Activated Monosubstituted Benzenes

Major variations in the reaction conditions are required to effect substitution within a reasonable time interval. Thus, the data for the highly deactivated aromatics are subject to the same limitations characterizing experimental assessment of the relative reactivity of the highly activated monosubstituted benzenes. 

Activated monosubstituted benzenes The major doubt concerning a general linear free-energy relationship for aromatic substitution is contained in the question whether resonance contributions to an electron-deficient transition state are sufficiently... 

After our success in nitrating moderately active monosubstituted benzenes with acetic anhydride and nitric acid over zeolite p,11 we decided to try the use of trifluoroacetic anhydride and nitric acid over zeolite p for nitration of deactivated substrates. Although trifluoroacetyl nitrate is known to be more active than acetyl nitrate, it has not been widely used in nitration reactions.15 Nitrobenzene has been successfully nitrated using fuming nitric acid and trifluoroacetic anhydride in equimolar proportions at 45-55 °C.16 However, no dinitration of toluene was reported. 

If, on the other hand, the encounter pair were an oriented structure, positional selectivity could be retained for a different reason and in a different quantitative sense. Thus, a monosubstituted benzene derivative in which the substituent was sufficiently powerfully activating would react with the electrophile to give three different encounter pairs two of these would more readily proceed to the substitution products than to the starting materials, whilst the third might more readily break up than go to products. In the limit the first two would be giving substitution at the encounter rate and, in the absence of steric effects, products in the statistical ratio whilst the third would not. If we consider particular cases, there is nothing in the rather inadequate data available to discourage the view that, for example, in the cases of toluene or phenol, which in sulphuric acid are nitrated at or near the encounter rate, the... 

The partial rate factors vary within wide limits. Electrophilic species of lower activity, such as molecular bromine, are more selective, i.e., more capable of discriminating either between thiophene and benzene or between positions a and j8 of thiophene. Quantitatively, a linear trend is observed (Fig. 1) between loga/j3 and logotf. This is a correlation formally analogous to the selectivity relationship proposed by Brown and Nelson188 for the reactions of monosubstituted benzenes. 

In toluene, as well as with many other monosubstituted benzenes, the substitution group (methyl, in the case of toluene) acts as an electron donor. This counters the electron-withdrawing effect of the previously substituted nitro groups and allows higher local nitronium ion activity, thus allowing a much easier trinitration step. This is the key, then, to inexpensive synthesis of trinitro-aromatic explosives. Figure 3.5 is the TNT molecule, the first, and most important (as far as quantity of production goes) of the monosubstituted TNBs. 

With monosubstituted benzenes, the tendency of OH to undergo ipso addition seems to be small (<10%). However, if the ipso position is activated by a second substituent like CH3O, HO or 0 , ipso addition may contribute up to 25% to the overall reactivity . Due to the small size of the OH radical, steric effects (i.e. the size of X) do not seem to be of mnch importance in determining the probability of OH attack at the ipso position. Oxidative replacement of halogen has been observed also with pentafluoro-, pentachloro-, pentabromo- and 2,4,6-triiodo-phenol, where it occurs in parallel to electron transfer". ... 

The kinetics of 1-5 ring closure were investigated in parallel for aliphatic and aromatic hydrocarbons on Pt-C (755-757). The apparent activation energy for dehydrocyclization is always higher (by 7-15 kcal/mol) in the case of monosubstituted benzenes (n-propyl-, sec-butyl-, and isobutyl-benzenes) than in the case of paraffins (ethylpentane, isooctane, n-hexane). The same is not true, however, for dehydrocyclization of o-ethyltoluene and isooctane, which occur with similar activation energies (757). This result is quite understandable if one considers that the first elementary step in the dehydrocyclization of monosubstituted benzenes but not of disubstituted benzenes results in a loss of aromaticity. 

Since the positions of the Is,min are the locations, on the average, of the most easily removed electrons, these should also be the sites that are most reactive toward electrophilic attack. This has been fully confirmed for a group of monosubstituted benzene derivatives [10,21]. The Is,min correctly predict the ortho/para- or meta- directing tendencies of the substituents, even the rather unusual NH3+, which is a metal para director [22]. Furthermore, the magnitudes of the Is,min relative to that of unsubstituted benzene correctly indicate whether each substituent activates or deactivates the aromatic ring toward electrophiles. These analyses have been extended to other aromatic systems, including azines and azine N-oxides [18,23,24]. 

Hydridoarene clusters of Rh and Ru are moderately active catalysts of hydrogenation of simple olefins [20]. Conversely, benzene and monosubstituted benzenes can be efficiently hydrogenated in aqueous biphasic systems with hydridoareneruthe-nium cluster catalysts, such as [Ru3(p2-H)2(p2 OH) (pj-O) (ri -C5Hg)(ri "-C5Me5)2] [21]. 

The activating or deactivated effects of the substituents may be quantitatively described through the use of partial rate factors [34]. These values estimate the reactivities of positions on an arene relative to the carbons of benzene. For example, partial rate factors may be calculated for a monosubstituted benzene (Ar) at the ortho, meta, and para positions. For a given electrophilic system, the partial rate factor,/, is calculated using the relative rates of reactions and and the fraction or percent of... 

Recently, studies of cross-migration of the triphenylmethyl group from PhNHCPhg and PhOCPhg to several monosubstituted benzenes gave the same activation sequence ... 

The substituent constant of the Hammett equation has been related successfully to the logarithm of the activity coefficient ratio at infinite dilution for a series of m- and / -phenyl isomers. Hammett stated that a free-energy relationship should exist between the equilibrium or rate of behavior of a benzene derivative and a series of corresponding meta- and para-monosubstituted benzene derivatives. The Hammett equation may be written as... 

Chapter 15 described the use of this transformation in the preparation of monosubstituted benzenes. In this chapter we analyze the effect of such a first substituent on the reactivity and regioselectivity (orientation) of a subsequent electrophilic substitution reaction. Specifically, we shall see that substituents on benzene can be grouped into (1) activators (electron donors), which generally direct a second electrophilic attack to the ortho and para positions, and (2) deactivators (electron acceptors), which generally direct electrophiles to the meta positions. We will then devise strategies toward the synthesis of polysubstituted arenes, such as the analgesics depicted on the previous page. 

In Section 14-8 we discussed the effect that substituents have on the efficiency of the Diels-Alder reaction Electron donors on the diene and acceptors on the dienophile are beneficial to the outcome of the cycloaddition. Chapter 15 revealed another manifestation of these effects Introduction of electron-withdrawing substituents into the benzene ring (e.g., as in nitration) caused further electrophilic aromatic substitution (EAS) to slow down, whereas the incorporation of donors, as in the Friedel-Crafts alkylation, caused substitution to accelerate. What are the factors that contribute to the activating or deactivating nature of substituents in these processes How do they make a monosubstituted benzene more or less susceptible to further electrophilic attack ... 

The reaction is regioselective, producing / ara-phenols from monosubstituted benzene derivatives. Furthermore, alkylarenes with reactive side-chain sp C-H bonds could be chemoselectively hydroxylated without significant formation of side-chain oxygenated products. Kinetic and mechanistic models of the oxidation of phenol with HP, catalysed by a new macrocyclic cobalt(II) complex, have been proposed. The catalytic system displayed high catalytic activity and the catalytic character of a metalloenzyme, although it did not attain the catalytic efficiency of enzymes. 

A hydroxyl group is a very powerful activating substituent, and electrophilic aromatic substitution in phenols occurs far- faster, and under milder conditions, than in benzene. The first entry in Table 24.4, for exfflnple, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reaction was carried out in the nonpolar- solvent 1,2-dichloroethane. In polar- solvents such as water it is difficult to limit the bromination of phenols to monosubstitution. In the following exfflnple, all three positions that are ortho or para to the hydroxyl undergo rapid substitution ... 

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