Efficient Synthesis of 2‐Substituted Phthalimides from Phthalic Acids in One Step

Abstract

Efficient procedures for synthesizing 2‐substituted phthalimide (isoindole‐1,3‐dione) analogues starting from phthalic acids have been developed by using experimental design. The phthalimide central fragment frequently appears in biologically active compounds, materials, catalysts, and fluorescent probes, and therefore the development of general, fast, and convenient synthetic methods to this scaffold under neutral, acidic, and basic conditions would be attractive. After an initial screening, the use of acetonitrile, acetic acid, or pyridine in combination with microwave heating proved most promising. Experimental design was applied to these conditions to optimize the time, temperature, and concentration. This strategy has successfully generated synthetic methods that have been used to synthesize a series of phthalimides from phthalic acids and various amines or anilines in excellent yields. The developed methods have proven to be general, fast, convenient, and economic, and thus are expected to have broad utility to efficiently construct novel compounds for future biological and chemical applications.

Efficient one-step synthesis of 4-amino substituted phthalimides and evaluation of their potential as fluorescent probes

“…24 Based on this, and the fact that S N Ar reactions can be conducted under similar conditions, we set out to develop a one step method to synthesize various 4-amino substituted phthalimides. 24 Based on this, and the fact that S N Ar reactions can be conducted under similar conditions, we set out to develop a one step method to synthesize various 4-amino substituted phthalimides.…”

“…We recently published an optimized method to synthesize phthalimides by simply heating phthalic acids together with an amine or aniline in acetonitrile, pyridine or acetic acid without additives and in equimolar quantities. 24 Based on this, and the fact that S N Ar reactions can be conducted under similar conditions, we set out to develop a one step method to synthesize various 4-amino substituted phthalimides. Test reactions using 4-fluorophthalic anhydride, morpholine, and p-toluidine in equimolar amounts without any additives gave promising results.…”

Development and Optimization of Simple One‐Step Methods for the Synthesis of 4‐Amino‐Substituted 1,8‐Naphthalimides

“…MWI has proven to be a valuable tool for high‐temperature reactions, because it enables fast heating allied to good temperature and time control, and we have previously developed methods to synthesize substituted phthalimides by using this heating source 19. This technique was therefore adopted in the search for straightforward one‐step methods to synthesize 4‐amino‐substituted 1,8‐naphthalimides.…”

Microwave-promoted synthesis of cyclic imides

“…Chorell has synthesized Nsubstituted phthalimides from phthalic acids and amines in one step employing acetonitrile, acetic acid or pyridine. 103 The method is general and good yields were obtained even when anilines with electron acceptor groups and sterically hindered amines were employed. Recently, a series of bispyromellitimides, 104 which is an important class of substrates in polymer chemistry, were synthesized through the condensation of pyromellitic dianhydride (PMD) with anilines in glacial acetic acid and few drops of pyridine and using MW irradiation in a modified domestic oven (Scheme 12).…”