Sulfuryl Fluoride Mediated Conversion of Aldehydes to Nitriles

Abstract

Aliphatic, aromatic, and heteroaromatic aldehydes were readily converted to corresponding nitriles in a one‐pot reaction sequence with hydroxylamine and sulfuryl fluoride. The reaction proceeds at room temperature, does not require metal catalysts and special precautions, and produces nitriles in excellent yields. It is compatible with a variety of functional groups, can be performed in aqueous and organic solvents, and is readily scalable to multigram quantities. Mild conditions and high selectivity of the reaction enabled the construction of polyfunctional probes containing nitrile, alkyne, azide, and fluorosulfate groups for further orthogonal derivatization.

Cascade Process for Direct Transformation of Aldehydes (RCHO) to Nitriles (RCN) Using Inorganic Reagents NH2OH/Na2CO3/SO2F2 in DMSO

“…Following the appearance of the Just Accepted version of this article, we wish to explicitly note the connection of our work (submitted on December 4, 2018/JAM online March 14, 2019) to that of Fokin et al (ref , submitted on October 12, 2018/online Oct 22, 2018). Readers of the two papers can discern that while there are some explicit similarities, there are also some differences in the experimental protocols and conditions for achieving these reactions.…”

Tandem Triphosgene-Assisted Metal-Free One-pot Preparation of Nitriles and Amides from Aldehydes and Ketones

“…Though the great progress made in the generation of nitriles from aldehydes and have well applied in the wide substrate scope of aldehydes, there are few suitable methodologies for the synthesis of both nitrile and amide from aldehydes and ketone respectively. Compared with traditional nucleophilic substitutions by using HCN or metal cyanides [8][9][10][11] as well as recent popular oximation−dehydration strategy 12 with the prepared reagents 13 or additional alkali [14][15] we designed an environmentally friendly alternative using triphosgene. This reagent is cheap and used without further preparation.…”

Preparation and odor characteristics of nitriles derived from aldehydes

“…It is the most commonly used method to prepare nitriles by dehydration of the corresponding primary amides or aldoximes. Various approaches have been developed continuously, including transition metal medicated or catalyzed processes, such as Co(III), 16 Cu(II), 17 Pd(II), 18 Ti(IV), 19 Ce(IV), 20 Zn(II), 21 Fe (III), 22 and Ru(II), 23 and miscellaneous non‐metal reagents, such as NH 2 OH/Na 2 CO 3 /SO 2 F 2 , 24 organoselenium reagents, 25 O ‐benzoyl hydroxylamine, 26 [Et 2 NSF 2 ]BF 4 , 27 Ac 2 O, 28 Vilsmeier‐Haack reagent, 29 DCC, 30 Burgess Reagent, 31 (COCl) 2 /Ph 3 PO 32 or DMSO, 33 sulfuryl fluoride, 34 an oxoammonium salt with HMDS, 35 and O ‐benzenesulfonyl oxime catalyzed by a Brønsted acid 36 . In our recent work about the application of sulfoxide/oxalyl halide in organic synthesis, oxalyl chloride combined with a catalytic amount of DMSO was found to promote the dehydration of primary amides or aldoximes very efficiently with a clean conversion and almost quantitative yields in most cases 37 .…”