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Zur Synthese von ( Z )‐ und ( E )‐3‐(1 H ‐Imidazol‐4‐yl)‐2‐propenamin und einigen 3‐(1 H ‐Imidazol‐4‐yl)propanaminen
Author(s) -
Sellier Christian,
Buschauer Armin,
Elz Sigurd,
Schunack Walter
Publication year - 1992
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199219920158
Subject(s) - chemistry , medicinal chemistry , amide , thionyl chloride , imidazole , nitrile , bromide , hydrogen bromide , phosphonium , stereochemistry , organic chemistry , chloride , bromine
Synthesis of ( Z )‐ and ( E )‐3‐(1 H ‐imidazol‐4‐yl)‐2‐propenamine and Some 3‐(1 H ‐imidazol‐4‐yl)propanamines 3‐(1 H ‐Imidazol‐4‐yl)propanamine ( 6 , homohistamine), an essential intermediate for the synthesis of potent impromidine‐type histamine H 2 receptor agonists, is efficiently prepared from trans ‐urocanic acid ( 1 ) by reduction of the methyl ester 2 and conversion to the saturated amide 4 . Dehydration with thionyl chloride yields the nitrile 5 which is subsequently reduced to 6 . Side‐chain methylated 3‐(1 H ‐imidazol‐4‐yl)propanamines 12 are available from 1 H ‐imidazole‐4‐carbaldehyde ( 7 ) and 1‐(1 H ‐imidazol‐4‐yl)ethanone ( 8 ), respectively, via unsaturated nitriles 10 and stepwise reduction. Cyclization of the appropriate 4‐bromo‐5‐oxohexanenitriles 14α with formamidine in liquid ammonia and reduction of the obtained nitriles 15 furnishes ring‐methylated amines 16 . ( E )‐3‐(1 H ‐Imidazol‐4‐yl)‐2‐propenamine [( E )‐ 23 ] is obtained in six steps from the trans ‐ester 2 while ( Z )‐ 23 is accessible by treating 7 with triphenyl(2‐phthalimidoethyl)phosphonium bromide ( 17 ) and final deprotection. These primary amines are valuable intermediates for the synthesis of impromidine analogues.