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HERO ID
4274476
Reference Type
Journal Article
Title
SHORT SYNTHESIS OF 5-SUBSTITUTED-2,3,4,5-TETRAHYDRO-BENZO[f][1,4]THIAZEPINES BY USING A MODIFIED PICTET-SPENGLER REACTION
Author(s)
Saitoh, T; Kitabatake, M; Sugihara, Y; Ono, Y; Horiguchi, Y; Mohri, K
Year
2017
Is Peer Reviewed?
Yes
Journal
Heterocycles
ISSN:
0385-5414
Volume
94
Issue
6
Page Numbers
1063-1073
Language
English
DOI
10.3987/COM-17-13705
Web of Science Id
WOS:000405540100004
URL
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020259432&doi=10.3987%2fCOM-17-13705&partnerID=40&md5=972c22c6ee39b18521639c76fb7b2c7b
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Abstract
5-Substituted-2,3,4,5-tetrahydrobenzo [f][1,4]thiazepines (6) were synthesized using a modified Pictet-Spengler reaction of N-formyliminium ion (4) as the key step. The cyclization of 4 was found to be affected by the acidity of the reaction media, which depended on the structure of the benzene ring. The cyclization of the substrates (4a-g) lacking an electron-donating substituent at the benzene ring proceeded smoothly by using a mixed acid catalyst of trifluoroacetic acid and a small amount of trifluoromethanesulfonic acid, thus giving N-formylbenzothiazepines (5a-g) in good yields. On the other hand, in the case of substrates (4h-j) with the OMe group at the benzene ring, although the cyclization proceeded by use of trifluoroacetic acid as the sole catalyst to give the products (5h-j), the mixed acid catalyst did not induce the cyclization reaction to any extent. The modified Pictet-Spengler reaction, which constitutes imination of 2-(phenylthio)ethanamine (la) with aldehydes (2), and formylation of the resulting imines (3), followed by the acid-catalyzed cyclization of N-formyliminium ion (4), could be carried out as a one-pot procedure, thus providing a convenient methodology for synthesizing various 5-substituted-2,3,4,5-tetrahydrobenzo [f] [1,4] thiazepines (6).
Keywords
Pictet-Splengler Reaction; 5-Substituted-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine; N-Formyliminium Ion; Short Synthesis
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