112966-26-4

Basic information

• Product Name: (R)-(4-Chlorophenyl)(pyridin-2-yl)methanol
• Synonyms: (R)-(4-Chlorophenyl)(pyridin-2-yl)methanol
• CAS NO: 112966-26-4
• Molecular Formula: C₁₂H₁₀ClNO
• Molecular Weight: 219.67
• Mol File: 112966-26-4.mol

Chemical Properties

• Boiling Point: 364.3 °C at 760 mmHg
• Flash Point: 174.1 °C
• Appearance: /
• Density: 1.275 g/cm³
• Refractive Index: 1.614
• PKA: 12.46±0.20(Predicted)
• CAS DataBase Reference: (R)-(4-Chlorophenyl)(pyridin-2-yl)methanol(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(4-Chlorophenyl)(pyridin-2-yl)methanol(112966-26-4)
• EPA Substance Registry System: (R)-(4-Chlorophenyl)(pyridin-2-yl)methanol(112966-26-4)

Safety Data

• Hazardous Substances Data: 112966-26-4(Hazardous Substances Data)

Usage

Uses

Due to the limited information available on (R)-(4-Chlorophenyl)(pyridin-2-yl)methanol, its applications are not extensively documented. However, given its chemical structure, it is likely used in specialized fields such as:
Used in Pharmaceutical Industry:
(R)-(4-Chlorophenyl)(pyridin-2-yl)methanol may be employed as an intermediate or building block in the synthesis of pharmaceutical compounds. Its unique structure could potentially contribute to the development of new drugs with specific therapeutic properties.
Used in Chemical Research:
In the field of chemical research, (R)-(4-Chlorophenyl)(pyridin-2-yl)methanol could serve as a subject of study for understanding the properties and reactivity of chiral compounds. Its synthesis and manipulation could provide insights into the development of novel chemical processes and methodologies.
Used in Material Science:
(R)-(4-Chlorophenyl)(pyridin-2-yl)methanol might be utilized in the development of new materials with unique properties, such as optically active materials or catalysts. Its incorporation into polymers or other materials could lead to advancements in material science applications.

InChI:InChI=1/C12H10ClNO/c13-10-6-4-9(5-7-10)12(15)11-3-1-2-8-14-11/h1-8,12,15H/t12-/m1/s1

Upstream product

• 17624-36-1 2-pyridyllithium 
• 104-88-1 4-chlorobenzaldehyde 
• 7677-24-9 trimethylsilyl cyanide 
• 74-86-2 acetylene 
• 1350476-55-9 o-(2-bromo-4-chlorophenyl)-2-pyridinemethanol 
• 116779-74-9 2-bromo-4-chlorobenzoyl chloride 
• 27652-89-7 (4-chlorophenyl)-2-pyridylmethanol 
• 6318-51-0 2-(4-chlorobenzoyl)pyridine 

Downstream Products

• 5583-33-5 (R)-(-)-α-phenyl-2-pyridylmethanol 

Relevant articles and documents

Preparation, Absolute Configuration and Conformation of Some α-Aryl-2-pyridylmethanols

The syntheses of five optically active α-aryl-2-pyridylmethanols 1-5 are described.It is shown by means of chemical correlation with the known (-)-(α-R,2S)-α-phenyl-2-piperidylmethanol 6 that all levo-rotatory isomers 1-4 are of R configuration.It is also found via the relative integral intensities in the infrared spectra of the bands due to free and intramolecularly bonded hydroxyl groups in the compounds 1-4 and the free hydroxyl groups in the model compounds 7-10, that the population of the conformers with an intramolecular OH...N bond in compounds 1-4 exceds 80percent.

Conformational Dynamics-Guided Loop Engineering of an Alcohol Dehydrogenase: Capture, Turnover and Enantioselective Transformation of Difficult-to-Reduce Ketones

Directed evolution of enzymes for the asymmetric reduction of prochiral ketones to produce enantio-pure secondary alcohols is particularly attractive in organic synthesis. Loops located at the active pocket of enzymes often participate in conformational changes required to fine-tune residues for substrate binding and catalysis. It is therefore of great interest to control the substrate specificity and stereochemistry of enzymatic reactions by manipulating the conformational dynamics. Herein, a secondary alcohol dehydrogenase was chosen to enantioselectively catalyze the transformation of difficult-to-reduce bulky ketones, which are not accepted by the wildtype enzyme. Guided by previous work and particularly by structural analysis and molecular dynamics (MD) simulations, two key residues alanine 85 (A85) and isoleucine 86 (I86) situated at the binding pocket were thought to increase the fluctuation of a loop region, thereby yielding a larger volume of the binding pocket to accommodate bulky substrates. Subsequently, site-directed saturation mutagenesis was performed at the two sites. The best mutant, where residue alanine 85 was mutated to glycine and isoleucine 86 to leucine (A85G/I86L), can efficiently reduce bulky ketones to the corresponding pharmaceutically interesting alcohols with high enantioselectivities (～99% ee). Taken together, this study demonstrates that introducing appropriate mutations at key residues can induce a higher flexibility of the active site loop, resulting in the improvement of substrate specificity and enantioselectivity. (Figure presented.).

Effect of inhibitor or immobilization on reduction of benzoylpyridines by baker's yeast

The stereochemical course of the reduction of benzolpyridine derivatives (1a-e) by baker's yeast can be modified by immobilization or by treating the reduction system with allyl alcohol or ethyl chloroacetate.

Unlocking the Stereoselectivity and Substrate Acceptance of Enzymes: Proline-Induced Loop Engineering Test

Protein stability and evolvability influence each other. Although protein dynamics play essential roles in various catalytically important properties, their high flexibility and diversity makes it difficult to incorporate such properties into rational engineering. Therefore, how to unlock the potential evolvability in a user-friendly rational design process remains a challenge. In this endeavor, we describe a method for engineering an enantioselective alcohol dehydrogenase. It enables synthetically important substrate acceptance for 4-chlorophenyl pyridine-2-yl ketone, and perfect stereocontrol of both (S)- and (R)-configured products. Thermodynamic analysis unveiled the subtle interaction between enzyme stability and evolvability, while computational studies provided insights into the origin of selectivity and substrate recognition. Preparative-scale synthesis of the (S)-product (73 % yield; >99 % ee) was performed on a gram-scale. This proof-of-principle study demonstrates that interfaced proline residues can be rationally engineered to unlock evolvability and thus provide access to new biocatalysts with highly improved catalytic performance.

Amino alcohols using the optically active amino alcohol derivative bi- Nord complex boron - -

Disclosed are an amino alcohol-boron-binol complex as an intermediate, including Complex 3-1-1 shown below, and a method for preparing an optically active amino alcohol by using the same, wherein a racemic amino alcohol is resolved in an enationselective manner using a boron compound and a (R)- or (S)-binol, whereby an amino alcohol derivative with high optical purity can be prepared at high yield.

Molecular switch manipulating Prelog priority of an alcohol dehydrogenase toward bulky-bulky ketones

Structure-guided rational design revealed the molecular switch manipulating the Prelog and anti-Prelog priorities of an NADPH-dependent alcohol dehydrogenase toward prochiral ketones with bulky and similar substituents. Synergistic effects of unconserved residues at 214 and 237 in small and large substrate binding pockets were proven to be vital in governing the stereoselectivity. The ee values of E214Y/S237A and E214C/S237 G toward (4-chlorophenyl)-(pyridin-2-yl)-methanone were 99.3% (R) and 78.8% (S) respectively. Substrate specificity analysis revealed that similar patterns were also found with (4’-chlorophenyl)-phenylmethanone, (4’-bromophenyl)-phenylmethanone and (4’-nitrophenyl)-phenylmethanone. This study provides valuable evidence for understanding the molecular mechanism on enantioselective recognition of prochiral ketones by alcohol dehydrogenase.

Engineering an alcohol dehydrogenase with enhanced activity and stereoselectivity toward diaryl ketones: Reduction of steric hindrance and change of the stereocontrol element

Steric hindrance in the binding pocket of an alcohol dehydrogenase (ADH) has a great impact on its activity and stereoselectivity simultaneously. Due to the subtle structural difference between two bulky phenyl substituents, the asymmetric synthesis of diaryl alcohols by bioreduction of diaryl ketones is often hindered by the low activity and stereoselectivity of ADHs. To engineer an ADH with practical properties and to investigate the molecular mechanism behind the asymmetric biocatalysis of diaryl ketones, we engineered an ADH from Lactobacillus kefiri (LkADH) to asymmetrically catalyse the reduction of 4-chlorodiphenylketones (CPPK), which are not catalysed by the wild type (WT) enzyme. Mutants seq1-seq5 with gradually increased activity and stereoselectivity were obtained through iterative "shrinking mutagenesis." The final mutant seq5 (Y190P/I144V/L199V/E145C/M206F) demonstrated the highest activity and excellent stereoselectivity of >99% ee. Molecular simulation analyses revealed that mutations may enhance the activity by eliminating steric hindrance, inducing a more open binding loop and constructing more noncovalent interactions. The pro-R pose of CPPK with a halogen bond formed a pre-reaction conformation more easily than the pro-S pose, resulting in the high ee of (R)-CPPO in seq5. Moreover, different halogen bonds formed due to the different positions of chlorine substituents, resulting in opposite substrate binding orientation and stereoselectivity. Therefore, the stereoselectivity of seq5 was inverted toward ortho- rather than para-chlorine substituted ketones. These results indicate that the stereocontrol element of LkADH was changed to recognise diaryl ketones after steric hindrance was eliminated. This study provides novel insights into the role of steric hindrance and noncovalent bonds in the determination of the activity and stereoselectivity of enzymes, and presents an approach producing key intermediates of chiral drugs with practical potential.

Two enantiocomplementary ephedrine dehydrogenases from arthrobacter sp. TS-15 with broad substrate specificity

The recently identified pseudoephedrine and ephedrine dehydrogenases (PseDH and EDH, respectively) from Arthrobacter sp. TS-15 are NADH-dependent members of the oxidoreductase superfamily of short-chain dehydrogenases/reductases (SDRs). They are specific for the enantioselective oxidation of (+)-(S) N-(pseudo)ephedrine and (-)-(R) N-(pseudo)ephedrine, respectively. Anti-Prelog stereospecific PseDH and Prelog-specific EDH catalyze the regio- A nd enantiospecific reduction of 1-phenyl-1,2-propanedione to (S)-phenylacetylcarbinol and (R)-phenylacetylcarbinol with full conversion and enantiomeric excess of >99%. Moreover, they perform the reduction of a wide range of aryl-aliphatic carbonyl compounds, including ketoamines, ketoesters, and haloketones, to the corresponding enantiopure alcohols. The highest stability of PseDH and EDH was determined to be at a pH range of 6.0-8.0 and 7.5-8.5, respectively. PseDH was more stable than EDH at 25 °C with half-lives of 279 and 38 h, respectively. However, EDH is more stable at 40 °C with a 2-fold greater half-life than at 25 °C. The crystal structure of the PseDH-NAD+ complex, refined to a resolution of 1.83 ?, revealed a tetrameric structure, which was confirmed by solution studies. A model of the active site in complex with NAD+ and 1-phenyl-1,2-propanedione suggested key roles for S143 and W152 in recognition of the substrate and positioning for the reduction reaction. The wide substrate spectrum of these dehydrogenases, combined with their regio- A nd enantioselectivity, suggests a high potential for the industrial production of valuable chiral compounds.

Preparation method of (R)-phenyl (pyridine-2-base) methanol derivative

The invention discloses a preparation method of a (R)-phenyl (pyridine-2-base) methanol derivative. The process comprises the following steps: - adding metal M complex and chiral ligand L * to solventA for 0.5-6 hours in argon atmosphere and at 10-40 DEG C to prepare catalyst [M]/ L *. The metal M in the metal M complex is any one of Ru, Rh, Ir or Pd, adding phenyl (pyridine-2-base) methyl ketonederivative, the prepared catalyst [M]/ L *, solvent B into a autoclave to perform an unsymmetrical hydrogenation reaction at 0-100 DEG C and hydrogen pressure of 0.1-10.0 MPa for 2-24 hours. After the reaction, the reaction solution is reduced pressure, concentrated and recovered solvent B, adding water, extracting by ethyl acetate, and separating into organic phase and water phase. The organic phase is dried and dissolved to obtain phenyl (pyridine-2-base) methanol derivative. According to the preparation method of the (R)-phenyl (pyridine-2-base) methanol derivative, in the asymmetric hydrogenation on phenyl (pyridine-2-base) methanol derivative, the yield is high, and (R)-phenyl (pyridine-2-base) methanol derivative is produced with high enantioselectivity and an e value above 99%.

Chirality-Economy Catalysis: Asymmetric Transfer Hydrogenation of Ketones by Ru-Catalysts of Minimal Stereogenicity

This manuscript describes the design and synthesis of Ru catalysts that feature only a single stereogenic element, yet this minimal chirality resource is demonstrated to be competent for effecting high levels of stereoinduction in the asymmetric transfer hydrogenation over a broad range of ketone substrates, including those that are not accommodated by known catalyst systems. The single stereogenic center of the (1-pyridine-2-yl)methanamine) is the only point-chirality in the catalysts, which simplifies this catalyst system relative to existing literature protocols.