2 Physical Methods Part (ii) Nuclear Magnetic Resonance By I. H. SADLER Department of Chemistry University of Edinburgh West Mains Road Edinburgh EH9 UJ It is of course impossible in a Report of this size to cover comprehensively all aspects of n.m.r. spectroscopy. This Report concentrates primarily therefore on two areas which are expanding rapidly namely chemically induced dynamic nuclear polarization and Fourier-transform spectroscopy. Some other aspects are treated briefly under Miscellaneous Studies. Papers concerned solely with the compilation of chemical shifts and coupling constants on series of related compounds with the routine use of n.m.r. for identification or structural work or with well-established procedures for studying exchange processes or conforma- tional problems have been largely excluded.This year marked the appearance of the first volume of the Specialist Periodical Reports in Nuclear Magnetic Resonance edited by R. K. Harris which is orientated towards a discussion of the phenomenon itself rather than towards a summary of the applications of n.m.r. in the various areas of chemistry. 1 Chemically Induced Dynamic Nuclear Polarization High-field Studies.-Two reviews have appeared which separately present the qualitative aspects' of CIDNP along with a simple classical explanation of the radical-pair theory and the quantitative applications' and extensions of the theory. A concise elementary review3 and a general review4 have also appeared. Kaptein' has critically re-examined the radical-pair theory for CIDNP in high magnetic fields and has presented an extended model which takes into account random-walk diffusion of the radicals within a pair.Such a modifica- tion is necessary since the lifetime of an initially formed radical pair is too short (< 10-s) for the nuclear-spin-dependent singlet-triplet (S-T,) mixing (and hence nuclear spin selection) to occur and therefore polarization is due to spin selection in subsequent encounters of the original pair. In many respects the model is similar to that proposed by Adrian.6 Differences arise in the treatment ' ' H. R. Ward. Accounts Chem. Res. 1972 5 18. R. G. Lawler Accounts Chem. Res. 1972 5 25. S. H. Pine J. Chem. Educ. 1972 49 664. A. L. Buchachenko and F. M. Zhidomirov Russ.Chem. Rev. 1971 40,801. R. Kaptein J. Amer. Chem. SOC.,1972 94 6251. ' F. J. Adrian J. Chem. Phys. 1970 53 3374; 1971 54 3912. 19 I.H. Sadler of pairs formed by radicals with uncorrelated spins and in the use of a finite rather than zero value for the electron-exchange integral (J). (However see Low-field Spectra.) An important feature of the revised model is the prediction that rela- tively long-lived radical pairs will contribute to the polarization. The diffusion model gives a description of the relative line intensities that is as good as or better than that provided by the previous radical-pair model. The diffusion model has been extended7 to cover situations where the conversion of a radical pair into a new pair by rearrangement fragmentation or transfer becomes competitive with product formation from the original pair.Such processes are often sufficiently rapid (ca. s) for the spin correlation of the original pair to be maintained in the new pair and thus polarization may be observed in the products of the new pair and of pairs formed by subsequent reactions. Calculations which show that secondary pairs formed after relatively long times (up to s) could still give rise to observable CIDNP effects have been supported by experiment.8 The revised quantitative treatment in no way affects the qualitative predictions that are possible using Kapteins rules.' A set of rules has also been developed" for the semiquantitative analysis of first-order multiplet spectra by a graphical met hod.Several detailed studies of the decomposition of diacyl peroxides have appeared. The polarizations of the proton resonances observed' ' during the thermal decomposition of acetyl peroxide in hexachloroacetone are consistent with Scheme 1 (R' = CH,). The decarboxylation process is slow enough for polariza- tion to occur in the acetoxyl-methyl radical pairs and be observed in the geminate -co -co -(R'CO,) + 2R'CO,. R'. R'CO,. --P 2R'. /R' C0,R' lR2X R'X + R2* Ri R'X+ R2* R' =Me E A E - R' = Et none - EfA AIE (E emission A absorption) Scheme 1 recombination product methylacetate. The unusual net polarization of the ethane resonance which cannot be due to S-To mixing in the methyl radical pair since net effects cannot arise from pairs of equivalent radicals arises from S-To mixing in the preceding pair.The polarization is retained in the methyl radical pair and R. Kaptein J. Amer. Chem. SOC.,1972 94 6262. ' R. A. Cooper R. G. Lawler and H. R. Ward J. Amer. Chem. SOC.,1972 94 552. R. Kaptein Chem. Comm. 1971 732. lo K. Muller J.C.S. Chem. Comm. 1972 45. '' R. Kaptein J. Brokken-Zijp and F. J. J. de Kanter J. Amer. Chem. SOC.,1972 94 6280. Physical Methods-Part (ii) Nuclear Magnetic Resonance appears in the final product. This phenomenon has been termed a memory eflect. CIDNP spectra obtainedI2 during the decomposition of higher acyl peroxides (R' = ethyl or lauryl) in solutions containing alkyl iodides,R2 = Et or Pr' show only multiplet effects arising from spin selection in the 2R'.alkyl radical pair. No polarization is observed in the ester R'C0,R' and the results are in accord with the rapid decarboxylation of the acyloxyl radicals. Multiplet polarization (E/A)is also observed in the reagent alkyl iodide and this results from spin selection in diffusive encounters of two R2 * radicals. During the decomposition' of phenyl acetyl peroxide in carbon tetrachloride- bromotrichloromethane mixtures decarboxylation is again sufficiently rapid that nuclear spin selection does not occur in pairs containing benzoyloxyl radicals. Polarization is only observed in the spectra of the non-cage products benzyl bromide (E) and l,l,l-trichloro-2-phenylethane(A)and again results from spin selection in benzyl-trichloromethyl radical pairs formed by diffusive encounters.A quantitative model is proposed to explain the variation in intensity of the benzyl bromide polarization with bromotrichloromethane concentration. CIDNP spectra of alkyl benzoates obtained* during the thermolysis of benzoyl peroxide in solutions containing alkyl iodides are interpreted in terms of rapid reaction of the alkyl iodide with a benzoyloxyl-phenyl radical pair to give iodo- benzene and a new benzoyloxyl-alkyl radical pair. Such a process which proceeds PhCO,. Ph- + RI + PhI + PhCO,. R. -+ PhC0,R with conservation of spin multiplicity is termed pair substitution. Spectra analo- gous to those arising from pair substitution were obtained by the thermolysis of the appropriate acyl benzoyl peroxide.The polarization observed for the proton resonances of the alkylbenzenes formed in these reactions arises from spin selection in a phenyl-alkyl radical geminate pair and from the rate of decarboxy- lation of the benzoyloxyl radical it is shown that the geminate pair must exist for up to 10-6-10-7 s. The intermediacy of arylcyclohexadienyl radicals in the homolytic arylation ofaromatic compounds has been dem~nstrated'~ using CIDNP techniques. The net effects observed for the products (1)and (2) obtained during the decomposi- tion of perdeuteriobenzoyl peroxide in hexachloroacetone-l,3,5-trichlorobenzene mixtures are in accordance with Scheme 2. Evidence that polarization of (2) does not occur where a hydrogen atom is abstrated by a single radical from a neutral molecule is provided by the use of hexamethylbenzene in place of trichlorobenzene.In this instance only unpolarized resonances are obtained for (2). CIDNP effects ~bserved'~ during the room-temperature photolysis of the trans-azo-compound (4)and the thermolysis of cis-isomer (3) in benzene (Scheme l2 R. A. Cooper R. G. Lawler and H. R. Ward J. Amer. Chem. SOC.,1972,94 545. l3 C. Walling and A. R. Lepley J. Amer. Chem. SOC.,1972 94 2007. l4 S. R. Fahrenholtz and A. M. Trozzolo J. Amer. Chem. SOC.,1972,94 282. Is N. A. Porter L. J. Marnett C. H. Lochmiiller G. L. Gloss and M. Shobataki J. Amer. Chem. Sac. 1972 94 3664. I. H. Sadler D,C,Cl + Cl,C.CO.CCI D5C6bC, J \r/ HCI radical pair 1 C6D,.C,H,C13 (A)+ C13C-CO-CHC12 (E) (1) (2) Scheme 2 3) show clearly that (a)photolysis of (4)only causes isomerization to the cis-compound (3) which decomposes thermally at room temperature; (b) loss of nitrogen does not occur via concerted cleavage of both C-N bonds but by a step- wise process involving the radical pair (5); and (c)the cis-compound undergoes thermal isomerization to the trans-isomer via the pair (5).The observation" of N=N / Ph (3) \CMe,Ph \ PhN,. *CMe,Ph -+ Ph. eMe,Ph + N, 11 J (5) \ / Ph \ free radicals N=N \ CMe,Ph (4) Scheme 3 multiplet effects (E/A) for the protons and to the carbon-magnesium bond obtained during the formation of Grignard reagents from ethyl and isobutyl iodides provides strong evidence that Grignard reagents are formed largely if not exclusively by radical routes.An unusual CIDNP spectrum has been obtained" during the photolysis of 2-phenylisobutyraldehyde in benzene. Cumene formed from a cumyl-formyl radical pair exhibits multiplet polarization (A/E)for the methyl triplet but pure l6 H. W. H. J. Bodewitz C. Blomberg and F. Bickelhaupt Tetrahedron Letters 1972,281. K. Schaffner H. Wolf S. M. Rosenfeld R. G. Lawler and H. R. Ward J. Amer. Chem. SOC.,1972 94 6554. Physical Methods-Part (ii) Nuclear Magnetic Resonance emission for the methine proton resonance. This is however consistent with a triplet multiplicity of the precursor and the extremely large hyperfine splitting in the formyl radical. Discrepancies between the simulated and observed multiplet patterns for the methine proton are explained by the difference in spin- lattice relaxation times (TI) of the methine and methyl protons.Under such conditions an anomalously large net enhancement is to be expected.’* Evidence is presented however which shows that in this system the CIDNP effects arise from a minor pathway involving triplet-born radical pairs and that the principal pathway to the products is a concerted process. Roth has examined” the triplet-sensitized and non-sensitized photodecomposition of diazornethane in toluene. In the former case a multiplet effect (A/E) was observed for triplet ethylbenzene consistent with formation oia a benzyl-methyl radical pair generated via a triplet precursor. In contrast no polarized signals were observed during the non-sensitized reaction although ethylbenzene was formed in high yield.This indicates that radical pairs are not involved in the latter case and that ethylbenzene formation from singlet methylene occurs via a one-step inser- tion process. The photolysis of the diazocyclohexadienones (6) and (7) in cyclo- hexane and carbon tetrachloride yields CIDNP spectra which indicate that the carbene (8) reacts in the singlet state whereas its di-t-butyl derivative (9) behaves as a triplet.20 A detailed analysis has been given2’ of the CIDNP spectra obtained during the photolysis of di-t-butyl ketone. N (6) R = H (8) R = H (7) R = CMe (9) R = CMe Remarkably few studies of carbon-13 CIDNP have been reported One obvious advantage over proton CIDNP is the possibility of observing tertiary radical sites.The initial work by Lippmaa and co-workers demonstrated” that the magnitude of polarization for I3C nuclei could be at least an order of magni- tude larger than for protons. Polarized 13Csignals for benzene (E) carbon di- oxide (E),biphenyl (A),and phenyl benzoate (A),formed during the thermolysis of a 25% solution of benzoyl peroxide in cyclohexanone were readily visible during a single scan at natural abundance levels under conditions where signals from unpolarized 3Cnuclei in the peroxide and reaction products did not exceed K. Muller and G. L. Closs. J. Amer. Chem. Soc. 1972 94 1002. l9 H. D. Roth J. Amer. Chem. Soc. 1971,94 1761. *’ M. L. Kaplan and H. D. Roth J.C.S. Chem.Comm. 1972 970. *’ M. Tomkiewicz A. Groem and M. Cocivera J. Chem. Phys. 1972 56 5850. 22 E. Lippmaa T. Pehk A. L. Buchachenko and S. V. Rykov Chem. Phys. Letters 1970 5 521. 24 I. H. Sadler the noise level. Such high concentrations of reagents are not always practicable and it is often necessary to time-average over 15-30 scans and employ proton noise decoupling to obtain satisfactory CIDNP spectra. Decoupling of the hydrogen nuclei has no measurable effect on the total intensity of a polarized I3C resonance. Normally only the 13C nuclei comprising or adjacent to the radical site show polarization. Multiplet effects only observable in the absence of proton noise decoupling are in general very weak in comparison with net effects.A more recent studyz3 of the decomposition of benzoyl peroxide in tetrachloroethylene confirms the earlier results.2 Most polarization results from spin selection in benzoyloxyl-phenyl radical pairs. The polarization of the major product trichlorostyrene (E) arises from the addition of a polarized phenyl radical to the solvent followed by rapid loss of chlorine. The signs of the product polarizations are in accordance with Kaptein's rule' for net effects. In some instances polarized signals were observed for as long as two hours after the start of the reaction. The above studies employed conventional continuous- wave techniques which necessarily restrict spectrum accumulation to within a small frequency range for very fast reactions. The use of pulsed Fourier- transform techniques enables the observation of the whole '3C chemical-shift range within seconds.It should then be possible to follow the time dependence of polarization at relatively close intervals providing it is possible to store separately the accumulated free induction decays from each batch of pulses. Such a technique has been employed to study the alkali-metal reduction24 of p-methoxybenzenediazonium fluoroborate. The observed polarized signals can be interpreted in terms of the intermediacy of a free-radical encounter between CH30C,H4. and CH30C,H4-N2-O* radicals ;however a detailed discussion is not given. The first report25 of nitrogen-15 CIDNP indicates the intermediacy of a radical pair in the azo-coupling reaction of benzenediazonium fluoro borate with alkaline solutions of phenol a reaction generally considered as electrophilic substitution.Strong polarization of the "N signals of both the product and the diazonium salt is consistent with a mechanism involving a reversible electron transfer as the first step (Scheme 4). ArA2 + 00-[ark -00]+ ArN=N Scheme 4 Several examples of fluorine-19 CIDNP have appeared. Some unusual emission-absorption patterns have been observed26 for the '9F resonance of 23 E. M. Schulman R. D. Bertrand D. M. Grant A. R. Lepley and C. Walling J. Amer. Chem. SOC.,1972,94 5972. 24 S. Berger S. Hauff P. Niederer and A. Rieker Tetrahedron Letters 1972 2581. zs N. N. Bubnov K. A. Bilevitch L. A. Poljakova and 0.Y. Okhlobystin J.C.S. Chem. Comm. 1972 1058.26 D. Bethell M. R. Brinkman and J. Hayes J.C.S. Chem. Comm. 1972 475 1323. Physical Methods-Part (ii) Nuciear Magnetic Resonance 25 2,2-diaryl-l-phenylethylfluorides obtained by the insertion of diarylmethylene into the benzylic C-H bond of benzyl fluoride. The use of diphenylmethylene leads to a fluorine quartet that is polarized AAEA at 56 MHz. At 94 MHz the emission intensity is greatly reduced and the third and fourth lines are split into doublets. This unusual behaviour is thought to result from the coupling of the polarized I9F nucleus with a polarized vicinal proton which is undergoing more rapid nuclear spin relaxation. The changes in '9Fpolarization patterns obtained using substituted diarylmethylenes are attributed to different g-values of the radicals within the pairs.Differences between the polarized and corresponding product 9Fresonances obtained27 during the decomposition of benzoyl peroxide in benzyl fluoride are interpreted in terms of the formation of a methylenecyclohexadiene intermediate which undergoes rearrangement to the isolable a,&-difluorobibenzyl (Scheme 5). 2PhkHF -P --* Ph-CHFCHF-Ph CHFPh Scheme 5 Low-field Studies.-Although polarizations resulting from reactions carried out at zero or low magnetic field (< 100G) have received comparatively little atten- tion two similar have appeared to account for the observed effects. Both are extensions of the radical-pair theory for high fields and differ only in the method of averaging the spin character of the radicals over the time during which they are eligible to react.In such experiments it is necessary to consider the mixing of the electronic singlet state (S) with all three triplet states (T+ To,T-). For reactions carried out in zero fields the resulting n.m.r. spectra show unusual characteristics. For two coupled groups of equivalent nuclei the low-field line of the upfield multiplet and the high-field line of the downfield multiplet are absent. Such an effect is observed during the photolysis of pro- pionyl peroxide in carbon tetrachloride-bromotrichloromethane mixtures where the low-field multiplet (CH,) of ethyl bromide shows three lines (A) and the high-field multiplet (CH,) two lines (E). In high-field reactions both resonances exhibit multiplet effects (AIE).Kaptein's rule for multiplet effects may be used for zero-field spectra providing that E/A is interpreted now as E for all resonances of nuclei appearing downfield in the spectrum and A for the upfield group. For reactions run in low and intermediate fields zero-field effects are modified by the relative contributions of S-T and S-To mixing. Unlike S-To transitions S-T transitions involve changes in nuclear spin. For a single group of nuclei polariza- tion resulting from S-T mixing is opposite for singlet and triplet precursors as 27 D. Bethell M. R. Brinkman and J. Hayes J.C.S. Chem. Comm. 1972 1324. 28 R. Kaptein and J. A. den Hollander J. Amer. Chem. SOC.,1972 94 6269. 29 J. I. Morris R. C. Morrison D. W. Smith and J. F. Garst J.Amer. Clrem. SOC.,1972 94 2406. 26 I. H. Sadler for S-To mixing but unlike the high-field case is the same for geminate recombina- tion products and for transfer products. In the case of a one-proton radical pair in a low magnetic field polarization results from S-T mixing only and can be shown to vary both in magnitude and sign with the field strength. The particular variation pattern that is observed depends upon the hyperfine coupling constant and electron-exchange integral. In some cases a double change in sign is predicted and this has been observed2’ for the proton resonance of chloroform formed during the photolysis of di-isopropyl ketone in carbon tetrachloride. Later work3’ has shown that the observed oscillation for the field dependence of the chloroform polarization may be reproduced using a zero exchange integral (J = 0) provided that all the protons and all the chlorine nuclei in the radical pair are included in the calculation.Similarly good agreement with experiment is obtained for high-field studies using J = 0 when all the nuclei coupled to the free electrons of the radicals even those which do not normally affect the n.m.r. spectrum are included. Since this parameter was previously assumed to have a value comparable with the hyperfine couplings and was chosen to give the best agreement with experiment its elimination is welcomed. It appears that the field dependence of low-field polarization will provide a good method for testing theoretical models of the radical-pair theory and the parameters involved.2 Fourier-transform Spectroscopy Carbon-13 Techniques and Results.-An excellent book3’ on 13C magnetic resonance aimed at the organic chemist and a collection32 of 500 assigned I3C n.m.r. spectra have appeared. It is now generally accepted that carbon-13 chemical shifts should be referenced to tetramethylsilane and a useful list33 of chemical shifts for common n.m.r. standards and solvents has been compiled. Natural-abundance carbon-13 spectra are largely obtained by Fourier-transform (FT) technique^.^^ While raising ’3C spectroscopy from the province of the specialist to the position of a routine operation FT spectroscopy has a number of deficiencies. Since the various 13Cnuclei in a molecule have different relaxation times (TI)and when proton noise decoupling is employed have dif- ferent nuclear Overhauser enhancements (NOE) large variations in line intensi- ties are observed often making integration pointless.This problem may be overcome by the addition of paramagnetic metal ions to reduce the Tl relaxa-tion times of the nuclei and thus eliminate the Overhauser effect. Such reagents however must be stable inert and soluble in organic reagents cause no contact or pseudocontact shifts and not seriously affect the T2 relaxation times so that 30 Ref. 28 footnote 24. ’’ G. C. Levy and G. L. Nelson ‘Carbon-13 Nuclear Magnetic Resonance for Organic Chemists’ Wiley New York 1972. ’’ L. F. Johnson and W. C. Jankowski ‘Carbon-13 NMR Spectra’ Wiley New York 1972.” G. C. Levy and J. D. Cargioli J. Mugn. Resonance 1972 6 143. 34 T. C. Farrar and E. D. Becker ‘Pulse and Fourier Transform NM R’ Academic Press New York 1971 ;R. Bell ‘Introduction to Fourier Transform Spectroscopy’ Academic Press New York 1972. Physical Methods-Part (ii) Nuclear Magnetic Resonance 27 undue broadening of resonances does not occur. Tris(acety1acetonato)-chromium(r1r) has been used effe~tively,~ in particular for organometallic car- bony1 compounds. At concentrations of relaxation reagent below 0.05 moll-’ negligible line broadening occurs and good intensity ratios are obtained. Similar results have been obtained36 for organic compounds using the corresponding iron(rI1) complex. Such relaxation reagents enable the pulse repetition rate to be increased thus allowing a shorter total time for a given quantity of material.The presence of paramagnetic species however would be inadvisable where line 13C-intensities from CIDNP reactions were required. The use of a gated proton- decoupling te~hnique,~’ however can suppress and virtually eliminate the NOE without affecting relaxation. In such an experiment the proton irradiation is switched on just (ca.0.1 s) before the I3Cexcitation pulse and switched off imme-diately after the acquisition (ca. 1 s) of the free induction decay (f.i.d.). Since the decoupling effect is almost instantaneous but the Overhauser intensity increase requires a time of the order of the T1 values for I3C then for many small and medium-sized molecules no signal enhancement is observed.A short delay (ca. 1 s) is required between the end of the acquisition of the f.i.d. and the next pulse. By varying the pre-irradiation time (t) of the proton resonances it is possible to measure both TI and the nuclear Overhauser enhancement,* since the signal intensity (S,)is given by S -S = (S -So) exp (-t/T,) where S is the signal observed with continuous decoupling. The reverse switch- ing of the decoupler so that it remains on at all times except during pulsing and acquisition of the f.i.d. yields un-decoupled spectra with Overhauser enhance- ments. In this operational mode a pulse delay of the order of TI is required which in some instances may result in no greater signal-to-noise ratio in a given period than would be obtained by continuous pulsing with no decoupling field.A technique referred to as selective-saturation Fourier transform (SSFT) has been described3* for the selective removal of any line in the transformed spectrum. A relatively long (1-2 s) burst of a single 13C radiofrequency is applied during the delay period between the end of the accumulation of one f.i.d. and the next pulse. This is of particular value for the removal of strong solvent ’3C resonances or for selectively saturating the major signal in studies of 13C-13Cinteractions in highly enriched samples. In a related technique,39 the decoupling power is swept rapidly (40 kHz s-’) over a selected region of the 13C spectrum during the delay period. This has been used to irradiate regions of 13C satellite resonances 35 0.A.Gansow. A. R. Burke and G. N. La-Mar J.C.S. Chem. Comm. 1972 456. 36 S. Barcza and N. Engstrom J. Amer. Chem. SOC., 1972.94. 1763. 37 R. Freeman H. D. W. Hill and R. Kaptein 1. Magn. Resonance 1972 7. 327. 3* J. Schaefer J. Mugn. Resonance 1972 6 670. 39 H.C. Darn and G. E. Maciel J. Phys. Chem. 1972 76 2972. * Unfortunately two definitions prevail at present and are not always clearly differen- tiated if a peak intensity in the absence of NOE is taken as unity then q is the relative increase in intensity. Sometimes however the roral relative intensity of the peak i.e. (I + q) is taken as the NOE. 28 I. H. Sadler in proton-noise-decoupled '3C spectra to assign '3C resonances where conven- tional off-resonance proton decoupling is not conclusive.A graphical method has been presented4' for the unambiguous assignment of 13C resonances using selective off-resonance decoupling. In such experiments the residual splitting (J,) and the coupling constant (JCH)are given by the expres- sion; yH2/271 = J, Av/J, providing that the decoupling power (?jH,/271) is considerably greater than the separation (Av) of the proton irradiation frequency and the resonant frequency of the proton causing the splitting. Under these circumstances J varies linearly with Av and by plotting the peak frequencies in the 3C spectrum against the proton irradiation frequencies straight lines are obtained which intersect at the chemical shifts of the directly bonded 13C and 'H nuclei.Where proton assignments are known it is possible to assign I3C nuclei unambiguously and oice versa. It is particularly applicable to closely spaced resonances where overlap may render the measurement of residual couplings difficult. In this manner it has been possible to assign4' the 13C resonances in NAD' and to correct41 misassignments in the proton spectrum of NADH. Non-linear plots are obtained however if the range of proton irradiation fre- quencies is too wide and/or where only a low decoupling power is employed since under such circumstances the above equation is not valid.42 Numerous papers have been concerned with the measurement and additivity relationships of 13C chemical shifts and 13CH coupling constants. The effect of deuterium substitution on the chemical shifts of benzene and a number of mono- substituted derivatives has been examined.43 The deuterium-bearing carbon atoms are shifted upfield by ca.0.3p.p.m. and the adjacent carbon atom by ca. 0.1 p.p.m. Deuterium shifts caused by deuterium labelling have been used for the assignment of I3C resonances in dim ethyl nor born an one^^^ and to assist in mechanistic studies of hom~enolization.~~ A of monohalogenobenzenes emphasizes the electronegativity dependence of the l3C-H coupling constant and shows that the three-bond couplings are larger in magnitude than the two-bond couplings. Substituent contributions to the 13C chemical shifts and 13C-H coupling constants for the monohalogenobenzenes calculated relative to benzene also account on an addi- tivity basis for observed couplings in a large number of symmetrical ortho-and meta-dihalogenobenzenes.Evidence for a Karplus-type relationship for vicinal three-bond '%-H couplings comes from a study4' of the rigid C(2)-enriched anhydrouridine derivatives (10)and (11).Dihedral angles were estimated from molecular models and the corresponding couplings in uridine suggest that it 40 B. Birdsall N. J. M. Birdsall and J. Feeney J.C.S. Chem. Comm. 1972 316. 41 B. Birdsall and J. Feeney J.C.S. Perkin ZI 1972 1643. 42 K. G. R. Pachler J. Magn. Resonance 1972,7,442. 43 R. A. Bell C. L. Chan and B. G. Sayer J.C.S. Chem. Comm. 1972 67. 44 J. B. Stothers C. T. Tan A. Nickon F. Huang R. Sridhar and R. Weglein J. Amei-. Chem. SOC.,1972,94,8581.4s D. H. Hunter A. L. Johnson J. B. Stothers A. Nickon J. L. Lambert and D. F. Covey J. Amer. Chem. SOC.,1972,94,8582. 46 A. R. Tarpley and J. H. Goldstein J. Phys. Chem. 1972 76 515. 47 R. U. Lemieux T. L. Nagabhusan and B. Paul Canad. J. Chem. 1972,50 773. Physical Methods-Part (ii) Nuclear Magnetic Resonance 0 H HO H (10) adopts the anti-conformation in solution. Recent INDO-MO calculation^^^ show that the conformation dependence of the three-bond 13C-H coupling (,JCH) in propane follows the relation 35,-H= 4.26 -1.00 cos4 + 3.56 cos24 where +is the dihedral angle. The values for the uridine derivatives lie approxi- mately 0.5-1.0 Hz below the curve for propane. Unfortunately very few data are available at present for testing the generality of the relation.A few papers are devoted to the measurement and correlation of 13C-13C coupling constants. These have been obtained by continuous-wave methods49 on singly and doubly labelled compounds or at natural abundance by examina-tion of 13C satellites of 3C resonances by Fourier-transform techniques with proton noise decoupling. Low values (10-15 Hz) in cyclopropane derivatives4' confirm the low s-character of the ring bonds. Couplings in Hi3C-I3C systems to are pr~portional~~ l3C-H couplings (Jcc = 0.27JCH)in similar bonding situations as predicted and observed earlier" for the correlation of carbon-proton and proton-proton couplings (JCH= 0.3 JHH). This close agreement suggests that the coupling mechanisms are similar.In ethyl isopropyl and t-butyl derivatives H3'3C-'3C coupling increases with the number of methyl groups.51 Coupling constants between the a and ring carbons in a series of benzyl compounds PhCH2X where X = CH, CH,OH CH,Cl C02H COCI or CN have been determined.52 Coupling to the rneta-carbon atom is greater than to the ortho-carbon atom (3J3,> 2J2a),and the one-bond coupling 'Jla increases with the degree of s-character of the a-carbon atom and the electronegativity of the substituent. Other uses of I3C n.m.r. spectroscopy include (a) the determinations3 of keto-enol ratios in acetylacetone ethyl acetoacetate isopropylidene malonate 48 R.Wasylishen and J. Schaefer Canad. J. Chem. 1972,50,2710. 49 F. J. Weigert and J. D. Roberts J. Amer.Chem. SOC.,1972,92,6021. G. J. Karabatsos J. D. Graham and F. M. Vane J. Amer. Chem. SOC..1962,84 37. K. D. Summerhays and G. E. Maciel J. Amer. Chem. SOC.,1972,94,8348. 52 A. M. Ihrig and J. L. Marshall J. Amer. Chem. SOC.,1972,94 1756. 5J J. H. Billmann S. A. Sojka,and P. R. Taylor J.C.S. Perkin II 1972 2034. 30 I. H. Sadler and ascorbic acid in which good agreement was obtained with ratios found by other analytical methods ; (b) the ob~ervation~~ of helix-coil transitions in polypeptides ;(c) the conformational analysis of methylcyclohexanes5 ’and of methylcycloheptane derivatives ;56(6)the demonstration” that small branches in low-density polyethylene are n-butyl groups thus supporting a previous sug- tion of an intramolecular hydrogen-abstraction process taking place during polymer formation ; and (e) the study58 of transannular interactions in eight-membered-ring carbonyl compounds.A method has been described59 to obtain high-resolution n.m.r. spectra of rare (e.g. 13C. ”N 2H) or chemically dilute magnetic nuclei in solids. However the practical aspects render it unusable at present for the majority of chemists. Carbon-13 Relaxation Studies.-Spin-lattice relaxation times (Tl) for I3Cnuclei are largely measured with complete proton decoupling by inversion-recovery,” saturation-recovery,6 or progressive-saturation62 Fourier-transform tech-niques. These methods are successful but can be very time-consuming particu- larly where TI is long. A method has been proposed63 for reducing the time required in these experiments.Measurements of line intensities S, S are obtained at two different pulse intervals t = a and t = b. The ratio of the two intensities of a given resonance is given by the expression S -1 -Kexp(-a/T,) I -S 1 -K exp (-b/T,) K = 2 for inversion-recovery method ; K = I for saturation methods. This intensity-ratio method applied to progressive saturation has been made the basis of a programme which automatically selects the pulse intervals to optimize the determination of TI. This method when applied to the I3C spectrum of cortisone acetate gives results in good agreement with those obtained by the conventional inversion-recovery technique. A theoretical treatment has appeared64 which indicates that in the absence of proton irradiation the apparent TI can differ significantly from the proton- decoupled value and tends to be longer when measured by pulse methods and shorter when measured by adiabatic rapid-passage (a.r.p.) techniques.Experi- mental results for benzene are in agreement with the proposals. Under proton- 54 L. Paolillo T. Tancredi P. A. Temussi E. Trivellone E. M. Bradbury and C. Crane- Robinson J.C.S. Chem. Comm. 1972 335; C. Boccalon A. s. Verdini and G. Giacometti J. Amer. Chem. SOC. 1972 94 3639. 55 D. K. Dalling and D. M. Grant J. Amer. Chern. SOC.,1972,94 5318. 56 J. D. Roberts and M. Christl J. Org. Chem. 1972 37 3443. 57 D. E. Dorman E. P. Otocka and F. A. Bovey Macromolecules 1972 5 574. 58 T. T. Nakashima and G. E. Macial Org.Magn. Resonance 1972 4 321. 59 A. Pines M. G. Gibby and J. S. Waugh J. Chem. Phys. 1972,56 1776. 6o R. Freeman and M. D. W. Hill J. Chem. Phys. 1970,53 4103. J. L. Markby W. J. Horsiey and M. P. Klein J. Chem. Phys. 1971 55 3604. 62 R. Freeman and H. D. W. Hill J. Chem. Phys. 1971,54 3367. 63 R. Freeman H. D. W. Hill and R. Kaptein J. Magn. Resonance 1972,7 82. 64 T. D. Alger R. Freeman and D. M. Grant J. Chem. Phys. 1972 57 2168. Physical Methods-Part (ii) Nuclear Magnetic Resonance 31 decoupled conditions the same value for Tl is obtained by both methods and can be regarded as valid. The measurement of nuclear Overhauser enhancements (q) together with Tl relaxation times can provide information concerning the relaxation mechanisms.Since the Overhauser effects arise only from I3C-' H dipole-dipole (d.d.) inter- actions the contribution TIdd due to this mechanism can for most small or average organic molecules be obtained65 from Tl according to the equation Tlddy,T1/2y,qcH and separated from contributions TIo,from other relaxa- = tion mechanisms viz. 11 1 -=----Tl 7-,dd T," + Other relaxation mechanisms include spin rotation (s.r.) chemical shift anisotropy (c.s.a.) scalar coupling (s.c.) and intermolecular processes caused for example by the presence of paramagnetic species such as dissolved oxygen. Since the dipolar contribution is related to the effective correlation time T~, in some cases it is possible to estimate barriers to rotation which are outside the range normally covered by variable-temperature n.m.r.studies. In the absence of relaxation processes other than d.d. takes the maximum value of 1.988 providing that molecular reorientation is sufficiently rapid (>10" rad s-I). This is not the case for large macromolecules where the NOE is reduced since the dipolar relaxation is affected by relatively slow segmental motion of the molecule. Theoretical treatments of the behaviour of the NOE and of relaxation times in such cases have been given.66 13C Spin-lattice relaxation in benzene67 is essentially by a d.d. mechanism (q = 1.6) with significant contributions from either s.r. or c.s.a. processes. In monosubstituted benzenes containing carbon oxygen or nitrogen as substi- tuents the d.d. mechanism again dominates.The carbon atom para to the substi- tuent shows faster relaxation than do the ortho-and rneta-carbon atoms indicating preferred rotation of the molecule about the axis bisecting the substi- tuent and the ring. Relaxation of the methyl carbon in toluene is dominated by spin rotation. The variation of TI with magnetic field strength together with NOE measurements on 1,4-diphenylbutadiyne (12) (Tl values in seconds) show6* that 60% of the relaxation of the P-carbon arises from a c.s.a. mechanism at 23 kG the remaining 40% being largely d.d. In the only previous example 65 K. F. Kuhlman D. M. Grant and R. K. Harris J. Chem. Phys. 1970 52 3439. 66 J. Schaefer and D. F. S. Natusch Macromolecules 1972 5 416; D. Doddrell V. Glushko and A. Allerhand J.Chem. Phys. 1972 56 3683. " G. C. Levy J.C.S. Chem. Comm. 1972,47. 68 G. C. Levy D. M. White and F. A. L. Anet J. Magn. Resonance 1972,6,453. 32 I. H. Sadler (carbon disulphide) where c.s.a. has been established this mechanism only contributes at very low temperatures and high field strength^.^^ In bromo- benzene,70 the relaxation of 13C nuclei bonded to bromine is dominated by scalar relaxation with 79Br and by scalar and/or d.d. relaxation with *'Br. A zero value for q indicates the absence of 13C-lH d.d. relaxation. Since the gyromagnetic ratios of 13C 79Br and 81Br are very nearly the same interactions are not un- expected. TI Measurements on substituted ferrocenes indicate7' that the rings are able to spin with respect to each other within the molecule independent of the overall tumbling of the molecule.A dynamic method for the measurement of Tl and NOES has been used72 to show that the 13Crelaxation of the 1- and 3-methyl groups in 1,2,3-trimethyl- benzene and 1,2,3,5-tetramethyIbenzeneis dominated by a d.d. mechanism but that a substantial s.r. contribution is present for the 2-methyl group and the 5-methyl group (where applicable). Comparison of T:* values for these carbon atoms and the unsubstituted ring carbon atoms confirms that the 2-methyl group is essentially a free rotor. The rotational barrier for the other methyl groups is estimated at ca. 1.5 kcal mol- *,in good agreement with values expected from other estimates. Analogous situations were previously dern~nstrated~~ in mesitylene and o-xylene.The slight variation of q Tl ,and T:d with magnetic field strength suggested the minor participation of a c.s.a. relaxation process. A number of smaller molecules have also been studied. Increased rotational free- dom at the free ends of the butyl groups in di-n-butylamide has been observed.74 A study7' of acetone l,l,l-trichloroethane dimethyl sulphoxide t-butyl chloride and methyl acetate shows the relative contributions of d.d. and s.r. mechanisms in each case and gives rotational barriers for the methyl group that are in good agreement with literature values. Relaxation in chloroform methanol and the methyl carbon in acetic acid is mainly uia a d.d. process with s.r. becoming impor- tant at higher temperatures for methanol.76 Methyl iodide and carbon di- sulphide (except as noted above) are dominated by s.r.; for bromoform scalar relaxation is probably the major process.76 For small medium and symmetric molecules the following observations can be made. (i) Relaxation for 13Cnuclei bonded to one or more protons is mainly dipolar and relatively unaffected by the presence of small amounts of dissolved oxygen. (ii) For non-protonated nuclei degassing is essential since relaxation by oxygen can become very significant. (iii) Spin rotation becomes significant for freely rotating methyl groups. (iv) Chemical shift anisotropy is not generally significant. (v) Scalar relaxation only contributes when a quadrupolar nucleus such as Br is directly bonded to the 3C 69 H.W. Spiess D. Schweitzer U. Haeverten and K. H. Hausser J. Mugn. Resonance 1971 5 101. '' G. C. Levy J.C.S. Chem. Comm. 1972 352. 71 G. C. Levy Tetrahedron Letters 1972 3709. 72 T. D. Alger D. M. Grant and R. K. Harris J. Phys. Chem. 1972,76,281. 73 K. F. Kuhlmann and D. M. Grant J. Chem. Phys. 1971,55,2998. 74 G. L. Levy and G. L. Nelson J. Amer. Chem. SOC. 1972,94 4897. '' J. R. Lyerla and D. M. Grant J. Phys. Chem. 1972 76 3213. 76 T. C. Farrar S. J. Druck R. R. Shoup and E. D. Becker J. Amer. Chem. SOC.,1972 94. 699. Physical Methods-Part (ii) Nuclear Magnetic Resonance 33 nucleus. (vi) Intermolecular effects although not usually important for '3C nuclei can be reduced or eliminated by working in dilute solution in a mag- netically inert solvent.Measurements of spin-spin relaxation times (T2)are comparatively rare. The most promising approach appears to be by the measurement of TIP,which is essentially equal to T in The spin-echo method (SEFT)has been used78 to measure T for 13C nuclei (and also 2H,'H and "F) in benzene methyl iodide toluene carbon disulphide and other small molecules. The authors suggest that a good approximation to T which is of general validity for organic molecules is given by 1 1 1 T2(13C)-T,(13C)+-2T,('H) Clearly the acceptance of this will depend upon the availability of data. The value of SEFT as a generally applicable method for the measurement of T2 is however q~estionable.~~ Other Nuclei.-The use of Fourier-transform methods in 'H n.m.r.spectroscopy while not necessary for the majority of studies allows the observation of molecules in very high dilution. The spectra of aziridine and N-deuterioaziridine have been obtainedSo in the gas phase to minimize intermolecular effects and barriers to inversion of 17.3 kcal mol- ' (68 "C) and 17.9 kcal mol- (79 "C) have been estimated. The same sort of spectral simplification obtained in a proton-noise- decoupled xiatural-abundance '3Cn.m.r. spectrum may be obtained by examin- ing 'fully' tleuteriated molecules containing randomly distributed H nuclei under conditions employing 2H decoupling. The spectra obtained are then first- order.81 All the proton resonances are visible as single lines for example using commercial perdeuteriomethylcyclohexane (1.1 % H).Since methods are avail- able for the synthesis of deuterio-compounds containing small amounts of randomly distributed 'H this procedure should be useful for simplifying complex 'H n.m.r. spectra although it should be remembered that small but not neces- sarily negligible isotopic shifts in resonance positions may occur. Fourier-transform spectroscopy is particularly suited to the study of the behaviour of biological mcllecules at very low concentrations (10-4-10-moll-l) in aqueous solutions. Even using deuterium oxide instead of water the intensity of the residual HDO resonance may exceed the resonances of interest by 2-3 orders of magnitude. Apart from obscuring the region of interest and possibly intro- ducing beat frequencies in the remainder of the spectrum this may result in the dynamic range of the computer being exceeded before sufficient desirable signal 77 R.Freeman and H. D. W. Hill J. Chem. Phys. 1971,55 1985. 78 U. Haeberlen H. W. Spies and D. Schweitzer J. Magn. Resonance 1972,6 39. '' T. C. Farrar A. A. Maryott and M.S. Holmberg Ann. Rev. Phys. Chem. 1972 23 193. Bo R. E. Carter and T. Drakenberg J.C.S. Chem. Comm. 1972 582. J. J. Katz G. N. McDonald and A. L. Harkness J.C.S. Chem. Comm. 1972 542. 34 I. H. Sadler is obtained. This may be overcome in principle by block-averaging the trans- forms. In practice this requires accurate phase setting for the first block which may prove difficult on the weak signals. A number of methods for the reduction or elimination of the residual HDO resonance have been reported.Water-eliminated Fourier-transform spectroscopy82 (WEFT) makes use of the large difference in TI between the resonances of large molecules (< 1 s) and HDO in D20 solution (5-15 s). Use of the 'inversion-recovery' pulse sequence (T-180"-t-90"), where Tis a relatively long waiting period [35Tl(HDO)] and t the time required for the HDO resonance to acquire zero magnetization eliminates HDO from the spectrum. Shorter values of Tand t may be used providing that t 3 5T,-(sample). An alternative sequence (180"-HSP-t-90"-T) where HSP is a homogeneity-spoiling pulse which destroys any residual transverse magnetiza- tion has also been proposed.83 The useg3 of a steady-state sequence of pulses (90"-T) with pulse interval T < T,(HDO) considerably reduces the intensity of the HDO resonance in comparison with signals of shorter relaxation times but does not eliminate it.The method is useful if the signals of interest are not in the regior of the HDO resonance. The possibility of obtaining nitrogen- 15 n.m.r. spectra at natural-abundance levels has recently been dem~nstrated.~~ Two major problems arise. First TI tends to be long particularly where the 15Natom possesses no directly bonded protons thus necessitating long pulse delays. Secondly considerably reduced or zero signals may result when proton noise decoupling is employed since the full negative nuclear Overhauser effect resulting in an inverted signal may be in part offset by non-dipolar relaxation processes which would not affect the normal positive signal.The addition of small amounts of bis(acety1acetonato)- chromium(rr1) to the sample overcomes these problems to some extent.85 At concentrations above ca. 0.1 moll-',line-broadening becomes apparent. Spectra have been obtained for quinoline," benzamides and ben~onitriles,~ 'methyl- and phenyl-hydroazines,88 and various amine~.*~ In the last-named compounds the 'sN shifts correlate linearly with the 13Cshifts of alkanes derived by replacing the nitrogen atom by an appropriately substituted carbon atom. Only three studies of silicon-29 resonances all continuous-wave have appeared prior to this year. The sensitivity of silicon-29 in natural abundance is only twice that of carbon-13 and the nucleus has a negative nuclear Overhauser effect.A recent Fourier-transform study" of the "Si resonances of tetramethylsilane diphenylsilane and octamethylcyclotetrasiloxane has been reported. It appears that tetramethylsilane would make a good standard above 0 "Csince the NOE S. L. Patt and B. D. Sykes J. Chem. Phys. 1972 56 3182. 83 F. W. Benz J. Feeney and G. C. K. Roberts J. Magn. Resonance 1972,8 114. " R. L. Lichter and J. D. Roberts J. Amer. Chem. Soc. 1971 93 3200; J. M. Briggs L. F. Farnell and E. W. Randall Chem. Cornm. 1971 680. 85 L. F. Farnell E. W. Randall and A. I. White J.C.S. Chem. Comm. 1972 1159. 86 P. S. Pregosin E. W. Randall and A. I. White J.C.S. Perkin II 1972 1. 8i P. S. Pregosin E. W. Randall and A. I. White J.C.S. Perkin II 1972 513.R. L. Lichter and J. D. Roberts J. Amer. Chem. SOC.,1972 94 4904. 89 R. L. Lichter and J. D. Roberts J. Amer. Chem. SOC.,1972,94 2495. '' G. C. Levy J. Amer. Chem. Soc. 1972 94,4793. Physical Methods-Part (ii) Nuclear Magnetic Resonance 35 is very low at room temperature and the spin-lattice relaxation time (TI = 20 s) is relatively short for silicon nuclei. Tl Values for hydrogen-bearing silicon atoms are expected to be about nine times as long as the analogous I3Cvalues. Nuclear Overhauser effects could be removed using gated decoupling method^.^' A large number of 29Si resonances have been obtained” by continuous-wave methods. The shift range is smaller than that for I3Cresonances. 3 Miscellaneous Studies A short reviewg2 and two more comprehensive reviewsg3 have appeared con- cerning the applications of shift reagents.A new readily prepared reagent tris(decafluoroheptanedionato)europium Eu(fhd) (13) has been reported.94 This complex is superior to the generally used reagents Eu(dpm) (14) and Eu(fod) (1 5)in that it is readily soluble in carbon tetrachloride (ca.300 mg rnl- ’) has no proton resonances which could obscure regions of the spectrum and shows somewhat larger shifts for protons remote from the substrate-complexing site. Replacement of europium by other lanthanides results in broadened resonances. A shift reagent of a different kind which combines specifically with amines is CH ,CH ,CH ,CH c=o’ N (13) R’ = Rz = C2F5 (14) R’ = R2 = CMe (15) R’ = CMe,; R’ = C,F H,CCH2CH2CH2 (16) provided95 by iron(n) phthalocyanine.This makes use of the large magnetic anisotropy of the ring system. The resulting complex (16) is diamagnetic and thus no line-broadening occurs. The alkyl resonances appear as clear multiplets over the region 1G14.r and the amine resonance at 175. The specificity of the new reagent should be of value when studying polyfunctional compounds. Y’ R. L. Scholl G. E. Maciel and W. K. Musker J. Amer. Chem. SOC.,1972 94 6376. ” M. R. Peterson and G. H. Wahl J. Chem. Educ. 1972 49 790. ’’ R. von Ammon and R. D. Fischer Angew. Chem. Internat. Edn. 1972 11 675; J. Grandjean Ind. chim. belge 1972 37 220. y4 G. A. Burgett and P. Warner J. Magn. Resonance 1972 8 87. 95 J.E. Maskasky J. R. Mooney and M. E. Kenney J. Amer. Chem. Sac. 1972 94 2132. 36 I. H. Sadler Shifts caused by the lanthanide reagents appear to be essentially of the pseudo- contact type ;96 however in some cases particularly where 7c-systems are in- ~olved,~' a contact interaction is also present and appears to be considerably more pronounced for I3Cnuclei than for protons.98 Increasing contact contribu- tions have been observed along the series Pr(fod) ,Yb(fod) ,Eu(dpm) ,Eu(fod) where substituted pyridine N-oxides and anilines are used as substrates. A method has been given99 for separating the contact and pseudocontact contribu- tions to shifts caused by europium nitrate. The conditions have been clarified"' under which the pseudocontact contribution is given by an expression of the type K(3COS'~ -1)-3 and a simple graphical method for the analysis of induced shifts has appeared.' O1 A new theoretical treatment of lanthanide- induced shifts has been proposed.lo2 Various workers99* 103-10s have studied the variations of the induced shift with concentration of shift reagent (L) and/or substrate (S),in an attempt to elucidate the equilibria involved. However there is disagreement over whether just the firstlo4 or bothIo5 of the equilibria L + SSLS,LS + S LS are necessary to obtain the best description of the systems. Spectra obtained at -80 "C from dideuteriomethylene chloride solutions of Eu(['H9]fod) with excess of dimethyl sulphoxide show resonances due to both the free and complexed substrate and under these conditions each molecule of shift reagent co-ordinates two molecules of substrate.Methods have been devised for the eliminati~n'~' of errors which may arise in plots of induced shift versus L:Sratio and from inaccurate estimates of concentrations and for the automatic sorting of signals in complex shift-reagent spectra. lo' The use of shift reagents for resonance and configuration assignments has been widespread. Chiral shift reagents have been sh~wn''~ to be capable of differentiating between enantiotropic protons at prochiral centres. Tris-[3-hepta- y6 W. D. Horrocks and J. P. Sipe J. Amer. Chem. SOC.,1971 93 6800; J. Reuben and J. S. Leigh J. Amer. Chem. SOC. 1972,94,2789; I. Armitage J. R. Campbell and L. D. Hall Canad.J. Chem. 1972 50 2139. 97 B. F. G. Johnson J. Lewis P. McArdle and J. R. Norton J.C.S. Chem. Comm. 1972 585. y8 A. A. Chalmers and K. G. R. Pachler Terrahedron Letters 1972 4033; R. J. Cushley D. R. Anderson and S. R. Lipsky J.C.S. Chem. Comm. 1972 636; M. Herayama E. Edagawa and Y. Hanyu J.C.S. Chem. Comm. 1972 1343. 99 J. R. M. Saunders S. W. Hanson and D. H. Williams J. Amer. Chem. SOC.,1972,94 5325. loo J. M. Briggs G. P. Moss E. W. Randall and K. D. Sales J.C.S. Chem. Comm. 1972 1180. lo' R. M. Wing T. A. Early and J. J. Uebel Tetrahedron Letters 1972 4153. lo2 B. Bleaney J. Magn. Resonance 1972,8,91; B. Bleaney C. M. Dobson B. A. Levine R. B. Martin R. J. P. Williams and A. V. Xavier J.C.S. Chem. Comm. 1972 791. lo3 D. R. Kelsey J.Amer. Chem. SOC. 1972,94 1764; R. K. Mackie and T. M. Shepherd Org. Magn. Resonance 1972 4 557. Io4 J. A. Wittstruck J. Amer. Chem. SOC.,1972 94 5130; I. Armitage G. Dunsmore L. D. Hall and A. G. Marshal Canad. J. Chem. 1972 50 21 19. lo5 B. L. Shaprio and M. D. Johnston J. Amer. Chem. SOC. 1972,94 8185. lo6 D. F. Evans and M. Wyatt J.C.S. Chem. Comm. 1972 312. '07 J. W. ApSimon and H. Beierbeck J.C.S. Chem. Comm. 1972 172; J. W. ApSimon H. Beierbeck and A. Fruchier Canad. J. Chem. 1972,50 2725. lo' J. W. ApSimon H. Beierbeck and A. Fruchier Canad. J. Chem.. 1972,50 2905. R. R. Fraser M. A. Petit and M. Miskow J. Amer. Chem. SOC. 1972 94 3253. Physical Methods-Part (ii) Nuclear Magnetic Resonance fluoropropylhydroxymethylene-(+)-camphorato]praseodymium(r~~)causes a chemical shift difference of up to 0.8p.p.m.for the benzylic protons in benzyl alcohol and its derivatives. Since the resonances now take the form of an AB quartet a value for the geminal coupling constant JHHmay be obtained. Care must be exercised in obtaining coupling constants from shift-reagent spectra since small changes in J with reagent :substrate ratio are sometimes observed. ' ' Chiral reagents have also been used to distinguish"' between rneso-and racemic diastereomers e.g. 2,3-epoxybutane. The non-chiral reagents Eu(dpm) and Eu(fod) will also induce differential shifting of diastereotopic protons e.g. the IT-methylene protons in 3-phenylpropan-1-01' l2 and the protons of the gern-dimethyl group in the ethylenehemithio-acetal ofmethyl isopropyl ketone.l3 In suitable cases shift reagents have provided a convenient means of varying the coalescence temperature of protons undergoing exchange where the separate resonances are shifted by different amounts. Such variations have been obtained for 4,4,7,7-tetramethy1cyc1ononanone' l4 in carbon disulphide in the presence of Eu(dpm) and for NN-dimethyl derivatives of formamide acetamide and propionamide' '' in tetracyanoethylene in the presence of Eu(fod) . A lanthanide shift reagent substrate ratio (L :S) of 0.5 raises the coalescence temperature of dimethylformamide to 164 "Cfrom 114 "C in the absence of shift reagent. Lower L :S ratios (0.3)are recommended. In this study a steady increase in AG* was obtained suggesting that the method may be helpful in obtaining accurate values of AS*.The method is however restricted to temperatures higher than 10 "C since below this level line-broadening effects and solubility problems arise. The use of total lineshape methods for the determination of exchange rates has been critically examined. 'l6 Serious systematic errors are liable to arise from improper temperature calibration neglect of linewidth changes over the tempera- ture range and ignorance of the temperature dependence of the chemical shifts between the exchanging sites. For these reasons total lineshape analyses should not be extended much above the coalescence temperature. Molecular geometries have been obtained from studies in nematic liquid crystals' l7 for a variety of molecules including cyclohepatrienone,' l8 which shows only slight bond alternation norbornadiene,' l9 1,4-naphthoquinone,' 2o 'lo B.L. Shapiro M. D. Johnston and R. L. R. Towns J. Arner. Chern. SOC.,1972 94 4381. M. Kainosho K. Ajisaka W. H. Pirkle and S. D. Beare J. Amer. Chem. SOC.,1972 94 5924. 'I2 P. S. Mariano and R. McElroy Tetrahedron Letters 1972 5305. 'I' P. Joseph-Nathan J. E. Herz and V. M. Rodriguez Canad. J. Chem. 1972 50 2788. G. Borgen Acta Chern. Scand. 1972 26 1740. H. N. Cheng and H. S. Gutowsky J. Amer. Chem. Soc.. 1972.94. 5505. ' I' R. R. Shoup E. D. Becker and M. I. McNeel J. Phys. Chem. 1972,76 71. 'I' P. Diehl and C. L. Khetrapal 'NMR Basic Principles and Progress' Springer-Verlag Berlin 1969 Vol. I p. 1 ;S.Meiboom and L. C. Snyder Accounts Chem. Res. 1971 4 81. C. A. Veracini and F. Pietra J.C.S. Chern. Comrn. 1972 1262. 'I9 E. E. Burnell and P. Diehl Canad. J. Chem. 1972 50 3566. J. M. Dereppe J. Degelaen and M. van Meerssche Org. Magn. Resonance 1972 4 551. 38 I. H. Sadler and benzonitrile.'21 To assist in such work a computer program SHAPE has been developed,' 22 which starts from trial orientation parameters and nuclear co- ordinates and the experimentally determined direct coupling constants and then determines iteratively the final degree of orientation and shape of the nuclear skeleton by a least-squares procedure. Two papers have been concerned with estimating the shielding effects of the cyclopropane ring. A ring-current model has been used'23 to construct a map from which shielding contributions to chemical shifts may be obtained with only the aid of molecular models good agreement with experimental values being obtained for over 40 compounds of known geometry.A compari~on'~~ of two other approaches the group-anisotropy and bond-anisotropy models indicates that the former is superior in predicting chemical shifts. A new set of tables for the estimation of the shielding effects on protons in the vicinity of a benzene ring has been derived'25 on a quantum-mechanical basis. It is shown that the presently used Johnson-Bovey tables' 26 over-estimate the deshielding effects in planar condensed hydrocarbons but that the new set under-estimates shielding at positions above the rings somewhat more so than the Johnson-Bovey set.Procedures have been described' 27for obtaining relative internuclear distances particularly in three-spin systems from nuclear Overhauser measurements. A number of conclusions have been drawn which are of particular value if the enhancements are to be used in a qualitative manner (a)a zero NOE does not necessarily imply that the two spins are distant since it may result from a cancel- lation of a direct and an indirect effect ;(b)in the absence of chemical exchange a negative NOE between two spins indicates that a third spin lies between them; (c)indirect effects through rapidly relaxing spins or groups of spins e.g. methyl protons are small; (d)the relative values of the enhancements of spin A when other spins are saturated is a better indication of the position of A with respect to those other spins than are their relative enhancements when A is saturated; (e)if qx and qy are the only large enhancements of spin A obtained on saturating spins X and Y then rAX/rAy = (qY/qx)%where TAX is the AX internuclear distance and similarly for rAy.It has been shown'28 experimentally and theoretically that the aromatic solvent-induced shift (ASIS) of a solute depends strongly in magnitude and sign on the internal reference used. It appears to bear virtually no relation to presumed specific interactions between the solute and solvent. Various procedures are described to eliminate the effects of the internal reference. ' C. A. Veracini P. Bucci and P. L. Barili Mol.Phys. 1972 23 59. Iz2 P. Diehl P. M. Henrichs and W. Niederberger Mol. Phys. 1971,20 139. 123 C. D. Poulter R. S. Boikess J. I. Braumann and S. Winstein J. Amer. Chem. SOC. 1972,94,2291. L24 R. C. Hahn and P. H. Howard J. Amer. Chem. SOC.,1972 94 3143. C. W. Haigh and R. B. Mallion Org. Magn. Resonance 1972,4 203. lZbC. E. Johnson and F. A. Bovey J. Chem. Phys. 1958 29 1012. '" R. E. Schirmer and J. H. Noggle J. Amer. Chem. Soc. 1972 94 2947. Iz8 F. H. A. Rummens and R. H. Krystynak J. Amer. Chem. Sor. 1972,94 6914. Physical Methods-Part (ii) Nuclear Magnetic Resonance Heteronuclear 1H-(2Dj INDOR spectroscopy has been used for the first time to measure' 29 deuterium chemical shifts notably in [2H,]acetone [2H,]benzene ['H ,]dimethyl sulphoxide and 1,2,5,6-di-O-isopropylidene-a-~-[3-Hlallofura-nose.It is emphasized that the values for the first three compounds will differ slightly from those of the related perdeuterio-derivatives. The following aspects and applications of n.m.r. have been reviewed :organo-phosphorus compounds ;I3' the assignment of stereochemistry about double bonds ;l 'conformational studies of cyclic polypeptides ;'32 the analysis and classification of AA'XX'and AA'BB' systems in 'H n.m.r. the effect of solvents on coupling constants high-field studies ;l 35 the orientation of molecules in electric fields recent developments,'37 and general aspects.l3' 129 J. R. Campbell L. D. Hall and P. R. Steiner Canad. J. Chem. 1972 50 504. 130 B. I. Ionin and T. N. Timofeeva Russ.Chem. Reu. 1972 41 390. 131 G. J. Martin and M. L. Martin Progr. N.M.R. Spectroscopy 1972 8 163. 132 F. A. Bovey A. 1. Brewster D. J. Patel A. E. Tonelli and D. A. Torchia Accounts Chem. Res. 1972 5 193. 133 H. Gunter Angew. Chem. Internat. Edn. 1972 11 861. S. L. Smith Fortschr. Chem. Forsch. 1972 27 117. 135 A. A. Grey Canad. J. Spectroscopy 1972 17 82. 136 C. W. Hilbers and C. MacLean in 'NMR Basic Principles and Progress' Springer- Verlag Berlin 1972 Vol. 7 p. 1. 13' E. D. Becker Appl. Spectroscopy 1972 26 421. 13' P. L. Corio S. L. Smith and J. R. Wasson Anulyt. Chem. 1972 44 407R.