13312-83-9

Upstream product

• 74-90-8 hydrogen cyanide 
• 104-88-1 4-chlorobenzaldehyde 
• 151-50-8 potassium cyanide 
• 99-35-4 1,3,5-trinitrobenzene 
• 143-33-9 sodium cyanide 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 74-11-3 para-chlorobenzoic acid 
• 7677-24-9 trimethylsilyl cyanide 
• 66985-46-4 (+/-)-2-(4-chlorophenyl)-2-(trimethylsiloxy)-acetonitrile 
• 108-05-4 vinyl acetate 
• 873-76-7 para-Chlorobenzyl alcohol 
• 106-43-4 para-chlorotoluene 
• 99074-23-4 cyano(4-chlorophenyl)methyl acetate 
• 613-90-1 benzoyl cyanide 

Downstream Products

• 126641-86-9 (R)-acetoxy(4-chlorophenyl)acetonitrile 
• 136983-95-4 (S)-2-acetyloxy-2-(4-chlorophenyl)acetonitrile 
• 125850-01-3 3,5-Dichloro-6-(4-chloro-phenyl)-[1,4]oxazin-2-one 
• 99074-23-4 cyano(4-chlorophenyl)methyl acetate 
• 41870-82-0 2-amino-1-(4-chlorophenyl)ethanol 
• 156-41-2 4-chlorophenylethylamine 
• 13312-83-9 (R)-(+)-4-chloromandelonitrile 
• 13312-83-9 (2S)-2-hydroxy-2-(4-chlorophenyl)acetonitrile 
• 1584127-67-2 (S)-(+)-methyl 2-acetoxy-2-(4-chlorophenyl)acetate 
• 32174-34-8 (4-chloro-phenyl)-hydroxy-acetic acid methyl ester 
• 32174-34-8 methyl 4-chloromandelate 
• 492-86-4 (R)-4-chloro-α-hydroxy-benzeneacetic acid 
• 18584-27-5 2-(4-chlorophenyl)-2-hydroxyacetamide 
• 53731-99-0 2-bromo-2-(4-chlorophenyl)acetonitrile 

Relevant academic research and scientific papers

Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization

In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.

CO2-Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO2-mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani–Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl- and arylaldehydes, KCN and an atmospheric pressure of CO2.

Synthesis of Acrylonitriles via Mild Base Promoted Tandem Nucleophilic Substitution-Isomerization of α-Cyanohydrin Methanesulfonates

Main observation and conclusion: We have developed an efficient synthesis of acrylonitriles via mild base promoted tandem nucleophilic substitution-isomerization of α-cyanohydrin methanesulfonates with alkenylboronic acids. This transition metal-free protocol works under simple and mild conditions and offers good chemical yields for a wide range of substrates and demonstrates good functional group tolerance. (Figure presented.).

Supported Ionic Liquid-Like Phases (SILLPs) as Immobilised Catalysts for the Multistep and Multicatalytic Continuous Flow Synthesis of Chiral Cyanohydrins

Supported Ionic Liquid-Like Phases have been found to be efficient organocatalysts for the synthesis of cyanohydrin esters under solvent-free conditions by an “electrophile-nucleophile dual activation” based on hydrogen bond formation. The combination of

Postfunctionalized Metalloligand-Based Catenated Coordination Polymers: Syntheses, Structures, and Effect of Labile Sites on Catalysis

In this work, pyridyl-appended Co3+ complexes (1 and 2) have been postfunctionalized by using 4-(bromomethyl)benzoic acid, thus changing the functionalities from pyridyl-N donors to carboxylate-O donors. Using two such postfunctionalized metalloligands (3 and 4), several homo and heterometallic coordination polymers (HCPs) have been synthesized. Single crystal structural analyses revealed that all HCPs presented intriguing one-dimensional catenated architectures. Postsynthetic modification induced flexibility was found to be responsible for the nearly identical architectures for two sets of HCPs starting from two different postfunctionalized metalloligands, 3 and 4. Two sets of HCPs differed by the presence (3a-3d) or absence (4a-4b) of labile coordinated water molecules that demonstrated a profound effect on the heterogeneous catalysis of Knoevenagel condensation reactions and cyanation reactions.

Preparation of chitosan-supported urea materials and their application in some organocatalytic procedures

An efficient and mild procedure was developed for the preparation of three chitosan-supported ureas containing electron-withdrawing groups. These catalysts were characterized and employed as organocatalysts in different transformations, including the enan

Acceptorless and Base-free Dehydrogenation of Cyanohydrin with (η6-Arene)halide(Bidentate Phosphine)ruthenium(II) Complex

Ruthenium-catalyzed dehydrogenation of cyanohydrins under acceptorless and base-free conditions was demonstrated for the first time in the synthesis of acyl cyanide. As opposed to the thermodynamically preferred elimination of hydrogen cyanide, the dehydrogenation of cyanohydrins could be kinetically controlled with ruthenium (II) bidentate phosphine complexes. The effects of the arene, phosphine ligands and counter anions were investigated in regard to catalytic activity and selectivity. Selective dehydrogenation can occur via β-hydride elimination with the experimentally observed [(alkoxide)Ru] complex. (Figure presented.).

High-Throughput Preparation of Optically Active Cyanohydrins Mediated by Lipases

Cyanohydrins are versatile compounds with high applicability in organic synthesis; they are used as starting materials for the synthesis of other chemical targets with high industrial added value. Lipase-mediated kinetic resolution reactions are a promising route for the synthesis of optically active cyanohydrins. These reactions can be carried out through the acylation of cyanohydrins or the deacylation of cyanohydrin esters, with different biocatalysts and under different reaction conditions. Unfortunately, depending on the substrate structure, long reaction times can be required to achieve suitable enantiomeric excesses. In this context, we present a high-throughput protocol for the production of optically active cyanohydrins in continuous-flow mode. The products were obtained with moderate to good enantioselectivity (E values from 8 up to >200) and with productivity values from 2.4 to 8.7 times higher in continuous-flow mode than in batch mode. Moreover, the reaction times were reduced from hours in batch mode to minutes in continuous-flow mode.

Solid phase behavior in the chiral systems of various 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives

The solid phase behavior of a series of monosubstituted F-, Cl-, Br-, I-, and CH3- and two 2,4-halogen-disubstituted 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives was investigated. The study includes detailed information about melting temperature, melting enthalpy, X-ray diffraction data, as well as selected binary phase diagrams of the respective chiral systems. Aside from the known metastable conglomerate 2-chloromandelic acid, evidence for two more metastable conglomerates was found.

Design of nitrilases with superior activity and enantioselectivity towards sterically hindered nitrile by protein engineering

Abstract The enantioselective hydrolysis of ortho-chloromandelonitrile with nitrilase is one of the most attractive approaches to prepare (R)-ortho-chloromandelic acid. To date, efforts to develop this nitrilase-mediated process were plagued by either insufficient eep (enantiomeric excess of product) or low activity due to the steric hindrance from the ortho-substituted substrate. To improve the nitrilase potential for producing (R)-ortho-chloromandelic acid, an enhancement of both activity and enantioselectivity towards sterically hindered nitriles would be highly desirable. Molecular docking of the (R)-ortho-chloromandelonitrile into the active site of wild-type 2A6 nitrilase (nitA) allowed the identification of proximal nitA active site residues. Several residues (52, 132, 189 and 190) were selected as targets for single and double point mutation to improve nitA activity and enantioselectivity towards ortho-chloromandelonitrile. Targeted mutagenesis yielded several nitA variants with superior activity and enantioselectivity. The best mutant T132A/F189T exhibited a 4.37-fold higher specific activity (7.39 U/mg) towards ortho-chloromandelonitrile than the wild-type nitA. More importantly, the enantioselectivity (E) was improved from 17.34 to >200, resulting in a highly enantiopure product. Molecular docking experiments further support the enhanced activity and enantioselectivity shown experimentally and the structural effects of this amino acid substitution on the active site of nitA are provided. The amino acids at sites 189 and 132 determine the activity and enantioselectivity towards ortho-chloromandelonitrile. With mutant T132A/F189T as a catalyst, a maximum of 450 mM of (R)-ortho-chloromandelic acid was produced with a 90% conversion and >99% eep within 3 h. This is the first time that a high productivity of (R)-ortho-chloromandelic acid of up to 671.76 g L-1d-1 using a nitrilase-mediated approach is reported. The engineered T132A/F189T variant represents a promising and competitive biocatalyst for practical application in synthesizing (R)-ortho-chloromandelic acid.