Reactivity of substituted benzenes

Treatment with water at the end of the reaction is often described as an aqueous workup  

Unlike carbocations, the intermediate acylium ion does not rearrange and is attacked by the benzene ring to give exclusively the unrearranged product The Gatterman-Koch reaction (which uses CO, HCl and AICI3) can be used to form an aromatic aldehyde (e.g. benzaldehyde, PhCHO), rather than a ketone. 

Sometimes copper(I) chlmide, CuCl, is added to the reaction 

The introduction of substituents on the benzene ring affects both the reactivity of Regioselectivity is introduced in the benzene ring and also the regioselectivity of the reaction (i.e. the position in Section 4.8 which the new group is introduced on the benzene ring). 

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In addition to electrophilic attack on the pyrrole ring in indole, there is the possibility for additions to the fused benzene ring. First examine the highest-occupied molecular orbital (HOMO) of indole. Which atoms contribute the most What should be the favored position for electrophilic attack Next, compare the energies of the various protonated forms of indole (C protonated only). These serve as models for adducts formed upon electrophilic addition. Which carbon on the pyrrole ring (C2 or C3) is favored for protonation Is this the same as the preference in pyrrole itself (see Chapter 15, Problem 2)1 If not, try to explain why not. Which of the carbons on the benzene ring is most susceptible to protonation Rationalize your result based on what you know about the reactivity of substituted benzenes toward electrophiles. Are any of the benzene carbons as reactive as the most reactive pyrrole carbon Explain. 

Relative reactivities of substituted benzenes and benzoate ions toward hydroxyl radicals have been correlated (4) with Hammett s equation. In the present work such a correlation has also been carried out using absolute rather than relative values. 

During the last two decades, the redox and acidity properties and the reactivity of substituted benzene radical cations in aqueous solution and organic solvents have been extensively studied pulse radiolysis, electrochemical techniques and photochemical techniques.[l,2,5-20]... 

Hydroxyl radicals possess week electrophilic properties as indicated by the order of reactivity of substituted benzenes and distribution of phenolic isomers, although the latter depends on the reaction conditions [28, 29]. The Fenton hydroxylation in aqueous solution reveals small (<5%) values of the NIH shift (i.e., migration of hydrogen atom from the site of hydroxylation to the adjacent carbon [30]). The reaction in CH CN demonstrated remarkably high shift values (30-40%) [31], which is typical of enzymatic processes [30]. Sawyer and coworkers proposed that the change in solvent might favor a mechanistic shift from HO to a metal-centered oxidant [32]. 

The table below gives first-order rate constants for reaction of substituted benzenes with w-nitrobenzenesulfonyl peroxide. From these data, calculate the overall relative reactivity and partial rate factors. Does this reaction fit the pattern of an electrophilic aromatic substitution If so, does the active electrophile exhibit low, moderate, or high substrate and position selectivity ... 

The data obtained allow us to make some generalizations for the heterocy-clization of the functionally substituted acetylenic derivatives of the benzene and pyrazole series. Studies of the heterocyclization of the functionally substituted acetylenic derivatives of substituted benzenes and pyrazoles reveal noticeable differences in their reactivities. 

Klasinc and Schulte-Frohlinde (1968), who also used HMO for the investigation of substituted benzene diazonium ions, were the first to realize that the remarkable distortion of bond lengths and angles of the benzene ring by the diazonio group (Sec. 4.2) has a significant influence on its reactivity. They found that the sp2-hybridization at the carbon atoms of the benzene ring varied from 1.75 for C(l) to 2.16 for C(2). 

Including aromatic amines (to be discussed below) the order of reactivities for substituted benzene and naphthalene coupling components is therefore O" > NR2 > NHR > NH2 > OR = OH > CH3 > unsubstituted (R = alkyl). 

The influence of the OH-group on the reactivity of the benzene ring is of great importance. All substitution processes which are traced back to preliminary addition reactions take place much more easily with the phenols than with the hydrocarbons as far as possible the groups which enter occupy the o- and p-positions. A number of reactions illustrating this statement is discussed below and in subsequent parts of this book. It may be mentioned here that by the action of bromine water, o-o-p-tnbromophenol is at once precipitated from an aqueous solution of phenol. (Method for the quantitative determination of phenol.)... 

A very reactive nitrogen atom is required to convert benzenes or naphthalenes into pyridines, and there are a number of such reactions which involve nitrenes or nitrenoid species. A number of substituted benzenes have been treated with sulfonyl diazide or carbonyl diazide and moderate yields of pyridines recorded (27CB1717). Thus p-xylene gives 2,5-dimethylpyridine there is no indication of the fate of the carbon atom which is lost. More controlled reaction is possible in intramolecular insertions. The examples in which o-nitrotoluene is converted into a derivative (759) of 2-acetylpyridine, and where 2,3-diazidonaphthalenes give 3-cyanoisoquinolines (760) are quoted in a review (81 AHC(28)231>. 

When substituted benzene undergoes electrophilic attack, groups already on the ring affect the reactivity of the benzene ring as weU as the orientation of the reachon. A summary of these effects of substituents on reachvity and orienta-hon of electrophihc substituhon of substituted benzene is presented below. 

We will restrict our consideration to reactions of substituted benzenes and to nitrogen heteroaromatic systems in which the reaction takes place first with the n system. The simplest example of reaction of a monosubstituted benzene with an electrophile (Lewis acid) is shown in Scheme 11.1. The electrophile may attach itself to the n system (step A) in four distinct modes, ipso, ortho, meta, and para. The reactivity of the aromatic ring and the mode of attachment of the electrophile will be influenced by the specific nature of the substituent group, which may be X , Z, or C type. Detachment of the electro-... 

Dewar,120 as well as Brown and Olah, respectively, raised the importance of initial n complexing of aromatics in alkylations.109121 Relevant information was derived from both substrate selectivities (usually determined in competitive alkylations of benzene and toluene, or other alkylbenzenes), and from positional selectivities in the alkylation of substituted benzenes. Olah realized that with reactive alkylating agents substrate and positional selectivities are determined in two separate steps. 

A quantitative description of the reactivity of monosubstituted benzenes to electrophilic substitution based on considerations of inductive effect parameters and con-jugative effect parameters from the 13 C chemical shifts of the aromatic compounds has been proposed.3 MO calculations on the proton migration in the ipso adducts formed in the reaction of CH3+ and SiH3+ with benzene have been described.4 With SiH3+ the ipso adduct is the most stable of possible isomers, whereas for CH3+ the >ara-protonated isomer is the most stable. 

Fig. 6.2. Variation in transition-state structure with electrophile reactivity in reactions of substituted benzenes. A, Activated benzene (e.g., anisole) B. deactivated benzene (e.g., nitrobenzene).

The value of o for N + OH has been determined as above by comparison of the reactivities of substituted pyridines and benzenes, giving 2.1 (phenoxides) and 2.3 (phenols) [68JCS(P2)866] and these are similar to... 

As mentioned above, there is a scarcity of data on how variations in ketone structure affect CT quenching rates. A comparison of the interactions of substituted benzenes with triplet acetophenone and triplet a-trifluoroacetophenone is interesting 182,182). The relative reactivities of various hydrocarbons towards triplet acetophenone are suggestive of direct hydrogen atom abstraction by the triplet ketone. The low reduction potential of the trifluroketone enhances the rate of CT quenching so much that photoreduction proceeds almost entirely by a... 

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