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Synthesis of 1,2‐Dihydropyridines, 2,3‐Dihydro‐4(1 H )‐pyridinone, and 1,2,3,4‐Tetrahydropyridines via N ‐Acyl N , O ‐Hemiacetal Formation
Author(s) -
Roduit JeanPaul,
Wyler Hugo
Publication year - 1985
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.19850680214
Subject(s) - chemistry , hemiacetal , aldehyde , hydrolysis , enol ether , medicinal chemistry , lactol , alcohol , organic chemistry , aldol condensation , acetal , stereochemistry , lactone , catalysis
New procedures are described for the synthesis of α,β‐ethylenic and acetylenic aldehydes from 2‐butene‐ and 2‐butyne‐1,4‐diol, respectively (see Scheme 1 ). These are applied to the preparation of a particular δ‐acetylamino‐α,β‐ethylenic aldehyde (( E )‐ 5 ) as well as of its acetylenic analogue 15 . On heating in the presence of a silyl enol ether, the former undergoes a complete dehydrative cyclization affording the N ‐acetyl‐1,2‐dihydropyridine 19 . The addition of HCl to aldehyde ( E )‐ 5 results in the production of the 4‐chloro‐1,2,3,4‐tetrahydropyridine 22 which is hydrolyzed to the corresponding alcohol 23 on silica gel. Similarly, the addition of HCl or HBr to the δ‐acetyl‐amino‐α,β‐acetylenic aldehyde 15 leads to the previously unknown 4‐halo‐1,2‐dihydropyridines 26 ; these are easily hydrolyzed to the 2,3‐dihydro‐4(1 H )‐pyridinone 27 . The ring‐forming process involves a N ‐acyl N , O ‐hemiacetal as intermediate which is eventually dehydrated.