What factors make it much more diffi cult to bring about electrophilic substitution of pyridine than ben-
zene? At which position does electrophilic substitution take place and why?
Nitration of aniline is not generally possible, yet nitration of 2- and 4-aminopyridines can be achieved
easily – why?
What are the structures of the products in the following reactions: (i) C 7 H 8 N 2 O 3 produced by treating
3-ethoxypyridine with f. HNO 3 –c. H 2 SO 4 at 100 °C, (ii) C 6 H 4 BrNO 2 produced by reaction of 4-methylpyri-
dine fi rst with Br 2 –H 2 SO 4 –oleum then with hot KMnO 4.
What are the structures of the compounds produced at each stage in the following sequence: 4-methylpy-
ridine reacted with NaNH 2 → C 6 H 8 N 2 , this then with NaNO 2 –H 2 SO 4 at 0 °C → rt → C 6 H 7 NO, then this
with sodium methoxide and iodomethane → C 7 H 9 NO and fi nally this with KOEt–(CO 2 Et) 2 → C 11 H 13 NO 4?
Detail, with explanations, the relative reactivities of bromobenzene, 2-bromopyridine, 3-bromopyridine
towards replacement of the halide with EtO on treatment with NaOEt.
What would result from treatment of 3-chloropyridine with LDA at low temperature?
What are the structures of the products in the following sequences: (i) 2-chloropyridine with LDA then
iodine→ C 5 H 3 ClNI; (ii) 3-fl uoropyridine with LDA then with acetone → C 8 H 10 FNO; (iii) 4-(diisopro-
pylaminocarbonyl)pyridine with LDA then with benzophenone, then with hot acid → C 19 H 13 NO 2 ; (iv)
2-bromopyridine with n-butyllithium at –78 °C then chlorotrimethylstannane (Me 3 SnCl) → C 8 H 13 NSn.
What would be the result of treating a 1:1 mixture of 2- and 3-methylpyridines with 0.5 equivalents of LDA
and then 0.5 equivalents of MeI?
A crystalline solid C 9 H 11 BrN 2 O 3 is formed when 2-methyl-5-nitropyridine is reacted with bromoacetone.
Subsequent treatment with NaHCO 3 gives C 9 H 8 N 2 O 2 – what are the structures and what is the mechanism
for the formation of the fi nal product?
Suggest a structure and explanation, for the product, C 16 H 22 N 2 O 5 resulting from the interaction of 4-vinylpy-
ridine with the sodium salt of diethyl acetamidomalonate (AcNHCNa(CO 2 Et) 2 ).
At which sites would deuterium be found when 1-butylpyridinium iodide is reduced with NaBD 4 in EtOH
forming 1-butyl-1,2,5,6-tetrahydropyridine.
What pyridones would be produced from the following combinations of reactants: H 2 NCOCH 2 CN
(cyanoacetamide) with: (i) EtCOCH 2 CO 2 Et; (ii) 2-acetylcyclohexanone; (iii) ethyl propiolate?
When the sodium salt of formyl acetone (MeCOCH=CHO–Na) is treated with ammonia, a pyridine,
C 8 H 9 NO is formed – what is its structure?
2,3-Dihydrofuran reacts with acrolein to give an adduct C 7 H 10 O 2 ; reaction of this with aq. H 2 NOH–HCl
gives a pyridine, C 7 H 9 NO; what is its structure?
