Substitution of Groups Other Than Hydrogen

The general mechanism for electrophilic substitution suggests that groups other than hydrogen could be displaced, provided the electrophile attacked at a substituted carbon. Substitution at a site already carrying a substituent has been called ipso 

The replacement of bromine and iodine during aromatic nitration has also been observed. p-Bromoanisole and p-iodoanisole, for example, give 30-40% of p-nitroanisole, a product resulting from displacement of halogen, on nitration  

Because of greater resistance to elimination of chlorine as a positively charged species, p -chloroanisole does not undergo dechlorination under similar conditions. 

Cleavage of f-butyl groups has also been observed in halogenation reactions. Minor amounts of dealkylated products are formed during chlorination and bromi-nation of t-butylbenzene. The amount of dealkylation increases greatly in the case of 1,3,5-tri-f-butylbenzene, and the principal product of bromination is 3,5-dibromo-t-butylbenzene.  

The most thoroughly studied group of aromatic substitutions involving replacement of a substituent group in preference to a hydrogen are electrophilic substitutions of arylsilanes  

Zollinger, Azo and Diazo Chemistry, translated by H. E. Nursten, Interscience, New York, 1961, Chap. 10 H. Zollinger, Adv. Phys. Org. Chem. 2, 163 (1964) H. Zollinger, Helv. Chim. Acta 38, 1597 (1955). 

The general mechanism for electrophilic substitution suggests that groups other than hydrogen could be displaced, provided the electrophile attacked at the substituted carbon. Substitution at a site aheady having a substituent is called ipso substitution and has been observed in a number of circumstances. The ease of removal of a substituent depends on its ability to accommodate a positive charge. This factor determines whether the newly attached electrophile or the substituent is eliminated from the cr-complex on rearomati2ation  

One example of substituent replacement involves cleavage of a highly branched alkyl group. The alkyl group is expelled as a carbocation, and for this reason, substitution is most common for branched alkyl groups. The nitration of l,4-bis(i-propyl)benzene 

The silyl group directs electrophiles to the substituted position. That is, it is an ipso-directing group. Because of the polarity of the carbon-sihcon bond, the substituted position is relatively electron-rich. The abdity of silicon substituents to stabdize carboca-tion character at jS-carbon atoms (see Section 6.10, p. 393) also promotes ipso substitution. The silicon substituent is easily removed from the cr-complex by reaction with a nucleophile. The desilylation step probably occurs through a pentavalent sihcon species  

The reaction exhibits other characteristics typical of an electrophdic aromatic substitution. Examples of electrophiles that can effect substitution for sdicon include protons and the halogens, as well as acyl, nitro, and sulfonyl groups. The fact that these reactions occur very rapidly has made them attractive for situations where substitution must be done under very mild conditions. 

Hegarty, in The Chemistry of the Diazomum and Diazo Groups, S. Patai, ed., John Wiley Sons, New York, 1978, Chap. 12 H. Mayr, M. Hartnagel, and K. Grimm, Liebigs Atm., 55 (1997). 

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The combination of the electrophilic substitution of hydrogen with the nucleophilic substitution of groups other than hydrogen supplies many methods for processing aromatic raw materials. Therefore, the interaction of aromatic compounds with electrophiles has been dealt with in many works. Nevertheless the mechanism of these reactions and the quantitative reactivity of aromatic compounds is not yet clear, as shown by recent studies. 

In addition to these two series of reactions based on the substitution of hydrogen, a third set of data may be derived from reactions which involve the replacement of groups other than hydrogen.1 Kuivila, Benkeser, and Eaborn and their associates employed this approach to study the effects of many substituents. For example, Kuivila and Hendrickson (1952) examined the bromodeboronation of substituted phenylboronic acids. 

The enantioselective hydrogenation of C=C bonds is included in Chapter 3, where the general nature of heterogeneous enantioselective hydrogenation is fully explored, so here we examine only the narrow subject. Enantioselective hydrogenation of C=C bonds occurs only on prochiral double bonds (at least one of the carbons substituted with two different groups other than hydrogen). A chiral environment is required. 

Groups other than hydrogen can be substituted by other atoms or groups of atoms. For example, the bromine atom of an alkyl bromide can be replaced with a hydroxyl group to form an alcohol. The mechanism of this type of reaction is often studied in introductory organic chemistry courses. 

The conformational properties of dihydrothiazine dioxides of type 250 have been examined by NMR spectroscopy.24 In general, N-unsubstituted derivatives, e.g., 260a-c, exist as a 1 1-3 1 mixture of the conformers 263 and 264. By contrast, N-substituted compounds, e.g. 261b and 262, favor the conformer 264. The conformer 263 is destabilized by an allylic interaction between R1 and R2, whereas the conformer 264 possesses an unfavorable 1,3-diaxial interaction between an oxide group and R1. Evidently, the latter interaction is less severe than the former when R1 and R2 are groups other than hydrogen atoms. 

Ipso substitution The displacement of a group other than hydrogen from an aromatic ring. 

If both ortho positions bear substituents other than hydrogen, the allyl group will further migrate to the para position. This reaction is called the para-Claisen rearrangement. The formation of the para-substituted phenol can be explained by an initial Claisen rearrangement to an ortho-2l y intermediate which cannot tautomerize to an aromatic o-allylphenol, followed by a Cope rearrangement to the p-allyl intermediate which can tautomerize to the p-allylphenol e.g. 6 ... 

Toluene (methylbenzene) is similar to benzene as a mononuclear aromatic, but it is more active due to presence of tbe electron-donating metbyl group. However, toluene is much less useful than benzene because it produces more polysubstituted products. Most of tbe toluene extracted for cbemical use is converted to benzene via dealkylation or disproportionation. Tbe rest is used to produce a limited number of petro-cbemicals. Tbe main reactions related to tbe cbemical use of toluene (other than conversion to benzene) are the oxidation of the methyl substituent and the hydrogenation of the phenyl group. Electrophilic substitution is limited to the nitration of toluene for producing mono-nitrotoluene and dinitrotoluenes. These compounds are important synthetic intermediates. 

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