SHORT SYNTHESIS OF 5-SUBSTITUTED-2,3,4,5-TETRAHYDRO-BENZO[f][1,4]THIAZEPINES BY USING A MODIFIED PICTET-SPENGLER REACTION

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...

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Bibliographic Details
Published inHeterocycles Vol. 94; no. 6; pp. 1063 - 1073
Main Authors Saitoh, Toshiaki, Kitabatake, Michikazu, Sugihara, Yuuko, Ono, Yuuki, Horiguchi, Yoshie, Mohri, Kunihiko
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier 01.06.2017
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
Pictet-Splengler Reaction
CONVENIENT SYNTHESIS
FORMYLIMINIUM ION
FACILE SYNTHESIS
N-Formyliminium Ion
SOLID-PHASE SYNTHESIS
TITANIUM(IV) ISOPROPOXIDE
5-Substituted-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine
1,2,3,4-TETRAHYDRO-BETA-CARBOLINES
DERIVATIVES
Short Synthesis
CYCLIZATION
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Summary: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).
ISSN:0385-5414
1881-0942
DOI:10.3987/COM-17-13705