Mechanism of aromatic nitration

Lin

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: Resultssupporting

confidence: 50%

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

Lin

et al. 1978

“…Although the elucidation of the classic S E Ar mechanism [ Fig. 1, involving the initial formation of a π-complex, followed by a transition state leading to a σ-complex (arenium) intermediate in the rate-controlling stage, and, finally, proton loss from the ipsoposition leading to the reaction product] is considered to be a triumph of physical organic chemistry (1,(31)(32)(33)(34)(35)(36)(37), an alternative addition-elimination pathway leading to substitution products has Significance Electrophilic substitution is universally regarded as the characteristic reaction of aromatic compounds. Arenium ions are widely accepted as obligatory intermediates in the two-stage (S E Ar) mechanism typically described in textbooks, monographs, and reviews.…”

mentioning

confidence: 99%

Arenium ions are not obligatory intermediates in electrophilic aromatic substitution

Galabov

Koleva

Hadjieva

et al. 2014

Our computational and experimental investigation of the reaction of anisole with Cl 2 in nonpolar CCl 4 solution challenges two fundamental tenets of the traditional S E Ar (arenium ion) mechanism of aromatic electrophilic substitution. Instead of this direct substitution process, the alternative addition-elimination (AE) pathway is favored energetically. This AE mechanism rationalizes the preferred ortho and para substitution orientation of anisole easily. Moreover, neither the S E Ar nor the AE mechanisms involve the formation of a σ-complex (Wheland-type) intermediate in the rate-controlling stage. Contrary to the conventional interpretations, the substitution (S E Ar) mechanism proceeds concertedly via a single transition state. Experimental NMR investigations of the anisole chlorination reaction course at various temperatures reveal the formation of tetrachloro addition by-products and thus support the computed addition-elimination mechanism of anisole chlorination in nonpolar media. The important autocatalytic effect of the HCl reaction product was confirmed by spectroscopic (UV-visible) investigations and by HCl-augmented computational modeling.organic chemistry | reaction mechanisms | alternative computed routes | autocatalysis

“…If the nitronium ion is the only effective-nitrating agent in all nitrations, as suggested by Ingold (13) and Ridd (14), then its activity still must be dependent on the medium. Changes in substrate selectivity and regioselectivity thus would reflect the change in reactivity of nitronium ion in media of varying nucleophilicity.…”

mentioning

confidence: 99%

Electrophilic and free radical nitration of benzene and toluene with various nitrating agents

Lin

et al. 1978

Electrophilic nitration of toluene and benzene was studied under various conditions with several nitrating systems. It was found that high ortlopara regioselectivity is prevalent in all reactions and is independent of the reactivity of the nitrating agent. The methyl group of toluene is predominantly ortho-para directing under all reaction conditions. Steric factors are considered to be important but not the sole reason for the variation in the ortho/para ratio. The results reinforce our earlier views that, in electrophilic aromatic nitrations with reactive nitrating agents, substrate and positional selectivities are determined in two separate steps. The first step involves a ir-aromatic-NO2 ion complex or encounter pair, whereas the subsequent step is of arenium ion nature (separate for the oftho, meta, and para positions). The former determines substrate selectivity, whereas the latter determines regioselectivity.Thermal free radical nitration of benzene and toluene with tetranitromethane in sharp contrast gave nearly statistical product distributions. Stable nitronium salts were introduced as new nitrating agents by Olah and coworkers (1) in 1956. In the course of these studies (2-5), the competitive nitration of benzene and toluene, as well as other aromatics, was carried out in organic solvents.Under usual conditions of electrophilic nitration, toluene reacts about 20 times more rapidly than benzene whereas, with nitronium salts, toluene was found to react only 1.7 times faster than benzene (2). The practical disappearance of intermolecular (substrate) selectivity was accompanied by no significant alteration of isomer distribution (regioselectivity). This observation led to the suggestion that the transition state of highest energy (which determines substrate selectivity) is of starting aromatic (i.e., 7r-complex) nature, which is then followed by separate a-complex formation (for the individual positions), determining positional selectivity.In a series of studies, we have found that, in electrophilic aromatic substitutions, the position of the transition state of NO2Y + R-Xhighest energy is not rigidly fixed (6) but can shift from "early" (r-complex-like) to "late" (u-complex-like) nature, depending upon the reactivity of the electrophiles and the basicity of the aromatic substrates.In order to further explore electrophilic nitration, we carried out a comprehensive study of nitration of benzene and toluene under various conditions. RESULTS AND DISCUSSION With Nitronium Salts. Although we had previously examined competitive nitration using high-speed mixing (7), it was considered of interest to extend the studies by using more advanced methods such as the mixing chamber of an efficient Durrum-Gibson stopped-flow apparatus. Competitive nitrations, with nitronium hexafluorophosphate in nitromethane, provided the data in Table 1. Whereas mixing still can be incomplete before reaction, with the nitration rates being very fast (or reaching the encounter-controlled limit), the data seem to indicate that, ...