616-45-5

Basic information

• Product Name: 2-Pyrrolidinone
• Synonyms: 2-Pyrrolidone Butyrolactam;2-AZACYCLOPENTANONE;2-P;2-KETOPYRROLIDINE;ALPHA-PYRROLIDONE;PIPERIDINIC ACID LACTAM;2-Oxopyrrolidine;2-Pyrol
• CAS NO: 616-45-5
• Molecular Formula: C₄H₇NO
• Molecular Weight: 85.1
• EINECS: 210-483-1
• Product Categories: API;Pyrrolidones;Solvent
• Mol File: 616-45-5.mol
• Article Data: 192

Chemical Properties

• Melting Point: 23-25 °C(lit.)
• Boiling Point: 245 °C(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless to pale yellow/Liquid or Low Melting Mass
• Density: 1.12 g/mL at 25 °C(lit.)
• Vapor Density: 2.9 (vs air)
• Vapor Pressure: 0.04 hPa (20 °C)
• Refractive Index: n20/D 1.487(lit.)
• Storage Temp.: 2-8°C
• Solubility: H2O: miscible (completely)
• PKA: 16.62±0.20(Predicted)
• Explosive Limit: 1.8-16.6%(V)
• Water Solubility: miscible
• Sensitive: Hygroscopic
• Stability: Hygroscopic
• Merck: 14,8016
• BRN: 105241
• CAS DataBase Reference: 2-Pyrrolidinone(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Pyrrolidinone(616-45-5)
• EPA Substance Registry System: 2-Pyrrolidinone(616-45-5)

Safety Data

• Statements: 22
• Safety Statements: 24/25
• RIDADR: 2810
• WGK Germany: 1
• RTECS: UY5715000
• TSCA: Yes
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 616-45-5(Hazardous Substances Data)

Usage

Chemical Properties

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.

Uses

Different sources of media describe the Uses of 616-45-5 differently. You can refer to the following data:
1. 2-Pyrrolidinone is a widely used organic polar solvent for various applications. 2-Pyrrolidinone is also an intermediate in the manufacture of polymers.
2. 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.

Preparation

Pyrrolidone is prepared from butyrolactone by a Reppe process, in which acetylene is reacted with formaldehyde.

Definition

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.

Production Methods

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).

Reactions

2-Pyrrolidone undergoes the reactions of a typical lactam, e.g. ring opening, attack on the carbonyl group, and replacement of hydrogens alpha to the carbonyl group. Strong acids and bases catalyze the hydrolysis of 2-pyrrolidone to 4-aminobutanoic acid (GABA). The hydrogen atom on the nitrogen atom is easily replaced by alkylation reactions with alkyl halide or sulfates, or reaction with acid anhydrides, acyl halides, ethylene oxide, and styrene. Condensation reactions with secondary amines and alcohols, and O-alkylation reactions occur at the carbonyl group. In the presence of anionic catalyst systems, 2-pyrrolidone is polymerized to polypyrrolidone, nylon-4 (Hort and Anderson 1978).

Health Hazard

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).

Flammability and Explosibility

Nonflammable

Pharmaceutical Applications

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.

Industrial uses

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).

Safety

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

Metabolism

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).

storage

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.

Incompatibilities

Pyrrolidone is incompatible with oxidizing agents and strong acids.

InChI:InChI=1/C4H7NO/c6-4-2-1-3-5-4/h1-3H2,(H,5,6)

Upstream product

• 123-56-8 Succinimide 
• 108-55-4 glutaric anhydride, 
• 4107-62-4 3-cyano-propionic acid methyl ester 
• 10137-67-4 ethyl 3-cyanopropionate 
• 13013-02-0 methyl 4-nitrobutyrate 
• 120-94-5 1-Methylpyrrolidine 
• 40051-83-0 2-Methylthiopyrrolin 
• 24549-12-0 methyl 3-(methylamino)propanoate 
• 23574-01-8 3-benzylamino-propionic acid methyl ester 
• 21911-84-2 methyl 3-(phenylamino)propanoate 
• 39629-53-3 rac-ethyl 3-benzylamino-3-phenylpropanoate 
• 42365-84-4 1-(1-acetoxy-2,2,2-trichloro-ethyl)-pyrrolidin-2-one 
• 2399-66-8 1-benzoylpyrrolidin-2-one 
• 111-86-4 n-Octylamine 

Downstream Products

• 103110-38-9 2-oxo-1-(2,4,6-trimethylphenyl)-tetrahydropyrrole 
• 61372-79-0 1-(3-nitrophenyl)-2-oxotetrahydropyrrole 
• 954-98-3 1-(2-(benzyloxy)acetyl)pyrrolidin-2-one 
• 31558-03-9 1-(3-oxo-3-phenyl-propyl)-pyrrolidin-2-one 
• 125393-02-4 1-[4-(diethylamino)benzenesulphonyl]-2-pyrrolidinone 
• 83191-29-1 N-(2,2,2-trichloro-1-benzenesulfonamidoethyl)pyrrolidone 
• 82878-48-6 N-(Dimethylphenylsilylmethylene)-2-pyrrolidone 
• 125659-45-2 1-(2-azidobenzoyl)azacyclopent-2-one 
• 3219-55-4 N-benzylmethacrylamide 
• 115539-43-0 4-benzyl-2,2-dimetyl-1-oxa-4,6-diazaspiro<4,4>nonan-3-one 
• 78877-71-1 3-Benzyl-2-benzylamino-2-isopropenyl-5,5-dimethyl-oxazolidin-4-one 
• 75995-62-9 2-benzylamino-2-(1-bromoisopropyl)-3-benzyl-5,5-dimethyloxazolidin-4-one 
• 94470-67-4 cromakalim 
• 104608-36-8 ethyl (4-benzothiazol-2-ylbenzyl)(2-oxopyrrolidino)phosphinate 

Relevant articles and documents

Comments on 'Unusual oxidative rearrangement of 1,5-diazadecalin'

Oxidation of cis or trans 1,5-diazadecalin with (PhIO)n yields 2-pyrrolidinone and not 1,6-diaza-2,7-cyclodecadione, as reported. This is shown by a comparison of the NMR data of the reaction product with those of 2-pyrrolidinone and 1,6-diaza-2,7-cyclodecadione.

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One-Step Conversion of Glutamic Acid into 2-Pyrrolidone on a Supported Ru Catalyst in a Hydrogen Atmosphere: Remarkable Effect of CO Activation

Glutamic acid, an abundant nonessential amino acid, was converted into 2-pyrrolidone in the presence of a supported Ru catalyst under a pressurized hydrogen atmosphere. This reaction pathway proceeded through the dehydration of glutamic acid into pyroglutamic acid, subsequent hydrogenation, and the dehydrogenation–decarbonylation of pyroglutaminol into 2-pyrrolidone. In the conversion of pyroglutaminol, Ru/Al2O3 exhibited notably higher activity than supported Pt, Pd, and Rh catalysts. IR analysis revealed that Ru can hydrogenate the formed CO through dehydrogenation–decarbonylation of hydroxymethyl groups in pyroglutaminol and can also easily desorb CH4 from the active sites on Ru. Furthermore, Ru/Al2O3 showed the highest catalytic activity among the tested catalysts in the conversion of pyroglutamic acid. Consequently, the conversion of glutamic acid produced a high yield of 2-pyrrolidone by using the supported Ru catalyst. This is the first report of this one-pot reaction under mild reaction conditions (433 K, 2 MPa H2)? which avoids the degradation of unstable amino acids above 473 K.

An Isolable Terminal Imido Complex of Palladium and Catalytic Implications

Herein, we report the isolation and a reactivity study of the first example of an elusive palladium(II) terminal imido complex. This scaffold is an alleged key intermediate for various catalytic processes, including the amination of C?H bonds. We demonstrate facile nitrene transfer with H?H, C?H, N?H, and O?H bonds and elucidate its role in catalysis. The high reactivity is due to the population of the antibonding highest occupied molecular orbital (HOMO), which results in unique charge separation within the closed-shell imido functionality. Hence, N atom transfer is not necessarily associated with the high valency of the metal (PdIII, PdIV) or the open-shell character of a nitrene as commonly inferred.

Thermal desorption of covalently bound fullerene C60 from poly-N-vinylpyrrolidone films

Kinetics of formation of thermolysis products in heating of thin films of poly-N-vinylpyrrolidone and of poly-N-vinylpyrrolidone with covalently bound fullerene C60 was studied by thermal desorption mass spectrometry.

Surface ligands enhance the catalytic activity of supported Au nanoparticles for the aerobic α-oxidation of amines to amides

The catalytic aerobic α-oxidation of amines in water is an atom economic and green alternative to current methods of amide synthesis. The reaction uses O2 as terminal oxidant, avoids hazardous reactants and gives water as the only byproduct. Here we report that the catalytic activity of silica-supported Au nanoparticles for the aerobic α-oxidation of amines can be improved by tethering pyridyl ligands to the support. In contrast, immobilization of thiol groups on the material gives activities comparable to Au supported on bare silica. Our studies indicate that the ligands affect the electronic properties of the Au nanoparticles and thereby determine their ability to activate O2 and mediate C-H cleavage in the amine substrate. The reaction likely proceeds via an Au catalyzed β-hydride elimination enabled by backdonation from electron-rich metal to the orbital. O2, which is also activated on electron-rich Au, acts as a scavenger to remove H from the metal surface and regenerate the active sites. The mechanistic understanding of the catalytic conversion led to a new approach for forming C-C bonds α to the N atoms of amines.

En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal-Organic Framework Catalysts

Peptide bond formation is a challenging, environmentally and economically demanding transformation. Catalysis is key to circumvent current bottlenecks. To date, many homogeneous catalysts able to provide synthetically useful methods have been developed, while heterogeneous catalysts remain largely restricted to the studies addressing the prebiotic formation of peptides. Here, the catalytic activity of Zr6-based metal-organic frameworks (Zr-MOFs) toward peptide bond formation is investigated using dipeptide cyclization as a model reaction. Unlike previous catalysts, Zr-MOFs largely tolerate water, and reactions are carried out under ambient conditions. Notably, the catalyst is recyclable and no additives to activate the COOH group are necessary, which are common limitations of previous methods. In addition, a broad reaction scope tolerates substrates with bulky and Lewis basic groups. The reaction mechanism was assessed by detailed mechanistic and computational studies and features a Lewis acid activation of carboxylate groups by Zr centers toward amine addition in which an alkoxy ligand on adjacent Zr sites assists in lowering the barrier of key proton transfers. The proposed concepts were also used to study the formation of intermolecular peptide bond formation. While intrinsic challenges associated with the catalyst structure and water removal limit a more general intermolecular reaction scope under current conditions, the results suggest that further design of Zr-MOF catalysts could render these materials broadly useful as heterogeneous catalysts for this challenging transformation.