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A Simple Synthesis of 5‐(2‐Aminophenyl)‐1 H ‐pyrazoles
Author(s) -
Janjić Monika,
Prebil Rok,
Grošelj Uroš,
Kralj David,
Malavašič Črt,
Golobič Amalija,
Stare Katarina,
Dahmann Georg,
Stanovnik Branko,
Svete Jurij
Publication year - 2011
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201100055
Subject(s) - chemistry , ketone , electrophile , pyrazole , nitro , ring (chemistry) , catalysis , combinatorial chemistry , electrophilic substitution , stereochemistry , medicinal chemistry , organic chemistry , alkyl
A four‐step synthesis of 1‐substituted 5‐(2‐aminophenyl)‐1 H ‐pyrazoles 5 as a novel type of histamine analogs and versatile building blocks for further transformations was developed. The synthesis starts from commercially available 2‐nitroacetophenone ( 12 ), which is converted into the enamino ketone 13 as the key intermediate. Cyclization of the key intermediate 13 with monosubstituted hydrazines 14a – 14l afforded the 5‐(2‐nitrophenyl)‐1 H ‐pyrazoles 17a – 17l . Finally, catalytic hydrogenation of the nitro compounds 17a, 17c – 17e , and 17g – 17j furnished the title compounds 5a, 5c – 5e , and 5g – 5j , respectively, in good yields. As demonstrated by some further transformations, additional functionalization of compounds 17 and 5 is feasible, either by electrophilic substitution at C(4) of the pyrazole ring, or at the NH 2 group.