Substitution reactions nitration

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

Isoxazoles are known at present to undergo the following electrophilic substitution reactions nitration, sulfonation, halogenation, chloroalkylation, hydroxymethylation, and mercuration. Repeated attempts to effect the Friedel-Crafts reaction in the isoxazole series in the authors laboratory failed. The isoxazole nucleus seems not active enough to react with weak electrophilic reagents. 

The central C-C double bond of dibenz[, /]oxepin displays the properties of an activated aromatic system and undergoes substitution reactions. Nitration and acid-catalyzed dcutcration gives the dibenzo[i>,/]oxepins 1 with the respective substituent in position 10.161... 

The importance of the steric effect accounts for the spread of the data for lf-N in the substitution reactions. Nitration and non-catalytic chlorination, reactions of modest steric requirements, define points which fall above the arbitrary reference line. Bromination, a reaction of somewhat greater steric requirements, is not accelerated to the extent anticipated on the basis of the results for nitration or chlorination. The benzoylation reaction with large steric requirements is two orders of magnitude slower than the equally selective chlorination reaction. The unusually small ratio for lf-N/2f-N for the acylation reaction is a further indication of the steric effects. Apparently, the direct substitution reactions of naphthalene respond to the retarding steric influence of the peri hydrogen in much the same way as for other ortho substituents. 

The ring system (1) did not undergo any other electrophilic substitution reactions (nitration, sulfonation, Friedel-Crafts, Vilsmeier formylation), was inert to sodamide, could not be metalated with butyllithium and could not be readily oxidized with hydrogen peroxide to an AC-oxide (66JOC265). Compound (1) could not be reduced at atmospheric pressure by hydrogen but at 3 atm using a palladium-charcoal catalyst the 5,6,7,8-tetrahydro derivative (90) was obtained (75G1291). 

Nitro groups are meta-directing. Both nitro groups of m-dinitrobenzene direct an incoming substituent to the same position in an electrophilic aromatic substitution reaction. Nitration of m-nitrobenzene yields 1,3,5-trinitrobenzene. 

There are several lines of evidence for formation of cr complexes as intermediates in electrophilic aromatic substitution. One particularly informative approach involves measurement of isotope effects on the rate of substitution. If removal of the proton at the site of substitution were concerted with introduction of the electrophile, a primary isotope effect would be observed in reactions in which electrophilic attack on the ring is rate-determining. This is not the case for nitration nor for several other types of aromatic substitution reactions. Nitration of aromatic substrates partially labeled by tritium shows no selectivity between protium- and tritium-substituted sites. Similarly, the rate of nitration of nitrobenzene is identical to that... 

The nitration reactions described in this experiment aU demonstrate one of the classic electrophilic aromatic substitution reactions. Nitration has been used extensively in organic synthesis since a nitro group on an aromatic ring may be readily reduced to an amino group. 

Reactions for detection and identification of aromatic hydrocarbons can be divided into substitution reactions (nitration, chlorosulfonation, acetylation), addition reactions (7r-complexes), and oxidative reactions (oxidation of aliphatic chains, oxidation of aromatic hydrocarbons to quinones). The... 

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