The Ortho Effect

It has been discovered that o-substituents in the palladacycle exert a steric effect that is able to orient the aryl group that attacks the palladacycle toward the aryl site of the palladacycle itself [7]. We have seen in Sect. 2.3, Eq. 8, that in the solid state an o-methyl group induces palladium to adopt an coordination and this probably is connected with some steric effect of the methyl group. The X-ray structure of the corresponding palladacycles stabilized by 

Reaction of Phenyinorbornylpalladium Chloride with Norbornene andlodobenzene 

It will be obvious that the treatment thus far includes only substituents that are meta or para to the reaction site. When Hammett plots are made with data for ortho-substituted reactants, scatter diagrams usually result. This failure might be attributed to steric effects, but this is not very helpful, and many attempts have been made 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent.  

The ortho effect may consist of several components. The normal electronic effect may receive contributions from inductive and resonance factors, just as with tneta and para substituents. There may also be a proximity or field electronic effect that operates directly between the substituent and the reaction site. In addition there may exist a true steric effect, as a result of the space-filling nature of the substituent (itself ultimately an electronic effect). Finally it is possible that non-covalent interactions, such as hydrogen bonding or charge transfer, may take place. The role of the solvent in both the initial state and the transition state may be different in the presence of ortho substitution. Many attempts have been made to separate these several effects. For example. Farthing and Nam defined an ortho substituent constant in the usual way by = log (K/K ) for the ionization of benzoic acids, postulating that includes both electronic and steric components. They assumed that the electronic portion of the ortho effect is identical to the para effect, writing CTe = o-p, and that the steric component is equal to the difference between the total effect and the electronic effect, or cts = cr — cte- They then used a multiple LFER to correlate data for orrAo-substituted reactants. 

Many other definitions of an ortho substituent constant have been made Shorter has reviewed these. Charton analyzed Oo in terms of Oi and CTr, i.e., = a(Ti -I- fpoR, finding that the distribution of inductive and resonance effects (the ratio a/b) varies widely with the substituent and, therefore, that no general Oo scale is possible. Charton also subjected to analysis according to Eq. (7-47), 

Fujita and Nishioka have attempted to place ortho effects on the same numerical scale as meta and para effects. They assume that the normal ortho electronic effect can be represented by the standard substituent constant appropriate to the reaction (cr, cr , cr, cr°), that the steric effect is given by E , and that the proximity effect is measured by the Swain-Lupton Then a multiple LFER is written 

Despite their associated problems, attempts have been made to incorporate results from ortho substituents in free energy correlations. It might be necessary, for example, to predict physico-chemical properties of a compound with an ortho substituent which acts as a drug or is a putative intermediate in a proposed mechanism. Quantitation of the ortho substituent effect requires that both steric and polar effects be considered. The ortho effect can be fitted to a modified version of the Pavelich-Taft equation (Chapter 2, Equation 15) where the values 

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The ortho effect has its origin in the ability of an ortho substituent to form a hydrogen bond with a hydrogen on the amine nucleophile58-61. The present... 

Hojo and colleagues155,156 have carried out numerous studies of ortho-effects, in particular on the ionizations of benzoic acids in DMSO-water mixed solvents. The ortho-effects are assessed by measuring the pKa values of ortho- and para- substituted benzoic acids in solvents containing from 0 to 95% v/v DMSO and expressing the results as equation 15 ... 

This is not the same as the ortho effect discussed on page 688. 

Much effort has been devoted to the attempt to set up scales of cr values of general applicability. Only very limited success has been achieved in this direction and it seems naive to suppose that any simple LFER analogous to the Hammett equation could be successful in connection with the ortho-effect, except in rather limited and special situations. On the whole the various essays at scales of cr values have not involved sulfinyl or sulfonyl... 

Fig. 13 The steric assistance mechanism for the ortho-effect. Energy profile for the para-isomer is given in dotted lines whereas data for ort/zo-isomer are shown in solid lines. Calculations were performed at the BLYP/6-31G (in bold) and B3LYP/6-31G levels. P stands for products, R stands for reactants. Adapted from reference49.

Ortho-Effect. The ortho-effect is one of the most widely known structural phenomena in organic chemistry. It is widely used in organic chemistry for synthetic purposes. The mass spectra of the majority of ort/jo-substituted aromatic compounds possess significant differences in comparison with the spectra of their meta- and para-isomers. A classic example of the ortho-effect in mass spectrometry involves fragmentation of alkylsalicylates. The intense peaks of [M - ROH]+ ions dominate in the El spectra of these compounds. These peaks are absent in the spectra of their meta- and para-isomers. The reaction leading to these ions may be represented by Scheme 5.12. 

A detailed review of the ortho-effect in mass spectrometry was published by H. Schwarz [22]. He classified the processes related to the ortho-effect, gave examples of unusual elimination reactions, processes of intramolecular cyclization, exchange and reduction processes. 

Certain analogies in the processes due to the ortho-effect in solution and in the ion source of a mass spectrometer allow realization of prognoses on the possibility of... 

Hydrogen transfer prior to fragmentation, e.g. the ortho effect. 

In Section IV.B we will discuss the ortho-effect of NO2 as manifested in the ionization of carboxylic and other acids and (in Section IV.C) in the reactions of substituted benzoic acids with diazodiphenylmethane (DDM). Only in the case of the latter system can really satisfactory correlation analysis be taken as the basis for discussion. For most of the other systems discussion will have to be qualitative or, at best, semi-quantitative. 

E. The Ortho-Effect of the Amino Group and Related Groups... 

Tajima, S. Azami, T. Shizuka, H. Tsu-chiya, T. An Investigation of the Mechanism of Single and Double Hydrogen Atom Transfer Reactions in Alkyl Benzoates by the Ortho Effect. Org. Mass Spectrom. 1979,14,499-502. 

Martens, J. Praefcke, K. Schwarz, H. Spectroscopic Investigations. IX. Analytical Importance of the Ortho Effect in Mass Spectrometry. Benzoic and Thiobenzoic... 

Spiteller, G. The Ortho Effect in the Mass Spectra of Aromatic Compounds. Monatsh. Chem. 1961,92,1147-1154. 

Smith, J.G. Wilson, G.L. Miller, J.M. Mass Spectra of Isopropyl B zene Derivatives. A Study of the Ortho Effect. Org. Mass Spectrom. 1975,10, 5-17. 

The influence of temperature on the ortho effect has been evaluated in the alkaline hydrolysis in aqueous DMSO solutions of ortho-, meta- and para-substituted phenyl benzoates (26). The alcoholysis of phthalic anhydride (27) to monoalkyl phthalates (28) occurs through an A-2 mechanism via rate-determining attack of the alcohol on a carbonyl carbon of the anhydride (Scheme 4). Evidence adduced for this proposal included highly negative A 5 values and a p value of 4-2.1. In the same study, titanium tetra-n-butoxide and tri-n-butyltin ethanoxide were shown to act as effective catalysts of the half-ester formation from (27), the mechanism involving alkoxy ligand exchange at the metal as an initial step. ... 

The authors explain the difference through the ortho effect that hinders o-Wuester azathiacrown ether from one-electron oxidation but assists in the mercury coordination inside the macrocycle (Sibert et al. 2006). 

A detailed analysis of substituent effects on the pKa values of imidazoles and tetrazoles as well as benzimidazoles and naphthimidazoles has been made.308 The ortho effect is shown to parallel that of 2-substituted pyridines and quinolines47 190 and application of the Hammett equation to the tautomerism of these systems is also considered. The equation also satisfies the effect of substituents on the basicity of the nitrogen in the 1-position for 1-pyrazolines.309... 

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