Nitroanisoles, reactions

The reaction of N bromosuccimmide with the following com pounds has been reported in the chemical literature Each compound yields a single product in 95% yield Identify the product formed from each starting material (a) p-tert Butyltoluene (b) 4 Methyl 3 nitroanisole... 

Various materials, present by accident or design, can alter the course of reduction by arresting the reaction at an intermediate product or by causing the formation of coupled products (94,95). These deviations can range from only a small yield loss to the formation of a major product. The work of Kosak (56) on o-nitroanisole is instructive in this regard, where small amounts of... 

First of all, there are the two products of O-coupling addition of methoxide ion to the diazonium ion, the (Z)- and (jE)-diazo methyl ethers. As discussed in Section 6.2, they are formed in reversible reactions with half-lives of the order of a fraction of a second (Z) to a minute (E). The two diazo ethers are, however, decomposed rapidly to the final dediazoniation products. We show in Scheme 8-47 the products obtained by Broxton and McLeish (1983 b) in the dediazoniation of 4-chloro-3-nitrobenzenedi-azonium ion (8.64) with methoxide ion in CH3OH. The products are 4-chloro-3-nitro-anisole (8.65, 49 9o), 2-chloro-nitrobenzene (8.66, 449o), and 2-nitroanisole (8.67). 

The positive bromination of aromatics ethers was first studied by Bradfield et al.193 and by Branch and Jones194. The reaction of hypobromous acid in 75 % aqueous acetic acid with benzyl 4-nitrophenyl ether and 4-nitrophenetole at 20 °C was very rapid and approximately second-order193. The value of k2/[H+] remained constant in the [H+] range 0.005-0.090 M for the effect of added mineral acids on the bromination of 4-nitroanisole and 4-nitrophenetole (at 19.8 °C)194. The variation in reaction rate with the percentage of acetic acid in the medium was also studied and showed a large increase in the 0-10 % range with a levelling off at approximately 25 % acetic acid (Table 52) this was attributed... 

Kinetic studies of molecular bromination have been carried out using a variety of solvents other than acetic acid. The bromination of 2-nitroanisole by bromine in water revealed that molecular bromine is the reactive species and that the tribromide ion is very unreactive191. By making allowance for the concentration of free bromine (which differs from the stoichiometric concentration through reaction with bromine ion), good second-order rate coefficients were obtained by application of equation (133) with k2 = 0.062 at 25 °C the dominance of the bimolecular mechanism is to be expected here in view of the trend observed on making acetic acid media more aqueous. 

Whilst molecular hypobromous acid can be a brominating species, it is not believed to be the active species in acetic acid solution. The bromination of 4-nitroanisole by hypobromous acid in 75 % aqueous acetic acid at 19.8 °C gave a second-order rate coefficient of 0.162, so that the brominating species here appears to be more reactive than molecular bromine194. In addition, the presence of 0.05 M sodium acetate caused the rate coefficient to fall to only 0.040, and both these observations were contrary to expectation if hypobromous acid was the brominating species, but are quite consistent with it being bromine acetate, BrOAc. Also, the addition of chloride ion caused the reaction to become immeasurably slow, due to the formation of the much less reactive bromine chloride. 

The chemistry of indium metal is the subject of current investigation, especially since the reactions induced by it can be performed in aqueous solution.15 The selective reductions of ethyl 4-nitrobenzoate (entry 1), 2-nitrobenzyl alcohol (entry 2), l-bromo-4-nitrobenzene (entry 3), 4-nitrocinnamyl alcohol (entry 4), 4-nitrobenzonitrile (entry 5), 4-nitrobenzamide (entry 6), 4-nitroanisole (entry 7), and 2-nitrofluorenone (entry 8) with indium metal in the presence of ammonium chloride using aqueous ethanol were performed and the corresponding amines were produced in good yield. These results indicate a useful selectivity in the reduction procedure. For example, ester, nitrile, bromo, amide, benzylic ketone, benzylic alcohol, aromatic ether, and unsaturated bonds remained unaffected during this transformation. Many of the previous methods produce a mixture of compounds. Other metals like zinc, tin, and iron usually require acid-catalysts for the activation process, with resultant problems of waste disposal. 

This iron-ate complex 19 is also able to catalyze the reduction of 4-nitroanisole to 4-methoxyaniline or Ullmann-type biaryl couplings of bis(2-bromophenyl) methylamines 31 at room temperature. In contrast, the corresponding bis(2-chlor-ophenyl)methylamines proved to be unreactive under these conditions. A shift to the dianion-type electron transfer(ET)-reagent [Me4Fe]Li2 afforded the biaryl as well with the dichloro substrates at room temperature, while the dibromo substrates proved to be reactive even at —78°C under these reaction conditions. This effect is attributed to the more negative oxidation potential of dianion-type [Me4Fe]Li2. 

A very large scale reaction to produce 2-nitroanisole from chloronitrobenzene and methanolic sodium hydroxide ran out of control and painted the town orange. This was attributed to reduction of the nitro group at temperatures above 100°C, a far more exothermic reaction than intended. This temperature was reached because the methanolic alkali was charged without agitation, and, the reaction not starting, the batch was heated to 90°C. The agitation was only then switched on. 

A calorimetric study of reaction with sodium or potassium hydroxides in ethanol or 2-propanol is given. At starting temperatures below 70°C the product is the appropriate nitrophenyl ether above that temperature, reduction of the nitro groups may come into play, to give much more energy and a variety of other products. This reaction is inhibited by oxygen. There is potential for runaway if such reactions are operated industrially with poor temperature control. The editor suspects that the stimulus for this study was an accident which sprayed the German environment with 2-nitroanisole. 

In the preparation of 2.2 -dimcthoxvazoxybenzcnc. solvent ethanol was distilled out of the mixture of 2-nitroanisole, zinc and sodium hydroxide before reaction was complete. The exothermic reaction continued unmoderated, and finally exploded. 

The observation of second-order kinetics (ku) for the spectral decay of the anisole cation radical in Fig. 15 points to the disappearance of AN + - after its separation from the initially formed triad in (63). Owing to the high yields of nitroanisoles obtained, such a process can be formulated as in Scheme 11 as the bimolecular (homolytic) reaction in (64) that produces the critical Wheland intermediate in aromatic nitration according to Perrin (1977) and Ridd (1991). 

When o-, m- and p-nitroanisole with 14C-labelled at the methoxy group were irradiated under identical conditions in methanol in the presence of sodium methoxide, only m-nitroanisole underwent methoxy exchange, with the limiting quantum yield (

labelled isotope experiments support a a complex intermediate and indicate an Sjv23Ar mechanism (direct substitution in the triplet state) for this reaction (equation 12) and for 4-nitroveratroles (equation 13). Further evidence from quenching and lifetime experiments also support a direct displacement SAr2Ar mechanism for the photosubstitution reaction of nitroaryl ethers with hydroxide ions13. 

Nitroani soles are also obtained by the catalysed displacement of a nitro group from dinitrobenzene. As expected, the 1,2- and 1,4-dinitrobenzenes are the more reactive, but 3-nitroanisole can be obtained in high yield after a prolonged reaction time [49]. 

Monooxygenase Assays. Incubation media contained the following (final concentrations) 0.05M phosphate buffer, pH 7.A, glucose-6-phosphate (G-6-P, 2.3 mM), G-6-P dehydrogenase (3 units), NADP (0.23 mM), and KC1 (2.8 mM), and various tissue preparations. Substrates were added in small volumes (25 yl or less) of MeOH. Samples (1.1 ml) were shaken in a thermostated (usually at 22°C) water bath and reactions terminated by enzyme denaturation. Specific analytical procedures for aldrin epoxi-dation (13), 1 CH30-p-nitroanisole 0-demethylation (1A), and 3H-benzo(a)pyrene oxidation (15) have been described. 

Other factors, however, should also be effective. A specific influence of the solvent 101,116) added detergents 12 ) and remote electron donating substituents 119) has been observed. Steric hindrance, which certainly is of influence in the nucleophilic photosubstitution reactions of a-nitronaphthalenes, has been found to alter the reactivity of nitroanisoles... 

The photolysis of 4-nitroanisole in degassed acetonitrile or benzene yields 4-nitro-soanisole and 2-nitro-4-methoxyphenol is). Triphenylene (Et = 67 kcal mole i 4-nitroanisole t=59.5 kcal mole i has been used to sensitize the reaction, which is suppressed completely by nitric oxide. A rationale for the formation of the products observed is given below. 

The catalytic reduction of nitro groups is usually achieved using heterogeneous catalysts, although the iridium complex 28 has been shown to be effective for the reduction of p-nitroanisole 29 to the corresponding aniline 30 using isopropanol as the hydrogen donor (Scheme 8) [30]. In the reduction of some nitroarenes, azo compounds (Ar-N=N-Ar) could be formed as by-products or as the major product by variation of the reaction conditions. 

The nitrophenyl radical can react with the iodide ion and solvent, methanol, as well. Transference of hydrogen radical from methyl alcohol to nitrophenyl radical gives rise to nitrobenzene and formaldehyde (CHjOH —> CH2O). Though carefully sought among the products of the reaction, 3-iodonitro-benzene and 4-nitroanisole were lacking. This completely rejects another possible mechanism of the reaction, cine-substitution, which involves the formation of dehydrobenzene as described earlier. 

It was recognized at an early stage that the fact that m-nitrophenyl phosphate and m-nitroanisole give a much cleaner and more efficient reaction than their ortho- and para-isomers, in itself, is not sufficient to conclude that the rate of reactions of the excited meta-compound with the nucleophile is higher. Such a more efficient photoreaction might also be explained by a longer lifetime of the excited metacompound, by a different intersystem crossing efficiency, etc. 

These optimistic views received a first blow by the discovery of another category of nucleophilic aromatic photosubstitutions occurring in liquid ammonia as a solvent and nucleophile. In this medium the nitroanisoles still show the pattern that had become familiar, i.e., photosubstitution of OCH3 by NH2 with preference for reaction at the position meta with respect to the nitro-group. However, nitrobenzene, dinitrobenzenes, and nitrohalogenobenzenes... 

In the range of leaving groups, fluorine has been recognized as a valuable substituent that has practically no heavy atom effect and that in many cases is smoothly replaced under the influence of irradiation (Brasem et al., 1972). With 2-fluoro-4-nitroanisole it even proved capable of efficient substitution by the weak nucleophile water, a reaction that has not been equalled by any other substituent. Curiously, the photosubstitution of fluorine by cyanide is generally less efficient than that by other nucleophiles. 

An early investigation concerned the photoreactions of p-nitroanisole. Letsinger and Steller (1969) elegantly demonstrated not only that its photosubstitution by hydroxide ion and by pyridine could be sensitized (by benzophenone), but also that the product distribution of the photohydrolysis (/ -nitrophenol/p-methoxyphenol 1 4) was the same whether it was the result of direct irradiation or of a sensitized reaction. 

The first systems with meta-activation deliberately investigated by sensitization (and quenching) experiments were m-nitroanisole in liquid ammonia (van Vliet et al., 1970) cmd l-methoxy-6-nitro-naphthalene in alkaline medium (Beyersbergen van Henegouwen and Havinga, 1970), In these two cases indications of a singlet reaction were found. 

With m-nitroanisole in liquid ammonia the benzophenone-sensitized reaction yields inter alia 2-methoxy-4-nitroaniline as a product and no m-nitroaniline, which is formed in very high yield upon direct irradiation in liquid ammonia as well as in NH3/CH3OH. In the latter instance l/4> varies linearly with 1/[NH3], suggesting that the reaction is either singlet or triplet but not of a mixed type. 

Already, with one of the first nucleophilic aromatic photosubstitutions encountered, curious behaviour was found when studying the rate of reaction as a function of pH. m-Nitrophenyl sulphate shows no increase in the quantum yield of photohydrolysis with increase of hydroxide ion concentration up to values as high as 0-1 M. This behaviour, also found with one other compound (5-chloro-3-nitroanisole), is in clear contradistinction to what is... 

Careful nitration of anisole (CH3OC6H5) with a new nitrating reagent gives a mixture of 4-nitroanisole and 2-nitroanisole. The section of the NMR spectrum below is from the aromatic region of the crude reaction mixture which is a mixture of the 4- and 2-nitroanisoles. Determine the relative amounts of the two products in the reaction mixture from the integrals in the spectrum. 

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