Synthesis of pyrrolidine-2,4-diones(tetramic acids) and some derivatives

Abstract

Pyrrolidine-2.4-dione (tetramic acid) has been obtained by heating its 3-ethoxycarbonyl derivative with water or nitromethane. Prolonged heating with water yields 4-hydroxy-3,4'-bi-A3-pyrrolinyl-2,2'-dione, the anhydroderivative of the dione. Iand 5-Methylpyrrolidine-2,4-diones and their anhydro-derivatives have been obtained, similarly. Previously reported syntheses of these pyrrolidine-2,4-diones are shown to be in error; the products obtained appear to have been the corresponding anhydro-derivatives, or their hydrates. Other derivatives of the diones are described. Condensation of ethyl-4-hydroxy-2-oxo-A3-pyrroline-3-carboxylate with aromatic aldehydes yields mainly the (€) -5-arylmethylene derivatives. PYRROLIDINE-2,4-DIONE (tetramic acid) (XVII) and its 1-and &methyl derivatives [(XVIII) and (XIX)]have been synthesised (Scheme l), apparently for the first time, although their synthesis has been claimed previously. Pyrrolidine-2,4-dione has hitherto been obtained1 only as its enol methyl ether, 4-methoxy-A3-pyrrolin-2-one (I) The first reported synthesis a s 3 of the corresponding dione (XVII) was shown e5 later to give the isomeric compound (11) (' iminotetronic acid I); the correction has not always been More recently Isowa and Ohtag have reported that hydrolysis of methyl 4-hydroxy-2-oxo-A3-pyrroline-1 D. J. Cram, 0. Theander, H.

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…The parent compound 398 is a relatively weak acid, (pK a ¼6.4 in water), which exists in the keto from in the solid state, whereas in aqueous solution a minor contribution from the enol 399 may be discerned [626]. The enolization behavior of 3-acetyltetramic acids is more complex; studies involving for instance the 3-acetyl-5-isopropyl derivative revealed a considerable contribution from the exo-enol tautomer 400 [627].…”

An Efficient Synthesis of Racemic 4‐Hydroxy‐2‐oxo‐1‐pyrrolidineacetamide (Oxiracetam) Using Tetramic‐Acid Intermediates

“…Chromatography, eluting with AcOEt, gave Ic as a light brown oil (2.7 g, 57% yield). IR ( Ethyl (4-Acetoxy-I,S-dihydro-2-oxo-2H-pyrrol-l-yl)acetate (8). Compound 4c (59.8 g, 300 mmol) was dissolved in AcOH (240 ml), at r.t., with stirring.…”

“…IR Spectra: Nicolet Model 20 SXB spectrometer; absorptions in crn-'. NMR Spectra: Varian Unity 400 (400 MHz for 'H-and 100.6 MHz for "C-NMR) spectrometer; chemical shifts (8) in ppm with reference to TMS; coupling constants ( J ) in Hz. MS: Hewlett-Packard HP 5989A.…”

“…174175'. IR (KBr): 3400, 3185, 1690, 1635, 1615 8;171.5;170.6;135.4;128.5;128.1;94.7;72.4;50.9;43.4. Anal.…”

Dysidin, ein neuartiger, chlorhaltiger Naturstoff aus dem Schwamm Dysidea herbacea

“…Verbindungen dieses Typs sind bereits friiher hergestellt worden [8]. Sie konnen durch Kochen in Wasser verseift und decarboxyliert werden, wahrend bei alkalischer Verseifung und Decarboxylierung Selbstkondensationsprodukte, Anhydrodimere, entstehen [9]. Diese einfache Methode, auf 8 angewandt, ergab nur massige und schlecht reproduzierbare Ausbeuten an 9, ohne dass die Bildung von Kondensationsprodukten verhindert werden konnte.…”