Isoindoles protonation

Isoindoles protonate to generate only one cation this electrophilic addition of protons sets the pattern for substitution in these systems, but there are relatively few clear cut examples, no doubt partly because of the instability of less substituted isoindoles, isobenzofurans and benzo[c]thiophenes. Detritiation studies showed the intrinsic reactivity of 2-methylisoindole in this electrophilic substitution to be 10" greater than that of 1-methyhndole. ... 

Although it has not been possible to study the protonation of isoindole itself, it is clear that isoindoles are more basic than indoles or pyrroles. For example, 2,5-dimethyl-1,3-diphenylisoindole (40) has a p/sTa of 4-2.05 protonation of isoindoles occurs at positions 1 or 3. The pK for protonation of indolizine (10) at position 3 is 4-3.94 and that for carbazole (41) for protonation on nitrogen is estimated at -6.0. 

It is of interest to compare the stability of the protonated forms of benzo[u], benzo[Z>] and benzo[c] fused pyrroles, i.e. the cations derived from indolizines, indoles and isoindoles. Indolizine gives a stable pyridinium ion and does not polymerize in the presence of acid. 

Isoindole, 2,5-dimethyl-1,3-diphenyl-protonation, 4, 47 Isoindole, 1,3-diphenyl-mass spectrometry, 4, 187... 

Isoindole has been isolated only in the C-alkyl form [173] (Bender and Bonnett, 1966). Nmr spectra show that its protonation... 

Predictably, isoindole is a stronger base than pyrrole, the conjugate acid of which has a pKa of -3.8 on the H0 scale (-4.4 on the Hr scale). From the few measurements that are available, isoindoles having phenyl groups at the 1,3-positions are protonated at the... 

The other type of carbamoyllithiums IIIc can also be prepared by reaction of CO with (V-lithioketimines, resulting from the addition of rert-butyllithium to aryl cyanides 10477,102. These intermediates 105 underwent selective cyclization to give 177-isoindole derivatives 10677 and six- (107)102 or seven-membered (108)102 cyclic products (Scheme 27). Compounds 107 result either by insertion of the carbene structure into the benzylic carbon-hydrogen bond, as in the case of carbamoyllithiums96, or by intramolecular protonation. 

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