Ketones hydroxylamine catalysts

TS-1 is a material that perfectly fits the definition of single-site catalyst discussed in the previous Section. It is an active and selective catalyst in a number of low-temperature oxidation reactions with aqueous H2O2 as the oxidant. Such reactions include phenol hydroxylation [9,17], olefin epoxida-tion [9,10,14,17,40], alkane oxidation [11,17,20], oxidation of ammonia to hydroxylamine [14,17,18], cyclohexanone ammoximation [8,17,18,41], conversion of secondary amines to dialkylhydroxylamines [8,17], and conversion of secondary alcohols to ketones [9,17], (see Fig. 1). Few oxidation reactions with ozone and oxygen as oxidants have been investigated. 

The Beckmann rearrangement of oximes to produce amides is promoted by perrhenate ions under phase-transfer catalytic conditions, in the presence of trifluoro-methanesulphonic acid in nitromethane [6]. Under these conditions, the rearrangement reaction is frequently accompanied by the solvolysis of the oxime to the ketone. This can be obviated by the addition of hydroxylamine hydrochloride. No reaction occurs in the absence of the ammonium catalyst or with the O-acetyl oximes. 

In 1999, Hajipour reported that silica gel, without any base, could be a useful catalyst for the preparation of oximes in dry media coupled with microwave irradiation. Hydroxylamine hydrochlorides were reacted with several aliphatic and aromatic aldehydes and ketones affording the desired oximes. 

Neutral alumina-supported sodium hydrogen sulfate was also used as a heterogenous catalyst for the one pot conversion of ketones to a great variety of amides in the presence of hydroxylamine under microwave irradiation in solvent-free conditions . ... 

Nitrones of several aryl methyl ketones were hydrogenated by a catalyst prepared in situ from [IrCl(COD)]2, (S)-BINAP, and (n-C4H9)4NBH4 in THF under 80 atm of H2 and at 0 °C to give the corresponding Af-hydroxylamines in up to 86% ee (Scheme 6) [14]. Substitution of halides at the 3 or 4 position of the ar-... 

Cyclodextrin ketones have been used as powerful catalysts of amine oxidation in the presence of hydrogen peroxide as the stoichiometric oxidant. This oxidation follows Michaelis-Menten kinetics and depending on the substrate the oxidation rate is increased up to 1100-fold. It has been proposed that hydrogen peroxide reacts with the ketone to form a hydroperoxide adduct and this adduct is responsible for oxidizing the amine, bound in the cavity, to the hydroxylamine.189... 

Since oximes are obtained from condensation reactions of ketones with hydroxylamine, the single-pot preparation of amides and lactams directly from ketones and H2NOH.HCI was achieved via in situ generated oximes, by using the above catalyst in nitromethane under azeotropic conditions. 

The enantioselective reduction of a C=N double bond is an interesting alternative for the production of chiral amines by hydrogenation of enamides. Required imines or oximes can be prepared by reaction of ketones with amines or hydroxylamines. However, to date, trials to reduce these substrates with ethyl-DuPHOS catalysts gave no satisfying results. Therefore, transformation of ketones or a-keto acids into acylhydrazones and subsequent enantioselective hydrogenation has proven advantageous (eq 12, Table 5). ... 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

A number of reactions of nitrogen-containing nucleophiles with aldehydes and ketones involve addition of the nitrogen to the carbon of the carbonyl group, followed by elimination of water to produce a double bond. Common examples are reactions of primary amines to produce substituted imines, reactions of secondary amines to produce enamines, reactions of hydrazine or substituted hydrazines to produce hydrazones, reactions of semicarbazides to give semicarbazones, and reactions of hydroxylamine to produce oximes. Usually these reactions are run with an acid catalyst. 

Titanosilicalite (TS-1)[165,166], a highly siliceous MFI type zeolite in which 0.1 to 2.5% of the Si atoms are replaced by Ti, is the most successful example for the use of isomorphously substitited zeolites. As a consequence of the high Si/Al ratio of TS-1 the material contains only a negligible concentration of strong Bronsted acid sites. In fact, the presence of acid sites is detrimental to the selectivity of the catalysts, as discussed below. TS-1 has been found to be a selective oxidation catalyst for a wide variety of reactions such as the conversion of alkenes to epoxides [167], alcohols to aldehydes [168], alkanes to secondary alcohols and ketones [169,170], phenol to hydroquinone and catechol [171] and amines to hydroxylamines [ 172]. A schematic representation of the chemistry is given in Fig. 7 which is adapted from ref [17]. 

Ammonia was oxidized with hydrogen peroxide in the presence of TS-1 first to hydroxylamine and then, further to nitrogen oxides if the hydroxylamine was not trapped. When this reaction was run in the presence of a ketone, the oxime was selectively formed (Eqn. 21.8).33 Oximes were also produced by the oxidation of primary aliphatic amines with TS-1 or TS-2 and hydrogen peroxide at ambient temperature. Linear amines such as n-propyl amine (6) gave the oxime in 73% yield at 32% conversion over the TS-1 catalyst (Eqn. 21.9).3 The isopropyl amine (7) was oxidized with somewhat higher selectivity over the larger pore TS-2 catalyst (Eqn. 21.10).34 Primary aryl amines were oxidized to the symmetrical azoxybenzenes under these conditions (Eqn. 21.11). ... 

Hydroxylamine-O-sulfonic acid or 0-mesitylenesulfonylhydroxylamine (Tamura s reagent) are effective catalysts for the conversion of ketones directly to lactams. For example, the rearrangement of... 

Though not proved, alkynyl-ketones could also be involved as reactive intermediates in the regioselective preparation of 3,5-diarylisoxazoles 19 through four-component coupling of terminal alkynes 17, hydroxylamine, carbon monoxide, and aryl iodides 18, in the presence of a palladium catalyst. The reaction proceeds at room temperature and an ambient pressure of CO in an aqueous solvent system <05OL4487>. 

Hydroxylamine hydrochloride (5.00 mmol) and the aldehyde or ketone 1 (5.00 mmol) were kneading ball-milled in a double-walled 10-mL stainless steel vessel with two balls of 12 mm diameter at 20-25 Hz for 10 min at 45-50 °C (a-e) or for 30 min at 65-70 °C (f-h). A quantitative yield of the oxime hydrochloride hydrate 2 was obtained. The salt 2 already carries the catalyst for most of the various synthetic uses of the oximes. Washing with aqueous NaHC03, if required, can liberate the free oximes 3. 

The carbon-nitrogen double bonds of nitrones N1-N3 (Fig. 14) were catalytical-ly reduced with diphenylsilane in the presence of Ru2Cl4(Tol-BINAP, L24)2(NEt3) to give hydroxylamines in high % ees [56]. The hydroxylamine HI was obtained in 63% yield with 86% ee (S) and the hydroxylamine H3 was formed in 91% ee. It was also proposed that this process opened a new access to optically active amines from racemic amines, via nitrones and hydroxylamines. The iron complex [(Cp)2Fe2(HPMen2> L25)(CO)2] was reported to be a catalyst in the asymmetric hydrosilylation of ketones under irradiation, where acetophenone was reduced in up to 33% ee [57]. 

Flavanones and Isoflavanones.- Reaction of the aryl benzyl ketone (120) with formaldehyde and dimethylamine has provided a new synthesis of isoflavanones in good yield.126 The same ketones can be cyclized to isoflavanones in good yield by treatment with di-iodomethane, a phase transfer catalyst (tetrabutylammonium iodide) and sodium thiosulphate.127 Flavanones react with hydroxylamine hydrochloride in ethanol-pyridine to give the oxime and not the oxazoline as previously claimed but when the oxime was heated with trifluoroacetic acid, the oxazoline was formed.128 The first triphenylmethane derivative to be found in nature, the flavanone melanervin (121), has been synthesized. Ammals (not animals, as printed in the abstract ) such as (122) have been applied to the... 

Another reaction commercialized by EniChem is the ammoximation of ketones, particularly the conversion of cyclohexanone to cyclohexanone oxime (47). This latter compound is an intermediate in the manufacturing of caprolactam, the monomer for Nylon 6. This reaction, outlined in Figure 10.13, proceeds with both high conversion and selectivity for the oxime product. Again, TS-1 is uniquely active for this reaction compared to other catalysts, and TS-1 can catalyze this reaction on a variety of substrates. It is believed that in all cases the hydroxylamine is first formed, followed by reaction with the ketone. TS-1 is currently used commercially by EniChem to produce 12,000 ton per year of cyclohexanone oxime. 

The formation of nitrones by reaction of aldehydes and ketones v/ith N-Methyl-N,0-bis(trimethylsilyl)hydroxylamine is accelerated when TMSOTf is used as a catalyst the acceleration is particularly pronounced when the carbonyl group is under a strong electronic influence (eq 20). ... 

Oximation of cyclododecane, a solid-liquid reaction, was studied by Janakiraman and Sharma (1985) by reacting finely ground particles of cyclododecanone (CD) with aqueous hydroxylamine sulfate (HAS) in a mechanically agitated contactor, with and without microparticles of carbon. The carbon particles are not catalysts but strongly adsorb the solid reactant (which is otherwise only sparingly soluble in the aqueous phase) and transport it to the aqueous bulk, where reaction occurs at an enhanced rate. The reaction was carried out at 2 °C, at an agitator speed of 1200 rpm, and a ketone holdup of 0.04 g/cm. Carbon microparticles of two sizes, 1.7 p and 4.33 p, were used, and volumetric rates (mol/scm aqueous phase) were determined at different microphase loadings for each size. These are presented in Table 23.2. 

Compared with unsaturated aldehydes, enones tend to be less reactive Michael acceptors. However, the addition of nitrogen-centered nucleophiles to enones can be promoted by certain primary amine catalysts by means of an iminium activation mechanism. Specifically, 9-amine-9-deoxy-epi cinchone derivatives (catalysts 9,36/37), in the presence of organic acids, have proven their usefiilness in catalyzing the addition of carbamate derivatives [75], protected hydroxylamine derivatives [76], and A/-heterocycles to acyclic [77, 78] and cychc unsaturated ketones [79] (Scheme 11.21). In general, aromatic ketones were less reactive and led to lower yields. 

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