Heterocyclic Chemistry at a Glance

Pyrroles 85

Exercises

1. Two isomeric mono-nitro-derivatives, C 5 H 6 N 2 O 2 , are formed in a ratio of 6:1, by treating 2-methylpyrrole
   with Ac 2 O-HNO 3. What are their structures and which would you predict to be the major product?


2. Starting from pyrrole, how would one prepare: (i) 2-bromopyrrole and (ii) 3-bromopyrrole (more than
   one step may be necessary)?


3. What would be the structures of the products from the following reactions: (i) pyrrole with CH 2 O-
   pyrrolidine–AcOH and (ii) pyrrole with NaH-MeI?


4. How could pyrrole be converted into pyrrol-2-yl-CH 2 CH(CO 2 Me) 2 (more than one step is required)?


5. How could pyrrole be converted into 2-phenylpyrrole (several steps are required)?


6. Which ring synthesis method and what reactants would be appropriate for the synthesis of a pyrrole,
   unsubstituted on the ring carbons but carrying CH(Me)(CO 2 Me) on nitrogen?


7. With what reactant would pentane-2,4-dione (MeCOCH 2 COMe) need to be reacted to produce
   3-acetyl-2-methyl-4,5-diphenylpyrrole?


8. With what reactant would TosMIC (TsCH 2 NC) need to be reacted to produce methyl
   4-ethylpyrrol-3-carboxylate?

Benzo[1,2-b:4,3-b']dipyrroles can be constructed using the pyrrole chemistry described earlier in this chapter in com-
bination with two van Leusen syntheses. For the fi rst van Leusen reaction, the substrate is ethyl sorbate. After masking
the pyrrole nitrogen in the product by N-phenylsulfonylation via the pyrryl anion, a second use of TosMIC generates a
second pyrrole unit. This intermediate has two pyrrole rings, but that with phenylsulfonyl on nitrogen is more deacti-
vated than the other, so Mannich substitution selects the other ring and, of the two available -positions on that ring,
that which is not ortho (deactivated by) to the ester. Quaternisation of the side-chain amine allows cyanide to displace
the dimethylamine unit (cf. page 82) and the product nitrile is converted into an acid chloride. Finally an intramole-
cular Friedel–Crafts acylation of the second pyrrole ring, catalysed by tin(IV) chloride, generates the six-membered
ring, initially as a ketone, but this immediately tautomerises to the phenolic structure.