Pyrrolines, preparation, from amines

Pyridazine 7V-ethoxycarbonylylides, prepared from pyridazines by N-amination and subsequent treatment with ethyl chloroformate, are transformed photochemically into 1-ethoxycarbony 1-pyrroles (80CPB2676) or 3-pyrrolin-2-one derivatives (85CPB3540). On the other hand, 1,2-bis(carbethoxy)pyridazines are transformed photochemically into 1-ethoxycarbonylpyrrolin-3-ones (87CB1597). 

Catalysts. Silver and silver compounds are widely used in research and industry as catalysts for oxidation, reduction, and polymerization reactions. Silver nitrate has been reported as a catalyst for the preparation of propylene oxide (qv) from propylene (qv) (58), and silver acetate has been reported as being a suitable catalyst for the production of ethylene oxide (qv) from ethylene (qv) (59). The solubiUty of silver perchlorate in organic solvents makes it a possible catalyst for polymerization reactions, such as the production of butyl acrylate polymers in dimethylformamide (60) or the polymerization of methacrylamide (61). Similarly, the solubiUty of silver tetrafiuoroborate in organic solvents has enhanced its use in the synthesis of 3-pyrrolines by the cyclization of aHenic amines (62). 

The original compound, maleimide (2,5-dioxo-A -pyrroline), is synthesized by the cyclo-condensation of ammonia and maleic acid. Similarly, primary amine is added to maleic anhydride, followed by cyclocondensation, to form N-substituted maleimide (Fig. 2). This reaction is applied to the preparation of bis-maleimides (BMl) [1]. At first, BMI was used as a crosslinking agent for natural rubber (NR). An o-dichlorobenzene solution of NR was crosslinked by BMI at I08-150°C in the presence of peroxides. The radicals generated from peroxides react with the double bonds of both BMI and NR [ 1 ]. 

Bis(bromomethyl)quinoxaline (41), prepared by direct synthesis from o-phenylenediamine and l,4-dibromo-2,3-butanedione (BrCH2COCOCH2Br), can be similarly converted into the bispyridinium bromide 42, and this on treatment with p-nitroso-iV,N-dimethylaniline and sodium cyanide yields the biscyanoanil 44. Reaction with secondary amines such as diethylamine yields pyrroline derivatives (e.g., 43, see chapter XXXV). 

There are few reports in the literature for the synthesis of 3-pyrrolin-2-ones so a simple method for the preparation of substituted 4-phenyl derivatives from phenylpropiolic ester, dimethyl sulphoxonium methylide and amines is welcome (Scheme 64). T-Azaspiroannelation has been described by Bryson and Wilson, ... 

Turner s group demonstrated that a variety of 3,4-substituted mcso-pyrrolidines can be enantioselectively oxidized by the monoamine oxidase (MAO) mutant. The -p3UToline products were converted to amino acids through the corresponding nitriles. In another application, the chiral A -pyrrolines were directly used to prepare prolyl peptides in an Ugj reaction. This reaction has been applied to an efficient synthesis of Telaprevir. The directed evolution of MAO from Aspergillus niger provided variant with a broadened substrate specificity and high enanhoselectivity for several a-methyl amines. In further enzyme evolution, an improved variant was identified for secondary amines [165,166]. 

---