Aromatic Side-Chain Reactivity

Phenylalanine and tryptophan contain aromatic side chains that, like the aliphatic amino acids, are also relatively non-polar and hydrophobic (Figure 1.4). Phenylalanine is unreactive toward common derivatizing reagents, whereas the indolyl ring of tryptophan is quite reactive, if accessible. The presence of tryptophan in a protein contributes more to its total absorption at 275-280nm on a mole-per-mole basis than any other amino acid. The phenylalanine content, however, adds very little to the overall absorbance in this range. 

The reactivity of aromatic side chains to undergo dealkylation is in line with the stability of the corresponding carbocations. This indicates the possible involvement of carbocations in dealkylation, which was proved to be the case. The intermediacy of the rm-butyl cation in superacid solution was shown by direct spectroscopic observation.228,229 Additional proof was provided by trapping the ferf-butyl cation with carbon monoxide during dealkylation 230... 

Curiously enough, variation of A in Eq. (4) and of the equivalent ratios in Eqs. (1) and (2) is quite clear-cut for passage of substituent effects across different aromatic and heteroaromatic systems, as will be emphasized in this review subsequently, but its deviation from unity in the case of reactivities of side chains of varying geometry is much less certain.8-10 Alternative sets of a, and aR values to those of Taft have been offered by Exner.11... 

This method is mainly restricted to the synthesis of amino acids with aromatic side-chains since the required unsaturated azlactones [e.g. (30)] are most readily prepared using aromatic aldehydes. Typically, benzaldehyde condenses under the influence of base with the reactive methylene group in the azlactone (29) which is formed by the dehydration of benzoylglycine (28) when the latter is heated with acetic anhydride in the presence of sodium acetate (cf. Expt 8.21). The azlactone ring is readily cleaved hydrolytically and compounds of the type (30) yield substituted acylaminoacrylic acids [e.g. (31)] on boiling with water. Reduction and further hydrolysis yields the amino acid [e.g. phenylalanine,... 

The general process begins with Cr(CO)3L3, in which the L unit can be CO (most common),MeCN, " o-alkylpyridine, ammonia, and other donor ligands (equation 91). The rate (reaction temperature) is related to the nature of L the most reactive readily available source of Cr(CO)3 is ( ] -naphthalene)Cr(CO)3, which undergoes favorable arene exchange under mild conditions with many substituted arenes. " The most general and convenient procedure employs a mixture of THF and di-n-butyl ether at reflux. " A variety of polar and nonpolar aprotic solvents has been used and, for some purposes such as complexation of a-amino acids with aromatic side chains, water-THF mixtures are effective. 

A marked contrast is observed in the behaviour of the simplest aromatic hydrocarbon-air mixtures at high pressures. No cool-flame phenomena or an ignition peninsula in the (p-Ta) diagram are observed. These are found only when sufficiently reactive aliphatic side-chains are associated with the aromatic ring. Burgoyne et al. [129] showed this to be the case for n-propylbenzene in a closed vessel (Fig. 6.18). The ortho- and meta-isomers of the xylenes also showed a similar reactivity. Benzene, toluene and ethylbenzene were found to undergo spontaneous ignition at temperatures only above 700 K. 

The reactivity of aromatic side-chain compounds toward brominating agents is also influenced by the nature of the solvent. Under comparable conditions, the percentage formation of benzyl bromide from bronnne and toluene in various solvents is as follows ... 

The widespread applications of polystyrene derived resins is due to the fact that styrene consists of a chemically inert aUcyl backbone carrying chemically reactive aryl side chains that can be easily modified. As discussed earlier, a wide range of different types of polystyrene resins exhibiting various different physical properties can be easily generated by modification of the crosslinking degree. In addition, many styrene derived monomers are commercially available and fairly cheap. Polystyrene is chemically stable to many reaction conditions while the benzene moiety, however, can be funtionalised in many ways by electrophilic aromatic substitutions or lithiations. As shown in Scheme 1.5.4.1 there are principally two different ways to obtain functionalised polystyrene/DVB-copolymers. 

Tyr possesses a weakly acidic functional group in its aromatic side chain with pK, = 10.1. The phenolic group forms hydrogen bond and the phenolic ring of Tyr is relatively reactive in electrophilic substitution reactions. 

Of the two contrasting properties of the Cr(CO)3 group, i.e., donor and acceptor, with respect to an aromatic side-chain, the inductive acceptor effect has been more widely explored with regard to its synthetic consequences. In particular, temporary complexation of an organic substrate favors proton abstraction from a carbon chain in basic media. This increased tendency toward anion formation thus permits the alkylation of substrates whose free ligands have little or no reactivity. 

Hammen equation A correlation between the structure and reactivity in the side chain derivatives of aromatic compounds. Its derivation follows from many comparisons between rate constants for various reactions and the equilibrium constants for other reactions, or other functions of molecules which can be measured (e g. the i.r. carbonyl group stretching frequency). For example the dissociation constants of a series of para substituted (O2N —, MeO —, Cl —, etc.) benzoic acids correlate with the rate constant k for the alkaline hydrolysis of para substituted benzyl chlorides. If log Kq is plotted against log k, the data fall on a straight line. Similar results are obtained for meta substituted derivatives but not for orthosubstituted derivatives. 

The reactivity of alkylthiazoles possessing a functional group linked to the side-chain is discussed here neither in detail nor exhaustively since it is analogous to that of classical aliphatic and aromatic compounds. These reactions are essentially of a synthetic nature. In fact, the cyclization methods discussed in Chapter II lead to thiazoles possessing functional groups on the alkyl chain if the aliphatic compounds to be cyclized, carrying the substituent on what will become the alkyl side chain, are available. If this is not the case, another functional substituent can be introduced on the side-chain by cyclization and can then be converted to the desired substituent by a classical reaction. 

OC-Methylstyrene. This compound is not a styrenic monomer in the strict sense. The methyl substitution on the side chain, rather than the aromatic ring, moderates its reactivity in polymerization. It is used as a specialty monomer in ABS resins, coatings, polyester resins, and hot-melt adhesives. As a copolymer in ABS and polystyrene, it increases the heat-distortion resistance of the product. In coatings and resins, it moderates reaction rates and improves clarity. Physical properties of a-methylstyrene [98-83-9] are shown in Table 12. 

Monomer Reactivity. The nature of the side chain R group exerts considerable influence on the reactivity of vinyl ethers toward cationic polymerization. The rate is fastest when the alkyl substituent is branched and electron-donating. Aromatic vinyl ethers are inherently less reactive and susceptible to side reactions. These observations are shown in Table 2. 

Rate data are also available for the solvolysis of l-(2-heteroaryl)ethyl acetates in aqueous ethanol. Side-chain reactions such as this, in which a delocalizable positive charge is developed in the transition state, are frequently regarded as analogous to electrophilic aromatic substitution reactions. In solvolysis the relative order of reactivity is tellurienyl> furyl > selenienyl > thienyl whereas in electrophilic substitutions the reactivity sequence is furan > tellurophene > selenophene > thiophene. This discrepancy has been explained in terms of different charge distributions in the transition states of these two classes of reaction (77AHC(21)119>. 

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