Chloroacetophenone Research Articles

Bioreduction of aromatic ketones: preparation of chiral benzyl alcohols in both enantiomeric forms

Substituted phenacyl chlorides are reduced with whole-cell biocatalysts to give (R)- or (S)-chlorohydrines in high yields and to make them good for high enantiomeric excess. Yields and enantiomeric purity of the S-enantiomer could be increased by performing bioreduction in the presence of polymeric absorbing resins. With this methodology, 2-chloro-1(S)-(3,4-dichloro-phenyl)-ethanol of 98% e.e. and 2-(R)-(4-nitro-phenyl)-ethanol of 92% e.e. have been prepared and used respectively as precursors in the synthesis of (+)-cis-1(S),4(S)-sertraline and of the β-blocker (R)-nifenalol®.

Effect of the molar ratio of an energy source to the substrate on yeast-mediated production of 2-chloro-α-methylbenzyl alcohol

Pachysolen tannophilus cells immobilized in Ca-alginate gels were shown to catalyze the asymmetric reduction of acetophenone (AP) and chloroacetophenones (Cl-APs) to their corresponding alcohols. The position of the Cl-group on the aromatic ring of AP greatly affected the reaction rate, and o-Cl-AP was the most readily reduced. For the reduction of o-Cl-AP to 2-chloro-α-methylbenzyl alcohol, the effect of the molar ratio of the energy source, glucose, to the substrate was examined in both batch and continuous operations, and a molar ratio much lower than that conventionally used was found to be sufficient for the reduction.

Asymmetric C–C bond forming reactions with chiral crown catalysts derived from d-glucose and d-galactose

New chiral monoaza-15-crown-5 derivatives anellated to methyl-4,6- O-benzylidene-α- d-glucopyranoside 2a, 2e, 2g– i and to methyl-4,6- O-benzylidene-α- d-galactopyranoside 3a, 3e, 3i have been synthesized. These crown ethers showed significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (87% ee), in the Darzens condensation of phenacyl chloride with benzaldehyde (71% ee) and in the self-condensation of phenacyl chloride (64% ee) to give 14. The absolute configurations of (−)-(2 R,3 S)-epoxy-3-(4-chlorophenyl)-1-phenyl-1-propanone 12 and (−)-4-chloro-(2 R,3 S)-epoxy-1,3-diphenyl-1-butanone 14 have also been determined by X-ray diffraction.

C-14 labelling of NVP VID400—a specific vitamin D3-hydroxylase inhibitor

The synthesis and analysis of [14C]NVP VID4001, a specific vitamin D3-hydroxylase inhibitor is reported. The key intermediate is (R)-2-amino-1-phenyl-[1-14C]ethanol 9 synthesized in an effective, enantioselective approach using a borane reduction of phenacyl chloride 6 in the presence of (R)-oxazaborolidine-catalyst 2. After N-acylation of 9 the resulting amide 10 was converted to the oxazoline 12, which when treated with imidazole ring-opened to the title compound 1. Both reactions—ring-closure and ring-opening—went with complete configurational inversion. The secondary isotope effect induced splitting 13C-NMR signals enabling the quantification of the isotopic purity and thereby the specific activity of 1 Copyright © 1999 John Wiley & Sons, Ltd.

C‐14 labelling of NVP VID400—a specific vitamin D3‐hydroxylase inhibitor

The synthesis and analysis of [14C]NVP VID400 1, a specific vitamin D3-hydroxylase inhibitor is reported. The key intermediate is (R)-2-amino-1-phenyl-[1-14C]ethanol 9 synthesized in an effective, enantioselective approach using a borane reduction of phenacyl chloride 6 in the presence of (R)-oxazaborolidine-catalyst 2. After N-acylation of 9 the resulting amide 10 was converted to the oxazoline 12, which when treated with imidazole ring-opened to the title compound 1. Both reactions—ring-closure and ring-opening—went with complete configurational inversion. The secondary isotope effect induced splitting 13C-NMR signals enabling the quantification of the isotopic purity and thereby the specific activity of 1 Copyright © 1999 John Wiley & Sons, Ltd.

Reaktionen von Ph 2SbH und p-TolSbH 2 mit organischen Verbindungen

p-TolSbH 2 reacts with styrene with formation of ethylbenzene and ( p-TolSb) n ( n=4, 5 in benzene). The action of phenyl acetylene on p-TolSbH 2 gives styrene. Addition of Ph 2SbH on phenyl acetylene in the presence of AIBN (azodiisobutyronitrile) yields 95% trans- and 5% cis-PhCHCHSbPh 2. Ph 2SbH reacts with benzaldehyde in the presence of AIBN with formation of benzylalcohol (98%) and with various prochiral ketones in the presence of chiral auxiliares to give alcohols in high optical yields. Benzotrichloride reacts with Ph 2SbH in the presence of PdCl 2 to give benzylidene chloride. 1-Bromo adamantane, dibromo cholestanol, 2-chloro acetophenone, cinnamic acid chloride, and chloro acetophenone react with Ph 2SbH/AIBN with substitution of the halogen atoms by hydrogen. Benzylbenzoate is formed the by action of Ph 2SbH/AIBN on benzoyl chloride.

Synthesis, extraction ability and application in asymmetric synthesis of azacrown ethers derived from D-glucose

A number of new chiral monoaza-15-crown-5 derivatives ( 4–9) and lariat ethers ( 10–15) anellated to phenyl-β-D-glucopyranoside have been synthesized. Their extracting ability was measured with alkali metal (Li, Na, K) and ammonium cations. The derivatives show significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (82% ee) although in low yield, and in the Darzens condensation of phenacyl chloride with benzaldehyde (74% ee). The substituent at the nitrogen atom of the crown ethers has a major influence on both the extraction ability and the enantioselectivity.

Stereochemical control in microbial reduction. Part 31: Reduction of alkyl 2-oxo-4-arylbutyrates by baker's yeast under selected reaction conditions

Treatment of baker's yeast with phenacyl chloride in an aqueous–organic solvent has been proven to be an effective method of inhibiting the enzymes that afford ( S)-enantiomers of α-hydroxy esters in the reduction of α-keto esters. The procedure is effective for the whole-cell system to produce the ( R)-product with high chemical yield and high enantiomeric excess.

Catalytic asymmetric Darzens condensation under phase-transfer-catalyzed conditions

Abstract The catalytic asymmetric Darzens condensation promoted by the quaternary ammonium salt (PTC A) derived from cinchonine as a phase-transfer catalyst is described. Treatment of phenacyl chloride with various aldehydes under mild reaction conditions afforded the corresponding desired product in good yield with good to moderate enantiomeric excess.

Stereochemical Control in Microbial Reduction. 30. Reduction of Alkyl 2-Oxo-4-phenylbutyrate as Precursors of Angiotensin Converting Enzyme (ACE) Inhibitors

Abstract Alkyl 2-oxo-4-phenylbutyrates are reduced to the corresponding alkyl (R)-2-hydroxy-4-phenylbutyrates, versatile chiral building blocks in organic synthesis, in high chemical yield (80—90%) with excellent stereoselectivity ( > 90%ee). The reaction has been run in aqueous diethyl ether at 30 °C for 24 h under the catalysis of bakers’ yeast (Saccharomyces cerevisiae) which was preincubated for 6 h in the presence of phenacyl chloride. The amount of water in the medium should be controlled strictly not to exceed 0.8 mL (g yeast)−1.

Synthesis and application in asymmetric synthesis of azacrown ethers derived from D-glucose

New chiral monoaza-15-crown-5 derivatives and lariat ethers anellated to phenyl β-D-glucoside have been synthesized which show significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (84% ee) and in the Darzens condensation of phenacyl chloride with benzaldehyde (74% ee).

Synthesis of Phenacylmethacrylate: Its Characterization and Polymerization

Phenacylmethacrylate (PAMA), a new monomer containing two carbonyl groups (C˭O), was obtained from phenacyl chloride and sodium methacrylate. The homopolymer of PAMA and its copolymer with styrene were prepared in dioxane by using benzoylperoxide (Bz2O2) as initiator. IR, 1H-NMR and 13C-NMR techniques were used to identify the structure of the monomer and polymers. The density of monomer, homopolymer and copolymer were found to be 1.13; 1.35 and 1.10 gr/ml respectively. Also, limit viscosity numbers, solubility parameters, glass transition and decomposition temperatures of polymers were determined.

Asymmetric C-C Bond Forming Reactions by Chiral Crown Catalysts; Darzens Condensation and Nitroalkane Addition to the Double Bond

A new, efficient crown ether 1 anellated to a sugar derivative has been prepared which shows significant asymmetric induction as phase transfer catalyst in the Michael addition of 2-nitropropane to chalcone (60% ee for the S antipode) and in the Darzens condensation of phenacyl chloride and benzaldehyde (64% ee), simultaneously changing the PT process from solid-liquid to liquid-liquid phase.

Mixed metal vinyl stabilizer synergism. VI: Lead stabilizer‐group II metal carboxylate blends

AbstractRelative rates are given for the reaction of a model compound, phenacyl chloride, with simple lead carboxylates and actual lead stabilizers. The data suggest that lead stabilization is more complex than previously indicated, with reaction products that are lead double salts, rather than simply lead dichloride. This is rationalized in terms of reactive site coordination to the extended lead stabilizer structure, as opposed to the stabilizer being merely a carrier of PbO.

Imidazole derivatives. XXVII. Synthesis and radioprotective activity of substituted phenacylthioimidazoline and 3-phenyl-5,6-dihydroimidazo[2,1-B]thiazole hydrochlorides

Previously, we described the synthesis of phenacylthioimidazolines and investigated the biological properties of the corresponding hydrochlorides. It was found that some hydorchlorides exhibited quite significant sympathicolytic and mutagenic activity. Due to the low solubility of substituted phenacylthioimidazoline hydrobromides in water and the fact that they can cyclize into imidazothiazoles it was difficult to convert the hydrobromides to the corresponding hydrochlorides. For this reason the phenacylthioimidazoline hydrochlorides were synthesized in the present work by reacting the phenacyl chlorides with 2-thio-2-imidazoline. 8 refs., 2 figs., 2 tabs.

Synthesis and Investigation of C2-Symmetric Optically Active Pyrrolidinium Salts as Chiral Phase-Transfer Catalysts.

C2-Symmetric optically active pyrrolidinium salts were synthesized by the reaction of 2, 3 : 4, 5-di-O-benzylidene-(3R, 4R)-dihydroxy-(2S, 5S)-bis(hydroxymethyl)pyrrolidine (2), (3R, 4R)-dimethoxy-(2S, 5S)-bis(methoxymethyl)-pyrrolidine (3), 2, 3 : 4, 5-Di-O-benzylidene-(3R, 4R)-dihydroxy-N-(2-hydroxyethyl)-(2S, 5S)-bis(hydroxymethyl)-pyrrolidine (5), and (3R, 4R)-dimethoxy-N-(2-hydroxyethyl)-(2S, 5S)-bis(methoxymethyl)pyrrolidine (7) with methyl iodide or α, ω-dibromoalkanes. They exhibited low chiral induction activity in the epoxidation of chalcone and in the Darzens condensation of p-chlorobenzaldehyde and phenacyl chloride under phase-transfer conditions.

Effects of omega-chloroacetophenone (CN) vapor inhalation on pulmonary immune system of mice.

Effects of omega-chloroacetophenone (CN) vapor inhalation on pulmonary immune system of mice.

Quasiphosphonium intermediates. Part 7. The preparation of trinorborn-1-yl phosphite and its reactions with halogeno compounds: stable intermediates of the Arbuzov and Perkow reactions and their structural characterization by X-ray diffraction, NMR spectroscopy, and fast atom bombardment mass spectrometry

Trinorborn-1-yl phosphite has been prepared and has been shown to give highly stable phosphonium salts in its reactions with iodomethane and with a number of α-halogenoketones. Phenacyl bromide and p-bromophenacyl bromide underwent reaction at room temperature to give the corresponding ketophosphonium halides (Arbuzov intermediates) as the exclusive products, whilst p-nitrophenacyl chloride gave the corresponding vinyloxyphosphonium chloride (Perkow intermediate) as the first example of a stable intermediate of this type. The structures of these two types of intermediate in the solid state were confirmed by X-ray diffraction measurements which revealed distorted tetrahedral arrangements around phosphorus, with P+⋯ Br– and P+⋯ Cl– interionic distances of 4.58 and 4.71 A for the phenacyl bromide and p-nitrophenacyl chloride adducts respectively. Phenacyl chloride, chloroacetone, and p-nitrophenacyl bromide gave mixed products, amongst which trinorborn-1-yl phosphate was always present. Possible reaction mechanisms are discussed. Thermal decomposition of the Arbuzov intermediates (149 °C) gave the expected phosphonates but the Perkow intermediate underwent elimination of alkyne under these conditions to give trinorborn-1-yl phosphate. 31P NMR and fast atom bombardment mass spectra of the quasiphosphonium salts are reported and discussed.

Use of batch and fed-batch fermentation for studies on the variation of glutathione content and its influence on the genotoxicity of methyl-nitro-nitrosoguanidine in yeast.

We have applied fermenter techniques to analyse the variations of glutathione (GSH) content in cultures of the diploid strain D7 of Saccharomyces cerevisiae. Choosing various experimental conditions of controlled batch and fed-batch fermentation we give evidence that the GSH levels of the yeast cultures depend on growth phase, the carbon source supply and the carbon source metabolism in an unexpectedly complex manner. Additionally, we analysed yeast cells with low GSH levels which were obtained either by depleting GSH with chloroacetophenone (CN) chemically or by using a GSH-deficient diploid strain (gsh1/gsh1). In order to study the relevance of the factors influencing the GSH concentration for genotoxicity testing in yeast we have used N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) which is activated by GSH. We show that in cells which are GSH proficient the extent of genotoxicity of MNNG correlates well with the GSH levels in the cells. Conditions of high GSH content (stationary phase of growth) corresponds with high genotoxic activity of MNNG, whereas conditions of low GSH content as logarithmic growth, glucose repression, GSH deficiency caused by the gsh1 mutation and GSH depletion by CN treatment correspond with a very moderate genotoxic effect of MNNG. These findings emphasize the necessity to use metabolically highly standardized cells for genotoxicity testing, since the carbon source catabolism, the concentration of glucose, growth rate and possibly other parameters influence the metabolization of xenobiotic agents in yeast.

ChemInform Abstract: Synthesis and Structure of 6,7‐Dihydro‐2,3‐disubstituted 5H‐2a‐Thia(2a‐S(IV))‐2,3‐4a,7a‐tetraazacyclopent(cd)indene‐1,4(2H,3H)‐dithione.

AbstractThe dianion generated from (I) reacts with phenacyl chloride (II) and the isothiocyanates (III) in a one‐pot reaction to give the symmetrical tetraazapentalenes (IV); unsymmetrical analogues such as (VII) are prepared from (IVa) via the thiadiazolopyrimidines (V).