Pyrroles undergo

Pyrrole undergoes electrophilic substitution much in the same way as benzene. 

A small number of pyrroles undergo addition of acetylenedi-carboxylic acid across the 2,5-positions yielding adducts similar to those obtained from cyclopentadiene. In the case of 1-benzylpyrrole and the acid, some (13) is formed, probably through the intermediary of a species such as (8) a strong case has been made for the supposition that the Diels-Alder reaction occurs in two distinct stages,... 

Although pyrrole appears to be both an amine and a conjugated diene, its chemical properties are not consistent with either of these structural features. Unlike most other amines, pyrrole is not basic—the pKa of the pyrrolin-ium ion is 0.4 unlike most other conjugated dienes, pyrrole undergoes electrophilic substitution reactions rather than additions. The reason for both these properties, as noted previously in Section 15.5, is that pyrrole has six 77 electrons and is aromatic. Each of the four carbons contributes one... 

It has been known that aromatic heterocycles such as furan, thiophene, and pyrrole undergo Diels-Alder reactions despite their aromaticity and hence expected inertness. Furans have been especially used efficiently as dienes due to their electron-rich properties. Thiophenes and pyrroles are less reactive as dienes than furans. But pyrroles with A-elecIron-withdrawing substituents are efficient dienes. There exists a limited number of examples of five-membered, aromatic heterocycles acting as dienophiles in Diels-Alder reactions. Some nitro heteroaromatics serve as dienophiles in the Diels-Alder reactions. Heating a mixture of l-(phenylsulfonyl)-3-nitropyrrole and isoprene at 175 °C followed by oxidation results in the formation of indoles (see Eq. 8.22).35a A-Tosyl-3-nitroindole undergoes high-yielding Diels-Alder reactions with... 

The kinetics and mechanism of pyrrole pyrolysis were investigated by ab initio quantum-chemical calculations. It was revealed that pyrrole undergoes tautomerization to form 2H- and 37/-pyrroles prior to any thermal decomposition. It has been shown that the major product, HCN, arises from a hydrogen migration in pyrrole to form a cyclic carbene with the NH bond intact. Ring scission of the carbene leads to an allenic imine of HCN and propyne which is the lowest energy pathway. The 277-pyrrole... 

Numerous N-substituted pyrroles undergo at elevated temperatures a conversion to C-substituted compounds. However, an analogous reaction course is not feasible since N-methylpyrrole also reacts with CF3SCI to give C-substituted derivatives ... 

The pyrolysis of pyrrole produces a variety of products hydrogen cyanide, propyne, allene, acetylene, c/ -crotonitrile, and allyl cyanide, among them. Lifshitz et al. hypothesized that pyrrole undergoes 1,2-bond (N—C) cleavage, then an internal H-atom transfer, to yield a radical intermediate that can isomerize to either c/ -crotonitrile or allyl cyanide, or dissociate to HCN and propyne.Bacskay et al. completed quantum chemical comparisons of the isoelectronic pyrrolyl and cyclopentadienyl radicals they hypothesized that pyrrolyl radical is formed via C—H bond scission in the intermediate pyrrolenine (2/f-pyrrole) rather than directly via N—H bond cleavage (Fig. 14). Mackie et al. explained a similar finding, postulating that it was the formation of pyrrolenine that dictated the rate at which pyrrole pyrolysis occurred. 

Indole, unlike pyrrole, undergoes substitution at C-3 rather than C-2. even when the 3-position of the substrate is occupied. In this case the substituents at C-3 in the reaction intermediate can migrate to C-2. The ease with which they do so depends upon their ability to sustain a partial negative charge. 

Bromo-l-(triisopropylsilyl)pyrrole undergoes initial reaction with butyllithium followed by reaction with A -fluorobis(phenylsulfonyl)amine (la) to give 3-fluoro-l-(triisopropylsilyl)pyr-role (8).144... 

A small number of pyrroles undergo addition of acetylenedicarboxylic acid across the 2,5 positions, yielding adducts similar to those derived from cyclopentadiene. For instance, 1-benzylpyrrole (1) gives some 4,69,70 but it is not known if the product is formed via a species such as 2 or by a concerted addition. 

Later, Linda and Marino84, 90, 180 were able to compare the relative reactivities of all four fundamental systems (furan, thiophene, selenophene, and pyrrole) toward bromination by molecular bromine in acetic acid. Unfortunately, the comparison could not be made on the unsubstituted rings for the following reasons first, the rates of substitution for furan and pyrrole were too high to be followed by standard kinetic techniques second, furan and pyrrole undergo ring fission and/or polymerization under the influence of the hydrobromic acid formed in the reaction finally, furan tends to give addition as well as substitution products in the reaction with bromine.1818. 

Thiophene, alkyl-substituted furans, and especially pyrrole, undergo Mannich reactions. 

Pyrrole undergoes electrophilic aromatic substitution more readily than benzene, and mild reagents and conditions are sufficient. These reactions normally occur at the 2-position rather than the 3-position, as shown in the following example. 

The derived quaternary salts (e.g., 246) give anhydro compounds (e.g., 247) on treatment with alkali. -Pentamethyl-pyrrolenine (2,3,3,4,5-pen tain ethyl-3//-pyrrole) undergoes quantitative conversion to the -isomer (2,2,3,4,5-penta-methyl-2//-pyrrole) either on heating (>200C) or in 1 M HC1 at room temperature. 3//-Indoles also undergo an acid-catalyzed rearrangement (e.g., 248 249), known as the Plancher rearrangement. 

Pyrroles are unstable in the presence of oxygen. In particular alkyl-pyrroles undergo rapid autoxidation on exposure to air, even in absence of light. Because of its affinity toward oxygen, pyrrole was proposed as an antioxidant by Ziegler and Ganicke.1... 

It was demonstrated that indole and substituted pyrroles undergo electrophilic substitution with al-kylmercaptochloromethyleneiminium chlorides giving heterocyclic iminium chlorides (122 equation Probably this reaction type is of more general applicability. 

The increase in yield of 15 a from ca 20% to over 40% in the presence of lithium perchlorate 77) has led to the suggestion of a template effect. However, recent experiments78) indicate that the higher yields correlate not with the metal ion but with the acidity of the reaction medium. In similar fashion, thiophene and pyrrole undergo acid-catalyzed condensations with acetone to yield 16 m> and 17 81). Benz-aldehyde also condenses with pyrrole 82but the initially formed compound loses six hydrogens to form the planar tetraphenylporphin 18. 

Michael reaction Catalyzed by HfCU, indoles and pyrroles undergo Michael reactions with enones at C-3, and C-2/C-5, respectively. The reaction of pyrazole and imidazole takes place at an N-atom. 

Trimethyl orthoformate is used in excess relative to 5-phenyldipyrromethane to promote reaction between these two species, because dipyrromethanes alone, in common with pyrroles, undergo self-condensation under acidic conditions to yield polypyrroles. 

Pyrroles undergo many reactions, the most important of which are described below. 

Pyrroles undergo hydroxymethylation in the 2-position with carbonyl compounds in the presence of acid. The products react further to give dipyrrolylmethanes (see p 484) ... 

---