Oximes hydroxylamine synthesis

Caprolactam Technologies Comparison. The ammoximation process simplifies a very complex part of the current CPL technology, namely the requirement of different hydroxylamine compounds for the cyclohexanone oxime synthesis. It is in Aese two steps, preparation of the hydroxylamine derivative and cyclohexanone oxime synthesis, that most of the undesired byproducts (NO SOj and ammonium sulfate) are formed. 

Figure 15.2. Comparison of the classical (black arrows) and green (green arrows) approaches to e-caprolactam synthesis. In the ammoximation step 2.8 kg/kg ammonium sulfate is co-produced, and is comprised of the salt produced during hydroxylamine sulfate preparation (Raschig process) and cyclohexanone oxime synthesis.

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

Concentrations are controlled to yield a molten oxime product layer and a saturated (ca 40 wt %) ammonium sulfate solution ca 125% (theoretical) ammonium sulfate or 2.9 kg/kg caprolactam is produced as a result of side reactions in the hydroxylamine synthesis. 

Af-Oxides, e.g. (125), were similarly prepared using hydroxylamine to give intermediates such as (124) (79JOC1695, 78H(9)1327), and an alternative synthesis of Af-oxides involves cyclization of 3-acylamino-2-aroylpyridine oximes (126) —> (127) (69MIP21500). 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

The addition of ( )-(3-trimcthylsilylallyl)boronate (10) to the racemic oxime 9 has been used in connection with a total synthesis of cannabisativine n. The results are congruent with the application of ( )-crotylboronatc as organometallic reagent9,, 0. The reaction is anti selective and generates the diastereomeric hydroxylamines 11 and 12, where 11 is converted to a tetrahydropyridine 13, a useful intermediate for the synthesis of cannabisativine11. 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

I.2. Oxidation of Amines Oxidation of primary amines is often viewed as a particularly convenient way to prepare hydroxylamines. However, their direct oxidation usually leads to complex mixtures containing nitroso and nitro compounds and oximes. However, oxidation to nitrones can be performed after their conversion into secondary amines or imines. Sometimes, oxidation of secondary amines rather than direct imine oxidation seems to provide a more useful and convenient way of producing nitrones. In many cases, imines are first reduced to secondary amines which are then treated with oxidants (26). This approach is used as a basis for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b). 

Although harmine 52 is frequently obtained by isolation (or purchase order), a synthesis of this compound as well as a number of analogs has recently appeared [47,48]. The key step to this synthesis was the thermal electrocyclization of oxime intermediate 55, which was prepared by acylation of vinylindole derivative 54 followed by treatment with hydroxylamine hydrochloride. Neither oxime 55 nor its ketone precursor were isolated— instead, the crude reaction mixture was heated at reflux in o-dichlorobenzene to ultimately yield harmine in 56% yield overall starting from 54 (Fig. 18). 

The Doering-Moore-Skattebol method including a cyclopropylidene-allene rearrangement is often used for the synthesis of allenes. However, the reaction conditions applied are often not compatible with acceptor substituents. One of the rare exceptions is the transformation 76 —> 77 (Scheme 7.11) [122]. The oximes 77 are not accessible by the classical route starting from allenyl ketone and hydroxylamine (see Section 7.3.2). 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

A small number of examples is available for the synthesis of E and Z isomers of oximes. In many cases, E isomers were obtained either from the Z forms (by the hydrochloride method) or isolated by column chromatography. Often, the reagents that have been used for oximation of aldehydes and ketones also catalyze the interconversion of Z and E isomers. The rate of equilibration of a mixture of Z and E isomers and the position of the equilibrium is temperature-dependent ". In 2001, Sharghi and Sarvani reported a convenient method for controlling the stereochemistry of the reaction of hydroxylamine hydrochloride with aldehydes or ketones in the solid state. The highly stereoselective conversion of aldehydes and ketones to their corresponding oximes... 

In 2002, Kanno and Taylor successfully developed a simple one-pot procedure using MnOi/NHiOMe-HCl for the conversion of activated primary alcohols into O-methyl oximes (Scheme 11). They also developed a modification using Amberlyst 15-supported alkoxylamines, which can be employed to prepare other types of 0-aUcyl oximes as well as the parent hydroxylamines. This latter procedure has been used as the cornerstone of an efficient synthesis of the antifungal natural product citaldoxime 11 (Scheme 11). Citaldoxime is an antifungal natural product first obtained as a radiation-induced stress metabolite of Citrus sinensis , and later isolated from the roots of several different citrus plants. ... 

The two reactions in Step A were taken from the literature and were improved for the present synthesis. All previously related syntheses of arylacetophenone oximes found in the literature have used a threefold excess of hydroxylamine hydrochloride that is, however, not necessary in the present protocol. 

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