The quantitative electrophilic reactivity of annulenes. Part 2. Partial rate factors for hydrogen exchange of azulene, cycl[3,2,2]azine, indolizine, N-methylisoindole, indole, and pyrrolo[2,1-b]thiazole, and attempted exchange in trans-9,10-dimethyldihydropyrene: the dramatic effect of creating aromaticity in the transition state for electrophilic substitution, and the importance of valence bond theory

Abstract

We have determined the rates of acid-catalysed detritiation of the 1-positions of azulene and cycl[3,2,2]azine in Aristar acetic acid at 70 °C. From the known exchange rate ratio between this acid and trifluoroacetic acid at 70 °C (1.58 × 108), the partial rate factors for exchange under the latter (standard) conditions are 9.93 × 1013 and 4.34 × 1013, respectively, yielding corresponding σ+ values of –1.60 and –1.56. From the literature rates of deuteriation of indolizine (1- and 3- position), N-methylisoindole (1-position), indole (3-position), and 6-methylpyrrolo[2,1-b]thiazole (7- and 5-position), partial rate factors under standard conditions may be calculated as 1.95 × 1016, 9.93 × 1016, 6.62 × 1017, 5.52 × 1013, 1.19 × 1017, and 1.68 × 1018, respectively. The corresponding σ+ values are –1.86, –1.94, –2.04, –1.57, –1.95, and –2.08. N- Methylisoindole appears to be the most reactive aromatic compound known. The extreme reactivity of these compounds (indole apart) is attributed to creation of aromaticity in their respective transition states, and is reflected in very small methyl substituent effects as required by the reactivity–selectivity principle. Decomposition at higher acidities prevented determination of rate data for any other sites in azulene or cycl[3,2,2]azine but maximumσ+ values for the 2- and 5–8-sites in indolizine may be estimated from literature data to be –1.57 and –1.30, respectively. The reactivity of the 3-position of indole is less than that of the 2-position in pyrrole (σ2+–1.70) as in acetylation. In acetic acid at 50 °C trans-9,10-dimethyldihydropyrene underwent decomposition at a rate comparable to that of detritiation and no reliable rate data could be determined. Valence Bond Theory provides an easily visualized explanation of positional reactivities. It shows the origin of the reactivity of the most reactive site, and accounts for the relative reactivities of N-methylisoindole, indolizine, and cycl[3,2,2]azine, and the positional reactivities in each of the latter two molecules as well as in azulene and 6-methylpyrrolo[2,1-b]thiazole. It accounts for differences in methyl substituent effects in some of the title molecules, for the predominant 1-substitution in formylation of imidazo[1,2-a]pyridine (previously considered anomalous), for the exclusive 3-bromination of 2-phenyl-2H-indazole, and shows that nitration of thieno[3″,2″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]pyrimidine must take place at the 2- and not the 1-position recently reported. It also accounts for the 1-substitution in azupyrene, and the protonation of pyrrolo[1,2-b]pyridazine at C-1 in contrast to both theoretical (MO) predictions and the results for the isomeric azaindoles.