Pyrrole, 3-acetyl-, bromination

In order to achieve 2-nitration, acetyl nitrate may be used as the reagent, but unlike pyrrole a semi-stable adduct, 5-acetoxy-2,5-dihydro-2-nitrofuran, is formed as an intermediate product (Scheme 6.22). This eliminates acetic acid when treated with pyridine. Furan also undergoes initial bromination or chlorination (X = Br or Cl) in ethanol at -40 °C, but then addition of two ethoxyl units occurs with the expulsion of halide ion (Scheme 6.23). 

Shkurko and Mamaev50,408 have studied the l//-benzothieno[3,2-6]-pyrrole system 391 extensively. Electrophilic substitution (e.g., Mannich reaction, acetylation, diazonium coupling) takes place at C-2, as predicted by MO calculations.4080 If position 2 is occupied, substitution occurs at C-3.44 The Vilsmeier reaction on the 2-aryl derivative gave the expected product, but bromination of the parent system 391 failed. A 3-bromo derivative was successfully obtained from the N-methyl compound 392 with bromine in chloroform.44... 

Snyder51 has studied the 5-carbethoxy derivative of thieno[3,2-Z>]-pyrrole (460, R = H) and shown that the Mannich reaction gives 6-substituted products and acetylation takes place at C-2. Bromination gave a 2,6-dibromo-compound, and the N-benzyl-derivative (460, R = CH2Ph) yielded a 2-lithium-compound with butyllithium which was converted to a 2-carbomethoxy derivative.5,b... 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared. Table 1 shows that the rates of substitution for (a) formylation by phosgene and V,iV-dimethylformamide, (b) acetylation by acetic anhydride and tin(IV) chloride, and (c) trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235) are all in the sequence furan > tellurophene > selenophene > thiophene. Pyrrole is still more reactive as shown by the rate for trifluoroacetylation, by the relative rates of bromination of the 2-methoxycarbonyl derivatives (pyrrole > furan > selenophene > thiophene), and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3]+ (Scheme 5) (2-methylindole ss V-methylindole > indole > pyrrole > furan > thiophene (73CC540)). 

Radical bromination of pyrrole and indole methyl substituents continues to be investigated, as does the substitution of the resulting bromo compound. Selective bromination of the 2-methyl group in 1-acetyl-2,3-dimethylindole can be achieved and the bromide ion displaced by malonate <85TL5253>. A recent example of an effective sequence of bromination and substitution is shown in Scheme 116 <928743, 930PP249,93TL3215>. 

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