Oxidative Conversion of Amines into Their Corresponding Nitriles Using o-Iodoxybenzoic Acid (IBX)/Iodine: Selective Oxidation of Aminoalcohols to Hydroxynitriles

Abstract

o-Iodoxybenzoic acid (IBX)/iodine in dimethyl sulfoxide at 65°C oxidatively and efficiently converted various amines into the corresponding nitriles in good to excellent yields. Under the reaction conditions, amines were selectively oxidized to the nitrile in the presence of a primary hydroxy group within the same molecule.Nitriles are very important intermediates in synthetic organic chemistry. 1 Consequently, their synthesis under various conditions has been continuously developed. While a wide variety of synthetic approaches to nitriles from diverse chemical sources have been developed, 2 nitrile synthesis from amines has been one of the classical routes. Numerous metal-based oxidants, such as nickel peroxide, 3a silver reagents, 3b,c Cu(I) or Cu(II) with O 2 , 3d-g copper reagents, 3h lead tetraacetate, 3i,j OsO 4 , 3k K 2 S 2 O 8 with Ni(II), 3l,m and ruthenium reagents 3n-r have all been used for carrying out this transformation. Other reagents are PhIO, 4a NaOCl in ethanol, 4b trichloroisocyanuric acid with TEMPO, 4c molecular iodine in aqueous ammonia, 4d and 1,3-diiodo-5,5-dimethylhydantoin in aqueous ammonia. 4e In addition, oxidations employing electrochemically generated reagents have also been addressed. 5In the past decade, hypervalent iodine reagents have attracted increasing interest because of their selective and mild properties as oxidizing agents in organic synthesis. 6 Of the various hypervalent iodine reagents known, iodine(V) reagents have received substantial attention in recent years, particularly Dess-Martin periodinane (DMP) 7 and o-iodoxybenzoic acid (IBX). 8 However, Dess-Martin periodinane is unstable upon prolonged storage and is thus best synthesized immediately prior to use. In contrast, IBX, the DMP precursor, is fairly stable -though it was reported to be explosive upon excessive heating or impact. Some recent applications of IBX in organic transformations include dehydrogenation of ketones and aldehydes to the corresponding a,b-unsaturated analogues, 9a dehydrogenation of amines to the corresponding imines and N-heterocycles, 9b,c oxidative cleavage of dithioacetals, 9c oxidative transformation of primary carboxamides into one-carbon dehomologated nitriles, 9d and conversion of 1,3-diols into 1,2-diketones. 9e As part of our interest in finding synthetic applications of IBX and its derivatives, 10 we envisaged the use of an IBX/I 2 combination for the transformation of amines into the corresponding nitriles (Scheme 1). To our knowledge, such a conversion has only been reported using the less stable iodine(V) compound, DMP. 11

The Mechanistic Perspective of IV Iodoxolones

“…No overoxidation occurs where tetraphenylphosphonium monoperoxysulfate is used as a co‐oxidant [38] . Molecular iodine reportedly reduces IBX 3 to 2IBAcid 1 by releasing iodic acid (IO 3 H), which as a powerful oxidant in its own right [39–41] . Iodine(V) aerobic synthesis can be based on iodobenzene with variants of a chelating substituent in the 2‐position, although the process requires a transition metal‐based initiator [42,43] .…”

“…[38] Molecular iodine reportedly reduces IBX 3 to 2IBAcid 1 by releasing iodic acid (IO 3 H), which as a powerful oxidant in its own right. [39][40][41] Iodine(V) aerobic synthesis can be based on iodobenzene with variants of a chelating substituent in the 2-position, although the process requires a transition metal-based initiator. [42,43] Thus, morphological variation of 3 can isolate the danger of explosion so a plethora of environmentally benign oxidations can be conducted in safety.…”

Progress in synthetic strategy and industrial preparation of aliphatic nitriles

“…(1) 需氧氧化腈化反应 Capdevielle等 [51] 报道使用O 2 作为氧化剂, 利用Cu (2) 无氧的氧化腈化反应 Giacomelli等 [63] 研究发现可以用三氯 异氰尿酸(TCCA)氧化脂肪族、芳香族和杂环初级胺 获得对应的腈化物.…”

A sustainable metal-free and additive-free olefination route to N-heteroazaarenes from methyl-substituted heterocycles and amines

“…The deamination of primary amines is another important transformation that can be employed to assemble unsaturated N -heteroaromatic structures. 7 This has been achieved by the aggressive oxidation of aliphatic amines using oxidants, although the potential scope of the reaction is limited due to its low selectivity and its tendency toward overoxidation. Recently, Gong et al and Susanta et al discovered that E -2-styrylquinolines could be prepared from 2-methylquinolines by reaction with primary amines in the presence of a stoichiometric amount of TBHP (2.0–4.0 eq., Scheme 1b(I) ).…”