Pyrrole nucleophilic substitution

N-alkylation, 4, 236 Pyrrole, 2-formyl-3,4-diiodo-synthesis, 4, 216 Pyrrole, 2-formyl-1-methyl-conformation, 4, 193 Pyrrole, 2-formyl-5-nitro-conformation, 4, 193 Pyrrole, furyl-rotamers, 4, 546 Pyrrole, 2-(2-furyl)-conformation, 4, 32 Pyrrole, 2-halo-reactions, 4, 78 Pyrrole, 3-halo-reactions, 4, 78 Pyrrole, 2-halomethyl-nucleophilic substitution, 4, 274 reactions, 4, 275 Pyrrole, hydroxy-synthesis, 4, 97 Pyrrole, 1-hydroxy-cycloaddition reactions, 4, 303 deoxygenation, 4, 304 synthesis, 4, 126, 363 tautomerism, 4, 35, 197 Pyrrole, 2-hydroxy-reactions, 4, 76 tautomerism, 4, 36, 198... 

Heterocycles with conjugated jr-systems have a propensity to react by substitution, similarly to saturated hydrocarbons, rather than by addition, which is characteristic of most unsaturated hydrocarbons. This reflects the strong tendency to return to the initial electronic structure after a reaction. Electrophilic substitutions of heteroaromatic systems are the most common qualitative expression of their aromaticity. However, the presence of one or more electronegative heteroatoms disturbs the symmetry of aromatic rings pyridine-like heteroatoms (=N—, =N+R—, =0+—, and =S+—) decrease the availability of jr-electrons and the tendency toward electrophilic substitution, allowing for addition and/or nucleophilic substitution in yr-deficient heteroatoms , as classified by Albert.63 By contrast, pyrrole-like heteroatoms (—NR—, —O—, and — S—) in the jr-excessive heteroatoms induce the tendency toward electrophilic substitution (see Scheme 19). The quantitative expression of aromaticity in terms of chemical reactivity is difficult and is especially complicated by the interplay of thermodynamic and kinetic factors. Nevertheless, a number of chemical techniques have been applied which are discussed elsewhere.66... 

The initial report within this area described the regiospecific alkylation of pyrroles using imidazolidinone 12 (20 mol%) as the catalyst [82]. A mixture of THF and water provided optimal reaction conditions, but low temperatures (-60 °C to -30 °C) were required to ensure the chemospecificity of the reaction. The functional group tolerance at the P-position of the substrate and A-substitution on the pyrrole nucleophile was explored (Scheme 15). It was noticed that subtle changes in the nature of the co-acid altered selectivities and this had to be modified depending on the substrates adopted. 

Although the hydroxy group is a relatively poor leaving group, its base-catalyzed nucleophilic substitution by the mechanism shown in Scheme 69 accounts not only for the hydrogenolysis of the 3-hydroxymethylindoles, but also for their SN reactions with ethoxide ions, cyanide ions and with piperidine. Nucleophilic substitution on 2-hydroxymethyl-pyrroles is generally precluded by the faster formation of the bis(2-pyrrolyl)methanes, but the synthesis of 2-cyano-2-(2,5-dimethyl-3-pyrroIyl) propanes from 2,5-dimethylpyrrole, propanone and potassium cyanide probably results from an SN reaction of the cyanide ion upon the initially formed 3-pyrrolylcarbinol (81USP4248784). The formation of (294)... 

The halogenoacetyl derivatives of pyrrole and indole undergo normal nucleophilic substitution reactions and with bifunctional nucleophiles they yield the expected heterocyclic derivatives, as, for example, in the formation of the thiazolylindole from the reaction of 3-(chloroacetyl)indole with thioacetamide (77IJC(B)473>. 

Pyrrole, 3-hydroxy-geometry, 4, 158 synthesis, 4, 343 tautomerism, 4, 36, 198 Pyrrole, 3-(a)-hydroxyalkyl)-cyclization, 4, 225 Pyrrole, 3-(2-hydroxyethyl)-chloroethylpyrrole from, 4, 279 Pyrrole, 2-hydroxymethyl-4,5-disubstituted reactions, 4, 272 nucleophilic substitution, 4, 273 oxidation, 4, 272 reduction, 4, 71 stability, 4, 272 Pyrrole, 3-hydroxymethyl-oxidation, 4, 272 reactions, 4, 272 reduction, 4, 273 Pyrrole, iodo-reactions... 

Detection of the Ovinyloximes 136a,d (Scheme 66) and the 0(2-chloroethyl)oxime 137 (Scheme 67) suggests two possible pathways for the formation of pyrroles from ketoximes and dichloroethane [89KGS901]. First, in a strongly basic medium, dichloroethane may act as an acetylene supplier (Scheme 66). Second, nucleophilic substitution of one chlorine atom in dichloroethane by the oximate-anion may lead to the 0(2-... 

The reactivity sequence furan > selenophene > thiophene > benzene has also been observed in the nucleophilic substitutions of the halogenonitro derivatives of these rings.21,22 This shows that the observed trend does not depend on the effectiveness of lone-pair conjugation of the heteroatoms NH, O, Se, and S and the 77-electron density at the carbon atoms. It is interesting to note that a good correlation is observed between molecular ionization potentials (determined from electron impact measurements) and reactivity data in electrophilic substitution, in that higher reactivities correspond to lower ionization potentials182 pyrrole furan < selenophene < thiophene benzene (see Table VII). This is expected in view of a... 

---