Pyrrolidinones rearrangement

In the following cases, the initially formed cycloadducts rapidly rearrange to pyrrolidinones [68, 69] ... 

It is evident that some leeway is available in the substituents tolerable in the m-position. The bronchodilator sulfonterol (28) is descended from this observation. Chloromethylanisole (29) is reacted with methylmereaptan to give 30, and the newly introduced group is oxidized to the methyl-sulfonyl moiety of 31 with hydrogen peroxide. Ether cleavage, acetylation and Fries rearrangement of the phenolic acetate produces 32, which is next brominated with pyrrolidinone hydrobromide tribromide and then oxidized to the glyoxal (33) with dimethyl sulfoxide. 

Several steroidal cyclobntanone oximes were nsed to investigate the rearrangement reaction. The oxime 338, treated with thionyl chloride in benzene solution at room temperature, gave the expected pyrrolidinone 339 in 71% isolated yield (equation 127). 

DBSA is also very sensitive to the nature of the organic solvent. Oh and coworkers103 reported that this NIR band is more intense in relatively nonpolar solvents such as chloroform than in the aromatic solvents m-cresol or benzylalcohol, and is markedly reduced in the polar solvents DMSO and /V-methyl pyrrolidinone (NMP) as well as blue-shifted to ca. 850-900 nm. These spectral changes were attributed to micelle formation by the DBSA and solvent interactions with the PPy chains. This leads to rearrangement of the polymer backbone from an extended coil conformation in chloroform to a relatively compact coil one in NMP and DMSO. 

Reduction of norsecurinine with zinc and suKuric acid gave the oily lactam 169 which was extremely unstable and thus was immediately converted into the hexahydropyrrolo[2,l-a]isoquinoUne 170. This rearrangement was predicted from the previous results of the same reaction effected on securinine and related alkaloids e.g., Section II, A, 1) and was confirmed by synthesis of compound 170 from the pyrrolidinone 171 in two steps. Thus the skeletal structure 164 of norsecurinine as originally proposed (60) was fully confirmed (62). 

The pyrrolidinone (125) reacts with formic acid to yield the bicyclic ester (127) by way of a [3,3] sigmatropic rearrangement of the cation (126), followed by electrocyclization and addition of formic acid (Scheme 4). ... 

However, there are occasions in which the use of a respiratory stimulant may be warranted. By far the leading respiratory stimulant marketed in the United States is doxapram [309-29-5] (13), prepared by a unique rearrangement of the pyrrolidine [3471-97-4] (14) to the pyrrolidinone [3192-64-1] (15), followed by alkylation using morpholine (15). 

Rearrangements arising by carbonyl hydrogen abstraction are frequently of value in the synthesis of nitrogen-containing heterocycles. The NN-disubstituted /S-keto-amides (133), on irradiation in benzene, are converted into the 4-hydroxy-2-pyrrolidinones (134), presumably by 8-hydrogen abstraction, in yields of up to 88%.107 Further reports of the cyclization of N-substituted phthalimides have been published. Irradiation of a series of TV-alicyclic phthalimides (135) provides a route to the benzazepines (136) via the cyclobutanols (137) 108 the cw-ring junction in the final product was confirmed by independent synthesis. The... 

In what may be regarded as a related reaction, l-phenyl-2-pyrrolidinone undergoes a photochemical Fries rearrangement to furnish l,2,3,4-tetrahydro-5 f-benz[6]azepin-5-one <93H(36)743> together with 1-phenyl-pyrrole. The highest yields of the azepine are obtained in methanol containing 5% v/v of the singlet state photosensitizer piperylene, whereby only a trace of the pyrrole is formed. 

Initial 1,3-dipolar addition of the nitrone (157) to the olefinic bond of diketen is followed by decarboxylation and rearrangement to give the 3-pyrrolidinone (158), which adds to diketen to give the product that could be isolated, 2-acetoacetyl-5-benzyl-1 -phenylpyrrolidin-3-one. 

In 2011, Stephensons group developed a tandem radical cyclization/sigmatropic rearrangement reaction [30] that was used to prepare tricyclic pyrrolidinone 96 from organic halide 95 through photoredox catalysis (Scheme 13.14). The possible intermediate 97 could be isolated and further transformed to the desired... 

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