Pyrrole Grignard reagents

Pyrroles do not react with alkyl halides in a simple fashion polyalkylated products are obtained from reaction with methyl iodide at elevated temperatures and also from the more reactive allyl and benzyl halides under milder conditions in the presence of weak bases. Alkylation of pyrrole Grignard reagents gives mainly 2-alkylated pyrroles whereas N-alkylated pyrroles are obtained by alkylation of pyrrole alkali-metal salts in ionizing solvents. 

C-Acylation and -carboxylation also occur with pyrrole Grignard reagents (p. 106). Whilst lithium pyrrole and lithium 2,4-dimethylpyrrole react with ethoxycarbonyl chloride to give ethyl pyrrole-2- and 2,4-dimethylpyrrole-5-carboxylate, respectively the corresponding potassium salts give the N-substituted pyrroles (p. 81). 

A number of instances have already been mentioned of reactions in which both N- and G-substitution occur. These are reactions of pyrroles with acid anhydrides (p. 64), alkylation and alkenylation of metallic derivatives of pyrroles (p. 66) and ethoxycarbonylation of metallic derivatives (p. 66 see also below). Most of the reactions of pyrrole Grignard reagents result in G-substitution, but occasionally N-substitution is also observed (p. 106). The Mannich reaction does not cause N-substitution (p. 70). Deuteration proceeds most easily at the nitrogen atom (p. 75), and reactions with metals (p. 61) cause displacement of hydrogen from nitrogen. 

Esters of other fatty acids have been used to prepare 2-acylpyrroles. Ethyl carbonate reacts with the pyrrole Grignard reagent mainly at the nitrogen atom, but a little ethyl pyrrole-2-carboxylate also results i c, 222 ... 

The formulation of the pyrrole Grignard reagents as ionic, but not highly dissociated, structures related to (104) enables the predominant C-substi-tution reactions to be formulated in the same way as the similar processes leading to C-substitution in the alkenylation of other metallic derivatives of pyrrole (p. 67). The reagents should be regarded as sources of more or less dissociated ambident pyrrole anions (p. 68). 

Grignard reagent from, acylation, 4, 237 nitration, 4, 211 reactivity, 4, 71-72 synthesis, 4, 149, 237, 341, 360 Pyrrole-3-carboxylic acids acidity, 4, 71 decarboxylation, 4, 286 esterification, 4, 287 esters... 

Noteworthy is the fact that one can utilize the appropriate bromopyrrole (e.g., 48) in conjunction with the desired Grignard reagent in a one-step operation to afford the corresponding substituted pyrroles (e.g., 49) [43]. The mixed pyrrole-pyridine heterocycle 50 was made in this fashion [45]. 

Although a limited range of Grignard reagents is available, the most widely used group is undoubtedly the lithio group introduced by direct lithiation (see Section 3.3.1.6.2). The ready formation of the lithio derivatives of pyrroles, furans and thiophenes and their benzo-fused derivatives has had a most important impact on the chemistry of these heterocyclic systems. Reaction of the... 

As in pyrrole, H NMR has been used to explore the nature of the indole anion with a range of counter cations, including indole Grignard reagents. H NMR data for Li+ and... 

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