James W. Barnett

Electrophilic aromatic substitution. Part 16. The nitration of anisole, o-methylanisole, and p-methylanisole in aqueous sulphuric acid

In the quantitative mononitration of anisole in 54–82% sulphuric acid at 25° the o : p ratio varies from 1.8 to 0.7. It is suggested that the rate-limiting step is the formation of an encounter pair between the nitronium ion and an anisole molecule which is hydrogen-bonded to a hydronium ion. The change in the o : p ratio may be due to competition between direct formation of Wheland intermediates from the hydrogen-bonded encounter pair, and loss of the hydronium ion to give a nitroniurn ion–anisole encounter pair, with subsequent formation of Wheland intermediates. With o- and p-methylanisole the products, and changes in product ratios with acidity are interpreted by considering the fates of the ipso-Wheland intermediates formed at C–Me. 4-Methyl-2-nitrophenol is an important product of the nitration of p-methylanisole, and results from ipso-attack by nitronium at C–Me, followed by attack of water and loss of methoxy.

Studies in azole chemistry. Part 2. Nitration of 1,4,5-trimethylimidazole 3-oxide and 1-methylpyrazole 2-oxide, and some reactions of the products

In sulphuric acid, 1,4,5-trimethylimidazole 3-oxide and 1-methylpyrazole 2-oxide are nitrated as the free bases at C-2 and C-5, respectively. At high acidities the pyrazole gives 1-methyl-3,5-dinitropyrazole 1-oxide. With phosphorus trichloride the pyrazole oxides were deoxygenated, and with phosphoryl chloride, 1-methylpyrazole 2-oxide gave 5-chloro-1-methylpyrazole. 1-Methyl-5-nitropyrazole 2-oxide with acetyl chloride gave 5-chloro-1-methyl-4-nitropyrazole.

Acid hydrolysis of phenylurea, 4-fluorophenylurea, and 3-methylphenylurea

The rate constants of hydrolysis of phenylurea and 4-fluorophenylurea have been measured over the acid range 2·5–60·1% and 2·5–70·0% w/w H2SO4 respectively at five temperatures in the range 70·0–110·4 °C; those of 3-methylphenylurea have been measured over the acid range 2·5–60·1% w/w H2SO4 at 100·1 °C. Attempts to correlate the rate data with Bunnett w and w*, Bunnett–Olsen linear free energy relationship, and Zucker–Hammett criteria of mechanism have proved unsatisfactory. Application of a two-term equation and high activation parameters provide evidence that these phenylureas hydrolyse by an A-1 mechanism. Rate constants of hydrolysis of the sulphonated derivatives of phenylurea and 3-methylphenylurea are reported over the range 70·0–95·0% w/w H2SO4 at 100·1 °C.

Electrophilic aromatic substitution. Part XIII. Kinetics, isomer yields, and the consequences of ipso-attack in the nitration of toluene and polymethylbenzenes in aqueous sulphuric acid, and their significance for the mechanism of aromatic nitration

Toluene, o-xylene, m-xylene, 1,2,4-, and 1,2,3-trimethylbenzene give yields of mononitro-isomers which vary with the percentage of sulphuric acid in a way which depends on (a) the medium dependence of the relative reactivities of the various substituted and unsubstituted positions in the molecule and (b) the partitioning of Wheland intermediates formed at substituted (ipso) positions between rearrangement and nucleophilic capture. Nitration of all the polymethylbenzenes studied occurs at closely similar rates, the encounter rate between the aromatic compound and the nitronium ion, yet positional selectivity does not disappear under these conditions, showing the necessity of including in the kinetic scheme an intermediate preceding Wheland intermediate formation.

Naphthalene tetrachlorides and related compounds. Part IV. Photochemical chlorination of 1-chloronaphthalene

The photochemical chlorination of 1-chloronaphthalene gives a mixture of dichlorides, which on further chlorination give several new 1-chloronaphthalene tetrachlorides. The structures of the latter have been elucidated by using 1H n.m.r. spectroscopy and by isomerisation with aluminium trichloride as the 1,1,r-2,t-3,c-4- and 1,1,r-2,-c-3,t-4-pentachlorotetralins; and the r-1,t-2,t-3,c-4,5-; r-1,t-2,c-3,c-4,5-; and r-1,t-2,c-3,t-4,5-pentachlorotetralins. Evidence is presented to suggest that the last compound, because of internal non-bonding strain, exists predominantly in an unusual ‘half-boat’ conformation. The results are compared with those obtained by heterocyclic chlorination, from which another isomer, r-1,c-2,t-3,t-4,5-pentachlorotetralin, is a minor product. The course and products of alkaline dehydrochlorination have been used to support some of the assignments of structure. The heterolytic chlorination of 1,2-dichloronaphthalene has been examined also; the major product is r-1,t-2,c-3,t-4,5,6-hexachlorotetralin, which also exists in a ‘half-boat’ conformation.

Electrophilic aromatic substitution. Part 22. The nitration of some reactive aromatics in methanesulphonic acid, and the question of positional selectivity in encounter rate nitrations of substituted naphthalenes and 1,2-diphenylethanes

Nitrations in aqueous methanesulphonic acid are shown by the steep acidity dependence of the rate constants, the identification of a kinetic form zeroth-order in the concentration of the aromatic, and the existence of a limiting rate constant identified as the encounter rate constant, most probably to involve the nitronium ion.2-Methyl-, 2-methoxy-, and 2-methoxy-6-methyl-naphthalene react at the encounter rate. In the last compound the ratio of reactivities of C-1 and C-5 is 6.5 : 1 (smaller than that reported by other workers because of the suppression of nitrosation). Comparison amongst the three compounds suggests that in the nitration of 2-methoxy-6-methylnaphthalene the rate-controlling step is the irreversible formation of an encounter pair which is sufficiently long-lived and mobile to allow selection between positions of differing reactivities in the following product-controlling step of σ-complex formation. The case resembles that of the nitration of 1,2,4-trimethylbenzene reported earlier.Mesitylene, 3,5-dimethoxytoluene, and 1-(3,5-dimethoxyphenyl)-2-(3,5-dimethylphenyl)ethane react at the encounter rate (with the two methoxylated compounds account has to be taken of the effect upon their performances of ring protonation). In the unprotonated diarylethane the ratio of reactivities (1.8) of the methoxylated and and the methylated rings is very close to the ratio of reactivities (1.4–1.5) of the mononuclear compounds. The small selectivity between the two rings in the unprotonated diarylethane shows that the compound is nitrated by the formation of two non-interconverting encounter pairs, formation of which is both rate- and (so far as intranuclear behaviour is concerned) product-determining.Although 1-(3,5-dichlorophenyl)-2-(3,5-dimethylphenyl)ethane also reacts at the encounter rate (being nitrated only in the methylated ring), comparison with the previously mentioned diarylethane shows that a statistical factor (not exactly 2 because of the slightly differing efficiencies of the two rings in the dimethoxylated compound in forming productive ion pairs) has to be taken into account in comparing the two compounds.The behaviour of these various compounds in no way requires the assumption of bonding forces between electrophile and aromatic in the encounter pair, but the performance of 1-(3,5-dimethoxyphenyl)-2-(3,5-dimethylphenyl)-ethane could be very easily understood if the two encounter pairs were π-complexes, or involved some other kind of stabilisation.

The acid-catalysed hydrolysis of acetanilide

The rate of hydrolysis of acetanilide has been measured over a wide range of acidities in HCl, H2SO4, and HClO4, In H2SO4 80%(w/w) acetanilide undergoes sulphonation in preference to hydrolysis. Application of the Bunnett criteria of mechanism fit the data in HCl and H2SO4 well, whereas the data in HClO4 are fitted by an empirical two-term rate equation. A revised value of the constant –pKAH+ has been determined in each acid.

Spectrophotometric determination of basicity constants. Benzamides and phenylureas

The basicity constants KBH+ of six 4-chlorobenzamides, four 4-methoxybenzamides, ten N-t-butylbenzamides, 3-bromo N-methylbenzamide, phenylurea, and seven substituted phenylureas have been evaluated in sulphuric acid at 25 °C. The protonation equilibria follow the HA acidity function.

Evidence for differences in interpretation of mechanism of acid-catalysed hydrolysis of aliphatic and aromatic amides

The rate constants of acid hydrolysis of aliphatic, but not aromatic, amides give linear Bunnett w and Bunnett-Olsen l.f.e.r. plots; aromatic amides follow an empirical two-term rate law.

Protonation equilibria of ureas

The basicity constants pKBH+ of phenylurea and five substituted phenylureas have been measured and their protonation equilibria have been found to follow the HA acidity function.