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Azirine/Oxindole Ring Enlargement via Amidinium Intermediates
Author(s) -
Mekhael Maged K. G.,
Bienz Stefan,
Linden Anthony,
Heimgartner Heinz
Publication year - 2004
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.200490216
Subject(s) - chemistry , azirine , aqueous solution , ring (chemistry) , oxindole , yield (engineering) , pyridine , medicinal chemistry , hydrolysis , amidine , organic chemistry , catalysis , materials science , metallurgy
A novel general method for the synthesis of oxindoles, namely the ‘azirine/oxindole ring enlargement via amidinium‐intermediates’ has been established: the reaction of 2 H ‐azirin‐3‐amines 1 with BF 3 ⋅OEt 2 in THF solution at −78° leads to 1,3,3‐trialkyl‐2‐amino‐3 H ‐indolium tetrafluoroborates 14 in good yields ( Scheme 5 ). Treatment of aqueous solutions of 14 at 0° with aqueous NaOH (30%) and extraction with CH 2 Cl 2 gives oily substances that are either hydrates of 1,3,3‐trialkyl‐2‐dihydroindol‐2‐imines 15 or the corresponding indolium hydroxides. These products are transformed to the corresponding 1,3,3‐trialkyl‐2,3‐dihydroindol‐2‐ones 17 in modest yields upon refluxing in H 2 O/THF. Reaction of 14 with Ac 2 O in pyridine at ca. 23° for 16 h followed by aqueous workup and chromatographic separation leads to mixtures of N ‐(1,3,3‐trialkyl‐2,3‐dihydro‐indol‐2‐yliden)acetamides 16 and oxindoles 17 ( Scheme 6 ). Hydrolysis of 16 with aqueous HCl under reflux for 1–2 h gives oxindoles 17 in a good yield. Several oxindoles, spiro‐oxindoles, and 5‐substituted oxindoles were synthesized by means of the reactions mentioned above.