Acidities for half-reaction are reported for the second protonation of some substituted phenylhydrazines, diazaheterocycles, and arninopyridines. The acidity functions followed for these second protonations are discussed with reference to the so-called H+ acidity function.
Kinetic investigations show that whereas 2.4and 2.5-dialkylthiazoles undergo nitration as their protonated forms at all acidities studied, 2-thiazolones are nitrated via a free base mechanism a t least a t the lower acidities. The reactivities are discussed in terms of standard rates extrapolated to 25" and H, -6.6.CONSIDERABLE knowledge of the quantitative aspects of thiazole chemistry is already available from one of our laboratories 2 9 3 including correlations of reactivity by quantum r n e t h o d ~. ~ Hydrogen exchange under basic conditions involves nucleophilic attack on the 2-hydrogen a t ~m . ~~~ Preparative studies show 6-8 that whereas thiazole itself is nitrated only under forcing conditions to give a poor yield of 5-nitro-together with some 4-nitrot h i a ~o l e , ~ the more reactive 2-methylthiazole is nitrated more easily (although in only 12% yield) in sulphuric acid to the 5-nitro-and 4-nitro-products (3.3 : 1).
Hydroxy-and 3-methoxy-pyridine undergo nitration as their corresponding conjugate acids at the 2-position. 6-Hydroxy-2(1 H ) -pyridone together with its N-methyl derivative and 6-methoxy-analogues are nitrated as free bases, a t or near the encounter rate, in the 3-position.
NorwichPREVIOUS work from this laboratory has indicated that the nitration of 2(1H)-and 4(1H)-pyridones usually occurs on the free-base species, except that, in acidities greater than ca. H, -8, 4(3H)-pyridone is probably nitrated as the conjugate acid.2 We have now extended this work in two directions: (a) to 3-hydroxypyridine and (b) to the highly activated 6-hydroxy-B(lH)-pyridone.The orientation of the nitration of 3-hydroxypyridine and its alkoxy-analogues was originally a matter of controversy. The hydroxy-compound was reported as nitrating in the 6-or the 2-position; 4 later authors confirmed the 2-orientation by chemical means,5 and the 6-isomer was isolated as a by-product in 1% yields.6 3-Ethoxypyridine was also originally considered to be nitrated at the 6-position but later it was shown that the 2-nitro-compound is formed!*@ probably together with a trace of the 6-is0mer.~ 3-Methoxypyridine was stated to undergo mononitration in the 2-position,1° but no direct evidence for the structure of the product was presented.De Selms quotes n.m.r. data for 3-hydroxy-2-nitropyridine, but the chemical shifts of the 4-and 5-protons are identical in deuteriochloroform as solvent and consequently no 4,5-coupling was evident (in the paper quoted this coupling is incorrectly equated to zero) ; both Jd6 and J M were stated to be 2.8 Hz. The n.m.r. spectrum in N-methylpyrrolidine as solvent is now found to be well resolved. Analysis of the ABC system by the LAOCOON I1 programme (12 lines fitted to 12 observed transitions; r.m.s. error = 0.018) provided the chemical shifts (cJ I) and three coupling constants of 4.44, 8.34, and 1.37 Hz., which are consistent with ap-, py-, and ocy-couplings. This confirms the structure; the aportho-coupling for pyridines is usually lower than the py-coupling. The n.m.r. spectrum of the S-methoxyanalogue in trifluoroacetic acid was analysed less completely because the lines due to two of the protons are superimposed and poorly resolved. The chemical shifts
Methods for extrapolating rates for nitrations in aqueous sulphuric acid to different temperatures and acidities are discussed. A standard procedure to obtain k, values at 25" and Ho -6.6 is applied t o literature data for 131 nitration rates. Allowance is made where necessary for minority species concentrations.NITRATION is perhaps the most common of the electrophilic substitution reactions of aromatic rings. It is widely used preparatively, and has been extensively studied kinetically in this and in other lab~ratories.~-~ Comparison of nitration rates of different compounds is complicated by their variation with solvent and acidity. Because of the considerable acidity dependence, kinetic rates can be obtained for compounds of widely differing reactivity in aqueous sulphuric acid of appropriate concentration. In this respect nitration kinetics resemble those for acid-catalysed hydrogen exchange : in previous work, we have given reasons for choosing pH = 0 and t The Kinetics and Mechanism of the Electrophilic Substitution
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.