Introduction of 2-Pyrrolidinone

General description 

2-Pyrrolidinone is a natural product found in Capparis spinosa, Ascochyta medicaginicola, and other organisms with data available. Pyrrolidin-2-one is the simplest member of the class of pyrrolidin-2-ones, consisting of pyrrolidine in which the hydrogens at position 2 are replaced by an oxo group. The lactam arising by the formal intramolecular condensation of the amino and carboxy groups of gamma-aminobutyric acid (GABA). It has a role as a polar solvent and a metabolite. Colorless or light yellow liquid or crystal. The freezing point is 25.6 ℃, lightning 129 ℃ and boiling point 245 ℃, which can be dissolved in most organic solvents such as water, alcohol, ether, chloroform, benzene, ethyl acetate and carbon disulfide. Insoluble in petroleum ether. 2-Pyrrolidinone moiety is not critical for the cognition-enhancing activity of piracetam-like drugs.

Application and Pharmacology

2-pyrrolidinone structure is not critical for nootropic activity of piracetam-like compounds.2-pyrrolidone (2-P for short) is the raw material for the production of polyvinylpyrrolidone, nylon-4 and Naofukang γ- Butyrolactone is obtained by ammoniation. A hydrophilic interaction high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for determination of 2-pyrrolidinone in swine liver was developed and validated. After the fortification of 2-pyrrolidinone-d6as the internal standard, 2-pyrrolidinone in swine liver was extracted by acetonitrile, and the supernatant was led through a C18+W AX mixed- mode solid phase extraction (SPE) cartridge. Furthermore, the eluate was adjusted to pH 5.0 and then led through a strong cationic exchange SPE cartridge. 2-Pyrrolidinone and 2-pyrrolidinone-d6were concentrated and eluted by acetonitrile containing 2% ammonium hydroxide. The final eluate was acidified and then injected for hydrophilic interaction LC-MS/MS analysis. Mass spectrometry detection was carried using positive turbo-ion spray ionization mode. The multiple reaction monitoring transitions were 86→69 for 2-pyrrolidinone and 92→75 for 2-pyrrolidinone-d6. T h e C 1 8 +W AX mixed-mode SPE cleanup greatly prevented the rapid contamination of mass spectrometer. 

2-pyrrolidone widely exists in various physiologically active natural products in nature. For example, it is the main structural unit of gonadotropin releasing hormone. At the same time, 2-pyrrolidone is an important raw material and intermediate of medicine, pesticide, dye, peptide and other chemicals. If it is used as the end chain of peptide, it also plays a stable role in the conformation of the compound. Many polysubstituted 2-pyrrolidones have been used in the synthesis and production of a variety of drugs and applied for patents[1,2].

Synthesis

Following the indications of previous work, 2-pyrrolidinone moiety of piracetam and piracetam-like compounds has been opened to the corresponding amide derivatives. As found previously in the case of 1,4-diazabicyclo[4.3.0]nonan-9-one compounds, the cognition-enhancing activity of 2-pyrrolidinone compounds is maintained in most cases, suggesting that this moiety is not crucial for activity[3].

As regards 2-pyrrolidinone bond that is cleaved, two of the most potent compounds(1 and 4) derived from the opening of the N-C bond 1-5.On the other hand, compounds 5and 11,that at least maintain the potency of parent compounds, were formally obtained by the opening oftheC-Cbond4-5.In general, it can be said that 2-pyrrolidinone ring can be replaced by a linear amide and that an NH group is more usefulthananN- CH,for high potency in the passive-avoidance test. considering the present results, as well as those previously reported, w e h ave shown that With the development of small ring compounds, cyclopropane chemistry has attracted much attention, especially in the synthesis of heterocycles, and this field has become a research hotspot. Many compounds such as pyrrolidone and pyrimidine can be prepared by cyclic pyrrolidone derivatives [9-6]. Based on the study of different cyclopropylamides [10-11], we designed to open and close the ring of cyclopropylamides, hoping to obtain a new class of 2-pyrrolidone compounds. In this paper, a series of α- Acetyl cyclopropyl amides react with NH2OH · HCl to prepare polysubstituted 2-pyrrolidone[4]. The synthetic route is shown in Figure 1. Another preparation method is obtained by hydrogenation and ammoniation with maleic anhydride as raw material, and the yield can reach 90% - 92%.

Figure 1 The Synthesis route of 2-pyrrolidinone 

Safety

Galvanized iron bucket, with a net weight of 200kg / barrel, shall be stored in a cool and ventilated warehouse, away from fire and heat source, and stored separately from oxidant. Handle with care to keep the package intact and prevent leakage.

References

1.Cheng J., Wu F. & Wang P. et al., "Flavoalkaloids with a Pyrrolidinone Ring from Chinese Ancient Cultivated Tea Xi-Gui," Journal of Agricultural and Food Chemistry, Vol.66, No.30(2018), pp.7948-7957.

2.Liu Y., Chen X. & Ji Y. et al., "Validated hydrophilic interaction LC-MS/MS method for determination of 2-pyrrolidinone residue: applied to a depletion study of 2-pyrrolidinone in swine liver," Analytical and Bioanalytical Chemistry, Vol.399, No.3(2011), pp.1371-1380.

3.Scapecchi S., Martelli C. & Ghelardini C. et al., "2-Pyrrolidinone moiety is not critical for the cognition-enhancing activity of piracetam-like drugs," Il Farmaco, Vol.58, No.9(2003), pp.715-722.

4.Wang Kewei, fan Yueqin, Meng Shuangming, etc.: synthesis of polysubstituted 2-pyrrolidone by one pot method, Journal of Shanxi Datong University (NATURAL SCIENCE EDITION), 2011, No. 03, pp. 45-47.