The ortho/para Ratio in Electrophilic Aromatic Substitution. Mercuration and Alkylation of Chlorobenzene and Anisole. Evidence for a Coordination Effect<sup>1</sup>

Lin

Proc. Natl. Acad. Sci. U.S.A.

et al. 1978

The nitration of toluene and anisole was studied with nitrating systems of varying reactivity. High regioselectivity of ortho-para over meta substitution was maintained in all nitrations, regardless of the reactivity of the nitrating system. At the same time, the amount of meta substitution stayed low (3% or less), even when the fast reactions may have reached the encounter-controlled limit. Because the nitration of o-xylene, in which both ring positions are activated by the effect of a methyl group, also does not show any diminishing of regioselectivity, the possibility of a dual mechanistic pathway, in which the activated position would react by a fast, encounter-controlled path, whereas the nonactivated meta position by a slower a-type path, can be ruled out. The data unambiguously prove that the high regioselectivity of electrophilic aromatic nitration is independent of the reactivity of the reagent, because no significant increase of meta substitution of toluene or anisole was observed, regardless of the activity of the nitrating system. No selectivity-reactivity relationship is thus evident and the ortho-para directing effect of primary substituents over meta substitution is always maintained. The variation in the amount of the meta isomer, up to the observed limit of about 3% in the case of toluene and <2% for anisole, is probably significant but, at the present time, cannot be quantitatively evaluated with the ±0.5% overall reproducible accuracy of the nitrations. Steric factors, such as increasing bulkiness of the nitrating agent, also can affect the ortho-para isomer ratios but are not considered to be the only reason for the observed variations, which reflect the specific nitrating systems, affecting the nature and position of the transition state of highest energy on the reaction pathway.Electrophilic aromatic nitration has been shown by Ingold's classical studies (2) to proceed via the formation of the nitronium ion (NO2+). The nitration of toluene and other substituted benzenes by different nitrating systems is generally accepted to show little variation in isomer distribution. This constancy of isomer distribution has been interpreted (3-5) as indicative of a common nitrating agent-i.e., the nitronium ion. Although there is a good evidence that reagents other than the nitronium ion, such as acetyl nitrate, can act in their own right as nitrating agents (4), Ingold's view that the NO2+ ion is indeed the common and only nitrating agent generally prevails. Solvation of this very reactive ion by the reaction medium should modify its reactivity, depending primarily upon the nucleophilicity of the solvent.We now report that, contrary to discussed general belief (2), the isomer distribution, particularly the ortho/para ratios, in the nitration of the studied substituted benzenes (e.g., toluene, anisole, o-xylene) shows a significant variation, depending upon the nature of the specific nitrating system used. The high ortho-para regioselectivity of these substrates, however, seems to be independent...

Section: Resultsmentioning

confidence: 90%

Variation of isomer distribution in electrophilic nitration of toluene, anisole, and o -xylene: Independence of high regioselectivity from reactivity of reagent

Lin

Proc. Natl. Acad. Sci. U.S.A.

et al. 1978

“…10,11,16,[25][26][27][28] In the first step, a proton from the catalyst attacks a double bond forming a carbocation (Scheme 2a). 10,11,16,[25][26][27][28] In the first step, a proton from the catalyst attacks a double bond forming a carbocation (Scheme 2a).…”

Section: Resultsmentioning

confidence: 99%

Phenolation of vegetable oils

Ionescu

Petrovìć

2011

J Serb Chem Soc

Novel bio-based compounds containing phenols suitable for the synthesis of polyurethanes were prepared. The direct alkylation of phenols with different vegetable oils in the presence of superacids (HBF 4 , triflic acid) as catalysts was studied. The reaction kinetics was followed by monitoring the decrease of the double bond content (iodine value) with time. In order to understand the mechanism of the reaction, phenol was alkylated with model compounds. The model compounds containing one internal double bond were 9-octadecene and methyl oleate and those with three double bonds were triolein and high oleic safflower oil (82 % oleic acid). It was shown that the best structures for phenol alkylation are fatty acids with only one double bond (oleic acid). Fatty acids with two double bonds (linoleic acid) and three double bonds (linolenic acid) lead to polymerized oils by a Diels-Alder reaction, and to a lesser extent to phenol alkylated products. The reaction product of direct alkylation of phenol with vegetable oils is a complex mixture of phenol alkylated with polymerized oil (30-60 %), phenyl esters formed by transesterification of phenol with triglyceride ester bonds (<10 %) and unreacted oil (30 %). The phenolated vegetable oils are new aromatic-aliphatic bio-based raw materials suitable for the preparation of polyols (by propoxylation, ethoxylation, Mannich reactions) for the preparation of polyurethanes, as intermediates for phenolic resins or as bio-based antioxidants.

“…Consequently, in methyl salicylate, the 3‐position ( ortho to –OH and meta to –CO 2 Me) and the 5‐position ( para to –OH and meta to –CO 2 Me) are the most reactive. The ortho / para ratio in electrophilic aromatic substitution reactions depends on several factors – steric considerations favour higher reactivity at the para position, complexation or coordination between the electrophile and the activating group can favour higher reactivity at the ortho position, and, because of the reversible nature of the reaction, the ortho / para ratio can vary according to whether the reaction is carried out under kinetic control or thermodynamic control conditions. In the present case, because of the possibility of intramolecular hydrogen bonding, the ortho ‐substitution product may be thermodynamically favoured.…”

Section: Guinea‐pig Maximization Test Data For 5‐capryloyl Salicylic mentioning

confidence: 99%

“…Overall, therefore, from consideration of the literature on electrophilic aromatic substitution , we expect significant quantities of 3‐CSA ( 6 ) (> 10% of the total of 3‐CSA plus 5‐CSA) to be formed, via its methyl ester 5 , in the synthetic route, as shown in Fig. .…”

Section: Guinea‐pig Maximization Test Data For 5‐capryloyl Salicylic mentioning

confidence: 99%

Contact allergy to capryloyl salicylic acid: a mechanistic chemistry and structure–activity perspective

Roberts

Aptula

2015

Contact Dermatitis