Ortho effect substitution

The effect substitution on the phenolic ring has on activity has been the subject of several studies (11—13). Hindering the phenolic hydroxyl group with at least one bulky alkyl group ia the ortho position appears necessary for high antioxidant activity. Neatly all commercial antioxidants are hindered ia this manner. Steric hindrance decreases the ability of a phenoxyl radical to abstract a hydrogen atom from the substrate and thus produces an alkyl radical (14) capable of initiating oxidation (eq. 18). 

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. 

Efremov and coworkers investigated the mass spectra of 18 methyl-substituted diphenyl (63)40 and substituted phenyl mesityl sulfones (64)41. The mass spectra of practically all the compounds showed by the rearrangement ions [M — OH]+, [M —H20]+ and [M — (H20 + OH)]+, the relative abundances of which depend on the position of the substituent in the phenyl moiety (ortho effect). It was also evident that in 63 the introduction of the first methyl substituent clearly decreases the contribution of the sulfone sulfinate isomerization (equation 30) to their fragmentation whereas the further substitution had little or no effect on the isomerization process in both 6340 and 6441. 

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 ... 

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. 

The electron impact induced ortho effects in 2-nitro-substituted aromatic sulphides containing e.g. 2-pyridyl, 2-(5-methylthio-l,3,4-thiadiazolyl) moieties have been studied105, the 2,6-bis(nitrophenylthio)pyridines being typical representatives for the compounds studied105. 

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. 

Sampling rates at different temperatures have been determined by Huckins et al. (1999) for PAHs at 10,18, and 26 °C, by Rantalainen et al. (2000) for PCDDs, PCDFs, and non-ortho chlorine substituted PCBs at 11 and 19 °C, and by Booij et al. (2003a) for chlorobenzenes, PCBs, and PAHs at 2,13 and 30 °C. The effect of temperature on the sampling rates can be quantified in terms of activation energies (A a) for mass transfer, as modeled by the Arrhenius equation... 

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. ... 

In the case of insertion toward fluorine (41), there is an even greater amount of positive-positive charge repulsion between the ortho and ipso carbons than in the transition state and this effect is responsible, in part, for a higher activation barrier for insertion toward F to form 41 than away from fluorine to form 40. Therefore, the origin of the pronounced influence of ortho,ortho-difluoro substitution on the lifetime of singlet arylnitrene and the increased activation energy of its cyclization is the result of combination of the steric effect and the extraordinary electronegativity of fluorine atom. 

The general reaction upon which the first of the above two methods is based is that described by Dakin in 1909 2 the demethylation of guaiacol to catechol has been effected by heating with aluminum chloride3 and with hydriodic acid.4 Other important methods of preparation consist in treating ortho halogen-substituted phenols with alkalies under suitable... 

Appropriately, ortho-substituted benzoates eliminate ROH through the general ortho effect described above under aromatic acids. Thus, the base peak in the spectrum of methyl salicylate is m/z 120 this ion eliminates carbon monoxide to give a strong peak at m/z 92. 

However, there are some contradictory reports on the composition of the products of toluene alkylation or benzene dialkylation at high conversions. In some cases, compositions corresponding to the thermodynamic equilibrium between ortho, meta and para isomers were found, and in other cases, kinetic control of orientation, giving mostly the ortho + para substitution, prevailed. Consecutive isomerisation of the ortho and para isomers to the more stable meta isomer seems to be the cause of the disagreement. More active catalysts gave more meta derivatives than the less active ones [343] and increasing the temperature has the same effect [351]. 

Substituent increments are obtained as usual by subtracting the reference shifts of naphthalene (C-1,4,5,8 127.7 C-2,3,6,7 125.6 C-9,10 133.3 ppm) from the individual data of C-l to C-10 in the substituted derivatives given in Table 4.55. It turns out that comparable Zx, Zmthn, Zmrta, and Zpara increments in naphthalene and benzene differ substantially in magnitude, as exemplified in Table 4.56. In 1-substituted naphthalenes, C-9 increments are attenuated in favor of C-2 relative to comparable ortho effects known from benzene C-3 and C-1 in 2-substituted naphthalenes behave correspondingly (Table 4.56). This can be explained by the cannonical formulae c, which do not contribute so much to the actual molecular state due to disrupted % electron sextets. Full inter-... 

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... 

This effect is made clear in the valence-bond structures for the ortho-para substitution intermediates from benzenol (phenol) ... 

Methoxy-substituted aromatic compound 4 is lithiated metalation with Buli in THF, a step in which it proves useful to include lithium chloride. Because of the greater basicity of /t-butyllithium relative to 4. direct metallation is in fact possible thermodynamically, but /i-butyllithium is generally present in solution as a tetra-mer, and this reduces its reactivity. Addition of lithium chloride destroys these aggregates, and that eliminates the kinetic inhibition. Lithiated aromatic species 18 is further stabilized through chelate formation between lithium and the orr/icr-methoxy groups (ortho effect).8... 

Substituted aromatics - the ortho effect. Aromatic compounds bearing substituents with an appropriately placed hydrogen atom will undergo a facile rearrangement involving a second substituent in the ortho position, e.g. 

A review of experimental work prompted the suggestion of the importance of dipolar interactions (Hammond and Hawthorne, 1956). de la Mare and Kidd (1959), observing a parallelism in the parajmeta and ortho/meta ratios, predicted the ortho effect to be primarily electronic in origin. Norman and Radda (1961) explored the general significance of this idea. They studied the orthojpara ratios for the substitution of a series of monosubstituted benzenes by two reagents with the same electrophilic properties but different steric requirements. The reactions, nitration by N02+ and chlorination by CI+, fulfill the requirements. The results are summarized in Table 3. 

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