Reduction Of Acetophenone Research Articles

Isolation of microbe for asymmetric reduction of prochiral aromatic ketone and its reaction characters

The favorable microbes for the asymmetric reduction of prochiral aromatic ketones was isolated from soil using acetophenone as the sole carbon source, when the asymmetric reduction of acetophenone (ACP) to chiral α-phenethyl alcohol (PEA) was chosen as the model reaction. Two microbe strains with excellent catalytic activity were obtained. They were Geotrichum candidum and Pichia pastoris identified by bacteria identification. The product of the asymmetric reduction of ACP catalyzed by Pichia pastoris was mainly R-PEA and that by Geotrichum candidum was mainly S-PEA. The yield and enantiomeric excesses (e.e.) could respectively reach 75% and 90% for Pichia pastoris, and 80% and 70% for Geotrichum candidum, much higher than those catalyzed by baker’s yeast.

Purification and characterization of an enantioselective carbonyl reductase from Candida viswanathii MTCC 5158

A highly enantioselective carbonyl reductase produced by a new yeast strain Candida viswanathii MTCC 5158, which was isolated using an acetophenone enriched medium, has been purified and characterized. The enzyme has been purified to near homogeneity using ammonium sulfate precipitation, ion exchange and gel filtration chromatography. The molecular properties of the carbonyl reductase suggested the native enzyme to be tetrameric, with an apparent molecular weight of 120 kDa, the monomer being about 29 kDa. Acetyl aryl ketones were found to be the preferred substrates for the enzyme and the best reaction was the enantioselective reduction of acetophenone. The enzyme yielded ( S)-alcohol in preference to ( R)-alcohol and utilized NADH, but not NADPH as the cofactor. The purified enzyme exhibited maximum enzyme activity at pH 7.0 and 60 °C. The enzyme retained about 80% of its activity after 7 h incubation at 25 °C in sodium phosphate buffer (50 mM, pH 7.0). The addition of reducing agents like dithiothreitol and β-mercaptoethanol enhanced the enzyme activity while organic solvents, detergents and chaotropic agents had deleterious effect on enzyme activity. Metal chelating agents like hydroxyquinoline and o-phenanthroline have significant effect on enzyme activity suggesting that the carbonyl reductase required the presence of a tightly bound metal ion for activity or stability. The maximum reaction rate ( V max) and apparent Michaelis–Menten constant ( K m) for acetophenone and NADH were 59.21 μmol/(min mg) protein and 0.153 mM and 82.64 μmol/(min mg) protein and 0.157 mM at a concentration range of 0.2–2 mM acetophenone (NADH fixed at 0.5 mM) and 0.1–0.5 mM NADH (acetophenone fixed at 2 mM), respectively.

Heterobimetallic [Ru(II)/Fe(II)] complexes: On the formation of trans- and cis-[RuCl 2(dppf)(diimines)

The synthesis and characterization of trans/ cis-[RuCl 2(dppf)(diimines)], dppf = 1,1′-bis(diphenylphosphino)ferrocene; diimines = 2,2′-bipyridine ( trans/ cis-( 1)), the new complexes with 4,4′-dimethyl-2,2′-bipyridine ( trans/ cis-( 2)) and 1,10-phenanthroline ( cis-( 3)) are presented. The complexes were synthesized using two routes and the trans/ cis-isomer formation is dependent upon conditions and the precursor applied. The trans-isomer (kinetic) readily isomerizes to the cis-isomer (thermodynamic) when exposed to light (fluorescent) and this process was followed by cyclic voltammetry and UV–vis. The electrochemical studies on these complexes reveal that Fe (III)/Fe (II) couples are insensitive to the isomer ( trans/ cis) formed, but the Ru (III)/Ru (II) couples are dependent on the isomer. Transfer-hydrogenation reactions for reduction of acetophenone were conducted using complexes cis-( 1) and cis-( 2) and the results are compared with that obtained for similar complexes. X-ray structure for cis-( 3) are presented and discussed.

Asymmetric reduction of acetophenone analogues by Alternaria alternata using ram horn peptone

Alternaria alternata EBK-4 fungus isolated from a plant sample was evaluated for the asymmetric reduction of acetophenone analogues. In a previous study, this isolate was used for the reduction of acetophenone to 1-phenylethanol in excellent enantiomeric excess. The substituted acetophenones were converted to the corresponding optically active alcohol by A. alternata EBK-4 under optimized conditions in up to >99% enantiomeric excess (ee). This is the first report on the enantiomeric reduction of acetophenone analogues by A. alternata using ram horn peptone from waste material.

New C 2-symmetric optically active salen ligands and their cobalt(II) complexes. Hydridoborate reduction of prochiral C=O and C=C bonds

Novel optically active salen ligands and their cobalt(II) complexes were synthesized on the basis of 1,3-dioxolane. Spectral parameters of the complexes and their catalytic activity in enantioselective reduction of carbonyl and unsaturated compounds with sodium tetrahydridoborate were studied. The catalytic reduction of acetophenone is characterized by quantitative yield, the optical yields ranging from 0 to 42%. Benzil and ethyl benzoylformate undergo noncatalytic reduction. The catalytic activity and enantioselectivity in the reduction prochiral C=C bond strongly depend on the solvent and change from low to moderate values in the reduction of methyl 2-acetylamino-3-phenylprop-2-enoate. Dimethyl 2-methylidenebutane-1,4-dioate is reduced in DMF and its mixtures with ethanol and toluene in quantitative yield; in chloroform, the optical yield reaches 89%, but the chemical yield sharply decreases.

Enzymatic ketone reduction: mapping the substrate profile of a short-chain alcohol dehydrogenase (YMR226c) from Saccharomyces cerevisiae

A short-chain alcohol dehydrogenase (YMR226c) from Saccharomyces cerevisiae was cloned and expressed in Escherichia coli, and the encoded protein was purified. The activity and enantioselectivity of this recombinant enzyme were evaluated with a series of ketones. The alcohol dehydrogenase (YMR226c) was found to effectively catalyze the enantioselective reductions of aryl-substituted acetophenones, α-chloroacetophenones, aliphatic ketones, and α- and β-ketoesters. While the enantioselectivity for the reduction of β-ketoesters was moderate, the acetophenone derivatives, aromatic α-ketoesters, some substituted α-chloroacetophenones, and aliphatic ketones were reduced to the corresponding chiral alcohols with excellent enantioselectivity. The enantiopreference of this enzyme generally followed Prelog’s rule for the simple ketones. The ester functionality played some role in determining the enzyme’s enantiopreference for the reduction of α- and β-ketoesters. The present study serves as a valuable guidance for the future applications of this versatile biocatalyst.

Highly enantioselective reduction of acetophenone by locally isolated Alternaria alternata using ram horn peptone

Enantiomerically pure compounds are important building blocks in the synthesis of natural products. In this study, the reduction of acetophenone to the ( S)-isomer of 1-phenylalcohol with a high enantiomeric excess (ee) by locally isolated Alternaria alternata using ram horn peptone (RHP) was investigated. Ten strains of A. alternata were isolated from different plant samples. These isolates were evaluated for the reduction of acetophenone (ACP) to 1-phenylethanol (PEA). Glucose, yeast extract and RHP in a shake flask and fermenter for growth of A. alternata cultures were used. A. alternata EBK-4 isolate was found to be an effective biocatalyst for the enantiomeric bioreduction of acetophenone. Conversions of up to 100% with excellent enantiomeric excesses (>99%) were obtained. Production of PEA was achieved via a fermenter. The yield was calculated as 86%. This is the first report on the enantioselective reduction of ACP by A. alternata using ram horn peptone from waste material.

Enantioselective reduction of substituted acetophenones by Aspergillus niger

Fourteen strains of Aspergillus niger were isolated from soil samples. These isolates were evaluated for the reduction of acetophenone to 1-phenylethanol. Among the tested isolates, whole cells of the A. niger EBK-9 isolate were found to be an effective biocatalyst for the enantioselective reduction of acetophenone. Under optimized conditions substituted acetophenones were converted to the corresponding optically active alcohol in up to 99% ee.

Electroenzymatic synthesis of chiral alcohols in an aqueous–organic two-phase system

The reduction of acetophenone to ( R)-phenylethanol catalysed by the alcohol dehydrogenase from Lactobacillus brevis in combination with electrochemical regeneration of NADPH mediated by a rhodium complex is reported. The reaction in buffer solution was optimised with regard to high productivity (up to 14 gL −1d −1) and enantioselectivity (>99.9%). Enzyme stability under the reaction conditions was increased either by addition of bovine serum albumin as a sacrificial protein or by immobilisation, leading to full conversion and enzyme ttn’s of up to 75,000. To improve the utilisation of cofactor and mediator as well as to broaden the substrate spectrum to more hydrophobic substrates, we introduced an organic phase of methyl tert-butyl ether. This is the first reported two-phase approach for electrochemical cofactor regeneration, which yielded mediator and cofactor ttn’s twice as high as in the one-phase approach. Furthermore, a concentrated product solution of 180 mM enantiopure ( R)-phenylethanol was obtained, facilitating product work-up.

Rhodium(I) Complexes Containing β‐Amino Alcohol and 1,2‐Diamine Ligands: Syntheses, Structures, and Catalytic Applications

AbstractThe bridge‐opening reaction of [(η4‐C8H12)2Rh2(μ‐Cl)2] with chiral and achiral β‐amino alcohol nucleophiles gave mononuclear complexes [(η4‐C8H12)RhCl{HN(R)∩OH‐κN}] containing the amino alcohol ligands in N‐monodentate coordination; HN(R)∩OH = ethanolamine (4), 2‐amino‐2‐methyl‐1‐propanol (5), and either enantiomer of (R)‐, (S)‐2‐amino‐3‐methyl‐1‐butanol (D‐, L‐valinol) [(R)‐6, (S)‐6], (R)‐, (S)‐2‐pyrrolidinemethanol (D‐, L‐prolinol) [(R)‐7, (S)‐7], (1S,2R)‐, (1R,2S)‐2‐amino‐1‐phenyl‐1‐propanol (D‐, L‐norephedrine) [(1S,2R)‐8, (1R,2S)‐8], and (1S,2R)‐, (1R,2S)‐cis‐1‐amino‐2‐indanol [(1S,2R)‐9, (1R,2S)‐9]. Coordination of the free hydroxy function of the N,O ligands was brought about by both dehydrochlorination, which furnished the neutral valinolato chelate complex [(η4‐C8H12)Rh{(S)‐H2NCH(CHMe2)CH2O‐κN,κO}], (S)‐10, and by precipitation of the metal‐bound chloride with TlO3SCF3 to produce ionic chelate complexes [(η4‐C8H12)Rh{HN(R)∩OH‐κN,κO}]O3SCF3; HN(R)∩OH = 2‐amino‐2‐methyl‐1‐propanol (11), (S)‐2‐amino‐3‐methyl‐1‐butanol [(S)‐12], (S)‐2‐pyrrolidinemethanol [(S)‐13], (1R,2S)‐2‐amino‐1‐phenyl‐1‐propanol [(1R,2S)‐14], and (1R,2S)‐cis‐1‐amino‐2‐indanol [(1R,2S)‐15]. Except for only two in situ characterized [{(R)‐binap}Rh(H2N∩OH‐κN,κO)]+ cations, where H2N∩OH = L‐valinol or L‐norephedrine, no compound containing the various N,O ligands in addition to mono‐ or bidentate phosphanes could be prepared. In contrast, theP2/N2‐coordinated chelate complexes [{(R)‐binap}Rh(H2N∩NH2)]BF4 with H2N∩NH2 = H2NCMe2CMe2NH2 [(R)‐(16)], (R,R)‐H2NCH(Ph)CH(Ph)NH2 [(R),(R,R)‐17], and (R,R)‐1,2‐(H2N)2C6H10 [(R),(R,R)‐18] were easily obtained from [(η4‐C8H12)Rh{(R)‐binap}]BF4 and 1,2‐diamines. Oxidative addition of HCl to (R),(R,R)‐17 produced trans‐[{(R)‐binap}Rh(H)(Cl){(R,R)‐H2NCH(Ph)CH(Ph)NH2}]BF4 [(R),(R,R)‐19]. If activated by strong base (KOH), (R),(R,R)‐17 and (R),(R,R)‐19 acted as moderately active and enantioselective catalysts for the reduction of acetophenone by both direct and transfer hydrogenation: eemax: 71 % (S). The crystal structures of 4, (S)‐6, (R)‐7, (1R,2S)‐8, (S)‐10, (1R,2S)‐14, (1R,2S)‐15, (R)‐16, (R),(R,R)‐17, and two alcohol/alcoholato addition compounds, [(η4‐C8H12)Rh(H2NCMe2CH2O‐κN,κO)][(η4‐C8H12)Rh(H2NCMe2CH2OH‐κN,κO)][(η4‐C8H12)RhCl2] [1·2], and [(η4‐C8H12)Rh(H2NCMe2CH2O‐κN,κO)][(η4‐C8H12)Rh(H2NCMe2CH2OH‐κN,κO)]Cl [1·3], were determined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Improvement of the Asymmetric Induction from Lactic Acid Derivatives Enhanced by ZnCl2

Lactic acid methyl ester, lactic acid ethyl ester, and (2S)‐ethyl‐2‐methoxy propanate were used as solvents for acetophenone reduction by boron hydrides. Moderate enantiomeric excess up to 60% was obtained in the presence of stoichiometric amounts of ZnCl2. There is evidence for an intermediate between the solvents, the Lewis acid and the ketone, as the prerequisite for chirality transfer. The importance of the Lewis acid is to strengthen interaction between solvent and educt compared to the hydroxy group.

Improvement the tolerance of baker's yeast to toxic substrate/product with cloud point system during the whole cell microbial transformation

The industrial process of a whole-cell microbial transformation is usually hindered by the toxicity or inhibition of a high substrate/product concentration. Especially in a biocatalytic redox process, the cofactor regeneration with the viable cells is a key of the whole cell microbial transformation. In present work, growing culture of Saccharomyces cerevisiae (baker's yeast) in a nonionic surfactant mediated cloud point system was carried out. Then the tolerances of baker's yeast cells against a high substrate/product concentration and a long term of biocatalytic reduction of acetophenone to produce 1-phenylethanol as a model were examined in the cloud point system. The long term of cofactor regeneration at a high substrate concentration in the cloud point system make the cloud point system potential for further development as a novel two-phase partitioning system for production of chiral compounds by microbial transformation.

Effect of conformational control of chiral oxazaborolidine by π–π stacking interaction of a pentafluorophenyl group toward asymmetric borane reduction

A pentafluorophenyl group can act as a stereo-controlling group in oxazaborolidine-catalyzed asymmetric borane reduction through intramolecular π–π stacking interaction with a phenyl group. The intramolecular π–π interaction in oxazaborolidine bearing pentafluorophenyl group is confirmed by calculations and 1H NMR study. The interaction affects the enantioselectivity of the asymmetric reduction of acetophenone while the extent is small.

4‐Hydroxyphenylglycine‐Based Oxazaborolidines for Enantioselective Reductions of Ketones

AbstractAmino alcohols 6 featuring the diphenylhydroxymethyl group are prepared from the commercial amino acid (R)‐4‐hydroxyphenylglycine 3. Oxazaborolidines generated in situ from the amino alcohols 6 and borane‐dimethyl sulfide serve as catalysts in enantioselective reductions of acetophenone. The para‐substituents of the phenyl ring at the stereogenic carbon atom have a substantial influence on the enantioselectivity. When mediated by the nonaflate 6d, the reduction of ketones 7, 9, 11, and 13 leads to the carbinols 8, 10, 12, and 14 in 90 to 96 % ee.

Monobromoborane - Dimethyl Sulfide—a Highly Promising Reagent for the Regio- and Chemoselective Brominative Cleavage of Terminal Epoxides into Vicinal Bromohydrins

Monobromoborane–dimethyl sulfide (BH2Br–SMe2) is a highly regio- and chemoselective reagent useful for the brominative cleavage of the epoxy moiety into bromohydrins in the presence of alkenes, alkynes, ethers, acetals, ketals, and acetonides at 0°C, besides being an excellent hydroborating reagent. Several reactive functional groups, such as chloride, ketones, esters, nitriles, nitros, and thioethers, have been accommodated during such transformations. Although the reduction of acetophenone was completely suppressed at –25°C, 4-chlorobenzaldehyde still underwent 12–13% reduction of an aldehydic group.

Reactivity of boranes with a titanium(iv) amine tris(phenolate) alkoxide complex; formation of a Ti(iv) tetrahydroborate complex, a Ti(iii) dimer and a Ti(iv) hydroxide Lewis acid adduct

Treatment of the titanium(IV) alkoxide complex [Ti(Oi Pr)(OC6Me2H(2)CH2)3N] (2) with BH3.THF, as part of a study into the utility and reactivity of (2) in the metal mediated borane reduction of acetophenone, results in alkoxide-hydride exchange and formation of the structurally characterised titanium(iv) tetrahydroborate complex [Ti{BH4}(OC6Me2H2CH2)3N] (3). Complex (3) readily undergoes reduction to form the isolable titanium(III) species [Ti(OC6Me2H2CH2)3N]2 (4). Reaction of (2) with B(C6F5)3 results in formation of the Lewis acid adduct [Ti(OC6Me2H2CH2)3N][HO.B(C6F5)3] (5). In comparison, treatment of the less sterically encumbered alkoxide Ti(Oi Pr)4 with B(C6F5)3 results in alkoxide-aryl exchange and formation of the organometallic titanium complex [Ti(Oi Pr)3(C6F5)]2 (6). The molecular structures of 3, 4, 5 and 6 have been determined by X-ray diffraction.

Mechanism for the reduction of ketones to the corresponding alcohols using supercritical 2-propanol

The mechanism for the reduction of ketones into the corresponding alcohols using supercritical 2-propanol under non-catalytic conditions was investigated. The studies of the kinetic-isotope effect and isotopic-labeling for the reduction of benzophenone and acetophenone were carried out using (CH 3) 2C D(OH), (CH 3) 2CH(O D), (C D 3) 2CH(OH), and (C D 3) 2C D(O D). It was clarified that the α- and hydroxyl hydrogens on 2-propanol, respectively, transfer to the carbonyl C and O in the rate-determining step. These isotope studies also suggested that this reaction proceeds via a six-membered cyclic transition state analogous to that of the Meerwein–Ponndorf–Verley reduction. The fact that Hammett's reaction constant for this reaction was low, i.e., ρ=0.33, and that the reduction of the prochiral ketones using optically active alcohols at supercritical or high temperature provided optically active products also supported the existence of a six-membered cyclic transition state.

Microwave‐Assisted Reduction of Acetophenones Using Ni—Al Alloy in Water.

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Chiral polyamino alcohols and polyamino thiols for asymmetric heterogeneous catalysis

A series of macroporous copolymer beads were synthesized by THE free radical suspension copolymerization of ( S)-glycidylmethacrylate (GMA), ( S)-thiiranylmethylmethacrylate (TMA), or ( R, R)-phenylglycidylmethacrylate (Ph-GMA) with ethyleneglycol dimethacrylate (EDMA) or divinylbenzene (DVB). This allowed for the evaluation of their chemical and physical properties (polymer matrix nature or the structure of the heterocyclopropane) and their influence on the catalytic efficiency. These chiral polymers were subsequently transformed into polyamino alcohol or polyamino thiol derivatives by the facile ring opening of the oxirane or thiirane group with benzylamine and methylamine. Complexed with [RuCl 2( p-cymene)] 2, these derivatives were shown to be effective in the asymmetric hydrogen transfer reduction of acetophenone. The best results (conversion: 94%, ee: 71%) were obtained with benzylamine grafted onto poly(GMA-co-EDMA) (30/70 % wt/wt).

Efficient transfer hydrogenation of ketones in the presence of ruthenium N-heterocyclic carbene catalysts

Novel ruthenium carbene complexes have been in situ generated and tested for the transfer hydrogenation of ketones. Applying Ru(cod)(methylallyl) 2 in the presence of imidazolium salts in 2-propanol and sodium-2-propanolate as base, turnover frequencies up to 346 h −1 have been obtained for reduction of acetophenone. A comparative study involving ruthenium carbene and ruthenium phosphine complexes demonstrated the higher activity of ruthenium carbene complexes.