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On the mechanism of the conversion of 6‐chloropyrido[2,3‐ B ]pyrazine into 1 h ‐lmidazo[4,5‐ b ] pyridine by potassium amide in liquid ammonia
Author(s) -
Nagel A.,
Van Der Plas H. C.,
Geurtsen G.,
Van Der Kuilen A.
Publication year - 1979
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570160222
Subject(s) - chemistry , pyrazine , pyridine , adduct , amide , medicinal chemistry , potassium , stereochemistry , liquid ammonia , contraction (grammar) , ring (chemistry) , ammonia , organic chemistry , medicine
The synthesis of a number of 2‐R 1 , 3‐R 2 ‐6‐X‐pyrido[2,3‐ b ]pyrazines (1) is reported and their reaction with potassium amide in liquid ammonia investigated. Ring contraction into a 2‐R‐1 H ‐imidazo[4,5‐ b ]pyridine was found to occur with X = Cl, R 1 = H, R 2 = C 6 H 5 (1b); X = Cl, R 1 = R 2 = C 6 H 5 ( 1c ); X = Cl, R 1 = H, R 2 = t ‐C 4 H 9 ( 1d ). Besides ring contraction, an increasing amount of dechlorination of 1 was found: 1a , 20%; 1b , 30%; 1d , 40%; 1c , 60%; 1g , 95%. 1e (X = Cl, R 1 = t ‐C 4 H 9 , R 2 = H) yields the unreactive anionic σ‐adduct at C‐3 i.e. , 3‐amino‐2‐ t ‐butyl‐6‐chloro‐3,4‐dihydropyrido[2,3‐ b ]pyrazine. The ring contraction only proceeds with X = Cl. 1b (X = F) gives an amino‐defluorination, 1b (X = Br) exclusively undergoes reductive debromination. The ring contraction of 1a (X = Cl, R 1 = R 2 = H) is investigated by 15 N‐ and 13 C‐labelling. It is concluded that the conversion into 1 H ‐imidazo[4,5‐ b ]pyridine proceeds via the reactive anionic σ‐adduct at C‐2, under exclusive elimination of C‐2.