Reactions of Aromatic Compounds

Theorists believe that the symmetry of the n system is imposed by the framework of a bonds. Bond alternation in the n system can be forced by the fusion of strained bicyclic rings [248] such as in [4]phenylene [249], tricyclobutabenzene [250], or trisbicyclo[2.1.1]-hexabenzene [251]  

Two novel forms of carbon, with formulas Qg [252] and [253] owe their stability to aromaticity with cyclic arrays of p orbitals which do not fall strictly into the class of cyclic systems discussed above  

Theoretical studies indicate that the allotrope, Qg, is a planar cyclic structure and therefore has one planar cyclic array of 18 electrons of the above type. It also has a second cyclic 18-electron array in the a framework, albeit the orbitals overlap in fashion [254]. The allotrope, [255], has a cyclic polyaromatic three-dimensional structure which has also been argued to be aromatic [256]. 

Thyroxine (see the model above ) is an aromatic compound and a key hormone that raises metabolic rate. Low levels of thyroxine (hypothyroidism) can lead to obesity, lethargy, and an enlarged thyroid gland (goiter). The thyroid gland makes thyroxine from iodine and tyrosine, which are two essential components of our diet. Most of us obtain iodine from iodized salt, but iodine is also found in products derived from seaweed, like the kelp shown above. An abnormal level of thyroxine is a relatively common malady, however. Fortunately, low levels of thyroxine are easily corrected by hormone supplements. After we study a new class of reaction in this chapter called electrophilic aromatic substitution, we shall return to see how that reaction is related to thyroxine in The Chemistry of... Iodine Incorporation in Thyroxine Biosynthesis.  

Some of the most important reactions of aromatic compounds are those in which an electrophile replaces one of the hydrogen atoms of the ring. 

A noteworthy example of electrophilic aromatic substitution in nature, as mentioned above, is biosynthesis of the thyroid hormone thyroxine, where iodine is incorporated into benzene rings that are derived from tyrosine. 

In the next section we shall learn the general mechanism for the way an electrophile reacts with a benzene ring. Then in Sections 15.3-15.7 we shall see specific examples of electrophiles and how each is formed in a reaction mixture. 

The TT electrons of benzene react with strong electrophiles. In this respect, benzene has something in common with alkenes. When an aUcene reacts with an electrophile, as in the addition of HBr (Section 8.2), electrons from the aUcene tt bond react with the electrophile, leading to a carbocation intermediate. 

The representation of benzene with a circle to represent the n system is fine for questions of nomenclature, properties, isomers, and reactions. For questions of mechanism or reactivity, however, the representation with three alternating double bonds (the Kekule picture) is more informative For clarity and consistency, this Solutions Manual will use the Kekule form exclusively. 

While the addition of water to the sigma complex can be shown in a reasonable mechanism, the product is not aromatic. Thus, it has lost the 152 kJ/mol (36 kcal/mole) of resonance stabilization energy. The addition reaction is not favorable energetically, and substitution prevails. 

The more stable the intermediate, the lowpr th S greater stabilization to this sigma complex 

Substitution generates HBr whereas the addition does not. If the reaction is performed in an organic solvent, bubbles of HBr can be observed, and HBr gas escaping into moist air will generate a cloud. If the reaction is performed in water, then adding moist litmus paper to test for acid will differentiate the results of the two compounds. 

17-12 Nitronium ion attack at the ortho and para positions places positive charge on the carbon adjacent to the bromine, allowing resonance stabilization by an unshared electron pair from the bromine. Meta attack does not give a stabilized intermediate. 

Para attack gives similar stabilization. Meta attack does not permit delocalization of the positive charge on the phenyl substituent. 

The unstable phenylpalladium intermediate 164 is formed by palladation of benzene with Pd(OAc)2, and then the following three reactions occur. 

formation of phenyl acetate (166) by displacement (reductive elimination)  

formation of the styrene derivative 167 by the coupling with alkene (insertion and -elimination). 

Oxidative homocoupling of aromatic and heteroaromatic rings proceeds with Pd(OAc)2 in AcOH. Biphenyl (165) is prepared by the oxidative coupling of benzene [104,105], The reaction is accelerated by the addition of perchloric acid. Biphenyl-tetracarboxylic acid (169), used for polyimide synthesis, is produced from dimethyl phthalate (168) commercially [106], Intramolecular coupling of the indole rings 170 is useful for the synthesis of staurosporine aglycone 171 [107]. 

Biaryls and 1,3-dienes can be synthesized by the Pd-promoted oxidative homocoupling of different substrates. The homocoupling of the arylstannane 172 and the alkenylstannane 175 gives the biaryl 173 and 1,3-diene 176 using a catalytic amount of Pd(OAc)2 and 02 in the presence of the iminophosphine ligand 174, or in the absence of ligand [107a]. 

Understand the mechanisms of electrophilic and nucleophilic aromatic substitutions. Predict the products of these reactions and use them in syntheses. 

Explain how substituents on the aromatic ring promote substitution at some positions but not at others. 

Q Predict the products of oxidation and reduction of the aromatic ring, including hydrogenation, chlorination, and Birch reduction. Predict the products of the oxidation of phenols. 

Aromatic compounds undergo many reactions, but relatively few reactions that affect the bonds to the aromatic ring itself. Most of these reactions are unique to aromatic compounds. A large part of this chapter is devoted to electrophilic aromatic substitution, the most important mechanism involved in the reactions of aromatic compounds. Many reactions of benzene and its derivatives are explained by minor variations of electrophilic aromatic substitution. We will study several of these reactions and then consider how substituents on the ring influence its reactivity toward electrophilic aromatic substitution and the regiochemistry seen in the products. We will also study other reactions of aromatic compounds, including nucleophilic aromatic substitution, addition reactions, reactions of side chains, and special reactions of phenols. 

Acyi halides are reactive compounds and react with nucleophiles without a catalyst, but they are activated further by forming the acylpalladium intermediates, which undergo insertion and further transformations. The decarbonyla-tive reaction of acyl chlorides as pseudo-halides to form the aryipalladium is treated in Section 1,1.1.1. The reaction without decarbonylation is treated in this section. 

Butyl vinyl ether reacts with aroyl chlorides using Pd(OAc)2 without a ligand to give the unsaturated ketone 839, which is a precursor of a 1-aryl-1,3-dicarbonyl compound. The reaction is regioselective /3-attack. Addition of PhjP inhibits the reaction[718]. 

The alkynyl ketones 840 can be prepared by the reaction of acyi chlorides with terminal alkynes, Cul in the presence of Et3N is the cocatalyst[719]. (1-Alkynyl)tributylstannanes are also used for the alkynyl ketone synthesis[720]. The a,. 3-alkynic dithio and thiono esters 842 can be prepared by the reaction of the corresponding acid chloride 841 with terminal alkynes[721,722]. 

The alkylphenylacetyi chloride 843 and benzoyl chloride undergo decarbo-nylative cross-condensation to give the enone 845 in the presence of EtiNf723]. The reaction is e.xplained by the insertion of the ketene 844 into the Pd-aryl bond and, 3-elimination. To support this mechanism, o, d-unsaturuted ketones are obtained by the reaction of ketenes with aroyl chlorides[724]. 

Acyl halides react with organometallic reagents without catalysts, but sometimes the Pd-catalyzed reactions give higher yields and selectivity than the Lincatalyzed reactions. Acyl halides react with Pd(0) to form the acylpalladium complexes 846, which undergo facile transmetallation. 

Like an alkene, benzene has clouds of pi electrons above and below its sigma bond framework. Although benzene s pi electrons are in a stable aromatic system, they are available to attack a strong electrophile to give a carbocation. This resonance-stabilized carbocation is called a sigma complex because the electrophile is joined to the benzene ring by a new sigma bond. 

The sigma complex (also called an arenium ion) is not aromatic because the sp -hybrid carbon atom interrupts the ring of p orbitals. This loss of aromaticity contributes to the highly endothermic nature of this first step. The sigma complex regains aromaticity either by a reversal of the first step (returning to the reactants) or by loss of the proton on the tetrahedral carbon atom, leading to the substitution product. 

Theoverall reaction is the substitution of an electrophile (E ) for a proton (H ) on the aromatic ring electrophilic aromatic substitution. This class of reactions includes 

Srep 1 Attack on the electrophile forms the sigma complex. 

Family General Formula Condensed General Formula Example Name 

Carboxylic acids R —C—OH RCOOH CH3 —C—OH Ethanolc acid (acetic acid) 

As we discussed in Section 20.8, alcohols are organic compounds containing the —OH functional group, or hydroxyl group, and they have the general formula R—OH. In addition to methanol and isopropyl alcohol, ethanol and 1-butanol (shown here) are also common alcohols. 

The names of alcohols are like the names of alkanes with the following differences  

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Similarly to mercuration reactions, Pd(OAc)2 undergoes facile palladation of aromatic compounds. On the other hand, no reaction of aromatic compounds takes place with PdClj. PdCl2 reacts only in the presence of bases. The aro-... 

Analogous plots for many other reactions of aromatic compounds show a similar linear correlation with the acid dissociation constants of the corresponding benzoic acids. 

In general, the dissection of substituertt effects need not be limited to resonance and polar components, vdiich are of special prominence in reactions of aromatic compounds.. ny type of substituent interaction with a reaction center could be characterized by a substituent constant characteristic of the particular type of interaction and a reaction parameter indicating the sensitivity of the reaction series to that particular type of interactioa For example, it has been suggested that electronegativity and polarizability can be treated as substituent effects separate from polar and resonance effects. This gives rise to the equation... 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

Keim and co-workers have carried out various alkylation reactions of aromatic compounds in ionic liquids substantially free of Lewis acidity [84]. An example is the reaction between benzene and decene in [BMIM][HS04], which was used together with sulfuric acid as the catalyst (Scheme 5.1-54). These authors have also claimed that these acid-ionic liquids systems can be used for esterification reactions. 

The most common reaction of aromatic compounds is electrophilic aromatic substitution. That is, an electrophile reacts with an aromatic ring and substitutes for one of the hydrogens. The reaction is characteristic of all aromatic rings, not just benzene and substituted benzenes. In fact, the ability of a compound to undergo electrophilic substitution is a good test of aromaticity- . 

Volume 8 Volume 9 Volume 10 Volume 12 Volume 13 Proton Transfer Addition and Elimination Reactions of Aliphatic Compounds Ester Formation and Hydrolysis and Related Reactions Electrophilic Substitution at a Saturated Carbon Atom Reactions of Aromatic Compounds Section 5. POLYMERISATION REACTIONS (3 volumes)... 

Ester Formation and Hydrolysis and Related Reactions 13 Reactions of Aromatic Compounds... 

In Volume 13 reactions of aromatic compounds, excluding homolytic processes due to attack of atoms and radicals (treated in a later volume), are covered. The first chapter on electrophilic substitution (nitration, sulphonation, halogenation, hydrogen exchange, etc.) constitutes the bulk of the text, and in the other two chapters nucleophilic substitution and rearrangement reactions are considered. 

Albini, A., Fasani, E. and Melia M. PET-Reactions of Aromatic Compounds. 168, 143-173... 

The heat of decomposition (238.4 kJ/mol, 3.92 kJ/g) has been calculated to give an adiabatic product temperature of 2150°C accompanied by a 24-fold pressure increase in a closed vessel [9], Dining research into the Friedel-Crafts acylation reaction of aromatic compounds (components unspecified) in nitrobenzene as solvent, it was decided to use nitromethane in place of nitrobenzene because of the lower toxicity of the former. However, because of the lower boiling point of nitromethane (101°C, against 210°C for nitrobenzene), the reactions were run in an autoclave so that the same maximum reaction temperature of 155°C could be used, but at a maximum pressure of 10 bar. The reaction mixture was heated to 150°C and maintained there for 10 minutes, when a rapidly accelerating increase in temperature was noticed, and at 160°C the lid of the autoclave was blown off as decomposition accelerated to explosion [10], Impurities present in the commercial solvent are listed, and a recommended purification procedure is described [11]. The thermal decomposition of nitromethane under supercritical conditions has been studied [12], The effects of very high pressure and of temperature on the physical properties, chemical reactivity and thermal decomposition of nitromethane have been studied, and a mechanism for the bimolecular decomposition (to ammonium formate and water) identified [13], Solid nitromethane apparently has different susceptibility to detonation according to the orientation of the crystal, a theoretical model is advanced [14], Nitromethane actually finds employment as an explosive [15],... 

Some reactions of aromatic compounds in water and methanol and of certain other compounds in water and ice have comparable specific rates. Due to considerable differences in solvation energies of both reactants and products, a transition state would require different barriers against reaction. 

Burkhardt, "Arthur Lapworth and Others," 143. C. K. Ingold, "The Significance of Tautomerism and of the Reactions of Aromatic Compounds in the Electronic Theory of Organic Reactions," JCS (1933) 1120 and C. 

Busy with the move from Leeds to London in 1930, Ingold afterward was in residence at Stanford University in California in 1932, with some leisure to work out generalizations of the results already at hand. He soon published two widely read pieces "Significance of Tautomerism and of the Reactions of Aromatic Compounds in the Electronic Theory of Organic Reactions," in the Journal of the Chemical Society, and the essay review, "Principles of an Electronic Theory of Organic Reactions," in Chemical Reviews.58... 

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