Nitrile Synthesis with Aldoxime Dehydratases: A Biocatalytic Platform with Applications in Asymmetric Synthesis, Bulk Chemicals, and Biorefineries

Abstract

Nitriles comprise a broad group of chemicals that are currently being industrially produced and used in fine chemicals and pharmaceuticals, as well as in bulk applications, polymer chemistry, solvents, etc. Aldoxime dehydratases catalyze the cyanide-free synthesis of nitriles starting from aldoximes under mild conditions, holding potential to become sustainable alternatives for industrial processes. Different aldoxime dehydratases accept a broad range of aldoximes with impressive high substrate loadings of up to >1 Kg L−1 and can efficiently catalyze the reaction in aqueous media as well as in non-aqueous systems, such as organic solvents and solvent-free (neat substrates). This paper provides an overview of the recent developments in this field with emphasis on strategies that may be of relevance for industry and sustainability. When possible, potential links to biorefineries and to the use of biogenic raw materials are discussed.

Tropylium‐BF4 as Organocatalyst for Efficient Synthesis of Nitriles from Aldoximes; Synthetic Scope and Mechanistic Insights

“…The IR spectra were recorded on a Nicolet-Impact-410 FT-IR spectrometer. NMR spectra ( 1 H/ 13 C) were recorded on DELTA2 400 MHz and Bruker DRX 400 MHz spectrometers using CDCl 3 and calibrated using internal standard ( 1 H NMR at 400 MHz and fully decoupled 13 C NMR at 100 MHz with δ values reported in ppm). GC-MS analyses were performed on a Shimadzu 2010 series mass selective detector instrument.…”

“…The latter reagent is closely related to triflyl‐imidazole reported by us for aldoxime to nitrile conversion almost a decade earlier [11] . Complementing these dehydration routes are chemoenzymatic methods developed for enantioselective synthesis of chiral nitriles [12,13] …”

“…[11] Complementing these dehydration routes are chemoenzymatic methods developed for enantioselective synthesis of chiral nitriles. [12,13] A recent study reported on the use of in-situ generated chlorotropylium chloride as catalyst for conversion of oximes to amides and nitriles. [14] The onium salt was generated from tropone and oxalyl chloride (loss of CO and CO 2 ) in MeCN solvent using syringe pump, followed by addition of DBU to effect deprotonation of the aldoxime-tropylium adduct to form nitrile.…”

On the fate of deep eutectic solvents after their use as reaction media: the CO2 production during downstream and ultimate disposal

“…41 One relevant conclusion derived from the E-factor is the need to establish intensied processes in which the use of resources may be properly optimized, namely reactions with high substrate loadings to minimize the use of solvents and water, and recycling systems that may reduce the waste. 39,[41][42][43][44] As a downside, however, the E-factor does not allow the direct comparison among types of waste and allocates the same environmental burden to one kilogram of waste, regardless of its nature and hazardousness. To overcome this, and to complement environmental metrics, recently the concept "Total Carbon Dioxide Release" (TCR) has been introduced.…”

Organoselenium functionalized SBA-15 as a new catalyst for the cyanide-free conversion of oximes to nitriles

“…In the past decades, several protocols including transition-metal heterogeneous catalysts have been reported for the synthesis of nitrile compounds [ 10 , 11 ]. However, these methods suffer from costly heterogeneous catalyst systems, metal or non-metal chemical dehydration, and producing a large number of waste products [ 12 ].…”