Definition
ChEBI: A member of the class of pyrrolidine-2-ones that is pyrrolidin-2-one in which the hydrogen attached to the nitrogen is replaced by a methyl group.
General Description
A clear colorless liquid with a "fishlike" odor. Denser than water. Flash point 199°F. Contact may irritate skin, eyes and mucous membranes. May be toxic by ingestion.
Reactivity Profile
This amine is a very mild chemical base. N-METHYL-2-PYRROLIDONE(872-50-4) does tend to neutralize acids to form salts plus water. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.
Air & Water Reactions
Soluble in water.
Hazard
Severe skin and eye irritant. Explosive lim-its 2.2–12.2%.
Health Hazard
Inhalation of hot vapors can irritate nose and throat. Ingestion causes irritation of mouth and stomach. Contact with eyes causes irritation. Repeated and prolonged skin contact produces a mild, transient irritation.
Fire Hazard
Special Hazards of Combustion Products: Toxic oxides of nitrogen may be formed in fire.
Description
N-Methyl-2-pyrrolidone is an aprotic solvent with a
wide range of applications: petrochemical processing,
surface coating, dyes and pigments, industrial and
domestic cleaning compounds, and agricultural and
pharmaceutical formulations. It is mainly an irritant,
but has also caused several cases of contact dermatitis
in a small electrotechnical company.
Chemical Properties
N-Methyl-2-pyrrolidone is a colourless or light yellow liquid with an amine odour. It can undergo a number of chemical reactions even though it is accepted as a stable solvent. It is resistant to hydrolysis under neutral conditions, but strong acid or base treatment results in ring opening to 4-methyl aminobutyric acid. N-Methyl-2-pyrrolidone can be reduced to 1-methyl pyrrolidine with borohydride. Treatment with chlorinating agents results in amide formation,an intermediate which can undergo further substitution, while treatment with amyl nitrate yields the nitrate. Olefins can be added to the 3 position by treatment first with oxalic esters, then with appropriate aldehyes (Hort and Anderson 1982).
Production Methods
1-Methyl-2-pyrrolidinone is manufactured by the reaction of buytrolactone with methylamine (Hawley 1977). Other processes include preparation by hydrogenation of solutions of maleic or succinic acids with methylamine (Hort and Anderson 1982). Manufacturers of this chemical include Lachat Chemical, Inc, Mequon, Wisconsin and GAF Corporation, Covert City, California.
Flammability and Explosibility
Nonflammable
Industrial uses
1) 1-Methyl-2-pyrrolidinone is used as a general dipolar aprotic solvent, stable and unreactive;
2) for extraction of aromatic hydrocarbons from lubricating oils;
3) for carbon dioxide removal in ammonia generators;
4) as a solvent for polymerization reactions and polymers;
5) as a paint stripper;
6) for pesticide formulations (USEPA 1985).
Other non-industrial uses of 1-Methyl-2-pyrrolidinone are based on its properties as a dissociating solvent suitable for electrochemical and physical chemical studies (Langan and Salman 1987). Pharmaceutical applications make use of the properties of 1-Methyl-2-pyrrolidinone as a penetration enhancer for a more rapid transfer of substances through the skin (Kydoniieus 1987; Barry and Bennett 1987; Akhter and Barry 1987). 1-Methyl-2-pyrrolidinone has been approved as a solvent for slimicide application to food packaging materials (USDA 1986).
Carcinogenicity
Rats were exposed to NMP
vapor at 0, 0.04, or 0.4 mg/L for 6 h/day, 5 days/week for
2 years.Male rats at 0.4 mg/L showed slightly reduced mean
body weight. No life-shortening toxic or carcinogenic
effects were observed in rats exposed for 2 years to either
0.04 or 0.4mg/L of NMP. By the dermal route, a group of 32
mice received an initiation dose of 25mg of NMP followed
2 weeks later by applications of the tumor promoter phorbol
myristate acetate, three times a week, for more than
25 weeks. Dimethylcarbamoyl chloride and dimethylbenzanthracene
served as positive controls. Although the NMP
group had three skin tumors, this response was not considered
significant when compared with that of the positive
controls.
Metabolic pathway
Rats are administered radio-labeled N-methyl-2-
pyrrolidinone (NMP), and the major route of excretion
by rats is via the urine. The major metabolite,
representing 70-75% of the administered dose, is
4-(methylamino)butenoic acid. This unsaturated intact
product may be formed from the elimination of water,
and a hydroxyl group may be present on the
metabolite prior to acid hydrolysis.
Metabolism
Male Sprague-Dawley rats were given a single intraperitoneal injection (45 mg/kg) of radiolabeled 1 -methyl-2-pyrrolidone. Plasma levels of radioactivity and compound were monitored for six hours and the results suggested a rapid distribution phase which was followed by a slow elimination phase. The major amount of label was excreted in the urine within 12 hours and accounted for approximately 75% of the labelled dose. Twenty-four hours after dosage, cumulative excretion (urine) was approximately 80% of the dose. Both ring- and methyl-labeled species were used, as well as both [14C]- and [3H]-labeled l-methyl-2-pyrrolidone. The initial labeled ratios were maintained during the first 6 hours after dosage. After 6 hours, the liver and intestines were found to contain the highest accumulations of radioactivity, approximately 2-4% of the dose. Little radioactivity was noted in the bile or respired air. High performance liquid chromatography of urine showed the presence of one major and two minor metabolites. The major metabolite (70-75% of the administered radioactive dose) was analyzed by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry and was proposed to be a 3- or 5-hydroxy-l-methyl-2-pyrrolidone (Wells 1987).
Purification Methods
Dry the pyrrolidone by removing water as the *benzene azeotrope. Fractionally distil at 10 torr through a 100-cm column packed with glass helices. [Adelman J Org Chem 29 1837 1964, McElvain & Vozza J Am Chem Soc 71 896 1949.] The hydrochloride has m 86-88o (from EtOH or Me2CO/EtOH) [Reppe et al. Justus Liebigs Ann Chem 596 1 1955]. [Beilstein 21 II 213, 21 III/IV 3145, 21/6 V 321.]
