Basicity of pyrrole

The low basicity of pyrrole is a consequence of the loss of aromaticity which accompanies protonation on the ring nitrogen or on carbon 2 or carbon 3 of the ring. The thermodynamically most stable cation is the 2H-pyrrolium ion, and the p/sTa for protonation at C-2 has been recorded as -3.8 the corresponding pK values for protonation at C-3 and at nitrogen are -5.9 and ca. -10 (Scheme 7). 

A comparison of the relative basicities of pyrrole, furan and thiophene may be made by comparing the pK values of their 2,5-di-t-butyl derivatives, which were found to be -1.01, —10.01 and —10.16, respectively. In each case protonation was shown by NMR to occur at position 2. The base-strengthening effect of alkyl substitution is clearly apparent by comparison of pyrrole and its alkyl derivatives, e.g. A-methylpyrrole has a pKa. for a-protonation of -2.9 and 2,3,4,5-tetramethylpyrrole has a pK of 4-3.7. In general, protonation of a-alkylpyrroles occurs at the a -position whereas /3-alkylpyrroles are protonated at the adjacent a-position. As expected, electron-withdrawing groups are base-weakening thus A-phenylpyrrole is reported to have a p/sTa of -5.8. The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

All this leads to the conclusion that the relative stabilities of the N- and C-protonated forms of enamines are not very different and that relatively minor structural differences or differences of medium favour one form over the other. 2-Alkyl substituents especially favour C-protonation (Hinman, 1968). They certainly greatly enhance the basicity of pyrroles which are C-protonated (see page 358). 

This is reflected in the basicity of pyrrole. Pyrrole is a particularly weak base, with pA a of the conjugate acid —3.8. First, we should realize that protonation of pyrrole will not occin on nitrogen nitrogen has... 

Comparison of the intrinsic acidities and basicities of pyrrole (I), imidazole (4), and pyrazole (6), together with complementary information coming from the azine held, illustrate the main effects that control the acidity and the basicity of unsubstituted azoles (86JA3237). Particularly important are the role of electrostatic interactions between adjacent charged nitrogens (NH) and between adjacent lone pairs (N), as well as the aza electronegative effects. 

An alternative approach to the experimental estimation of REs utilizes equilibrium (protonation) data rather than thermochemical data, the idea being that comparisons of the basicities of pyrrole and its benzo fused analogues with those of non-aromatic systems which form cations of 7r-electron structure similar to the aromatic compounds should furnish a measure of the loss of RE accompanying protonation of the aromatic system (76T1767, 72CI(L)335). Thus, for the a-protonation of N-methylpyrrole, the model non-aromatic system was chosen as (20). Combination of pKa values for the protonation of the aromatic and non-aromatic molecules, taking into account the intrinsic resonance stabilization of the... 

Resonance effects also influence the basicity of pyrrole. Pyrrole is a very weak base, with a pKb °f about 15. As we saw in Chapter 15, pyrrole is aromatic because the nonbonding electrons on nitrogen are located in a p orbital, where they contribute to the aromatic sextet. When the pyrrole nitrogen is protonated, pyrrole loses its aromatic stabilization. Therefore, protonation on nitrogen is unfavorable, and pyrrole is a very weak base. 

The pyrrole molecule possesses the NH group typical of secondary amines. The basicity of pyrrole, pX a = -3.8 for the conjugated acid is, however, much less than that of dimethylamine (pX = 10.87). This large difference is due to the incorporation of the nonbonding electron pair of the N-atom into the cyclic conjugated system of the pyrrole molecule. The protonation, moreover, does not occur on the N-atom, but to the extent of 80% on C-2 and of 20% on C-3. 

In solution, reversible proton addition occurs at all positions, being by far the fastest at the nitrogen, and about twice as fast at C-2 as at C-3. In the gas phase, mild acids like C4H9 and NH4 protonate pyrrole only on carbon and with a larger proton affinity at C-2 than at C-3. Thermodynamically the stablest cation, the 2H-pyrrolium ion, is that formed by protonation at C-2 and observed values for pyrroles are for these 2-protonated species. The weak A -basicity of pyrroles is the consequence of the absence of mesomeric delocalisation of charge in the H-pyrrolium cation. 

The somewhat similar, but nonaromatic, compounds, 1,2- and 1,4-dihydropyridine, are both much stronger bases, which undergo protonation as also shown in Scheme 10. The differences between the basicities of pyrrole and the model compounds can be used to calculate the aromatic stabilization energy of pyrrole, according to the method of Scheme 11... 

Section 21.7) in connection with a discussion of the relative basicity of pyrrole versus pyridine. Pyrrole is a constituent of coal tar and it is found in bone oil. It is obtained by heating alb unin or by the pyrolysis (heating to elevated temperatures) of gelatin. 

The NH group lends to pyrrole the functionality of a base as weU as that of an acid [99]. The basicity of pyrrole is very weak (pfQ, = —3.8 for the conjugated acid) compared to cyclic aliphatic amines (e.g., pyrrolidine, pfQ, = +11.3). This large difference is due to incorporation of the nonbonding N-electron pair into the 6it-electron system of pyrrole. In principle, reversible proton addition to pyrrole may occur at all positions, but leads to cations of different thermodynamic stability ... 

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