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Reactions of aromatic ketones with 3‐mercapto‐1,2‐propanediol. Synthesis of cis ‐ and trans ‐2‐alkyl‐2‐aryl‐(1,3‐oxathiolane‐5‐methanols and 1,3‐dioxolane‐4‐methanethiols)
Author(s) -
Upadhyaya Subhash,
Bauer Ludwig
Publication year - 1992
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.5570290504
Subject(s) - chemistry , diastereomer , aryl , medicinal chemistry , dioxolane , alkyl , ketone , benzene , organic chemistry
Aromatic ketones react with 3‐mercapto‐1,2‐propanediol ( 1 ) in refluxing benzene under the catalytic influence of a sulfonic acid and with azeotropic removal of water to yield a mixture comprised predominantly of cis ‐ and trans ‐2‐alkyl‐2‐aryl‐1,3‐oxathiolane‐5‐methanols 7, accompanied by lesser amounts of cis ‐ and trans ‐2‐alkyl‐2‐aryl‐1,3‐dioxolane‐4‐methanethiols 8 (up to 30%). It was discovered that 8 is the kinetic product and is isomerized by 4‐toluenesulfonic acid in hot benzene to the thermodynamically more stable 7 . Under these conditions, ortho ‐ and α‐substituted aromatic ketones tend to produce more of 8 , which can be attributed to steric hindrance encountered by the thiol as it attacks the ketone. Ketalizations of 1‐aryl‐2‐(1 H ‐imidazol‐1‐yl)‐1‐ as well as 1‐aryl‐2‐(1,H‐1,2,4‐triazol‐1‐yl)‐1‐ethanones by 1 fail under these conditions, even after 24 hours of reflux in toluene. However, 1‐(4‐chlorophenyl)‐3‐(1 H ‐imidazol‐1‐yl)‐1‐propanone and 1‐(4‐bromophenyl)‐4‐(1 H ‐imidazol‐1‐yl)‐1‐butanone are ketalized by 1 as expected. Interestingly, the reaction of 2‐bromo‐4′‐chloroace‐tophenone with 1 produces 1‐(4‐chlorophenyl)‐2,8‐dioxa‐6‐thiabicyclo[3.2.1]octane. Characterization of all isomers and separation of some diastereomers is described. Nuclear Overhauser enhancement experiments are utilized to establish the stereochemistry of 1,3‐oxathiolanes.