Pyrrole anions

Pyrazoles and imidazoles exist partly as anions (e.g. 108 and 109) in neutral and basic solution. Under these conditions they react with electrophilic reagents almost as readily as phenol, undergoing diazo coupling, nitrosation and Mannich reactions (note the increased reactivity of pyrrole anions over the neutral pyrrole species). 

The replacement of two CH groups in benzene by a neutral NR, O or S introduces into the new ring an electron-donating heteroatom. This electron-donor character is accentuated in the pyrrole anion where N is introduced. Thus the five-membered rings with one heteroatom are electron rich (rr-excessive), and the chemistry of pyrrole, furan and thiophene is dominated by this effect and is again considered together as a whole in Part 3. 

Although pyrrole is a much weaker base than most other amines, it is a much stronger acid (p/C, 15 tor the pyrrole versus 35 for diethylamine). The N—H proton is readily abstracted by base to yield the pyrrole anion,... 

Ab initio and density functional calculations indicate that the first step of the abnormal Reimer-Tiemann reaction involves barrierless formation of an intermediate by nucleophilic attack on CCl2 of the /3-carbon of pyrrole anion. " This is followed by a single, concerted step to give the product, 3-chloropyridine. 

A-alkylation, A-acylation, and A-sulfonation. Note particularly that whereas pyrrole reacts with electrophiles at carbon, usually C-2, the pyrrole anion reacts at the nitrogen atom. 

That in the case of pyrrole the formation of the pyrrole anion and the nature of its reactions is of importance, and for furan the reason why cycloaddition reactions occur readily... 

Although pyrrole is a very weak acid (pA 17.7), it can be deprotonat-ed by a strong base, such as butyllithium. Its acidity is much greater than a typical aliphatic secondary amine, say pyrrolidine [tetrahydropyrrole, (pAT ca. 27)]. Unlike pyrrole itself, resonance within the pyrrole anion does not involve charge separation (Scheme 6.8). 

Although pyrrole is much less acidic than phenol (pAT ca. 10), many reactions of the pyrrole anion are reminiscent of those of the phenolate anion. Examples include A-alkylation, -acylation and -sulfonylation (Scheme 6.9). For the phenolate anion these reactions occur at oxygen. 

The pyrrole anion also undergoes the Kolbe carboxylation reaction The Kolbe reaction is best... 

Salts containing the pyrrole anion can easily be prepared by this way. The parr of nonbonding electrons on N in pyrrole is much less available for protonation than the parr on ammonia. Thus, pyrrole is much less basic than NH3 (pA a = 36), i.e. a much stronger acid than NH3. 

Aromatic species include the neutral molecules pyrrole, furan and thiophene (1 Z = NH, O, S) and the pyrrole anion (2). The radicals derived from these rings are named pyrryl, furyl and thienyl. The 2-furylmethyl radical is called furfuryl. Compounds in which two pyrrole nuclei are joined by a CH2 group are called dipyrromethanes when the linkage is by a CH group, they are named dipyrromethenes . The 2- (3) and 3-pyrrolenines (4) are isomeric with the pyrroles, but are nonaromatic as the ring conjugation is broken by an. s/r -hybridized carbon atom. 

Compounds containing methylene groups activated by both a cationic ring and another electron-withdrawing group easily form stable anhydro-bases, e.g. (636) — (637), (638) — (639). Stabilization is also achieved by utilization of the aromatic character of the cyclopentadiene anion or the pyrrole anion compounds of type (640 Z = NR, O, S) and (643) readily lose protons to give the mesomeric anhydro-bases (as 641 <- 642) which are called pseudoazulenes. 

Electrophilic attack at ring heteroatoms is rare for the neutral compounds, although examples are known for thiophenes and selenophenes. However, pyrrole anions undergo easy reaction with electrophiles at both C and N atoms. 

Neutral pyrroles and indoles also are not susceptible to attack at the cyclic nitrogen. However, the pA d of carbazole and 9-methylcarbazole equal to — 6.0 and — 8.2, respectively, (in H2S04-Et0H, 4 1) refer to N-protonation (71JA5102). Pyrrole anions undergo easy reaction with various electrophiles. 

The methyl group in position 2 causes a considerable increase in the rate of vinylation of the 2-methyl-3-(2-pyrrolyl)indole (26, R1 = R3 = R4 = H, R2 = Me). This is due, in the author s opinion, to a distortion of coplanarity of the molecule causing the pyrrole moiety to become more accessible to acetylene attack. Also possible, however, is an enhanced nucleophilicity of the corresponding pyrrolate-anion, owing to the electron-donating effect of the methyl group. 

Addition of the pyrrole anion 104 to the methylthioethyne 103, which is assumed to be formed in small quantities from acetylene via the adduct 102... 

The best results were obtained at 130°C (3 hr) and with the oxime 121/KOH ratio 1 6 in DMSO. The total yield of pyrroles 122 and 123 attains 56%. Replacement of methyl by ethyl in the alkyl moiety of ketox-ime under comparable reaction conditions does not affect the total yield of pyrroles very much. However, on going from aryl methyl ketoximes (118) to aryl ethyl ketoximes (121), a downward trend in the yields for the corresponding N-vinylpyrroles (123) becomes evident. This is likely to be due to a decrease in polarizability and, consequently, to nucleophilicity of the 1-pyrrole anion as a result of distortion of the benzene and pyrrole ring coplanarity. 

While interesting neutral alternatives to the unsaturated expanded porphyrin derivatives, calix[n] pyrroles (n = 4, 5, 6, 8) are relatively limited in their scope for anion binding because of the constraints of the cavity size. Nevertheless pyrroles linked by an sp3 hybridised carbon atom are of considerable interest because of their resemblance to the anti-cancer agents the prodigiosins (Section 4.2.4), moreover pyrrole anion-receptor chemistry is synthetically versatile and hence a range of acyclic pyrroles and hybrid amidopyrroles such as 4.50-4.52 have been developed, particularly by the groups of... 

Crystals of both compounds were obtained by slow evaporation of acetonitrile solutions in the presence of excess tetrabutylammonium fluoride. It was determined that both compounds crystallized as the tetrabutylammonium salts of the doubly deprotonated pyrrole anions Figure 12). Each individual dianion essentially possesses a planar conformation and forms the interlocking arrangement previously seen Figure 10). 

Gale, P. A., Navakhun, K., Camiolo, S., Light, M. E., Hursthouse, M. B. (2002) Anion-anion assembly A new class of anionic supramolecular polymer containing 3,4-dichloro-2,5-diamido-substituted pyrrole anion dimers, J. Am. Chem. Soc. 124, 11228-11229. 

Undoubtedly, the future will bring further progress in this area and more developments on the synthesis of calix[4]pyrrole anion receptors. However, the design of anion receptors is still a challenging task. 

Pyrrole anion is unreactive in liquid ammonia under irradiation with PhBr or 1-chloro-naphthalene. However, the reactions of aryl chlorides (p-chlorobenzonitrile, 3- and 4-chloropyridines and 4-chlorodiphenyl sulphone) with 2,5-dimethylpyrrole anion under electrochemical inducement in the presence of a redox mediator gave the C3-substituted product in moderate yields (35-40%) (equation 120)225. The rate constant of the coupling reaction between this nucleophile and aryl radicals is about 5-8 x 109 M"1 s 1 determined by electrochemical methods225. 

The electrochemically induced S l reaction of aryl chlorides with redox mediators and pyrrole anion gave mainly 2-aryl pyrroles (52-67%) and, in a lower amount, 3-aryl pyrroles... 

In the reaction of /7-chlorobenzonitrile and 4-chloropyridine with the indolyl anion under the same experimental conditions as with pyrrole anion, only the substitution product in position 3 was formed in 60% yield (equation 122)226. 

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