The Halogenation of Benzene

The electrophile (Y ) adds to the nucleophilic benzene ring, thereby forming a carbocation intermediate. The structure of the carbocation intermediate can be approximated by three resonance contributors. 

A base in the reaction mixture ( B) removes a proton from the carbocation intermediate, and the electrons that held the proton move into the ring to reestablish its aromaticity. Notice that the proton is always removed from the carbon that has formed the bond with the electrophile. 

We will look at each of these five electrophilic aromatic substitution reactions individually. As you study them, notice that they differ only in how the electrophile (Y ) that is needed to start the reaction is generated. Once the electrophile is formed, all five reactions follow Ihe same two-step mechanism for electrophihc aromatic substitution that was just shown. 

The bromination or chlorination of benzene requires a Lewis acid catalyst such as ferric bromide or ferric chloride. Recall that a Lewis acid is a compound that accepts a share in an electron pair (Section 2.12). 

Why does the reaction of benzene with Br, or Cl, require a catalyst when the reaction of an alkene with these reagents does not require a catalyst Benzene s aromaticity 

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Halogenation. Depending on the conditions either substitution or addition products can be obtained by the halogenation of benzene. 

The halogenation of benzene to synthesize aryl halides is the oldest method known. 

In the halogenation of benzene, an iron catalyst is used. The iron is converted to iron(lll) halide (FeXs). Iron(lll) halide reacts further to polarize the X2 molecule. 

Although a stable dibromide cannot be isolated for a similar study of the bromination of benzene, the kinetics of the iodine catalyzed bromina-tion of benzene is identical with that of phenanthrene.26 Consequently it is very probable that the mechanism of the halogenation of benzene is the same as that proposed for phenanthrene. The kinetics of chlorination,27 bromination,28 and iodination by iodine chloride29 are also in agreement with this interpretation. The halogenation of phenols, however, appears to be a different, more complex process. 0... 

In recovering the hydrogen chloride from the hydrolytic step, it is essential to use only a limited quantity of water in the washing operations so that a 17 per cent solution is delivered to the acid evaporators. This is suitable for the subsequent step involving the halogenation of benzene. Operating in a closed cycle, the hydrochloric acid picks up impurities so that part of it must be purged continuously. This loss and that involved in the production of polychlorobenzenes constitute the replacement requirements of acid. 

High temperature or light is necessary. The halogenation of benzene involves transfer of a positive halogen (X+) (which is protonated by acid catalysts). This means that the position of attack (whether on the benzene or on the side chain) will depend on the nature of the attacking species (an ion or a radical). Since the conditions in this problem are those that favor the production of bromine radicals, halogenation occurs exclusively to the n-propyl side chain. Hence,... 

In Summary The halogenation of benzene becomes more exothermic as we proceed from I2 (endothermic) to F2 (exothermic and explosive). Chlorinations and brominations are achieved with the help of Lewis acid catalysts that polarize the X-X bond and activate the halogen by increasing its electrophilic power. 

The halogen carriers or aromatic halogenation catalysts are usually all electrophilic reagents (ferric and aluminium haUdes, etc.) and their function appears to be to increase the electrophilic activity of the halogen. Thus the mechanism for the bromination of benzene in the presence of iron can be repre-sfflited by the following scheme ... 

Piperazinothiazoies (2) were obtained by such a replacement reaction, Cu powder being used as catalyst (25. 26). 2-Piperidinothiazoles are obtained in a similar way (Scheme 2) (27). This catalytic reaction has been postulated in the case of benzene derivatives as a nucleophilic substitution on the copper-complexed halide in which the halogen possesses a positive character by coordination (29). For heterocyclic compounds the coordination probably occurs on the ring nitrogen. 

Cation (Section 1 2) Positively charged ion Cellobiose (Section 25 14) A disacchande in which two glu cose units are joined by a 3(1 4) linkage Cellobiose is oh tamed by the hydrolysis of cellulose Cellulose (Section 25 15) A polysaccharide in which thou sands of glucose units are joined by 3(1 4) linkages Center of symmetry (Section 7 3) A point in the center of a structure located so that a line drawn from it to any element of the structure when extended an equal distance in the op posite direction encounters an identical element Benzene for example has a center of symmetry Cham reaction (Section 4 17) Reaction mechanism m which a sequence of individual steps repeats itself many times usu ally because a reactive intermediate consumed m one step is regenerated m a subsequent step The halogenation of alkanes is a chain reaction proceeding via free radical intermediates... 

The halogens of halothiophenes are more labile than those of the corresponding benzenes in accordance with theoretical considera-tions which indicate that thiophenes should also undergo nucleophilic substitutions more rapidly than benzenes. Hurd and Kreuz" found that in qualitative experiments 3,5-dinitro-2-chlorothiophene was more reactive toward piperidine and methanolic potassium hydroxide than 2,4-dinitrochlorobenzene. A quantitative study on the reaction of the six isomeric bromonitrothiophenes with piperidine (Table V) shows that the thiophenes react about one thousand times... 

Inasmuch as the conjugation properties of a double bond and a benzene ring are closely similar,11 we expect for the halogen substituted benzenes interatomic distances similar to those for the halogen ethylenes. De Laszlo12 has reported the values C-Cl = 1.69 A., C-Br = 1.88 A., and C-I = 2.05 A., corresponding to 14., 6, and 10% double bond character, respectively.15... 

The oxidation of benzene to phenol and 1,4-dihydroxybenzene (Figure 2.11a) (Hyman et al. 1985), both side chain and ring oxidation of ethyl benzene, and ring-hydroxylation of halogenated benzenes and nitrobenzene (Keener and Arp 1994). 

During this period of time we, and a number of other research groups, have been investigating the reactions of highly halogenated aiynes and hetarynes with aromatic hydrocarbons, for the reasons outlined in the introduction. In a reaction of pentafluorophenylmagnesium chloride with ethylene oxide in the presence of benzene, it was shown that, as well as 3-pentafluorophenylethanol (23) a by-product of molecular formula C12H6F4 was produced 43>. 

Unlike the alkanes, however, the reaction of benzene with the halogens is catalyzed by iron. The relative lack of reactivity in aromatic hydrocarbons is attributed to delocalized double bonds. That is, the second pair of electrons in each of the three possible carbon-to-carbon double bonds is shared by all six carbon atoms rather than by any two specific carbon atoms. Two ways of writing structural formulas which indicate this type of bonding in the benzene molecules are as follows ... 

This reaction set may be regarded as parallel reactions with respect to consumption of species B and as a series reaction with respect to species A, V, and W. Common examples include the nitration and halogenation of benzene and other organic compounds to form polysubstituted compounds. To characterize the qualitative behavior of such systems, it is useful to consider reactions 9.3.3 and 9.3.4 as mechanistic equations and to analyze the effects of different contacting patterns on the yield of species V. We shall follow the treatment of Levenspiel (7). 

Nor can there be any question of real tautomerism in the case of phenol. In its chemical properties phenol resembles the aliphatic enols in all respects. We need only recall the agreement in the acid character, the production of colour with ferric chloride, and the reactions with halogens, nitrous acid, and aromatic diazo-compounds (coupling), caused by the activity of the double bond and proceeding in the same way in phenols and aliphatic enols. The enol nature of phenol provides valuable support for the conception of the constitution of benzene as expressed in the Kekule-Thiele formula, since it is an expression of the tendency of the ring to maintain the aromatic state of lowest energy. In this connexion the hypothetical keto-form of phenol (A)—not yet obtained—would be of interest in comparison with... 

In the case of mono-olefins halogen substituents again reduce the basicity, as in the case of benzene. Unfortunately no information is available which would permit a comment as to whether the halogen atom causes this effect only if it is directly linked to the C=C double bond or whether an effect is also still exerted by an adjacent saturated halogen-substituted C-atom. With multiple halogen substitution the basicity falls even more as may be seen from the examples of chlorine-substituted ethylenes in Table 17. 

The usual halogenation of benzene takes place in the presence of a Lewis acid, such as FeBrs (Unit 10, Class XII), which polarises the halogen molecule. In case of phenol, the polarisation of bromine molecule takes place even in the absence of Lewis acid. It is due to the highly activating effect of -OH group attached to the benzene ring. 

Over recent years, the electrochlorination of a wide range of substrates has been reported. The direct halogenation of benzene has been studied at Pt and Rh electrodes and the in situ spectro-electrochemical monitoring of the process with confocal microprobe Raman methods allowed optimization of the reaction conditions [80]. Toluene has been chlorinated at DSAs and the kinetics of this process have been explored in detail [81]. The electrochlorination of 1,4-dimethoxy-2-tert-butylbenzene has been reported in CCI4 and in acetonitrile environments [82]. A difference in mechanism has been proposed to explain the observation of l,4-dimethoxy-2-tert-butyl-5-chlorobenzene and l,4-dimethoxy-2-tert-butyl-6-chlorobenzene, respectively, as the main products. Succinimide is electrochlo-rinated to give A -chlorosuccinimide at platinum electrodes, but the process has been reported to be relatively inefficient due to side reactions (when compared... 

Adams platinum oxide catalyst is readily prepared from chloroplatinio acid or from ammonium chloroplatinate, and is employed for catalytio hydrogenation at pressures of one atmosphere to several atmospheres and from room temperature to about 90°. Reduction is usually carried out with rectified spirit or absolute alcohol as solvents. In some cases (e.g., the reduction of benzene, toluene, xylene, mesitylene, cymene and diphenyl ), the addition to the absolute alcohol solution of 2-5 per cent, of the volume of rectified spirit which has been saturated with hydrogen chloride increases the effectiveness of the catalyst under these conditions chlorobenzene, bromobenzene, o-, m- and p-bromotoluenes, p-dichloro- and p-dibromo-benzene are reduced completely but the halogens are simultaneously eliminated. Other solvents which are occasionally employed include glacial acetic acid, ethyl acetate, ethyl acetate with 17 per cent, acetic acid or 8 per cent, of alcohol. In the actual hydrogenation the platinum oxide Pt02,H20 is first reduced to an active form of finely-divided platinum, which is the real catalyst allowance must be made for the consumption of hydrogen in the process. 

A systematic study of the alkylation of benzene with optically active 1,2-, 1,3-, 1,4-, and 1,5-dihaloalkanes showed that the stereochemical outcome depends on the halogens and the chain length.142 Retention of configuration in alkylation with (S)-1,2-dichloropropane was explained by invoking double inversion and the involvement of a bridged cation such as 27. (S)-l-Bromo-2-chloropropane, in contrast,... 

A similar transformation was observed with the rhodium trifluoroacetate catalyzed decomposition of diazo ketones in the presence of benzene (Scheme 32).130 The cycloheptatrienes (147) formed in this case were acid labile and could be readily rearranged to benzyl ketones (148) on treatment with TFA. The reaction was effective even when the side chain contained reactive halogen and cyclopropyl functionality, but competing intramolecular reactions occurred with benzyl diazomethyl ketone. A more exotic example of this reaction is the rhodium(ll) trifluoroacetate catalyzed decomposition of the diazopenicillinate (149) in the presence of anisole, which resulted in the formation of two cycloheptatriene derivatives (150) and (151) (equation 35).m... 

Strong differences in the reactivity of the aromatic C=C double bond compared to the reactivity of the C=C double bond of olefins are observed olefinic electrophilic additions are faster than aromatic electrophilic substitutions. For instance, the addition of molecular bromine to cyclohexene (in acetic acid) is about 1014 times faster than the formation of bromobenzene from benzene and bromine in acetic acid113,114. Nevertheless, the addition of halogens to olefins parallels the Wheland intermediate formation in the halogenation of aromatic substrates. 

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