124-12-9Relevant articles and documents
Iridium-catalyzed α-alkylation of acetonitrile with primary and secondary alcohols
Sawaguchi, Takuya,Obora, Yasushi
, p. 1055 - 1057 (2011)
Acetonitrile is successfully alkylated with primary and secondary alcohols in the presence of t-BuOK using [Ir(OH)- (cod)]2 as a catalyst. This method provides a very clean and atom-economical convenient direct route to substituted nitriles, which are very important raw materials in organic and industrial chemistry.
Heterogeneous Catalysts “on the Move”: Flow Chemistry with Fluid Immobilised (Bio)Catalysts
Adebar, Niklas,Gr?ger, Harald
, p. 6062 - 6067 (2020)
As both, continuous synthesis and (bio-)catalysis gained increasing interest in research as well as for industrial applications, ways for merging these fields enables novel opportunities for modern sustainable process development. In this contribution, an alternative approach for the application of immobilized enzymes in continuous flow processes is presented utilizing heterogeneous biocatalysts as a mobile phase. Based on superabsorber-entrapped enzymes and whole cells as a “fluid heterogeneous phase”, a segmented hydrogel/organic solvent system was developed. Its applicability was investigated with two entirely different model reaction systems, namely the alcohol dehydrogenase (ADH)-catalysed reduction of acetophenone, and the aldoxime dehydratase (Oxd)-catalysed dehydration of octanal oxime. In particular for solvent labile catalytic systems, this approach offers an alternative for the application of immobilized biocatalysts in a continuously running process beyond the “classic” packed bed and wall coated reactors.
-
Miyaura,N. et al.
, p. 255 - 258 (1976)
-
Stereoretentive Deuteration of α-Chiral Amines with D2O
Hale, Lillian V. A.,Szymczak, Nathaniel K.
, p. 13489 - 13492 (2016)
We present the direct and stereoretentive deuteration of primary amines using Ru-bMepi (bMepi = 1,3-(6′-methyl-2′-pyridylimino)isoindolate) complexes and D2O. High deuterium incorporation occurs at the α-carbon (70-99%). For α-chiral amines, complete retention of stereochemistry is achieved when using an electron-deficient Ru catalyst. The retention of enantiomeric purity is attributed to a high binding affinity of an imine intermediate with ruthenium, as well as to a fast H/D exchange relative to ligand dissociation.
An elimination reaction of N-carbomethoxy-N,N-dimethylhydrazonium salts to alkyl nitriles
Xiao, Zejun,Timberlake, Jack W.
, p. 12715 - 12720 (1998)
A new kind of elimination of hydrazonium salts to alkyl nitriles has been developed. The reaction of hydrazones and chloroformates results in the formation of hydrazonium salts, which react in situ with water to afford alkyl nitriles. The elimination is adapted to a range of solvents and gives good yields of α-secondary and tertiary alkyl-substituted nitriles.
Biotransformations in Pure Organic Medium: Organic- Solvent-Labile Enzymes in the Batch and Flow Synthesis of Nitriles
Hinzmann, Alessa,Adebar, Niklas,Betke, Tobias,Leppin, Monja,Gr?ger, Harald
, p. 6911 - 6916 (2019)
In recent years, there has been an increasing tendency to use biocatalysts in industrial chemistry, especially in the pharma and fine chemical sector. Preferably, enzymes or whole cells, applied as catalysts for a specific biotransformation, are utilized in aqueous reaction media since water is the natural medium for enzymes. In numerous examples of biocatalytic systems, however, a major problem is the insolubility of hydrophobic substrates in such aqueous reaction media. Apart from lipases, many enzymes are highly sensitive to organic solvents and are inactivated by an organic medium. Therefore, a change of solvent for biotransformations from water to organic solvents is usually challenging. In this study, we investigated the synthesis of nitriles by an organic solvent-labile aldoxime dehydratase in pure organic solvents, exemplified for the dehydration of n-octanaloxime to n-octanenitrile. We present a method for applications in batch as well as flow mode based on an “immobilized aqueous phase” bearing the whole cells in a superabsorber as solid phase, thus enabling the use of a purely organic solvent as “mobile phase” and reaction medium.
-
Orere,Reese
, p. 280 (1977)
-
Segmented Flow Processes to Overcome Hurdles of Whole-Cell Biocatalysis in the Presence of Organic Solvents
Adebar, Niklas,Gr?ger, Harald,L?we, Jana,Nastke, Alina
, p. 15863 - 15869 (2021)
In modern process development, it is imperative to consider biocatalysis, and whole-cell catalysts often represent a favored form of such catalysts. However, the application of whole-cell catalysis in typical organic batch two-phase synthesis often struggles due to mass transfer limitations, emulsion formation, tedious work-up and, thus, low yields. Herein, we demonstrate that utilizing segmented flow tools enables the conduction of whole-cell biocatalysis efficiently in biphasic media. Exemplified for three different biotransformations, the power of such segmented flow processes is shown. For example, a 3-fold increase of conversion from 34 % to >99 % and a dramatic simplified work-up leading to a 1.5-fold higher yield from 44 % to 65 % compared to the analogous batch process was achieved in such a flow process.
-
Ralston,Selby,Pool
, p. 682 (1941)
-
Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate
Nonnhoff, Jannis,Gr?ger, Harald
, (2021/12/14)
The access towards chiral nitriles remains crucial in the synthesis of several pharmaceuticals. One approach is based on metal-catalyzed dehydration of chiral aldoximes, which are generated from chiral pool-derived aldehydes as substrates, and the use of a cheap and readily available nitrile as co-substrate and water acceptor. Dehydration of N-acyl α-amino aldoximes such as N-Boc-l-prolinal oxime catalyzed by copper(II) acetate provides access to the corresponding N-acyl α-amino nitriles, which are substructures of the pharmaceuticals Vildagliptin and Saxagliptin. In this work, a detailed investigation of the formation of the amide as a by-product at higher substrate loadings is performed. The amide formation depends on the electronic properties of the nitrile co-substrate. We could identify an acceptor nitrile which completely suppressed amide formation at high substrate loadings of 0.5 m even when being used with only 2 equivalents. In detail, utilization of trichloroacetonitrile as such an acceptor nitrile enabled the synthesis of N-Boc-cyanopyrrolidine in a high yield of 92 % and with full retention of the absolute configuration.