2-пирролидинон

Химические свойства

2-Pyrrolidinone occurs as a colorless or slightly grayish liquid, as white or almost white crystals, or colorless crystal needles. It has a characteristic odor. miscible with water, alcohol, ether, chloroform, benzene, ethyl acetate and carbon disulfide, insoluble in petroleum ether.

Методы производства

The synthesis of 2-pyrrolidone was first reported in 1889 as the product of dehydration of 4-aminobutanoic acid. It is produced commercially by condensation of butyrolactone with ammonia, a method first described in 1936. Other synthetic routes include carbon monoxide insertion into allylamine, hydrolytic hydrogenation of succinonitrile, and hydrogenation of ammoniacal solutions of maleic and succinnic acids (Hort and Anderson 1978).

Определение

ChEBI: 2-Pyrrolidinone 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.

Угроза здоровью

Exposure to 2-pyrrolidone produces irritation to the eyes, mucous membranes, and skin. Although reported to be a skin sensitizer in animal tests, there is no indication that 2-pyrrolidone is a skin sensitizer in human exposures (Anon 1975). 2-Pyrrolidone has been reported to enhance the permeability of human skin for methanol, but reduced the permeability for octanol (Southwell et al 1983).

Фармацевтические приложения

Pyrrolidone and N-methylpyrrolidone are mainly used as solvents in veterinary injections. Pyrrolidone has been shown to be a better solubilizer than glycerin, propylene glycol, or ethanol. They have also been suggested for use in human pharmaceutical formulations as solvents in parenteral, oral, and topical applications. In topical applications, pyrrolidones appear to be effective penetration enhancers. Pyrrolidones have also been investigated for their application in controlled-release depot formulations.

Промышленное использование

2-Pyrrolidone is used as an intermediate for synthesis of l-vinyl-2-pyrrolidone and various TV-methylol derivatives used as textile-finishing agents; as a solvent for various polymers, chlordane and DDT, d-sorbitol, glycerin, and sugars; and as a decolorizing agent for kerosene, fatty oils, and rosins. N-methyl-2-pyrrolidone and 2-pyrrolidone are utilized in petroleum refining to selectively extract aromatics from paraffinic hydrocarbons. 2-Pyrrolidone is used as a plasticizer and coalescing agent for acrylic latices and acrylic/styrene copolymers in emulsion coatings, i.e. floor waxes. A linear high molecular weight polyamide polymer of 2-pyrrolidone, nylon-4, is used as a textile fiber, injection molding compound, and film-forming polymer (Anon. 1975; Hort and Anderson 1978).

Безопасность

Pyrrolidones are mainly used in veterinary injections and have also been suggested for use in human oral, topical, and parenteral pharmaceutical formulations. In mammalian species, pyrrolidones are biotransformed to polar metabolites that are excreted via the urine. Pyrrolidone is mildly toxic by ingestion and subcutaneous routes; mutagenicity data have been reported.
LD50 (guinea pig, oral): 6.5 g/kg
LD50 (rat, oral): 6.5 g/kg

Метаболизм

A metabolite of 2-pyrrolidone, 4-aminobutanoic acid has been identified in animals (Lundgren et al 1980). 2-Pyrrolidone has been reported to be an endogenous constituent in the brains of mice (Callery et al 1978) and bovine (Mori et al 1975). The aliphatic polyamine putrescine has been demonstrated to be metabolized to 2-pyrrolidone in rat liver slices (Lundgren and Hankins 1978; Lundgren et al 1985) and to lesser extent by slices of spleen and lung, but not in tissue slices from kidney, brain, heart, or rear leg muscle (Lundgren and Hankins 1978). The metabolism of putrescine is catalyzed by the microsomal enzyme diamine oxidase (EC 1.4.3.6) to 4-aminobutyraldehyde, which is subsequently oxidized to the neurotransmitter 4-aminobutanoic acid (4-aminobutyric acid, GAB A) or is cyclized to delta1-pyrroline (Seiler 1980; Lundgren et al 1980; Callery et al 1980), which is in turn oxidized to 5-hydroxy-2-pyrrolidone (Lundgren and Fales 1980). There is evidence that 5-hydroxy-2-pyrrolidone is further metabolized to succinimide, malimide, 2- and 3-hydroxysuccinamic acids, maleamic acid, and carbon dioxide (Bandle et al 1984). An enzyme system residing in the soluble fraction of rabbit liver catalyzes the conversion of delta'-pyrroline to ?-aminobutyric acid and its lactam, 2-pyrrolidone (Callery et al 1982). 2-Pyrrolidone has been identified as a urinary metabolite of N-nitrosopyrrolidine (Cottrell et al 1980) and the drug methadone (Kreek 1980).

хранилище

Pyrrolidone is chemically stable and, if it is kept in unopened original containers, the shelf-life is approximately one year. Pyrrolidone should be stored in a well-closed container protected from light and oxidation, at temperatures below 20°C.

Несовместимости

Pyrrolidone is incompatible with oxidizing agents and strong acids.