Propiophenone reduction

The complexes of chiral amino-alcohols of type (13) with borane are reported to reduce aryl alkyl ketones to alcohols in optical yields up to 60% [for propiophenone reduction with (13 R = CHMe2)]/ whereas the asymmetric reduction of phenyl alkyl ketones with amine-boranes formed from chiral amines (such as 1-phenylethylamine or various L-a-amino-esters) has been found to give low optical yields of alcohols, i.e. up to 23%. ... 

Reduction of the ethylenic compound gives a ketone, propiophenone (III), with one more methylene group than the ketone used in the original preparation ... 

The use of such an oxazaborolidine system in a continuously operated membrane reactor was demonstrated by Kragl et /. 58] Various oxazaborolidine catalysts were prepared with polystyrene-based soluble supports. The catalysts were tested in a deadend setup (paragraph 4.2.1) for the reduction of ketones. These experiments showed higher ee s than batch experiments in which the ketone was added in one portion. The ee s vary from 84% for the reduction of propiophenone to up to >99% for the reduction of L-tetralone. The catalyst showed only a slight deactivation under the reaction conditions. The TTON could be increased from 10 for the monomeric system to 560 for the polymer-bound catalyst. 

Propanol with magnesium in reduction of chlorobenzene, 47, 104 Propionic acid, 2-(2,4,5,7-tetranitro-flcoken-9-ylideneamtnooxv)-, (+)- AND (-)-, 48, 120 Propionyl fluoride, 45, 6 Propiophenone, condensation with paraformaldehyde, 48, 91 -Propylaminc, 45, 85 -Propylhydrazine, 45, 85 C-( -Propyl)-N-phenylnitrone, generation from phenylhydroxylamine and -butyraIdehyde, 46, 97 Purification of tetrahydrofuran (Warning), 46,105 477- Pyran-4-0ne, 2-6-dimethyl-3,5-DIPHENYL-, 47, 54... 

In an attempt to further elucidate the mechanism of this process, these workers monitored the reaction between propiophenone enolsilane and fumaroylimide by in situ infrared (IR) spectroscopy, Scheme 25 (240). In the absence of alcoholic additives, the accumulation of an intermediate is observed prior to appearance of product. When i-PrOH is introduced, immediate decomposition of the intermediate occurs with concomitant formation of product. Evans suggests that the intermediate observed in this reaction is dihydropyran (374). Indeed, this reaction may be viewed as a hetero-Diels-Alder cycloaddition followed by alcohol induced decomposition to the desired Michael adduct. That 374 may be acting as a competent inhibitor was suggested by an observed rate reduction when this reaction was conducted in the presence of IV-methyloxazolidinone. 

A 1,2-amino alcohol, ( + )-(lR,4S)-3-exo-anilino-2-exo-hydroxybornane (103), was synthesized from (-I-)-camphor and converted to its LAH complex (eq. [26]). Reduction of acetophenone, propiophenone, and butyrophenone at low... 

Phenylpropanolamine Phenylpropanolamine, D,L-erythro-1 -phenyl-2-methylamino-propanol-1 (11.3.7), is synthesized from propiophenone by nitrosation into an isonitroso derivative (11.3.6). Reduction of this by hydrogen in hydrochloric acid while simultaneously using two catalysts, palladium on carbon and platinum on carbon, gives norephedrine (11.3.7) [56-59]. 

Table 1. Reduction of (S)-2-[(Ethoxycarbonyl)amino]propiophenone (74) to Ephedrine (75a) and Pseudoephedrine (76 b)...

These intermediates were used to synthesize optically pure ephedrines and amphetamines without recourse to resolution, since the chirality of the amino acid educt was entirely conserved throughout the process. The reduction of (S)-2-(ethoxycarbo-nyl)amino-propiophenone (74) first produced a mixture of alcohols (75a, b) Lithium aluminium hydride reduction then produced the desired secondary amino alcohols (76a, b). Table 1 illustrates the reduction scheme and the diastereomer ratios obtained "K... 

Growth conditions in deep-well microtiter plates were optimized with respect to optimal expression of active enzymes (Fig. 2.2.1.1). The best results were obtained with an expression time of 20 h at 37 °C (Fig. 2.2.1.1, lanes 7-9). Subsequently, E. coli cells were enzymatically disrupted by lysozyme treatment, and the carboligase activity was monitored by a modified tetrazolium salt color assay [16], This color assay is based on the reduction of the 2,3,5-triphenyltetrazolium chloride (TTC) 13 to the corresponding formazan 15, which has an intense red color (Fig. 2.2.1.2A). Before screening ofa BFD variant library, substrates and products were tested in the color assay. Neither substrate, benzaldehyde 4 nor dimethoxy-acetaldehyde 8, reduced TTC 13 however, the product 2-hydroxy-3,3-dimethoxy-propiophenone 10 already caused color formation at low concentrations of 2.5-10 mM (Fig. 2.2.1.2B). Benzoin 12 as the product also gave a color change at a similar concentration (data not shown). 

In a closely related reaction, asymmetric reduction of 3-(2V-benzyl-7V-methylamino)propiophenone using H2, [Rh(COD)Cl]2 and the chiral phosphine (2S,4S-(l-(A-methyl-carbamoyl)-4-(dicyclohexylphosphino)-2-[diphenylphosphino)methyl]-pyrrolidine ((2S,4S)-MCCPM), followed by debenzylation and addition of the alcohol to l-chloro-4-(trifluoromethyl)benzene gave (R)-fluoxetine (4-(/ )). ... 

Isosorbide (3) and isomannide (4) act as chiral auxiliaries for the sodium borohydride reduction of some prochiral ketones optical yields of up to 20% were achieved. It seems that the isohexides form chiral complexes with sodium borohydride, whereby the chiral information is transferred to the substrate.219 Optical active alcohols were obtained by reduction of appropriate ketones with sodium or lithium borohydride in the presence of isosor-bide.219 Asymmetric reduction of propiophenone using sodium borohydride, modified with (+)-camphoric acid and isosorbide, resulted in C -phenylethylcarbinol in 35% enantiomeric excess.2,9b... 

A complex prepared in situ from CuCl, (R)-3,5-Xyl-MeO-BIPHEP, and t-C4H9ONa promoted the hydrosilylation of several alkyl aryl ketones (substrate Cu ligand base=33 l l l) with PMHS in toluene at -50 or -78 °C to afford the corresponding R products with high optical purity (Scheme 18) [35]. The reduction of propiophenone gave 97% ee. 4 -Trifluoromethylacetophenone and 2 -ac-etonaphthone were converted to the corresponding R alcohols in 95% ee. 1-Te-... 

The chiral Rh catalyst systems described above for the reduction of 1 have been shown to achieve high enantioselectivity (>90% ee) for aryl alkyl ketones 30-37. Propiophenone 30 and... 

Experimental procedures are given in Expt 6.107 for o- and p-hydroxy-propiophenones (R = Et). The ortho-para ratio in the product is influenced by the nature of the alkyl residue, the temperature, the solvent and the amount of aluminium chloride used generally low temperatures favour the formation of p-hydroxyketones. It is usually possible to separate the two hydroxyketones by fractional distillation under reduced pressure through an efficient fractionating column or by steam distillation the ortho isomers, being chelated, are more steam volatile. It may be mentioned that Clemmensen reduction (cf. Sections 5.1.3, p. 476 and 6.1.1, p. 826) of the hydroxyketones affords an excellent route to alkyl phenols. 

Chiral 1,2-aminodiols. Morrison el al.1 have prepared five chiral 1,2-aminodiols related to Darvon alcohol. The only useful one for asymmetric reduction of ketones in conjunction with LiAlH4 is 1, prepared from (S)-propylene oxide and (S)-ot-methylbenzylamine. Acetophenone and propiophenone are reduced by LiAlH4-l to the corresponding (R)-alcohols in 77-82% ee. In this case, the three (S)-centers reinforce one other. 

The hydrosilylation of carbonyl compounds with polymethylhydrosiloxane (PMHS) or other alkoxysilanes can be catalyzed by TBAF, at high efficiency [9]. The asymmetric version of this process has been developed by Lawrence and coworkers using chiral ammonium fluoride 7c prepared via the method of Shioiri [10]. The reduction of acetophenone was performed with trimethoxysilane (1.5 equiv.) and 7c (10 mol%) in THF at room temperature, yielding phenethyl alcohol quantitatively with 51% ee (R) (Scheme 4.6). A slightly higher enantioselectivity was observed in the reduction of propiophenone. When tris(trimethylsiloxy)silane was used as a hydride source, the enantioselectivity was increased, though a pro-... 

Al complexes prepared in situ from Al[OCH(CH3)2]3 and two equivalents of (K)-BINAPHTHOL (9) and (i )-H8-BINAPHTHOL (10) promoted the enanti-oselective reduction of propiophenone with borane-dimethyl sulfide and gave the S alcohol in 83% and 90% ee, respectively (Scheme 7) [47]. The reaction was much slower and afforded a racemic product in the absence of Al[OCH(CH3)2]3 under otherwise identical conditions. The addition of a catalytic amount of Al(OC2H5)3 increased both the rate and enantioselectivity in the hydroboration of ketones with a chiral amino alcohol [48]. 

The most remarkable feature of this method is that even acyclic enamines undergo reductive alkylation with good diastereoselectivity. The reaction of propiophenone enamines 31-33 with primary carbon-centered radicals substituted by different electron-... 

Disposition in the Body. Readily absorbed after oral administration. Metabolised by A-dealkylation, reduction, deamination, and A-hydroxylation primarily to active metabolites keto-reduction is stereoselective resulting in the formation of threo-hydroxylated metabolites glucuronide formation also occurs along with the formation of hippuric and mandelic acids. About 80 to 90% of a dose is excreted in the urine the amount excreted in the urine is reduced when the urine is alkaline of the urinary excreted material, A-ethylaminopropiophenone, norephedrine (phenylpropanolamine), and hippuric acid are the main metabolites together with small amounts of unchanged drug, amino-propiophenone, A-diethylnorephedrine, and A-ethylnor-ephedrine. 

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