3-Hydroxy-2-pyrrolidones

The importance of ring size holds also for tautomerism of -pyrrol-5-ones and. d -dihydro-6-pyridones. While the former compounds behave as cyclic 1-methyl-2-alkyl-2-hydroxy-5-pyrrolidones 179) (76) [or, on distillation, as the dehydrated l-methyl-2-alkyl-J -pyrrolones (77)], the latter compounds exist as acyclic N-methylamides of 8-oxo-acids (78) [as shown by infrared spectroscopy (/80)j. The dehydration of 78 during distillation to form l-methyl-2-alkyl-. -dihydro-6-pyridones (79) is achieved only with difficulty. 

The name hydroxamic acid was first used by Losseii in 1869, in the case of oxalohj droxamic acid, obtained from diethyl oxalate and hydroxylamine. Where this grouping forms part of the main cyclic system, however, the compound is named as a derivative of this system. In this review, 2 and 3 would be named as 1-hydroxy-2-pyrrolidone and l-hydroxy-2-pyridone, respectively. 

MMA, styrene, 2-hydroxy ethyl methyacrylate, 2-hy-droxypropyl methacrylate, acrylic and methacrylic acids, acrylamide and N-vinyl pyrrolidone (NVP) [64]. By this process, polyurethane is partially converted to N-chloro or N-bromo derivatives by a short immersion... 

Die Reduktion von 9-Brom-ll/3-hydroxy-steroiden mit Chrom(II)-Salzen, insbeson-dere mit Chrom(II)-acetat fiihrt zu 11/3-Hydroxy-steroiden (s. S.515), A9 (11)-Ste-roiden (s. S.518) und 5,9-Cyclo-steroiden. Die Cyclopropan-Bildung wird durch Chrom(II)-acetat in Dimethylsulfoxid bzw. Dimethylformamid begiinstigt. So laufen beim 9a-Brom-l l/3-hydroxy-3-oxo-l 7/ -acetyl-ostren-(510) in waBr. Aceton, THF, 1,4-Di-oxan oder N-Methyl-pyrrolidon Substitution, Eliminierung und Cyclisierung nebeneinan-der ab, in Dimethylsulfoxid oder Dimethylformamid erhalt man fast ausschlieBlich ///3-Hydroxy-3-oxo-17 3-acetyl-5,9-cyclo-dstran5 ... 

However, morpholine-4-carboxylic acid 2-hydroxy-1-methyl-ethyl ester is formed by the reaction of PC and the substrate morpholine in an undesired side reaction. By use of 1.4-dioxane or the pyrrolidones as mediator s3 about 30 to 45% of the morphoUne is consumed by this side reaction. The by-product is contained in the PC phase and can not be extracted to the non-polar product phase. The selectivity to the desired amines is lowered, because of the consiunption of the morphoUne. Thus, PC has to be substituted by another polar solvent (e.g. water, methanol or ethylene glycol) in future experiments. The lactates react with the morphoUne, too resulting in the corresponding amide. Overall, the hydroaminomethylation in the TMS systems PC/dodecane/lactate results in a conversion of 1-octene of about 80%, but in selectivities to the amines of only 50 to 60%. 

Sorm and Beranek39 used an intramolecular acylation in their synthesis of l-azoniumtricyclo[3.3.3.0]undecane (66). Condensation of nitromethane with acrylonitrile in the presence of an alkaline catalyst resulted in the formation of tris-(2-cyanoethyl)nitromethane (60), which afforded the triethyl ester 61 on hydrolysis followed by esterification. The ester was reduced catalytically to give a pyrrolidone (62). The derivative (62) gave rise to 8-(j8-carboethoxyethyl)-3,5-dioxo-pyrrolizidine (63) on heating. Reduction of 63 resulted in the formation of 8-(y-hydroxypropyl)pyrrolizidine (64). Replacement of the hydroxy group by bromine (65), followed by cyclization, afforded the tricyclic compound 66. 

Ammonium quaternary salt containing a double bond such as [2-hydroxy-3-(methacryloyloxy)propyl]trimethylammonium chloride can be used as a grafting reagent to improve the hydrophylic properties of polyamides (63). Still other compounds as vinyl pyrrolidone (23) and methacryloxy stannane (64), seem to be useful for Nylon grafting under cobalt-60 irradiation. 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

The above mentioned hydroxy and epoxy functional silanes represent reactive intermediates which can be transformed into ionic trimethyl silane derivatives. To give an example, hydroxyhexyltrimethylsilane can be reacted with sulfamic acid in the presence of a polar aprotic solvent such as f -methyl pyrrolidone or dimethyl formamide. The transformation of the ammonium salt into the appropriate alkyl ammonium derivative is readily achieved by addition of amine under generation of ammonia gas. 

Bovine Plasma Protein Adsorption onto Radiation-Grafted Hydrogels Based on Hydroxy ethyl Methacrylate and N-Vinyl-pyrrolidone... 

The sodium salt of 2-hydroxypyrazine with thiophosphoryl chloride at room temperature gave 2-(dichlorophosphinothioyloxy)pyrazine (1112, 1113) and in N-methyl-2-pyrrolidone with ( ,6)-diethyl phosphorochloridothioate [(EtO)2P(=S)Clj it gave 2-(diethoxyphosphinothioyloxy)pyrazine (1114, 1115), also prepared in the absence of A(-methyl-2-pyrroIidone (1116). The potassium salt of 2-hydroxy-pyrazine in t-butanol-dioxane with 0,0-diphenyl phosphorochloridothioate... 

Such compounds are treated as hydroxyl compounds even if their dominant tautomeric form is the keto tautomer. Reduction usually takes place either in the nucleus or at the carbonyl group. Simple examples of the first type are maleic imide [393, 394] and hydra-zide [395] in many other examples a second reduction leads to a ring contraction. Reduction of the keto group leads to a hydroxyl group in many cases water is eliminated and a further reduction takes place. An example of this is the reduction of AT-methylsuc-cinimide to AT-methylpyrrolidone [396]. Oxidation of hydroxy-substituted dihydrohetero-cycles may introduce a double bond an example is the oxidation of 1,2-dihydro-3-methoxycarbonyl-4-hydroxyquinoline in AcOH/7-BuOH to 1,4-dihydro-4-oxo-3-methox-ycarbonylquinoline [397]. The use of pyrrolidone as a probase is discussed in Chapter 30 [398]. 

Akesson B and Jonsson BAG (2000) Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker. Scandinavian Journal of Work, Environment and Health 26 213-218. 

GC Determination of(hydroxy-methyl)-butylpyrrolidone (= "2-propanol-vinyl-pyrrolidone adduct") in copovidone... 

C4 chiral synthetic units are also important for the syntheses of pharmaceuticals and their intermediates. For example, optically active 4-chloro-3-hydroxybutyrate (CHB) and 4-chloro-3-hydroxybutyronitrile (BN) are key compounds as C4 chiral building blocks for the syntheses of L-carnitine [16], l-GABOB [17], / -hydroxybuty-ric acid, 3-hydroxy-y-butyrolactone, and 4-hydroxy-2-pyrrolidone. Recently, CHB has been reported as being used for synthesizing an intermediate for HMG-CoA reductase inhibitor for hyperlipidemia (Fig. 11) [18]. 

Earlier, the reduction of y-nitro esters with zinc and ammonium chloride had been shown49 to provide a suitable route to iV-hydroxy 2-pyrrolidones, e.g., 42. Various catalytic hydrogenation procedures can also effect the same reductive cyclization.49,80... 

Some commonly used graft monomers are acrylates, such as methacrylic acid (to enhance adhesion), acrylic esters and hydroxy functional acrylates (that can couple with polar materials, as wood). Maleic anhydride and n-vinyl pyrrolidone are also used, but with care taken to avoid potential volatilization during processing. The former is used as an adhesion promoter, the latter to enhance bio-compatibility. Specific properties depend both on the backbone or base material that is being grafted and on the graft monomer (Fig. 1). 

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... 

PVAL has been noted to be miscible with various polymers including poly(vinyl pyrrolidone) [Thyagavajan and Janarthanan, 1989], hydroxy-propyllignin [Cielniecki and Glasser, 1988], and cellulose [Nishio and Manley, 1988]. 

When /8-propiolactone is heated under pressure with anhydrous ammonia, /3-hydroxypropionamide is obtained. A mole of /3-propiolactone (72 g) is heated under pressure with 5.87 moles (100 g) of ammonia for 16 hr at 100 C to obtain a 50 per cent yield of crude /3-hydrox5rpropionamide, which can be purified by vacuum distillation. By a dehydration reaction, the amination of the lactone of a y-hydroxycarboxylic acid yields a stable cyclic amide or lactam, as is the case when y-butyrolactone is converted to a-pyrrolidone. However, owing to the instability of the four-membered ring, a lactam cannot be formed from ammonia and the lactone of a /8-hydroxycarboxylic acid, such as -propiolactone. When hydroxy-propionamide is dehydrated, no lactam is formed. Only unsaturated acid derivatives can be obtained, as shown in the equation below. 

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