Nitration, aromatic substituent effects

The limiting reaction rate does not arise from the rate of formation of the electrophile since the reactions remain first-order with respect to the aromatic substrate. The limiting rate does not arise from a general breakdown in the additivity principle, e.g. as a result of the saturation of substituent effects, since the limiting rate is not found in some related reactions in which the substituent effects in deactivated systems are similar to those in nitration. This is illustrated by the results for bromination by positive bromine discussed in Section 5. Coombes et al. suggest that the limit arises from rate-determining formation of an encounter pair (ArH.NOJ between the nitronium ion and the aromatic substrate (Scheme 5). 

Substituent effect, in nitration 253 in nitrosation 314 on basicity 176-179, 181-187 on inductive effect 209 on reactivity of C=N linkage 352 Sulfonation, of aromatic amines 255, 256... 

Rate and Regioselectivity in the Nitration of (Trifluoromethyl)benzene 474 Substituent Effects in Electrophilic Aromatic Substitution Activating Substituents 476 Substituent Effects in Electrophilic Aromatic Substitution Strongly Deactivating Substituents 480 Substituent Effects in Electrophilic Aromatic Substitution Halogens 482 Multiple Substituent Effects 484 Retrosynthetic Analysis and the Synthesis of Substituted Benzenes 486 Substitution in Naphthalene 488 Substitution in Heterocyclic Aromatic Compounds 489... 

Table 2 summarizes some of the transformations of substituents which have been carried out on azetidines without effect on the ring <79CRV33l). Other transformations of interest are the base catalyzed epimerization, H exchange and alkylation of the activated H-3 in azetidines (26) (69JHC153) and the nitration, reduction, diazotization and hence further modification of the aromatic ring in 3-phenyl-fV-acetylazetidine (27) (61LA 647)83). 

Because nitration has been studied for a wide variety of aromatic compounds, it is a useful reaction with which to illustrate the directing effect of substituent groups. Table 10.3 presents some of the data. A variety of reaction conditions are represented, so direct comparison is not always valid, but the trends are nevertheless clear. It is important to remember that other electrophiles, while following the same qualitative trends, show large quantitative differences in position selectivity. 

While at Leeds from 1924 to 1930, Ingold s laboratory focused on three main topics of research (1) the nature and mechanism of orienting effects of groups in aromatic substitution (mainly nitration) (2) the study of prototropic rearrangements (shifts of H+) and aniontropic rearrangements (shifts of anions) as the ionic mechanisms of tautomerism and (3) the effect of polar substituents on the velocity and orientation of addition reactions to unsaturated systems. One of Ingold s students at Leeds, John William Baker, wrote a widely read book on tautomerism. 16... 

Halogen substituents withdraw electron density from the aromatic nucleus but direct olp-through resonance effects. The result is that halobenzenes undergo nitration with more difficulty relative to benzene. The nitration of chlorobenzene with strong mixed acid gives a mixture of 2,4- and 2,6-isomeric dinitrochlorobenzenes in which the former predominates." The nitration of 2,4-dinitrochlorobenzene to 2,4,6-trinitrochlorobenzene (picryl chloride) requires an excess of fuming nitric acid in oleum at elevated temperature. Both are useful for the synthesis of other polynitroarylene explosives but only 2,4-dinitrochlorobenzene finds industrial importance (Sections 4.8.1.2 and 4.8.1.3). 

The nature of the substituents presence in an aromatic substrate has a large effect on which positions are substituted on nitration. The isomeric ratio of products obtained on nitration is also dependent on the nitration conditions, nitrating agent, nitrating medium and its acidity, acid composition and concentration etc., but often to a lesser extent. 

The syntheses of iron isonitrile complexes and the reactions of these complexes are reviewed. Nucleophilic reagents polymerize iron isonitrile complexes, displace the isonitrile ligand from the complex, or are alkylated by the complexes. Nitration, sulfonation, alkylation, and bromina-tion of the aromatic rings in a benzyl isonitrile complex are very rapid and the substituent is introduced mainly in the para position. The cyano group in cyanopentakis(benzyl isonitrile)-iron(ll) bromide exhibits a weak "trans" effect-With formaldehyde in sulfuric acid, benzyl isonitrile complexes yield polymeric compositions. One such composition contains an ethane linkage, suggesting dimerization of the transitory benzyl radicals. Measurements of the conductivities of benzyl isonitrile iron complexes indicate a wide range of A f (1.26 e.v.) and o-o (1023 ohm-1 cm.—1) but no definite relationship between the reactivities of these complexes and their conductivities. 

An HNO3/H2SO4 mixture is therefore also suitable for nitrating deactivated aromatic compounds. Aromatic amines are included in this category In the very acidic reaction medium, they are protonated quantitatively. Thus, for example, the actual substrate of the nitration of A,A-dimethylaniline is an aromatic compound A, in which the ammonium substituent directs the attacking nitronium ion to the meta position because of its -I-effect ... 

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