Electron-Poor Aromatic Compounds

Reports on the ring hydroxylation of electron-poor aromatic componnds are relatively scarce. Chlorobenzene, nitrobenzene, benzonitrile, benzaldehyde, and benzoic acid are inert toward hydroxylation with over TS-1 [81]. The hydroxylation of benzene derivatives XC j (X=F, Cl, Br, NOj) by and in the presenee of eatalytie amonnts of [V0(02)(pie)(H20)2] prodnced corresponding phenols in moderate yields [94]. The reaction was proved to be a radical chain process where initiation prodnces a radical anion of the peroxovanadium complex as the actnal oxidizing species [34]. 

Hydroxylation of benzonitrile and fluoro- and chlorobenzenes was realized with N O over ZSM-5 zeolite [101]. In this system, chlorobenzeneprodncedchlorophenol(o m=28 72) with 58% selectivity at 23% substrate conversion [101a], while benzonitrile gave hydroxybenzonitrile 

Even more rare are oxidations with dioxygen [102]. Khenkin et al. found that heating a 0.01 M solution of H5[PVjMOjjO J in neat nitrobenzene at 140°C under 2 bar Oj selectively ( 99%) yielded 2-nitrophenol at a 5% maximum yield [102a]. Liu et al. have developed a Cu-catalyzed oxygenase-type aerobic oxidation of arenes [102b]. The yield of 2,3,5,6-tetrachlorophenol reached 89% (Eq. 14.29). 

5 orfAo-Hydroxylation Driven by Arene Functionai Group 

No reaction was observed with stoichiometric amounts of Pd(OAc)j under argon, suggesting that Oj is likely involved in the product formation step rather than reoxidation of Pd(0). Labeling studies using and supported a direct oxygenation of the arylpalladium intermediates with Oj instead of an acetoxylation/hydrolysis sequence. Pyridyl group also enabled direct Cu-catalyzed orf/io-selective acetoxylation of aryl C—H bonds with in AcOH/ACjO [39]. 

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In addition, electron-rich as well as electron-poor aromatic compounds react with BAN in the presence of and, generally, high yields of the desired aromatic ketones are obtained (Table 4.20).i i By using chiral anhydrides such as (S)-2-methylbutyric anhydride, the pure... 

Unlike most free radicals, 02 has little tendency to add to carbon-carbon double bonds it has been shown to be inert with most simple olefins as well as many aromatic hydrocarbons. It reacts with electron-poor aromatic compounds such as quinones and nitro derivatives to produce radical anions (Wilshire and Sawyer,... 

For aromatic compounds, again there is some, but not much, discrimination based on electron density of the ring. The electron-rich compound anisole (methoxy-benzene), for example, has a rate constant for reaction with HO- only 2.6 times larger than that of nitrobenzene, a much more electron-poor aromatic compound (Zepp et al., 1987b). Addition to the aromatic ring (to form the intermediate cyclo-hexadienyl radicals 21) often predominates by a factor of approximately 10 over... 

X - and especially X -phosphorins are electron-rich aromatic compounds, comparable with aniline, whereas pyridine and pyridinium ions are electron-poor and are comparable to nitrobenzene. Many chemical properties can be easily understood once this fact is taken into account. 

Nucleophilic substitutions of simple aromatic compounds which formally involve a hydride displacement are difficult to achieve because of the poor leaving group and the high electron density of the aromatic nucleus which repels approach of a nucleophile. However, rc-electron deficient aromatic compounds such as metal carbonyl complexes are susceptible to attack by certain carbon nucleophiles. Studies of this chemistry have shown [16] an opposite jegioselectivity to the corresponding electrophilic substitutions, in agreement with the polarity alternation rule. 

DiMauro and co-workers [67] have developed a rapid and efficient synthesis of 3-amino-imidazopyridines 16 using a microwave-assisted one-pot cyclization. The intermediate 15 was further reacted with various aryl bromides in the presence of a catalytic amount of Pd(dppf)Cl2 to yield the target compounds 16. The reaction scope is quite broad with respect to the aldehyde and aryl bromide components which might be electron-rich, electron-poor, aromatic, aliphatic, or sterically encumbered (Scheme 15). 

Electron-poor aromatic hctcrocycles, such as pyridines and related compounds, are not reduced under ionic hydrogenation conditions. Therefore, this method is limited to the more reactive five-membered-ring heteroaromatics. 

Chen and coworkers hypothesized that n-n stacking may also be modulated by n -electron donor-acceptor interactions." Under this theory, pristine, jr-electron-rich CNTs adsorb r-electron-poor nitroaromatic compounds more strongly than nonpolar aromatic compounds, and the adsorption affinity increases with an increasing number of nitro groups. 

The Ullmann reaction has also been successfully employed in the preparation of unsyuunetrical biaryl compounds. However, the results are ofteu not satisfying, and such reactions are only applicable to a limited type of substrates where both coupling partners clearly differ in reactivity (electron-rich vs. electron-poor aromatic substrates) aud steric demands. Usually, the less reactive coupling partner also must be used in excess. 

Copper-catalyzed N-arylation of 2-imidazolines has been carried out by Davis et al. (2013). The reaction provides compounds with advantageous lead-like characteristics in good yields with useful simplicity under inexpensive, ligand-free conditions. The cross coupling was successful with electron-rich and electron-poor aromatic iodides. Substrates having halides, esters, nitriles, and free hydroxyls are well tolerated, providing reactive handles for further functionalization. In addition, the regi-oselective N-arylation of 4-substituted imidazoline has also been reported. 

Compound 45 is susceptible to nucleophilic aromatic substitution at position 5 due to the highly electron-poor thiadiazole ring in addition to the effect of the ester functionality. 

One of the great attractions of fullerenes is the ability to apply to C60 much of the olefin and aromatic chemistry already developed with traditional organic compounds. This activity is still in its early stages. One of the earliest accomplishments was the use of organometallic chemistry by Paul Fagan to demonstrate that C60 could react as an electron-poor olefin similar to tetracyanoethylene. 

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