Methoxybenzene, nitration

The trisubstituted benzene 14 was used by Woodward as a starting material for his synthesis of the natural product reserpine.5 It too has to be made. We shall not add the MeO group but buy anisole (methoxybenzene) as starting material. Both nitrogens will be added by nitration but in which order ... 

The nitration of methoxybenzene (anisole) proceeds 10,000 times faster than does nitration of benzene and produces predominantly the ortho and para isomers of ni-troanisole. 

Arrange the following compounds in order of their reactivity towards nitration and give the formulae of the major products of the reactions (a) benzene, benzonitrile, methoxybenzene, tri-fluoromethyObenzene (b) acetanilide, benzoic acid, chlorobenzene, acetophenone (c) phenol, ethyl benzoate, nitrobenzene, bro-mobenzene. 

N-CIDNP was used to investigate photoinduced nitrations of aromatic compoimds ArH with tetranitromethane. The polarizations invariably arise from radical pairs ArH NO, but the experiments reveal different pathways of formation of these pairs. With a substrate such as 1,2-dimethoxybenzene, the precursor multiplicity is triplet and the pairs are produced by a dissociative electron transfer from the aromatic compound to tetranitromethane, which then cleaves into an NO2 radical and C(N02)3. In contrast, the very similar substrate anisole (methoxybenzene) exhibits polarizations indicating a singlet precursor, and the radical pair is thought to be formed by decomposition of a preceding unstable diamagnetic intermediate, most probably a nitro-trinitromethyl adduct. ... 

Judgment must be exercised in cases where two of the general resonance criteria are in conflict. For example, the structure B is an important contributor to the resonance hybrid for the intermediate in the nitration of methoxybenzene (anisole), even though the structure has a positive charge on oxygen. This unfavorable feature is compensated for by the additional covalent bond present in structure B compared with the other major contributor, structure A, in which the positive charge is on carbon. 

What about disconnection bl While direct electrophilic amination of arenes is (like aUcoxylation or hydroxylation) not viable, we know that we can achieve it indirectly through a nitration- eduction sequence (Section 16-5). Thus, the problem reduces to a nitration of l-chloro-4-methoxybenzene. Will it proceed with the desired regioselectivity Guideline 2 in Section 16-4 answers in the affirmative. This analysis provides l-chloro-4-methoxybenzene as a new relay point, available, in addition to its ortho isomer, by chlorination of methoxybenzene. 

Write the structure(s) of the major product(s) that you expect from each of the following electrophilic aromatic substitutions, (a) Snlfonation of methoxybenzene (anisole) (b) bromination of nitrobenzene (c) nitration of benzoic acid (d) Friedel-Crafts acetylation of chlorobenzene. 

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