Name: Pyrrolidone
CAS No: 2-Pyrrolidinone [616-45-5
BP: Pyrrolidone PhEur: Pyrrolidon
g-Aminobutyric acid lactam; 4-aminobutyric acid lactam; gaminobutyric lactam; g-aminobutyrolactam; g-butyrolactam; butyrolactam; 2-ketopyrrolidine; 2-oxopyrrolidine; 2-Pyrol; apyrrolidinone; pyrrolidin-2-one; a-pyrrolidone; pyrrolidonum; 2- pyrrolidone; Soluphor P.
2-Pyrrolidinone [616-45-5
C4H7NO ,85.11
Pyrrolidone and N-methylpyrrolidone (see Section 17) are mainly used as solvents in veterinary injections. Pyrrolidone has been shown to be a better solubilizer than glycerin, propylene glycol, or ethanol.(1) 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.(2–6) Pyrrolidones have also been investigated for their application in controlled-release depot formulations.(4,7
Pyrrolidone occurs as a colorless or slightly grayish liquid, as white or almost white crystals, or colorless crystal needles. It has a characteristic odor.
See Table I.
Acidity/alkalinity pH = 8.210.8 for a 10% v/v aqueous solution. Antimicrobial activity Pyrrolidone has also been shown to possess strong antimicrobial activity against Gram-positive and Gram-negative bacteria, and mold. Boiling point 2458C Dipole moment 2.3 Debye at 258C Enthalpy of vaporization 48.21 3.0 kJ/mol Flash point 1298C (open cup) Refractive index nD 25 = 1.480–1.490 Solubility Miscible with ethanol (95%), propan-2-ol, and water. Also miscible with other organic solvents such as aromatic
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 208C.
Pyrrolidone is incompatible with oxidizing agents and strong acids
Pyrrolidone is prepared from butyrolactone by a Reppe process, in which acetylene is reacted with formaldehyde.
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.(8,9) Pyrrolidone is mildly toxic by ingestion and subcutaneous routes; mutagenicity data have been reported.(10) LD50 (guinea pig, oral): 6.5 g/kg(10) LD50 (rat, oral): 6.5 g/kg
Observe normal precautions appropriate to the circumstances and quantity of material handled. Some pyrrolidones in their pure state are considered toxic, corrosive, and flammable; contact with skin and eyes should be avoided. Vapors or sprays should not be inhaled. Suitable eye and skin protection and a respirator are recommended. When heated to decomposition, pyrrolidone emits toxic fumes of NOx.
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N-Methylpyrrolidone. N-Methylpyrrolidone Synonyms 1-Methyl-2-pyrrolidinone; 1-methyl-5-pyrrolidinone; N-methyl-a-pyrrolidinone; N-methyl-g-butyrolactam; Nmethyl-2-pyrrolidinone; 1-methylazacyclopentan-2-one; Nmethylpyrrolidonum; MP; NMP; Pharmasolve; m-Pyrol. Empirical formula C5H9NO Molecular weight 99.14 CAS number [872-50-4] Description N-Methylpyrrolidone occurs as a clear, hygroscopic liquid with a mild amine odor. Typical properties Boiling point 2028C Dielectric constant 32.2 at 258C Dipole moment 4.09 Debye at 258C Enthalpy of evaporation 43.82 3.0 kJ/mol Flash point (closed cup) 938C Flash point (open cup) 968C Freezing point/melting point 248C Heat of combustion 719 kcal/mol Refractive index nD 25 = 1.4690 Solubility Miscible with ethanol (95%), water, and most other organic solvents. Specific gravity 1.028 at 258C Surface tension 40.7 mN/m (40.7 dyne/cm) at 258C Vapor pressure 0.33 mmHg at 23.28C; 5.00 mmHg at 65.08C. Viscosity 1.65 mPa s (1.65 cP) at 258C Safety N-Methylpyrrolidone is considered a poison when injected via the intravenous route. It is moderately toxic by ingestion, skin contact, and intraperitoneal routes. It is an experimental teratogen; mutagenicity data have been reported.(11) LD50 (mouse, IP): 3.05 g/kg(11) LD50 (mouse, IV): 0.155 g/kg LD50 (mouse, oral): 5.13 g/kg LD50 (rabbit, SC): 8.0 g/kg LD50 (rat, IP): 2.472 g/kg LD50 (rat, IV): 0.0805 g/kg LD50 (rat, oral): 3.914 g/kg Handling precautions In the UK, the workplace exposure limits for N-methylpyrrolidone are 103 mg/m3 (25 ppm) long-term (8- hour TWA) and 309 mg/m3 (75 ppm) short-term (15 minutes).(12) Comments N-Methylpyrrolidone is produced by the condensation of butyrolactone with methylamine. The EINECS number for N-methylpyrrolidone is 212-828-1. A specification for Nmethylpyrrolidone is included in the PhEur 6.0 and Japanese Pharmaceutical Excipients (JPE).(13)
The EINECS number for pyrrolidone is 204-648-7. The PubChem Compound ID (CID) for pyrrolidone is 12025.