Nitration regioselectivity

The latter compounds 88 are unstable and readily hydrolyzed to isocou-marin 89 and deoxybenzoin 90 by analogy with /3-diketonic enol ethers (cf. Section III,F,2,d). The only example of electrophilic substitution in an aromatic ring conjugated with the cationic ring was described for the nitration regioselectively yielding the meta isomer 91 (84MI1). 

HMordenite, HFaujasite-780, HFaujasite 720 and Na-Faujasite zeolites. Among the different catalysts, HFaujasite-720 was the most active and selective catalyst towards 2,4-dinitrotoluene, achieving a yield of dinitrotoluenes of 92 % with a ratio of 2,4- to 2,6- isomers of 4.3 1 in 3 min reaction time. Using this zeolite, l-chloro-2-nitrobenzene and pyrazole were also nitrated regioselectively to obtain l-chloro-2,4-dinitrobenzene in a l-chloro-2,4-dinitro l-chloro-2,6-dinitro ratio of 30 1, and 1,4-dinitropyrazole in 80% yield, respectively. The authors proposed a nitration mechanism in which the protons in the zeolite are replaced by nitronium ions derived from N2Os in a fast pre-equilibrium process. This produces active sites for transfer of nitronium ion from faujasite to aromatic in the rate-controlling step. 

Nitration. Regioselective mononitration (but no further) of moderately deactivated arenes is accomplished with urea nitrate or nitrourea, despite their use in excess. 

How do the charges on the ring carbons of toluene and (tri fluoromethyl)benzene relate to the regioselectivity of nitration" ... 

The relative ease of preparation of condensed thiazole derivatives is a consequence of facile thiazole ring closure, and therefore also benzothiazole amines with an amino group on the benzene ring (except for the weakly regioselective nitration of benzothiazoles) are very easily accessible and useful substrates for the Gould-Jacobs reaction. 

Regioselectivity of Nitration of Fluorene and Its Reversal by a Spiro Conjugation... 

Ohwada and Shudo [26] showed that the regioselectivity of the nitrations was reversed by a remote carbonyl group (Scheme 27). The 4-position is more reactive than the 2-position. The reversed selectivity is explaned by the orbital mixing rules. The orbitals closest in energy to the HOMO are the next HOMO (NHOMO), i.e.. 

Scheme 27 Reversal of the regioselectivity of nitration by a spiro carbonyl group...

In a modified version of a previously published procedure <83JOC3214>, the thallium induced transposition of 3-acetyl-1-tosylpyrrole to the corresponding 2-(3-pyrrolyl)acetic acid has been reported employing thallium(III) nitrate supported on acidic montmorillonite K-10 <96SC1289>. In this sequence, Af-tosylpyrrole (39) undergoes regioselective C-3 acylation to afford 40 which is rearranged with T1(III)/K-10 in methanol to yield the ester 41. 

O-acetylophiocarpine (381) with ethyl chloroformate afforded the C-8—N cleaved urethane 382 in quantitative yield. Sequential treatment of 382 with silver nitrate, PCC, sodium hydroxide, and p-toluenesulfonic acid in ethanol furnished acetal 384, which was reduced with lithium aluminum hydride followed by hydrolysis to afford the hemiacetal 385. Oxidation of 385 with PCC provided (+ )-a-hydrastine (369). Similar treatment of O-acetylepi-ophiocarpine (386) afforded ( )-/J-hydrastine (368) however, in this case, C—N bond cleavage of 386 with ethyl chloroformate proceeded without regioselectivity. 

Smith and coworkers have screened the solid catalysts for aromatic nitration, and found that zeolite (3 gives the best result. Simple aromatic compounds such as benzene, alkylbenzenes, halogenobenzenes, and certain disubstituted benzenes are nitrated in excellent yields with high regioselectivity under mild conditions using zeolite (3 as a catalyst and a stoichiometric quantity of nitric acid and acetic anhydride.11 For example, nitration of toluene gives a quantitative yield of mononitrotoluenes, of which 79% is 4-nitrotoluene. Nitration of fluorobenzene under the same conditions gives p-fluoronitrobenzene exclusively (Eqs. 2.1 and 2.2)... 

Phenols are easily mononitrated by sodium nitrate in a two-phase system (water-ether) in the presence of HC1 and a catalytic amount of La(N03)3.13 Various lanthanide nitrates have been used in the nitration of 3-substituted phenols to give regioselectively the 3-substituted 5-nitrophenols.14... 

The alternative electrophilic mechanism for the nitration of ESE with TNM requires a close approach of a hindered ESE to a N02 group on the quaternary carbon center of TNM. However, this transition state is sterically very demanding, and it will not readily account for the observed reactivity. Furthermore, the observed lack of regioselectivity in the nitration of the isomeric enol silyl ethers of 2-methylcyclohexanone that leads to the same 2-methyl-2-nitrocyclohexanone (in thermal as well as photochemical nitration) is not readily reconciled by a concerted (electrophilic) mechanism (equation 18). 

Electrophilic attack at carbon is a well-documented reaction which occurs regioselectively at the C-3 position. It was illustrated by numerous examples, including nitrations, halogenations, acylations, and Mannich reactions in CHEC(1984) and CHEC-II(1996) <1996CHEC-II(8)249>. Table 1 reports some additional recent examples. It should be noted that all these synthetic transformations were carried out in the field of medicinal chemistry. 

---