Electrophilic aromatic substitutions definition

This is the synthesis of a somewhat controversial food preservative called BHT. It is an antioxidant that has been put in packaging to keep foods from becoming rancid from air oxidation. A balanced reaction would require two molecules of the alkene for each of the starting aromatic. The aromatic ring is relatively electron rich with two donors attached to it. With sulfuric acid present, the medium is definitely acidic. The first step is to generate the excellent electrophile needed for electrophilic aromatic substitution. For simplicity, let s symbolize sulfuric acid as H-A. The Markovnikov addition of a proton to isobutylene gives the tert-butyl carbocation, an excellent electrophile. 

Regarding the possible mechanism, notably, toluene, ethylbenzene and terf-butylbenzene are less reactive than benzene, which is not consistent with the expected order for an electrophilic aromatic substitutions, such as that found with the classic Fenton reagent. There are also other differences with respect to the Fenton chemistry. In particular, under biphase conditions the reaction is definitely more selective although comparisons are difficult due to the huge amount of data, sometimes inconsistent, on the Fenton system (for which most of the data have been obtained with the iron used in stoichiometric amounts) it seems that selectivities dose to those observed under biphase conditions are only attained at a conversion around of 1%. Furthermore, in the biphase system, only a negligible amount (<1%) of biphenyl was detected among secondary products, whereas in the classic Fenton oxidation this compound is formed by radical dimerization of hydroxycydohexadienyl radicals in typical yields ranging from 8 to 39%. 

The Stolle reaction is thought to occur via a typical mechanism for amide formation from an amine and acid chloride, followed by Friedel-Crafts alkylation or acylation. No definitive mechanistic work has been performed on this reaction, but incorporating the mechnistic understandings of two steps provides a firm basis for understanding the mechanism of this reaction. Formation of the mono-amide from oxalyl chloride and aniline provides intermediate 4, which in the presence of AICI3 undergoes intramolecular electrophilic aromatic substitution to the desired 2,3-dioxindole (isatin) 7 via intermediates 5 and 6. 

Friedel-Crafts catalysis is a powerful method for effecting electrophilic aromatic substitution one broad definition of the Friedel-Crafts reaction is that given by George Olah [21]. 

Recently, it has been shown that 3-pyridinecarboxal-dehyde undergoes the same reaction in weaker acid solutions of sulfuric acid with H, values around -9. NMR analysis definitively established that the dication shown below is generated under the reaction conditions, and the two positive charges enhance the electrophilic aromatic substitution with benzene. 

Studies of the reactions of flavan-3-ols and particularly those of catechin have been central to the elucidation of the structure and development of uses for the condensed tannins. This work, initiated by Freudenberg and his colleagues at Heidelberg in the 1920s [see Weinges et al. (377) for a thorough review], continues to be an important aspect of condensed tannin chemistry. A wide range of electrophilic aromatic substitution reactions has been examined to obtain definitive evidence for the location of substitution (i.e. C-6 or C-8) of proanthocyanidins and to establish the influence of steric hindrance on the relative reactivity of these nucleophilic centers in flavan-3-ols. 

Probably the most important development of the past decade was the introduction by Brown and co-workers of a set of substituent constants,ct+, derived from the solvolysis of cumyl chlorides and presumably applicable to reaction series in which a delocalization of a positive charge from the reaction site into the aromatic nucleus is important in the transition state or, in other words, where the importance of resonance structures placing a positive charge on the substituent - -M effect) changes substantially between the initial and transition (or final) states. These ct+-values have found wide application, not only in the particular side-chain reactions for which they were designed, but equally in electrophilic nuclear substitution reactions. Although such a scale was first proposed by Pearson et al. under the label of and by Deno et Brown s systematic work made the scale definitive. 

Aromatic bromides (3, 286). The definitive paper on electrophilic aromatic bromination with bromine and thallium(lll) acetate has been published. The two most oul.standingfeaturc.s are I) monobromination is observed in almost all cases, and 2) exclusive para substitution is observed with almost all monosubstituted benzenes. Electron-withdrawing groups inhibit bromination of monosubstituted benzenes. It... 

The results of these studies allow the behavior of the aromatic portion of a ligand to be predicted with some degree of confidence, if that of the free ligand is known or can be surmised. Coordination appears to have a small but definite effect on the nature of the transition state for electrophilic substitution (or its ease... 

We consider as dihydro derivatives those rings which contain either one or two 5p3-hybridized carbon atoms. According to this definition, all reactions of the aromatic compounds with electrophiles, nucleophiles or free radicals involve dihydro intermediates. Such reactions with electrophiles afford Wheland intermediates which usually easily lose H+ to re-aromatize. However, nucleophilic substitution (in the absence of a leaving group such as halogen) gives an intermediate which must lose H and such intermediates often possess considerable stability. Radical attack at ring carbon affords another radical which usually reacts further rapidly. In this section we consider the reactions of isolable dihydro compounds it is obvious that much of the discussion on the aromatic heterocycles is concerned with dihydro derivatives as intermediates. 

Thiophene is far more reactive than benzene in electrophilic substitution reactions. Reaction with bromine in acetic acid has been calculated to be 1.76 x 109 times faster than with benzene (72IJS(C)(7)6l). This comparison should, of course, be treated with circumspection in view of the fact that the experimental conditions are not really comparable. Benzene in the absence of catalysts is scarcely attacked by bromine in acetic acid. More pertinent is the reactivity sequence for this bromination among five-membered aromatic heterocycles, the relative rates being in the order 1 (thiophene) and 120 (furan) or, for trifluoroacetylation, 1 (thiophene), 140 (furan), 5.3 xlO7 (pyrrole) (B-72MI31300, 72IJS(C)(7)6l). Among the five-membered heteroaromatics, thiophene is definitely the least reactive. 

An attempt has been made to analyse whether the electrophilicity index is a reliable descriptor of the kinetic behaviour. Relative experimental rates of Friedel-Crafts benzylation, acetylation, and benzoylation reactions were found to correlate well with the corresponding calculated electrophilicity values. In the case of chlorination of various substituted ethylenes and nitration of toluene and chlorobenzene, the correlation was generally poor but somewhat better in the case of the experimental and the calculated activation energies for selected Markovnikov and anti-Markovnikov addition reactions. Reaction electrophilicity, local electrophilicity, and activation hardness were used together to provide a transparent picture of reaction rates and also the orientation of aromatic electrophilic substitution reactions. Ambiguity in the definition of the electrophilicity was highlighted.15... 

Electrophilic substitution This is not meant to be a definitive account of aromaticity. It will suffice if we consider only one tj of chemical reaction and two of the physical properties of benzene to demonstrate the point. 

---