A-Methylpyrrole

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. 

Directive effects on lithiation have also been studied. The regiospecific /3-metallation of A-methylpyrrole derivatives and 2-substituted furans has been effected by employing the directive effect of the oxazolino group (82JCs(Pl)1343). 2-Substituted furans and thiophenes are metallated in the 5-position. The formation of 2-lithio-3-bromofuran on treatment of... 

The benzyne adducts prepared from A -methylpyrrole (and A -methylisoindole) are deaminated conveniently by dichlorocarbene generated under phase-transfer conditions (81JOC1025 to give a convenient route to substituted naphthalenes (134) (and anthracenes) (Scheme 49). 

A -Methylpyrrole oxidatively adds to [Ru(C=C=C=CH2)(PPli3)2(Cp)][PF6] via its C2 center, the product being the allenylidene species 38 [98JCS(D)467]. Alkyne mesomeric form 39 was postulated to make a significant contribution, which explains well the nature of the deprotonated product 40, obtained from 38 and n-butyllithium. 

A -Methylpyrrole also polymerizes readily. A crystalline dimer or trimer has not, however, yet been isolated. 

In recent years further concepts have been developed for the construction of polymer-based diodes, requiring either two conjugated polymers (PA and poly(A-methyl-pyrrole) 2 > or poly(A-methylpyrrole in a p-type silicon wafer solid-state field-effect transistor By modifying the transistor switching, these electronic devices can also be employed as pH-sensitive chemical sensors or as hydrogen or oxygen sensors 221) in aqueous solutions. Recently a PPy alcohol sensor has also been reported 222). 

Even the simplest A -substituted pyrrole, A -methylpyrrole, electropolymerizes much slower than pyrrole itself Furthermore, the conductivity of polymers... 

A new acidity scale has been developed based on calorimetric measurement of A-methylimidazole and A-methylpyrrole in bulk solvents. A revised version of this method was shown to give better results in some cases. Another scale of solvent acidities was developed based on the hydrogen-bond donor acidities in aqueous DMSO. ... 

When the same [NiI (NHC)2] complexes are employed as alkene dimerisation catalysts in ionic liquid (IL) solvent [l-butyl-3-methylimidazolium chloride, AICI3, A-methylpyrrole (0.45 0.55 0.1)] rather than toluene, the catalysts were found to be highly active, with no evidence of decomposition. Furthermore, product distributions for each of the catalyst systems studied was surprisingly similar, indicating a common active species may have been formed in each case. It was proposed that reductive elimination of the NHC-Ni did indeed occur, as outlined in Scheme 13.8, however, the IL solvent oxidatively adds to the Ni(0) thus formed to yield a new Ni-NHC complex, 15, stabilised by the IL solvent, and able to effectively catalyse the dimerisation process (Scheme 13.9) [25-27],... 

Following the discovery of the unique electronic properties of polypyrrole, numerous polymers of pyrrole have been crafted. A copolymer of pyrrole and pyrrole-3-carboxylic acid is used in a glucose biosensor, and a copolymer of pyrrole and A-methylpyrrole operates as a redox switching device. Self-doping, low-band gap, and photorefractive pyrrole polymers have been synthesized, and some examples are illustrated [1,5]. 

In most cases, the oxidative addition process consumes stoichiometric amount of Pd(OAc>2. One of the earliest examples of the use of palladium in pyrrole chemistry was the Pd(0Ac)2 induced oxidative coupling of A-methylpyrrole with styrene to afford a mixture of olefins 18 and 19 in low yield based on palladium acetate [28]. 

As will be seen in this chapter and in the rest of the book, the Heck reaction and its numerous variations represent a fantastically powerful set of tools available to the heterocyclic chemist. Although most Heck chemistry that involves pyrroles is intramolecular or entails synthesis of the pyrrole ring, a few intermolecular Heck reactions of pyrroles are known. Simple pyrroles (pyrrole, A-methylpyrrole, A-(phenylsulfonyl)pyrrole) react with 2-chloro-3,6-dialkylpyrazines under Heck conditions to give mixtures of C-2 and C-3 pyrrole-substituted pyrazines in low... 

Figure 3.6 A-Methylpyrrole DCL building blocks (Balasuhramanian and coworkers).

A different mode of cycloaddition occurs with 7-azabicyclo[2.2.1]-heptadiene derivatives, in which the nucleophilicity of the nitrogen atom determines the point of attachment of the electrophilic dienophile. The addition depicted in 87, which may occur in two steps via a zwitterionic intermediate rather than by a concerted mechanism, accounts for the structures (88) of 1 2 adducts obtained with A-methyl- or A-benzyl-pyrrole and dimethyl acetylenedicarboxylate. At a higher temperature the reaction with A-methylpyrrole also afforded the indole tetraester... 

Partial and total reduction of A -methylpyrrole was achieved with zinc [433], and of a pyrrole derivative to a dihydropyrrole derivative with phos-phonium iodide [287] (p. 34, 35). The pyrrole ring is not reduced by sodium. 

A -methylpyrrole. It was assumed that pyrolysis occurred at the inlet temperature and that ficine and isoficine consisted of chrysin substituted with M-methylpyr-role at positions 8 and 6, respectively. The presence of chrysin as part of the molecule was confirmed by its formation from 4 by alkaline hydrolysis. 

Furans react readily with benzynes, e.g. 2-acetoxyfuran yields (185). A-Methylpyrrole also reacts normally across the 2,5-positions, but pyrrole itself yields 2-phenylpyrrole,... 

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of Af-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive to hydroxide addition at the carbonyl carbon than A-methylpyrrole-2-carbaldehyde (76JOC1952). Pyrrole-2-aldehydes fail to undergo Cannizzaro and benzoin reactions, which is attributed to mesomerism involving the ring nitrogen (see 366). They yield 2-hydroxymethylpyrroles (by NaBH4 reduction) and 2-methylpyrroles (Wolff-Kishner reduction). 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. 

Bailey described the first application of the Stille coupling to pyrroles, and one of the earliest examples of any such reaction involving heterocycles [66]. Lithiation of A/-methylpyrrole and quenching with trimethylstannyl chloride gives 2-(trimethylstannyl)pyrrole (76), and palladium-catalyzed coupling with iodobenzene afforcts l-methyl-2-phenylpyrrole (46) in good yield. 

Several studies75,78,85 including the use of conductometric titration18,76,77 showed that for pyridine and A-methylpyrrole in CH2C12 complex formation occurs, but for the weaker... 

Ar = benzene, Cl-benzene, diMeO-benzene, naphthalene, indole, A/-methylpyrrol, thiophene... 

The first vinylpyrroles studied as diene systems in Diels-Alder reactions were the /3-nitrovinyl-A/-methylpyrroles because they are stable and readily available from condensation of the corresponding carboxaldehydes with nitromethane. The /3-nitro vinylpyrrole 117 added to MA and yielded the corresponding N-methylindole-4,5-dicarboxylic anhydride 118. The process is believed to follow the normal Diels-Alder [4 + 2]-cycloaddition pathway, with subsequent loss of nitrous acid to give the fully aromatized adduct [73JCS(P 1)2450]. 

Doak and Corwin94 have studied the kinetics of the iodination of some trisubstituted derivatives of pyrrole and A-methylpyrrole. Both free iodine and hypoiodous acid are supposed to be the iodinating agents in this reaction. The similar reactivity exhibited by pyrrole and A-rn ethyl py rrole contradicts the hypothesis previously proposed,95 that the great reactivity of pyrroles in iodination may be due to a reaction either of the dissociated anion or the pyrrolenine tautomer. 

Pyrrole, like thiophene, does not react with benzophenone to give the corresponding oxetane. However, pyrrole reacts with aliphatic aldehydes and ketones to the corresponding 3-pyrryl carbinols. The alcohols derive from the cleavage of the corresponding oxetanes (Scheme 3.48) [94]. The yields increase when A -methylpyrrole is used as substrate, while the reactivity is depressed in the presence of substituents on the pyrrole ring. 

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