Pyrrolidines 2-pyrrolidones

Pyrrolidone is first reacted with sodium hydride, then with ethyl chloroacetate to give ethyl 2-OXO-1 -pyrrolidine acetate. 

Figure 3. Experimental displacement isotherms of poly (vinyl pyrrolidone) from silica in water/displacer mixtures. NMP N-methyl pyrrolidine PYR Pyridine NEM N-ethyl morpholine DMSO dimethylsulfoxide...

Chloropropyl)-2-piperidone and 1 -(2-chloroethyl)-2-pyrrolidone were reacted with phosgene in toluene, and the 2-chloro derivatives (466, n = 0, 1, R2 = H, R3 = (CH2), C1, m = 2, 3, R5 = Cl) were then reacted with Meldrum s acid (421) in the presence of triethylamine to give isopropylidene [l-(3-chloroalkyl)piperidin-2-ylidene]malonate and [l-(2-chloroethyl)pyrrolidin-2-ylidene]malonate (468, n = 0, 1 R2 = H ... 

Nicotine Nicotine, l-methyl-2-(3-piridyl)pirrolidine (13.1.27), is an alkaloid that is isolated from the plant Nicotiana (Nicotiana tabacum, Nicotiam rustica, and others) and can be synthesized in varions ways [33-36]. In particular, it is proposed to proceed from nicotinic acid ethyl ester, which is condensed with iV-methylpyrrolidone, giving l-methyl-2-nicotinoyl pyrrolidone-2 (13.1.23). Acidic hydrolysis of this compound leads to an opening of the pyrrolidine ring giving the intermediate (13.1.24), which under the reaction conditions is decarboxylated to the /-aminoketone (13.1.25). The carbonyl group is reduced to an alcohol and the resnlting prodnct (13.1.26) undergoes dehydration to nicotine (13.1.27). 

An unusual rearrangement provides the key to the preparation of a highly substituted pyrrolidone, doxapram (26-7), that is used as a respiratory stimulant. The synthesis starts with the displacement of chlorine on pyrrolidine (26-1) by the carbanion from diphenylacetonitrile (26-2) to give (26-3) as the product. The quite hindered nitrile is then hydrolyzed to the corresponding carboxylic acid (26-4) by basic hydrolysis. The reaction of acid with thionyl chloride presumably proceeds initially to form the corresponding acid chloride. The close proximity of that group to basic... 

The dibasic side chain at position 7 can be alternatively provided by a substituted amino alkyl pyrrolidine. Preparation of that diamine in chiral form starts with the extension of the ester function in pyrrolidone (46-1) by aldol condensation with ethyl acetate (46-2). Acid hydrolysis of the (3-ketoester leads to the free acid that then decarboxylates to form an acetyl group (46-3). The carbonyl group is next converted to an amine by sequential reaction with hydroxylamine to form the oxime, followed by catalytic hydrogenation. The desired isomer (46-4) is then separated... 

The principal product of prolonged irradiation of the oxaziridine (175), formed from 3,5,5-trimethyl-l-pyrroline 1-oxide, is 3,5,5-trimethyl-2-pyrrolidone (176). In this instance, the 1,2-shift of a hydrogen atom, possible in pyrrolidines not containing an alkyl substituent on C-2, is preferable to pyrrolidine ring cleavage. A similar effect is observed in the photolysis of 5,5-dimethyl-l-pyrroline 1-oxide.147... 

Addition of DMAD to l-methyl-2-pyrrolidine dimethylacetal (69) in dioxane108 gave no 70, but the indoline 75, the isomeric pyrrolidones 71 and 72, and the pyrroline 76 were obtained using benzene as solvent the 1 1 adduct (73) was the major product. With DMAD, compound 73 gave 75, presumably via 74. 

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]. 

The apparently simple procedures of partial dehydrogenation of pyrrolidines and partial hydrogenation of pyrroles afford Zl1-pyr-rolines. However, the reaction is complex and is of little preparative value.97-98 A 1-Pyrrolines may be obtained by isomerization of A 3-pyrrolines.100 From the preparative point of view, partial hydrogenation of quaternary pyridine salts in strongly alkaline media to give 1-alkyl-id 2-piperideines is more important.101 Formation of heterocyclic enamines was observed in the reduction of i -methyl-pyrrolidone with lithium aluminum hydride,102 -alkylpiperidones with sodium in ethanol,103,104 and in the electrolytic reduction of N-methylglutarimide.106... 

Pyrrolidine and pyrrolidone derivatives with phosphorus-containing substituents 93MI1. 

Auch cyclische Carbonsaure-amide sind der beschriebenen Reaktion [phosphorige Sau-re/Phosphor(III)-chlorid]zuganglich4 aus l-Methyl-2-pyrrolidon erhalt man in 41%iger Ausbeute l-Methyl-pyrrolidin-2,2-diphosphonsaure (Schmp. 207°). 

Reaction of succinylhydrazide derived from (A)-amino-2-methoymethylpyrrolidine (SAMP) with benzylmagne-sium chlorides allows us to prepare a number of enantiopure 5-arylmethyl-pyrrolidones and -pyrrolidines.265 An enantioselective desymmetrization of anhydrides was reported by Fu. Arylmagnesium chlorides react in toluene in the presence of 1 equiv. of (—)-sparteine with 3-substituted glutaric anhydrides, giving aryl ketones with 87-92% ee (Scheme 90).266... 

Oxidations with peroxybenzoic acid are carried out in solutions in dichloromethane, chloroform, benzene, ether, or ethyl acetate at or below room temperature and include epoxidation of double bonds [295, 296, 297, 298, 299, 300, 301], oxidation of benzaldehydes to carboxylic acids or phenols [302], the Baeyer-Villiger reaction of ketones [303, 304, 305, 306, 307], and oxidation of sulfides to sulfoxides [308, 309]. Peroxybenzoic acid is also used for the anti hydroxylation of double bonds [310], the oxidation of pyrrolidines to pyrrolidones [377] and of pyrroles to succinimides [377], and the preparation of azoxy compounds from azo compounds [372]. 

Bases Alumina, see p-Toluenesulfonylhydrazine. Dehydroabietylamine. 1,5-Diazabicyclo [4.3.0]nonene-5. 1,4-Diazabicyclo[2.2.2]octane. l,S-Diazabicyclot5.4.0]undecene-5. 2,6-Di-/-butylpyridine. N,N,-Diethylglycine ethyl ester, see /-Amyl chloroformate. 2,6-Dimethyl-piperidine. Ethanolamine. Lithium diisopropylamide, see Diphenylsulfonium isopropylide. Lithium nitride. Magnesium methoxide. N-Methylmorpholine. Piperidine. Potassium amide. Potassium hydroxide. Potassium triethylmethoxide. Pyridine. Pyrrolidine. Sodium methoxide. Sodium 2-methyl-2-butoxide. Sodium thiophenoxide. Thallous ethoxide. Triethyla-mine. Triphenylphosphine, see l-Methyl-2-pyrrolidone. 

Geissman and Waiss (i<3 )have effected the first stereospecific synthesis of retronecine (CXLIV in 1) by a series of reactions which is shown in Chart I. Ethyl A-carbethoxy-3-aminopropionate (LI) was added to diethyl fumarate and the product ring-closed to the pyrrolidone, LII, which on hydrolysis and reduction yielded the required 3-hydroxy-pyrrolidine-2-acetic acid lactone (LIII). Reaction of this lactone with ethyl bromoacetate gave the A-acetic ester, LIV which by ring closure... 

Cotlnlne, I-Methyl-5-(3-pyridinyli-2-pyrrolidin-one N-methyl-2-(3-pyridyl)-5-pyrrolidone. C.tH.2N20 mol wt 176.21. C 68.16%, H 6.86%, N 15.90%, O 9.08%. Nicotine metabolite first described by Pinner, Arch. Pharm. 231, 378 (1893). Isolated from autoxidized nicotine, nicotine treated with hydrogen peroxide, from nicotine irradiated with ultraviolet light Frankenburg, Vaitekunas, J. Am. 

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