Synthesis of 5-methoxylated 3-pyrrolin-2-ones via the rearrangement of chlorinated pyrrolidin-2-ones

Functional rearrangement of polychlorinated pyrrolidin-2-ones to 5-imino-lactams promoted by n-propylamine

“…Therefore, it is reasonable to assume that the same type of mechanism is occurring in both transformations. In agreement with our previous proposal 34 and taking 1b as a model pyrrolidin-2-one, we believe that the reaction starts with a base-promoted dehydrohalogention. This is an exo or endo elimination according to the ease with which the required antiperiplanar conformation is attained.…”

“…This result contrasts with the reaction of 1a with sodium methoxide in methanol, which led to 5-methoxy-4-methyl-3-pyrrolin-2-one. 34 For reaction with PA, the double bond of the FR product is located between C(5) and the exocyclic nitrogen and not, as foreseen, between the C(3) and C(4) positions.…”

“…13,15,[30][31][32] Previous studies of alcohols with polychlorinated pyrrolidinones showed the importance of the alcohol structure (on increasing the size of the alkyl group in the alcohol from methyl to ethyl, yields decrease to some extent) and reaction conditions in the FR (e.g., no FR occurred when methanol was combined with a weak base, like carbonate). 34 Based on this work, amines appeared to be the most appropriate nitrogen nucleophiles with which to study the functional rearrangement of polychlorinated pyrrolidin-2-ones.…”

“…33 During our recent studies on the synthesis and reactivity of 4-methyl-pyrrolidin-2-ones (A) chlorinated at the C(3) and C(6) positions, we disclosed that when treated with a solution of alkaline methoxide (in methanol under mild conditions), these compounds were converted into the corresponding N-substituted 5-methoxy or 5,5-dimethoxy-4-methyl-3-pyrrolin-2-ones (B) (Scheme 2). 34 The transformation involves a series of eliminations/substitutions that give rise to a remarkable functional rearrangement (FR) in which the oxidation state of the starting molecule is preserved and the functionalities repositioned. In practice, two or three of the C-Cl groups at the C(3) and C (6) positions of A are replaced by a double bond at C(3)-C (4) and, respectively, one or two methoxy groups at C (5).…”

Structural aspects of partial solid solution formation: two crystalline modifications of a chiral derivative of 1,5-dihydro-2H-pyrrol-2-one under consideration

“…Among the compounds of this class, substances with antimicrobial, anti-inflammatory, antitumor, analgesic, antiviral, nootropic, antiaggregant and other types of biological activities have been found. [33][34][35][36][37][38] In the present work, the polymorphism of an unsaturated γ-lactam, racemic 3-chloro-5-hydroxy-1-(4-methylbenzyl)-4-[(4-methylphenyl)sulfanyl]-1,5-dihydro-2H-pyrrol-2-one 1, was investigated. It is important to note that 1 includes the hydroxyl group OIJ5)-HIJ5) (marked with blue color in Chart 1) in its structure.…”