Oximes to hydroxylamines

Scheme 7.9 Hydrolysis of cyclohexanone oxime to hydroxylamine with nitric oxide formation.

Lithium cyanoborohydride reduces oximes to hydroxylamines in good yield. Careful pH control is not necessary in this case and reduction can be done efficiently in the presence of acetic acid at pH 5 . Lithium borohydride reduces oximes as well. Sodium borohydride in acetic acid or on silica gel has been used for reduction of oximes, but reported yields were low to moderate only. Lithium aluminum hydride " and DIBAL are capable of reducing oximes, but are sufficiently chemoselective for reduction of polyfunctional oximes. 

Diborane in THF has been successfully used for reduction of aliphatic and aromatic oximes to hydroxylamines. Reported yields are highly variable although the low... 

Oximes undergo hydrogenation to hydroxylamines and/or amines depending on reaction conditions. Platinum oxide is the most frequently used catalyst for selective hydrogenation of oximes to hydroxylamines. Reduction of chiral oxime 96 over palladium catalyst (equation 66) proceeds in high yield and stereoselectivity. High stereoselectivity was observed in catalytic hydrogenation of a-alkoxyoximes . 

Reduction of C=N to CHNH by Metal Hydrides Table 11 Reduction of Oximes to Hydroxylamines... 

In organic acid media, NaCNBHj is converted to acyloxycyanoborohydrides whose reactivity is comparable to that of NaBH4 in CF3COOH, especially concerning the reduction of imines to amines, tosylhydrazones to saturated hydrocarbons, oximes to hydroxylamines, or reductive amination. Depending on the substrate, NaBH4 or NaCNBHj is recommended (Sections 3.3.1, 3.3.4) [GNl]. 

Mixtures of hydrosilanes and acid reduce oximes to hydroxylamines in good yields 4 3 an (e) -oxime gave erythro-l-phenyl-l-benzyloxyamino propan-2-ol in 99% selectivity (Scheme 186) the reduction with lithium aluminium hydride gave only an 82 18 ratio of the (E)- to (Z)-isomers. 

Hydroxylamines and Oximes. For RNH—OH compounds, prefix the name of the radical R to hydroxylamine. If another substituent has priority as principal group, attach the prefix... 

Dimethyl ketals and enol ethers are stable to the conditions of oxime formation (hydroxylamine acetate or hydroxylamine hydrochloride-pyridine). Thioketals and hemithioketals are cleaved to the parent ketones by cadmium carbonate and mercuric chloride. Desulfurization of thioketals with Raney nickel leads to the corresponding methylene compounds, while thioenol ethers give the corresponding olefin. In contrast, desulfurization of hemithioketals regenerates the parent ketone. ... 

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

Hydrogenation of oximes to primary amines usually can be made to proceed smoothly despite the potential complications cited earlier. Many of the same considerations applicable to control of nitrile reductions hold for oxime reductions as well. Oximes, unlike nitriles, can be reduced to hydroxylamines. 

Oximes have been reduced in a different way, to give imines (RR C=NOH RR C=NH), which are generally unstable but can be trapped to give useful products. Among reagents used for this purpose have been BU3P—SPh3 and Ru3(CO)i2. " Oximes can also be reduced to hydroxylamines (16-24). 

As shown in Fig. 6.4, primary amines are converted to oximes, secondary amines to hydroxylamines, and tertiary amines to N-oxides.34... 

Oxidation of primary amines with DMD or other oxidants leads to the formation of a complex mixture of nitroso, oximes, and nitro compounds (76). Utilization of DMD in acetone affords dimethyl nitrone (22). This is likely to be a result of the initial oxidation of primary amine (19) to hydroxylamine (20) with the subsequent condensation of acetone and oxidation of imine (21) (Scheme 2.9) (77). 

Oximes generally demonstrate good stability in the solid state when stored at low temperature. Simple oximes show reasonable stability in neutral aqueous solution but hydrolyze to hydroxylamine and the parent ketone under acidic or basic catalysis [2], As noted, nitro-containing oximes, such as FK409 (9), spontaneously decompose... 

Imanaka—heterogenization of Rh complexes. In 1991, Imanaka and coworkers124 reported the heterogenization of Rh complexes by binding them to aminated polymers. As discussed previously, these findings led to fruitful research by Ford, Pardey, and others. The isolated polymer-bound Rh carbonyl anion complex was found to be reusable for reactions such as water-gas shift and reduction of nitro compounds. The polymer-bound Rh complexes were characterized by infrared spectroscopy. Water-gas shift activity (80 mol H2 per mol Rh6(CO)i6 in 24 hours) was recorded using the Rh complexes at 100 °C with 0.92 atm of CO, 2.16 ml H20, 0.05 mmol Rh6(CO)16, aminated polystyrene, 5.0 mmol of N, 5.56 ml ethoxyethanol and reduction of nitro-compounds (e.g., aliphatic nitro compounds to nitriles, oximes to nitriles, hydroxylamines to nitriles, and N-oxides to amines) occurred at 40 °C. 

Electrochemical reduction of benzylic nitro compounds (27) in an ethanolic aqueous acetic acid buffer (35 65) affords a mixture of the corresponding oxime and hydroxylamine (equation 6)48. The hydroxylamine can subsequently be oxidized back to the oxime (28) (via the intermediate nitroso compound) conversions as high as 90% can be obtained. 

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. 

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde Formation of the oxime with hydroxylamine is fol-... 

The common name caprolactam comes from the original name for the Ce carboxylic acid, caproic acid. Caprolactam is the cyclic amide (lactam) of 6-aminocaproic acid. Its manufacture is from cyclohexanone, made usually from cyclohexane (58%), but also available from phenol (42%). Some of the cyclohexanol in cyclohexanone/cyclohexanol mixtures can be converted to cyclohexanone by a ZnO catalyst at 400°C. Then the cyclohexanone is converted into the oxime with hydroxylamine. The oxime undergoes a very famous acid-catalyzed reaction called the Beckmann rearrangement to give caprolactam. Sulfuric acid at 100-120°C is common but phosphoric acid is also used, since after treatment with ammonia the by-product becomes... 

Before ending this chapter, we would like to draw attention to another type of electrostatic intermolecular interaction that could be quite relevant to hydroxylamines, oximes and hydroxamic acids. We refer to a-hole bonding. This is a highly-directional, nonco-valent interaction between a region of positive electrostatic potential (or cr-hole) on an outer portion of a Group V, VI or VII covalently-bonded atom and a negative site on... 

Oximes also have been reduced to hydroxylamines with bis(trifluoroacetoxy) borane " and photochemically with PhSetf . 

B. Hydroxylamines through [3 + 2] Cycloaddition Reactions of Nitrones and Oximes to Alkenes... 

SCHEME 150. Ti-catalyzed oxidation of primary amines to hydroxylamines or oximes... 

The product (15-2) from aldol condensation of meto-nitrobenzaldehyde with the dimethyl acetal from ethyl 4-formylacetoacetate (15-1) provides the starting material for a dihydropyridine in which one of the methyl groups is replaced by a nitrile. Reaction of (15-2) with the eneamine from isopropyl acetoacetate gives the corresponding dihydropyridine hydrolysis of the acetal function with aqueous acid affords the aldehyde (15-3). That function is then converted to its oxime (15-4) by reaction with hydroxylamine. Treatment of that intermediate with hot acetic acid leads the oxime to dehydrate to a nitrile. There is this obtained nilvadipine (15-5) [16]. 

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