Of 2-pyrrolidones

A/ -Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (8UOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

The reactivity of the methylene group adjacent to the lactam group affords the possibility of a Claisen condensation. Thus, treatment of 2-pyrrolidone or 2-piperidone with ethyl oxalate leads to the J -pyrroline-carboxylic (70) and, d -piperideine-2-carboxylic acids (71), respectively. N-methyl lactams furnish N-methyl derivatives (72,73) (Scheme 3). 

In some cases, the products of Claisen condensation of two molecules of 2-pyrrolidones (20) can be hydrolyzed to 2-alkylidenepyrrolidines (21) (74). 

In the photoaddition of 2-pyrrolidone the 5-alkyl isomer (69) always predominates, usually in a ratio of 2 1. The formation of anti-Markovnikov 1 1 adducts, telomers, and dehydrodimers of structure (71) supports a free radical mechanism. Similarly, formamide undergoes olefin addition under... 

Warshel, Levitt, and Lifson derived a partially optimised consistent force field for amides and lactams (25). It is composed of an alkane part and an amide-part. The former was taken over from analogous earlier calculations for saturated hydrocarbons (17). The potential constants of the amide-part were optimised with the help of a large number of experimental frequencies (taken from TV-methylform amide, acetamide, iV-methylacetamide, and several deuterated species) as well as experimental geometry data for 7V-methylacet-amide. The resulting force field was used for the calculation of vibrational and conformational properties of 2-pyrrolidone, 2-piperidone and e-caprolactam. 

Pterolactam (48) was isolated from bracken (Pteridium aquilinum Kuhn), a fern belonging to a monotypic genus (86). Its IR spectrum strongly resembles the IR spectrum of 2-pyrrolidone the structure of 48 was established by 1H-NMR spectroscopy. It is interesting to note that 48 possesses a weak but definitive optical rotation ([a]D —2.0°). 

The nitrosation of 2-pyrrolidone with dinitrogen tetroxide is said to be capricious, particularly when attempted for the first time. The problems appear to occur during the carbonate washing, but solutions for the problem have not been worked out. Furthermore, the nitroso product may detonate when distillation is attempted. Therefore the product is used without purification [46],... 

In a well-ventilated hood, to a rapidly stirred mixture of 50.2 gm (0.546 mole) of dinitrogen tetroxide and 123 gm (1.5 mole) of anhydrous sodium acetate in 150 ml of carbon tetrachloride prepared at Dry Ice temperature is added, over a 1 hr period, a solution of 46.5 gm (0.546 mole) of 2-pyrrolidone in 50 ml of... 

The step 4 product (equivalent to 20 g solid polymer) was mixed with A -(2,4-dinitrophenyl)-l,4-phenylenediamine (Disperse Yellow 9 dye) (1 g) containing 20 ml water and smaller amounts of 2-pyrrolidone and ethylene glycol. The product was isolated containing at least a portion of the dye covalently bound to the latex particulates. 

According to the 1981-83 National Occupational Exposure Survey (NOES, 1997), approximately 27 000 workers in the United States were potentially exposed to y-buty-rolactone (see General Remarks). Occupational exposures may occur in its production, in the production of 2-pyrrolidone and related chemicals, and when it is used as a solvent. 

Southwell, D., and B.W. Barry. 1983. Penetration enhancers for human skin Mode of action of 2-pyrrolidone and dimethylformamide on partition and diffusion of model compounds water, -alcohols and caffeine. J Invest Dermatol 80 507. 

A mild and simple procedure for the esterification of penicillanic acids is an essential technique. The EG base derived from the electroreduction of 2-pyrrolidone has been... 

In the reaction of 2-pyrrolidone with equimolar amount of methylphosphonic acid dichloride in absolute ether at -10 to -15°C [129] small yields of (2-pyrrolidonyl)methylphosphonic acid chloride (137) and di(2-pyrrolidonyl)dimethylpyrophosphonate (138) were obtained ... 

The N-silyl derivatives of alkylpyrrolidine are phosphorylated both at position 2, and at the nitrogen atom with the formation of compounds 142 [134] and 143 [135] respectively, while the analogous derivatives of 2-pyrrolidone react at the nitrogen atom, forming compound 144 [136] ... 

The products of this photoalkylation reaction are 3-alkylated-2-pyrro-lidones and 5-alkylated-2-pyrrolidones (1 2). It is noteworthy that in this reaction the alkylation at the carbon alpha to the nitrogen atom is the predominating reaction, whereas the alkylation at the carbon alpha to the carbonyl yields the minor product of the reaction. Similar results have been obtained in the thermal process (48). The light-induced addition of 2-pyrrolidone to olefins when induced directly leads to traces only of the desired 1 1 adducts. However, the use of acetone as a photosensitizer enables this reaction to proceed in relatively high yields. 

The light-induced addition of 2-pyrrolidone to olefins when induced directly by light leads to traces only of the desired 1 1 adducts. On the other hand, when acetone is used as a photosensitizer for this reaction it results in relatively high yields of the 1 1 adducts and may be exploited for synthetic purposes in some cases. As in the case of y-butyrolactone the initiation step can be regarded involving a hydrogen atom abstraction process from the lactam by the excited acetone molecule,... 

Free Radical Addition of 2-Pyrrolidone to alpha Olefins. Izvest. Akad. Nauk SSSR, Ser. Khim. 1964, 1843. 

The assembling tendency of donorfunctionalized ligands was investigated in detail in heterobimetallic complexes derived from hydroxypyridine and the anion of 2-pyrrolidone. The diversity of structural types is controlled inter alia by solvent, kind of 6-substitution of the pyridine ring, type of additional counterions and work up procedures. LnxCuy-complexes derived from hydroxypyridine exhibit Ln Cu ratios of 1 3, 2 2, 2 4, 2 8, 4 4 and 8 12 [141-144]. The anion of 2-pyrrolidine forms polymeric macrocyclic chain structures of type LnHg2 n and Ln2Hg3 n dependent on the size of the lanthanide element [145]. 

Polymerization of 2-pyrrolidone is also activated by various A-acyl lactams, especially by iV-acetyl-2-pyrrolidone, lower lactones, CO, and JV-benzoyllac-tams [211]. 

Anodic oxidation of amides and carbamates on the other hand are far more useful than those of amines. Scheme 46 shows the synthesis of a pharaoh ant trail pheromone in which the anodic oxidation of 2-pyrrolidone is an important step [270]. 

The production of the 2-pyrrolidone anion by direct cathodic electrolysis of 2-pyrrolidone has been referred to [33,34] and examples of its use as an ex situ reagent presented (Scheme 2). Despite the early promise of this conveniently prepared strong base [pXa(2-pyrrolidone) = 24.1], it is only recently that its advantages have been exploited more widely. The 2-pyrrolidone anion is formed as an ex situ reagent by direct cathodic electrolysis at —2.5 V (VS.SCE) and a further example of its use is given in Scheme 8, in which reaction the tetraalkylammonium counterion was essential in preventing defluorination [35]. 

Southwell D, Barry BW. Penetration enhancement in human skin effect of 2-pyrrolidone, dimethylformamide and increased hydration on finite dose permeation of aspirin and caffeine. Int J Pharm 1984 22 291-298. 

Other amido acids may be prepared via formaldehyde amidocarbonylation using dicobalt octacarbonyl in the presence of A -substituted acyclic amides or cyclic amides. Amidocarbonylation of 2-pyrrolidone and -caprolactam [22] affords N-(2-pyrrolidone)-2-acetic acid and A-(e-caprolactam)-2-acetic acid, respectively (eqs. (12) and (13)). The side products shown can be recycled and eventually converted to the desired amido acetic acids. 

Dissolve reference substances (50 mg of N-vinylpyrrolidone, about 300 mg of 2-pyrrolidone and 50 mg of vinyl acetate in the case of copovidone) in methanol and dilute with the same solvent. Further dilutions are done with eluent A. 

Concerning the determination of 2-pyrrolidone, calibration up to about 1.5 g per 100 g of sample usually is linear. 

Calculation of 2-pyrrolidone resp. N-vinylpyrrolidone resp. vinyl acetate in the sample ... 

FP = Peak area of 2-pyrrolidone resp. N-vinylpyrrolidone resp. vinyl acetate in the sample chromatogram [mV s] fi(P) = calculated concentration of the sample solution [mg/io ml]... 

The content of 2-pyrrolidone and N-vinylpyrrolidone was determined in povidone before and after addition of two different amounts of the reference substances (Table 38). 

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