201939-72-2

Usage

Uses

Used in Pharmaceutical Synthesis:
(S)-(1-(3’-aminophenyl)ethanol) is used as a chiral building block for the synthesis of biologically active molecules and pharmaceutical drugs. Its unique stereochemistry allows for the creation of enantiomerically pure compounds, which is crucial for the development of effective and safe medications.
Used in Fragrance and Flavor Production:
(S)-(1-(3’-aminophenyl)ethanol) is also utilized in the production of fragrances and flavors, where its ability to form a variety of chemical structures contributes to the creation of distinct scents and tastes.
Used in Specialty Chemicals:
(S)-(1-(3’-aminophenyl)ethanol) finds application in the production of specialty chemicals, where its dual functional groups enable the development of tailored chemical products for specific industrial needs.

Upstream product

• 99-03-6 1-(3-aminophenyl)ethanone 
• 587-02-0 m-ethylaniline 

Downstream Products

• 252268-56-7 3-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-phenylamine 
• 252268-57-8 C₃₀H₅₄N₃O₃PSi₂ 

Relevant academic research and scientific papers

Use of the Trost Ligand in the Ruthenium-Catalyzed Asymmetric Hydrogenation of Ketones

The Trost ligand, (1S,2S)-1,2-diaminocyclohexane-N,N′-bis(2′-diphenylphosphinobenzoyl) (L), is reported for the first time as a ligand for the asymmetric hydrogenation (AH) of ketones. Ligand (S,S)-L was screened in the presence of several metal salts and was found to form active catalysts if combined with ruthenium sources in the presence of hydrogen and a base. Reaction optimization was performed by screening different Ru sources, solvents, and bases. Under the optimized conditions, the complex formed by the combination of (S,S)-L with RuCl3(H2O)x in the presence of Na2CO3 was able to promote the AH of several ketones at room temperature in good yields with up to 96 % ee. The reaction kinetics measured under the optimized conditions revealed the presence of a long induction period, during which the initially formed Ru species was transformed into the catalytically active complex by reaction with hydrogen. Remarkably, a ketone that is a precursor of the antiemetic drug aprepitant was hydrogenated in excellent yield with a good ee value.

Enantioselective Reduction of α,β-Unsaturated Ketones and Aryl Ketones by Perakine Reductase

This report describes the enantioselective reduction of structurally diverse α,β-unsaturated ketones and aryl ketones by perakine reductase (PR) from Rauvolfia. This enzymatic reduction produces α-chiral allylic and aryl alcohols with excellent enantioselectivity and most of the products in satisfactory yields. Furthermore, the work demonstrates 1 mmol scale reactions for product delivery without any detrimental effect on yield and enantioselectivity. The catalytic mechanism, determined by 3D-structure-based modeling of PR and ligand complexes, is also described.

Extreme halophilic alcohol dehydrogenase mediated highly efficient syntheses of enantiopure aromatic alcohols

Enzymatic synthesis of enantiopure aromatic secondary alcohols (including substituted, hetero-aromatic and bicyclic structures) was carried out using halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii (HvADH2). This enzyme showed an unprecedented substrate scope and absolute enatioselectivity. The cofactor NADPH was used catalytically and regenerated in situ by the biocatalyst, in the presence of 5% ethanol. The efficiency of HvADH2 for the conversion of aromatic ketones was markedly influenced by the steric and electronic factors as well as the solubility of ketones in the reaction medium. Furthermore, carbonyl stretching band frequencies ν (CO) have been measured for different ketones to understand the effect of electron withdrawing or donating properties of the ketone substituents on the reaction rate catalyzed by HvADH2. Good correlation was observed between ν (CO) of methyl aryl-ketones and the reaction rate catalyzed by HvADH2. The enzyme catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that HvADH2 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.

The reaction mechanism of chiral hydroxylation of p -OH and p -NH 2 substituted compounds by ethylbenzene dehydrogenase

Ethylbenzene dehydrogenase (EbDH; enzyme commission (EC) number: 1.17.99.2) is a unique biocatalyst that hydroxylates alkylaromatic and alkylheterocyclic compounds to (S)-secondary alcohols under anaerobic conditions. The enzyme exhibits a high promiscuity catalyzing oxidation of over 30 substrates, inter alia, para-substituted alkylphenols and alkylanilines. Secondary alcohols with OH and NH2 substituents in the aromatic ring are highly valuable synthons for many biologically active compounds in the fine chemical industry. EbDH hydroxylates most of the studied compounds highly enantioselectively, except for five substrates that harbour OH and NH2 groups in the para position, which exhibit a significant decrease in the percent enantiomeric excess (% ee). This phenomenon is inconsistent with the previously suggested enzyme mechanism, but it may be linked to a stabilization of the carbocation intermediate by deprotonation of the OH or NH2 substituent in the active site that yields a transient quinone (imine) ethide species. This would initiate an alternative reaction pathway involving the addition of a water molecule to a C=C double bond. This hypothesis was cross-validated by density functional theory (DFT) cluster modelling of the alternative reaction pathway with 4-ethylphenol, as well as by experimental assessment of the pH dependency of enantiomeric excesses. The results reported herein suggest that the alternative reaction pathway may significantly contribute to the overall reaction if the carbocation intermediates are stabilized by deprotonation.

Origin of enantioselectivity in the Ru(arene)(amino alcohol)-catalyzed transfer hydrogenation of ketones

The origin of the enantioselectivity in the ruthenium-catalyzed transfer hydrogenation has been studied by means of experiment and density functional theory calculations. The results clearly show that electrostatic effects are of importance, not only in the T-shaped arene-aryl interaction in the favored transition state but also between the aryl of the substrate and the amine ligand in the disfavored TS. In addition, the electrostatic interaction between the alkyl substituent of the substrate and the catalyst is of importance to the enantioselectivity. The major cause of enantioselection is found to be of nonelectrostatic origin. This inherent property of the catalytic system is discussed in terms of dispersion forces and solvent effects. Finally, a minor but well-characterized steric effect was identified. The success of this class of catalysts in the reduction of alkyl aryl ketones is based on the fact that all factors work in the same direction.

Preparative asymmetric reduction of ketones in a biphasic medium with an (S)-alcohol dehydrogenase under in situ-cofactor-recycling with a formate dehydrogenase

The substrate range of a novel recombinant (S)-alcohol dehydrogenase from Rhodococcus erythropolis is described. In addition, an enzyme-compatible biphasic reaction medium for the asymmetric biocatalytic reduction of ketones with in situ-cofactor regeneration has been developed. Thus, reductions of poorly water soluble ketones in the presence of the alcohol dehydrogenase from R. erythropolis and a formate dehydrogenase from Candida boidinii can be carried out at higher substrate concentrations of 10-200 mM. The resulting (S)-alcohols were formed with moderate to good conversion rates, and with up to >99% ee.

A simple protocol for the one pot synthesis of chiral secondary benzylic alcohols by catalytic enantioselective reduction of aromatic ketones

A simple and efficient protocol for the one-pot catalytic enantioselective reduction of prochiral aromatic ketones mediated by in situ prepared catalysis derived from (S)-(-)-diphenyl-pyrrolidin-2-yl-methanol, is reported.

Remote dipole effects as a means to accelerate [Ru(amino alcohol)]catalyzed transfer hydrogenation of ketones

A new generation of 2-azanorbornyl amino alcohol ligands for the catalytic transfer hydrogenation reaction of aromatic ketones was synthesized. Extremely active catalysts were formed by introducing a ketal functionality at the rear end of the ligand. Acetophenone was reduced in 96% ee at low catalyst loading, substrate to catalyst ratio, S/C 5000, within 90 minutes with isopropyl alcohol as the hydrogen donor. It was found that the dioxolane substituent in the ligand increased the turnover frequency, TOF50, from 1050 h-1 to 3000 h-1 at an S/C ratio of 1000. Introduction of a methyl group at the carbinol carbon resulted in TOF50 as high as 8500 h-1. Transfer hydrogenation of a range of aromatic ketones was evaluated and found to reach completion within 30 minutes at room temperature, and excellent enantioselectivity, up to 99% ee, was obtained. A possible explanation for the enhanced activity was provided by density functional calculations, which showed that the presence of a remote dipole in the ligand lowered the transition state energy.

2-Azanorbornyl alcohols: Very efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic ketones

2-Azanorbornyl-derived amino alcohols were prepared and evaluated as ligands in the Ru(II)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. To improve selectivity and rate, the structure of the ligand was optimized. Acetophenone was reduced using 0.5 mol% catalyst in 40 min in 94% ee. This system was also able to reduce a wide range of aromatic ketones to the corresponding alcohols, while maintaining high enantioselectivities and yields. The effects of catalyst loading and the presence of cosolvents in the reaction vessel were examined, and a linearity study was also done.

Synthesis and electrospray mass spectrometric studies on a chiral, non- racemic, phosphoramide receptor molecule

The synthesis of a class of macrocyclic receptors containing a phosphoramide is described. The preliminary evaluation of this new receptor for interactions with several homochiral amines using electrospray ionisation mass spectrometry is also described.