Benzene electrophilic hydroxylation

It is well-recognized that phenols are completely protonated in superacidic solutions.420 This raised the possibility that protonated phenols, once formed in these media, might resist further electrophilic attack. Electrophilic hydroxylations of aromatics with hydrogen peroxide (98%) in superacidic media has been achieved by Olah and Ohnishi617 in Magic Acid, which allows clean, high-yield preparation of monohydroxylated products. Benzene, alkylbenzenes, and halobenzenes are efficiently hydroxylated at low temperatures. The obtained yields and isomer distributions are shown in Table 5.36. Subsequently, Olah et al.618 found that benzene and... 

Olah, G.A. and Ohnishi. R. (1978) Oxyfunctionalization of hydrocarbons. 8. Electrophilic hydroxylation of benzene, alkylbenzenes, and halobenzenes with hydrogen peroxide in superadds. /. Org. Chem., 43, 865-867. 

In connection with the possible role of n-complexes attempt was made to explain the orientation in electrophilic hydroxylation by ipso-attack. Table 57 lists the benzene derivatives hydroxylated by hydrogen peroxide in HSO3F—SOjClF at —78 °C Part of the reaction products are formed with a shift of the CH3 group. Since the parent compounds do not isomerize under reaction conditions the shift of the CH3 group must be realized in hydrobenzenium ions formed as HO" is added to the substituted ring carbons. 

Chemical reactions can also be carried out at sites that are vulnerable to electrophilic or nucleophilic attack. Structures such as benzene rings, hydroxyl groups, double bonds, halogen, and the like qualify for such attacks [41]. 

Many of the properties of phenols reflect the polarization implied by the resonance description The hydroxyl oxygen is less basic and the hydroxyl proton more acidic in phenols than m alcohols Electrophiles attack the aromatic ring of phenols much faster than they attack benzene indicating that the ring especially at the positions ortho and para to the hydroxyl group is relatively electron rich... 

A hydroxyl group is a very powerful activating substituent, and electrophilic aromatic substitution in phenols occurs far- faster, and under milder conditions, than in benzene. The first entry in Table 24.4, for exfflnple, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reaction was carried out in the nonpolar- solvent 1,2-dichloroethane. In polar- solvents such as water it is difficult to limit the bromination of phenols to monosubstitution. In the following exfflnple, all three positions that are ortho or para to the hydroxyl undergo rapid substitution ... 

Benzene and alkyl-substituted benzenes can be hydroxylated by reaction with H2O2 in the presence of an acidic catalyst. What is the structure of the reactive electrophile Propose a mechanism for the reaction. 

Hydroxylation of benzene appears to proceed through an electrophilic aromatic substitution since electronwithdrawing substituents cannot be hydroxy-lated with TS-1 and H202.36 A possible rationale for this mechanism comes... 

Hydroxylation may also take place at nitrogen atoms, resulting in hydroxyl-amines (e.g., acetaminophen). Benzene, polycyclic aromatic compounds (e.g., benzopyrene), and unsaturated cyclic carbohydrates can be converted by mono-oxygenases to epoxides, highly reactive electrophiles that are hepato-toxic and possibly carcinogenic. 

Lead(IV) trifluoroacetate is a strong electrophilic and oxidizing reagent It is a valuable reagent for the hydroxylation of aromatic compounds [5S, 59] Lead(IV) trifluoroacetate also reacts with silylated benzenes with the exclusive formation of the corresponding trifluoroacetate esters [59] (equation 28)... 

The hydrated electron is obviously a nucleophile and its reactions are affected by substituents correspondingly. The hydroxyl radical is expected to behave as an electrophile and this behaviour was, indeed, demonstrated with aromatic compounds. The low reactivity of O toward aromatic and olefinic ir-systems suggests that this species behaves as a nucleophile because of its charge. The behaviour of hydrogen atoms is not easily predictable the effect of substitution in benzene demonstrated a slight electrophilicity. 

Reaction of pentafluorophenol with rerf-butyl hypobromite starts as an electrophilic substitution in the benzene ring. The electrophile is formed by dissociation of tert-butyl hypobromite to tert-butoxy anion and bromine cation. The bromine cation attacks the para position and forms a positively charged Wheland complex, a nonaromatic species that is converted by ejection of proton from the phenolic hydroxyl to a quinon-oid compound, 4-bromopentafluorocyclohexa-2,5-dienone [39]. 

The mechanism is shown next. Sulfuric acid reacts with nitric acid to form the nitronium ion (+N02), a powerful electrophile. The mechanism is similar to other sulfuric acid-catalyzed dehydrations. Sulfuric acid protonates the hydroxyl group of nitric acid, allowing it to leave as water and form a nitronium ion. The nitronium ion reacts with benzene to form a sigma complex. Loss of a proton from the sigma complex gives nitrobenzene. 

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