952 74 145. 19* Roberts and Chambers J. Amer. Chem. Soc. 1951,73 5034. Ig5 Caserio Graham and Roberts Tetrahedron 1960 11 171. 100 QUARTERLY REVIEWS by ion-pair return. It is more difficult however to decide whether these ions are classical or non-classical. Roberts and his co-workers direct ionisation to one of the non-classical ions (244) (245) and (246) which undergo a rapid but not instantaneous equilibration this interpreta- tion being preferred to one which involves ihe symmetrical ion Y (247) because in certain non-solvolytic reactions there is incomplete equilibra- tion of the methylene groups.This explanation however has been rendered unlikely by the results of Hart et ul.lg6 who showed that each replacement of an isopropyl group by a cyclopropyl group in the series of compounds (248)-(251) (Table 24) produced a similar increase in the rate of solvolysis. TABLE 24. The eflect of cyclopropyl groups on the rates of solvolysis of tertiary-alkyl p-nitr0benzoates.l 96 (248) (249) (250) (251) Pri,CX C,H5-CPri,-X (C3H5),CPri.X (C3H5),CX Relative rate 1 240 23,500 23,500 x 1080 (X = p-nitrobenzoate) Hence if the increased rate produced by one cyclopropyl group were due to stabilisation of the intermediate ion by non-classical resonance as implied by structure (252) the ion derived from the tri(cyclopropy1)methyl compound would have to have the unlikely structure (253).* In the Re- viewer’s opinion a more likely explanation is that of Gould,lg7 that there is a rapidly interconvertible set of classical ions stabilised by the direct field effects of the electrons in the bent bonds which make up these small rings,198 or that of Hart et ~ 2 1 .~ ~ ~ that the ions are stabilised by hyperconjugative electron-release as expressed by structures (254)-(255). Both these expla- nations are consistent with the cumulative effects of successive insertions of cyclopropyl groups (Table 24) and account for the very high reactivity of the tri(cyclopropy1)methyl compound.The tri(cyclopropy1)methyl car- pi- (255) I’-t- c--t \254 4 *The opposite view has recently been taken as to the likelihood of this structure see Breslow in “Molecular Rearrangements,” ed. de Mayo Interscience New York 1963 p. 270. Ig6 Hart and Sandri J. Amer. Chem. SOC. 1959 81 320; Hart and Law ibid. 1962 84 2462. Ig7 Gould “Mechanism and Structure in Organic Chemistry,” Henry Holt and Company New York 1959 p. 588. lS8 Coulson and Goodwin J. 1962,2851 ; 1963,3161. CAPON NEIGHBOURING GROUP PARTICIPATION 101 bonium ion is stable in concentrated sulphuric acid and it is to be hoped that investigations on these solutions will provide more definite evidence on the mechanism by which cyclopropyl groups stabilise carbonium ions. Another reaction in which participation by a cyclopropyl ring has been considered to occur is the acetolysis of cis-bicyclo [3,1 ,O]hex-3-y1 toluene-p- sulphonate (256) which proceeds at a slightly enhanced rate shows special salt effects and yields the cis-acetate with retention of configuration.200a The trans-toluene-p-sulphonate (257) reacts somewhat more slowly shows no special salt effect and yields a mixture of olefin and cis-acetate formed with inversion of configuration.When toluene-p-sulphonates deuterated at position 3 are used acetate obtained from the cis-isomer has deuterium equally distributed at positions 1 3 and 5 but in that from the trans-isomer there is little redistribution. These results led Winstein and Sonnenberg200a to suggest that the solvolysis of the cis-isomer pro- ceeded by way of the symmetrical trishomocyclopropenyl cation (258a) related to the cyclopropenyl cation by the interpolation of a CH group between the CH groups on all three sides of the molecule.Some doubt has however been thrown on this interpretation by the observation of Corey and Hisashi Uda200b that the 1,5-diphenyl substituted compound (258b) does not react with an increased rate. Phenyl substitution stabilises the &OE (258b) cyclopropenyl cation200c and therefore would presumably be expected to stabilise a trishomocyclopropenyl cation. Hence if this ion were the initially formed intermediate phenyl substitution should cause an increased rate. Corey therefore prefers a mechanism involving a rapidly equilibrat- ing set of isomeric ions (258c) in which there is a weak interaction between the vacant orbital at membered ring.It is required. *+ position 3 and the loose electrons of the three- clear though that more work on this system is (258c) Hodge Houser and Wisotsky J . Amer. Chem. SOC. 1962 lg9 Deno. Richev. Liu - . 84 2016. 200 (a) Winstein and Sonnenberg J. Amer. Chem. Soc. 1961,83,3235 3244; (6) Corey and Hisashi Uda J. Amer. Chem. Soc. 1963 85 1788; (c) Breslow Lockhart and Chang,J. Amer. Chem. SOC. 1961,83,2375; (d) Corey and Dawson J. Amer. Chem. SOC. 1963 85 1782. 102 QUARTERLY REVIEWS The deamination of cis-bicyclo [3,1 ,O]hex-3-ylamine definitely does not involve a trishomocyclopropenyl cation since experiments with the deuterated compound show that the cis-bicyclo [3,1 ,O]hexan-3-01 obtained is formed with very little rearrangement.200d Participation by Akyl Groups.-Migration of a methyl group in reac- tions of neopentyl derivatives occurs frequently [e.g.as Scheme (XLVIII)] but there is no evidence for any rate enhancement associated with these EtOH (XLViII) Me&-CH,CI -+ Me,C(OEt)-CH,Me + Me,C=CHMe migrations.201 The methyl group must therefore commence its migration after the rate-determining step. In reactions of more highly branched molecules [e.g. (259)] alkyl-group migration is sometimes associated with a rate enhancement.202 However the familiar problem as to whether Me,C Me,C- Me Me2C+ Me3C{0CO.~H~NO2- Me,C-+’ - Me3C Me,C J Me3C (259) Me -&.CMe M%$CMe :=el2 - ‘?Me Me3C Me,C to ascribe this to steric acceleration or anchimeric assistance generally remains unsolved. Methylene migrations in reactions of bicyclic systems* are commonly found e.g.in the Wagner-Meerwein rearrangement of camphene hydro- chloride to isobornyl chloride.203 The most thoroughly investigated are probably those of norborn-2-yl derivatives which have been discussed in an earlier section (see p. 98). Neighbouring Hydrogen Although many reactions are known in which migration of hydrogen occurs between carbon centres it would appear that direct nucleophilic participation in a rate-determining step occurs in only very few if any of them. The 40-80 fold greater rates of solvolyses of neomenthyl chloride204 X ’ ’ (261) *For an excellent review of carbonium ion rearrangements in bridged bicyclic systems see Berson in “Molecular Rearrangements,” ed. de Mayo Interscience New York 1963 p. 111. ,01 See Streitwieser Chem.Rev. 1956 56 706. 202 Bartlett and Stiles J. Amev. Chem. Soc. 1955 77 2806. ,03 See Streitwieser Chem. Rev. 1956 56 698. ,04 Hughes Ingold and Rose; J. 1953 3839. CAPON NEIGHBOURING GROUP PARTICIPATION 103 and arenenesulphonates (260)170 over those of the corresponding menthyl derivatives have been ascribed to hydrogen participation [as (261)],170 but since the major product is menth-3-ene the high rates may equally well be due to a facile elimination of the diaxial hydrogen and halogeno- or arenesulphonate groups.zo4 It has been claimedzo5 that the formolysis of optically active neomenthyl toluene-p-sulphonate yields racemic menth-3- ene although under the solvolysis conditions used menth-3-ene is optically stable. Unfortunately details of this work have not been pub- lished but if correct it would be strong evidence for hydrogen participa- tion since it indicates the intervention of a symmetrical intermediate which would most likely be carbonium ion (262) formed by hydrogen migration.It has also been claimed that participation by the tertiary hydrogen atoms of 1,2-dimethylpropyl toluene-p-sulph~nate~~~~ and of the 2-cyclo- hexyl- 1-methylpropyl toluene-p-sulphonatezo5c occurs in the rate-determin- ing ionisations of their solvolyses all of which yield large amounts of olefins. Transannular hydride-shifts occur in the reactions of a number of medium-ring compounds,z06 some of which proceed at enhanced rates but these are most probably due to steric acceleration (decrease in I-strain) and not to the formation of a hydrogen-bridged ion in the rate-determining step.Apparently conclusive evidence that this is so for the acetolysis of cyclodecyl toluene-p-sulphonate has been claimed by P r e l ~ g ~ ~ ~ who reported that when the migrating hydrogen is replaced by deuterium there is no observable isotope effect.* An example of a reaction which does show an isotope effect (kH/kD = 1-24) when the migrating hydrogen is replaced by deuterium is the acetolysis of the p-bromobenzenesulphonate (263) which proceeds about lo3 times faster than that of norborn-7-yl p-bromo- benzenesulphonate.zos However in the Reviewer’s opinion the possibility that this is due to steric acceleration there being less acceleration with the *It would nowappear that there is in fact a small isotope effect but this does not result from a difference in the rate of C-H and C-D bond breaking since the proportion of products formed with transannular migration is unchanged.(Prelog and Borcic un- published observations reported by Prelog and Traynham in “Molecular Rearrange- ments,’ ed. de Mayo Interscience New York 1963 p. 612.) 205 (a) Winstein and Schwartz unpublished results quoted by Streitwieser Chem. Rev. 1956 56 715; (6) Winstein and Takahashi Tetrahedron 1958 2 316; (c) Cram and Tadanier J. Amer. Chem. SOC. 1959 81 2737. 206 See Sicher Progr. Stereochem. 1962 3 243. 207 Unmblished observations of BorEiC reDorted bv Prelog. Record of Chemical I Progress,* 1957 18 256. 208 Winstein and Hansen J. Amer. Chem. Soc. 1960 $2 6206. 104 QUARTERLY REVIEWS deuterated compound because of the smaller steric requirements of has not been excluded.Neighbouring Group Participation in Radical Reactions So far only neighbouring group participation in heterolytic reactions has been considered but there is increasing interest in participation in radical reactions. The best authenticated example of anchimeric assistance in a radical reaction was discovered by Bentrude and Martin,21oa who showed that the introduction of an o-phenylthio- or o-methylthio-sub- stituent into t-butyl perbenzoate causes a 103-104-fold increase in the rate of radical decomposition but that the introduction of a p-methylthio- substituent causes only a 3-fold increase. Reaction products include 3,l -benzoxathian-4-one and di-2-carboxyphenyl disulphide. The reactions are considered to involve a transition state which is a hybrid among structures (264)-(266) with structure (265) as the most important con- tributor.210 o-Iodo-substituents which also increase the rate of radical decomposition of aromatic peresters,211 although not so powerfully may act similarly.A number of radical-migrations by aryl residues have been observed212 but there appears to be no clear evidence for anchimeric assistance in any of these reactions. Migration by a methylene group to yield isocamphane occurs in the radical decomposition of 2-azobornane213 but not in that of 2-forrnylb0rnane.~~~ It has been suggested that the facile reaction of norbornadiene with t-butyl perbenzoate to yield 7-t-butoxynorbornadiene proceeds through an anchimerically assisted hydrogen abstraction to yield the radical (267).215 209 See Brown in “The Transition State,” Chem.SOC. Special Publ. No. 16 1962 p. 89; Chem. Eng. News. July 8th 1963 p. 44; Mislow Graeve Gordon and Wahl J. Amer. Chem. SOC. 1963,85 1199. 210 (a) Bentrude and Martin J. Amer. Chem. SOC. 1962 84 1561 ; (6) Tuleen Ben- trude and Martin J. Amer. Chem. SOC. 1963,85 1938. 211 Leffler Faulkner and Petropoulos J. Amer. Chem. SOC. 1958,80 5435. 212 See e.g. Winstein Heck Lapporte and Baird Experientia 1956 12 138; Smith and Anderson J. Amer. Chem. SOC. 1960 82 656; Martin ibid. 1962 84 1986; Wilt and Schneider J. Org. Chem. 1961,26,4196; Riichardt and Hecht Tetrahedron Letters 1962,957,961 ; Riichardt and Trautwein Chem. Ber. 1963,96,160; Bonner and Mango J. Org. Chem. 1964,29,29. 213 Berson Olsen and Walia J. Amer. Chem. SOC. 1962 84 3337. 214 Berson and Olsen J. Amer. Chem. SOC. 1962 84 3178.215 Story J. Org. Chem. 1961 26 287. CAPON NEIGHBOURING GROUP PARTICIPATION 105 Factors Influencing the Ease of Ring-closure Many of the reactions discussed in the previous sections involve ring closure of acyclic compounds through intramolecular nucleophilic dis- placements. The rates at which these reactions take place depend markedly on the size of the ring that is formed but as the reader will have noted the ring size which is associated with the fastest rate varies from one reaction to another. Also the rates of these ring-closure reactions depend on the degree of alkyl substitution of the chain the rate generally increasing with increasing number of alkyl substituents. These two factors will now be discussed in more detail. Ring Size.-The dependence on ring size is determined by an interplay of several quantities.216 First formation of a ring results in loss of rota- tional freedom and hence is accompanied by an entropy decrease.With increasing length of the chain that is closed the loss of rotational freedom increases. Hence there is an increasing unfavourable loss of entropy on ring-closure with increasing ring size. There is also an unfavourable strain factor on ring formation which decreases on going from a three- to a six-membered ring then increases with ring size up to nine members and decreases again with rings of larger size. Finally there are the electronic effects of the leaving and neighbouring groups on one another. Since most leaving and neighbouring groups are electron-withdrawing inductively these effects act to decrease the nucleophilicity of the neighbouring group and to decrease the tendency of the leaving group to depart.They therefore tend to decrease the rate of ring formation the decrease being greatest for three-membered rings when neighbouring and leaving group are attached to adjacent carbon atoms and decreasing with increasing ring size. The results given in Table 25 indicate that the balance of these factors may result in formation of three- five- or six-membered rings being most rapid depending on the reaction type.* With ring-closures of unsubstituted polymethylene chains involving an intramolecular nucleophilic attack on a saturated carbon centre five- membered-ring formation is most highly favoured when the element of the nucleophilic group is oxygen or nitrogen [reactions (1)-(4) in Table 251.With the more highly polarisable thioether group [reactions ( 5 ) and (6)] or an aryl ring [reactions (7)-(9)] the ring-strain factor and the electronic effect appear to have decreased since the three-membered ring is most readily formed. It would be interesting to know if this more rapid *An interesting example of the interplay of entropy and enthalpy factors is given by the ASS and d H f values for the acid-catalysed formation of 6-valerolactone (AS = -25.4 cal. deg-I AH = 13.8 kcal. mole-l) and y-butyrolactone (ASS = - 11.5 cal. deg.-l AH3 = 18.9 kcal. mole-’) in aqueous 1,2-dimethyo~ethane.~~’ The entropy of activation is more favourable for the formation of the five-membered ring but the en- thalpy of activation favours six-membered-ring formation. The result for this reaction is that the six-membered ring is formed fastest.216 See Eliel “Stereochemistry of Carbon Compounds,” McGraw-Hill New Y ork 1962 p. 198. *17 Matuszak Thesis Ohio State University 1957; Diss. A h . 1958,18,792. TABLE 25. The rates of ring-closure redctions as a function of ring size. 1. The Acetolysis of MeO. [CH,],-,.OBs 2. The hydrolysis of HO. [CH,],-,-Cl 3. The cyclisation of H,N. [CH,],-l-Br 4. The cyclisation of -0. [CH,],,.Cl 5. The solvolysis of PhS.[CH,],-,Cl in 6. The solvolysis of PhS. [CH,],-,Cl in 7. The Ar-n ring-closure of 8. The Arl-n ring-closure of 9. The Ar,-n ring-closure of 50% aqueous acetone aqueous dioxan -OC6H4. [CH2],-l-Br in methanol? p-Me0.C6H4* [CH,],,-OBs in acetic acid 2,4-(MeO),.CBH,. [CH2],-1.0Bs in acetic acid Temp. 25 O 70-5 O 25 O 18" 80" 100" 25 O 75" 75 O n=3 [0-00043] [0*0010] 0.0012 0.2 - 5.0 -1 100 147 262 Relative rates* 4 5 6 7 [0*00096] 1-00 0.187 0.001 8 [0*0045] 1.00 0.041 - [O.ooOo2] 1.00 0.017 040003 - 1.0 0.001 - - 1.0 0.013 - - - [0.026] 1.0 - 1.0 0.2 1.0 - - - - - 1.0 0.014 - Ref.76 29 30 30 31 53 lo w 71 2 72 145 146 8 159 159 E E 5 * The values in brackets probably do not refer to ring-closure reactions which therefore have even smaller relative rates. 7 The rate for the methanolysis of the anion of 4-(p-hydroxyphenyl)butyl bromide was assumed to be one-tenth that for the corresponding p-bromobenzenesulphonate. n 10. The hydrolysis of -0,C- [CH,],-,-Cl 1 1. The hydrolysis of -0,C- [CH,],_,CHBrMe 12. The acetolysis of o-MeOC,H,. [CH,],-,-OBs ; 13. The acetolysis of MeO-n participation o-MeO.C,H,-CMe,- [CH,],,,.OTs ; MeO-n participation 14.The Ar2-n ring-closure of 3,5-(Me0),.c6H3* [CH,],_,*OBs in formic acid 15. The Ar2-n ring-closure of rn-MeO.C,H,. [CH,],-,-OBs in formic acid 16. The lactonisation of HO. [CH2],-,C02H 17. The hydrolysis of HO- [CH2]n-2-C0.NH2 18. The hydrolysis of Me,N. [CH2],-2.C02Ph 19. The lactamisation of 20. The hydrolysis of H,N- [CH2],-,CH(NHTs)C0,Me -02C. [CH,],-,.CO,.C,H,.OMe-p TABLE 25.-continued 37.5" - - 25 O O.ooOo8 0*00006 25" I - 1.0 1.0 1.0 1.0 1.0 1.00 1 -00 1.00 1.00 1.00 1.0 1.2 100 17 6.4 2.6 0.389 0.20 76 5 5 E 76 2 z 161 Q Q 161 217 8 58 $ =! 59 3.03 - + 0-0066 - 116 3 z c s 108 QUARTERLY REVIEWS formation of three-membered rings also occurs with other intramolecular nucleophiles containing elements of Group I1 and higher Groups.For instance does 1-3 and Br-3 participation provide more anchimeric assist- ance than 1-5 and Br-5 participation?* Introduction of an unsaturated group into the chain undergoing ring- closure increases its rigidity and hence the entropy loss on ring-closure is reduced but ring formation is now probably accompanied by a greater increase in strain. These two factors favour formation of six-membered rings relative to that of five- or three-membered rings so that with reac- tions (10)-(19) the ratios k,/k are greater than with reactions (1)-(9) and with several reactions six-membered rings are formed fastest of all. The steric-strain factor is particularly significant in determining the rate of ring-closure reactions at aromatic centres [reactions (14) and (1 91. Here perpendicular approach to the ring is necessary and the transition state for the formation of the five-membered ring (268) is highly strained.Qualitative results on other reactions of this type viz. intramolecular acylation2ls and ring- closure of the nitrenes Ph. [CH2],-3-N:,219 also indicate a greater ease of formation of six-membered over five-membered rings. The only reactions in Table 25 of compounds with two unsaturated groups are the hydrolyses of the half-esters of succinic and glutaric acids [reaction (20)] which are thought to proceed by way of the cyclic anhy- drides. The ring-closure of the succinate proceeds lo2-lo3 times faster than that of the glutarate owing to a more favourable entropy of activa- tion. A possible explanation is that the close proximity of the carboxylate Q) (268) TABLE 26.The eflects of methyl substituents on the rates of ring-closure of chlorohydrins and chloroeth~~lamines. Epoxide formation in aqueous alkali at 18"* 103k (I. mole-l sec.- l) C1*CH2.CH2*OH 5 ClCH,.CH.Me-OH 110 Cl-CH,CMe,.OH 1300 Ring-closure at 25"t Estimated lo% (sec.-l) k for ring- closure of the anion223 5 CI.CH2CH2.NH2 8 130 CICH,.CHMe-NH 250 2500 C1CH,CMe2-NH 7500 * Nilsson and Smith Z. phys. Chem. (Leipzig) 1933 166A 136. t Freundlich and Salomon Z. phys. Chem. (Leipzig) 1933 166A 175. *It has recently been disclosed that there is some evidence that the driving force for the formation of five-membered halonium rings is not large (unpublished studies by Win- stein and Glick reported by Peterson and Allen J. Arner. Chem. SUC. 1963 85 3611 footnote 15).218 See Johnson Org. Reactions 1944 2 114. 219 Barton and Morgan J. 1962 622. CAPON NEIGHBOURING GROUP PARTICIPATION 109 and ester groups in the succinate restrict rotational freedom so that there is a decreased loss in entropy on going to the transition state. Alkyl Substitution.-It has been known for many years that substituents especially geminal substituents increase the rate of ring-closure reactions and the thermodynamic stability of ring forms over acyclic forms (see Tables 11 and 26-28 for examples). This was widely studied qualitatively TABLE 27. The eflect of methyl substituents on the stability and rate of formation of lactones in acqueous solution at 25”. 0 0 Lactones (A) Unsu bst. 4-Me 4,4-Me2 2- Me % Lactone at equilibrium 72.8 95.4 93.0 98.2 Rate of formation k ( r n h - l ) 0.0377 0.2 0.010 0.465 Lactones (B) Unsubst.2-Me 5-Me 5,5-Me2 3-Me-5,5-Me2 4-Me-5,5-Me2 % Lactone at equilibrium 9.0 16.5 21.2 25-1 95.5 75-0 k ( r n h - l ) 0.24 0.36 0.56 0.052 3.02 0.399 * Sebelius Inaugural Dissertation Lund 1927 quoted by Huckel “Theoretical Principals of Organic Chemistry,” trans. Rathmann Elsevier Amsterdam 1958 p. 895. TABLE 28. The eflect of methyl substituents on the rates of hydrolyses of mono-p-bromophenyl esters of glutaric and succinic acid.l17 (B) 0 (A) (A) (A) (A) (A) (B) (B) 105k (sec.-l) 7.4 32.3 142 26.7 170 500 by Ingold Thorpe and their co-workers,220 and Ingold suggested2,’ that it was due to the fact that the substituents decreased the bond angle be- tween the remaining valencies hence bringing the groups undergoing ring-closure “into closer proximity”.Alternatively alkyl substituents may be regarded as distorting the angle between the remaining valencies towards the value found in the ring. Some evidence for this effect has recently been produced by Schleyer222 who studied hydrogen-bonding in alkyl-substi- tuted propane-1,3-diols. It can be of only minor importance in ring- closure reactions however since the influence of alkyl substituents on the formation of five- and six-membered rings which are almost free of angle strain is almost as great as on the formation of the highly strained smaller rings. Unsubst. P-Me PP-Me aa-Me Unsubst. aa-Me 2 p o See Ingold and Thorpe J. 1928 1318 and previous papers. 2?1 Ingold J. 1921 308. 22p Schleyer J. Amer. Chem. SOC. 1961 83 1368. 110 QUARTERLY REVIEWS Another explanation was advanced by W i n ~ t e i n ~ ~ ~ who observed that the anchimeric assistance provided by several neighbouring groups (e.g.halogen methoxyl aryl) in reactions of the type shown in Scheme (XLIX) was greatly increased by ,8-alkyl substituents. It was suggested that this was due to stabilisation of the intermediate ion (269) by resonance with structures of type (270) which would be greatest when C is tertiary. However large enhancements of rate are also observed wien the sub- stituents are attached to carbon atoms other than that bearing the neigh- bouring group (see Tables 6 and ll) and these clearly cannot be caused in this way. Also the effect of alkyl substituents is as large when the neighbouring group is alkoxide or amino (see Tables 11 and 26) as when it is carbon although less stabilisation would be expected for an ion such as (271) bearing a positive charge on nitrogen by resonance with struc- ture (272) bearing a positive charge on carbon.It is clear therefore that stabilisation of an intermediate in this way can only be a minor contribut- ing factor to the “gem di-alkyl effect.” More recently it has been suggested by Bruice and Panditll’ that “the ring closure proceeds at a higher rate on geminal (or alkyl) substitution because of the resultant decrease in unprofitable rotamer distribution.’’ Thus it is argued with an aryl hydrogen succinate the population of the profitable rotamer (273) is increased relative to that of the unprofitable rotamer (274) when R is alkyl instead of hydrogen because of non-bonded interactions between the alkyl groups.In terms of the transition-state s R RX$CO; R R& b 2 P h (274) theory this would seem to imply that the increased rate of alkyl substitu- tion is due to an increased initial-state free-energy because the participat- ing group and reaction centre are brought closer together. This could be due to repulsion between these groups or to desolvation of one or both of them. Another explanation which is probably more satisfactory since it is formulated thermodynamically is that of Allinger and Z a l k o ~ . ~ ~ ~ These 223 Winstein and Grunwald J. Amer. Chem. SOC. 1948 70 828. 224 Allinger and Zalkow J. Org. Chem. 1960,25 701. CAPON NEIGHBOURING GROUP PARTICIPATION 1 1 1 workers showed that alkyl substitution causes a decrease in AH and an increase in AS for the reaction hexane+cyclohexane + hydrogen and were able to explain both changes quantitatively.On formation of cyclo- hexane from hexane there will be six additional gauche-interactions but on ring-closure of an alkyl substituted cyclohexane the additional gauche- interactions will be less than six. Hence AH for the formation of a six- membered ring and AH for the formation of a six-membered cyclic transition state should be decreased on alkyl substitution. In addition alkyl substituents will restrict rotation in the acyclic form225 and thus decrease the rotational entropy. Hence loss of rotational entropy on ring- closure of an alkyl substituted chain or on going to the transition state for such a ring-closure will be less than for an unsubstituted chain. Therefore alkyl substitution will cause a decrease in the free-energy of formation of a six-membered ring from an open chain through more favourable AH and TAS terms.With rings of other sizes it is more difficult to decide what the effect of alkyl substituents on AH and AH$ will be but a qualitative paral- lelism of five-membered rings with six-membered rings is claimed.224 The effect of alkyl substituents on A S or ASS however would be expected to be such so as to favour ring-closure whatever the ring size since alkyl substituents will always reduce rotational freedom in the acyclic form and it is suggested that this factor is the most important one in the operation of the gem-dialkyl effect. I thank Dr. C. W. Rees for many stimulating discussions. 225 See Hammond in “Steric Effects in Organic Chemistry,” ed. Newman Wiley New York 1956 p. 468.

ISSN:0009-2681    

DOI:10.1039/QR9641800045

出版商:RSC    

年代:1964

数据来源: RSC

摘要:

CUMULATIVE INDEXES VOLUMES I-XVIII (1 947-1 964)

ISSN:0009-2681    

DOI:10.1039/QR9641800415

出版商:RSC    

年代:1964

数据来源: RSC