Oxime intermediates

Treatment of the sulpholene (19) with hydroxylamine in refluxing ethanol has led to the formation of isothiazol-3-sulpholenes (21) which presumably progressed via the oxime intermediate (20). Subsequent heating of (21) in toluene at 185°C in a sealed tube led to the generation of the diene (22) which could be trapped with 1 -phenylmaleimide and with DMAD, thus providing a new route to 1,2-benzisothiazole derivatives <96TL4189>. 

Ammonia also reacts with the acrolein intermediate, via the formation of an imine or possibly oxime intermediate which transforms faster to the acrylonitrile than to the acrylamide intermediate. This pathway of reaction occurs at lower temperatures in comparison to that involving an acrylate intermediate, but its relative importance depends on the competitive reaction of the acrolein intermediate with the ammonia species and with catalyst lattice oxygens. NH3 coordinated on Lewis sites also inhibits the activation of propane differently from that absorbed on Brsurface reaction network in propane ammoxidation. 

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 oxidation of NH3 to NH2OH forms the basis of a process for the ammoximation of cyclohexanone to the oxime because the NH2OH formed in solution readily reacts with the ketone (non-catalytically) to give the oxime (231). Table XXX (165) illustrates the conversions and selectivites obtained for a few typical ketones and aldehydes. The ammoximation of aldehydes is faster than that of ketones. The oxime selectivity is also higher. The ammoximation of cyclohexanone by this method offers a more eco-friendly alternative route to the cyclohexanone oxime intermediate for the production of Nylon-6. The current route coproduces large quantities of ammonium sulfate and involves the use of hazardous chemicals such as oleum, halides, and oxides of nitrogen. 

Similar behavior has also been found in the reaction of an oxime with a sulfinyl chloride (Brown et al., 1978). Reaction of an oxime with a sulfinyl chloride at —30° yields an O-sulfinyl oxime intermediate [43] that decomposes rapidly at +30° in the manner shown in (147). The involvement of radical intermediates was definitely established. 

Over the last 30 years an ever increasing amount of information on the biosynthesis of oxime intermediates in plant metabolism and on interactions of oximes with enzymes has accumulated. Enzymatic reactions that were characterized with respect to oximes as products, substrates or inhibitors are listed in Table 2. 

Diacetyl (DA) is used as a flavour enhancer in the food industry and is currently manufactured from methyl ethyl ketone (MEK) in homogeneous systems via an oxime intermediate (ref.1). In principle, DA can also be manufactured by the selective oxidation of MEK and several reports have appeared in the literature which apply heterogeneous catalysts to this task (refs. 2-4). A number of reports have specified the importance of basic or weakly acidic sites on the catalyst surface for a selectively catalysed reaction and high selectivities to DA at moderate conversions of MEK have been reported for catalysts based on C03O4 as a pure oxide and with basic oxides added conversely scission reactions have been associated with acidic oxide additives (refs. 2-4). Other approaches to this problem have included the application of vanadium phosphorus oxide (VPO) catalysts. Ai (ref. 5) has shown that these catalysts also catalyse the selective oxidation of MEK to DA. Indeed this catalyst system, used commercially for the selective oxidation of n-butane to maleic anhydride (ref.6), possesses many of the desired functionalities for DA formation from MEK, namely the ability to selectively activate methylene C-H bonds without excessive C-C bond scission. 

Nitroalkenes react with benzene derivatives at low temperature in triflic acid to afford a-aryl ketones after quenching with methanol182,183 [Eq. (5.74)]. At higher temperature the 0-protonated oxime intermediate may react further to yield 4//-1,2-benzoxazines (see Section 5.14.1.3). a-Nitrocarbonyl compounds show similar characteristics as alkylating agents to yield oximes with the involvement of the tricationic intermediate 44.181... 

As part of such investigations, ortho-substituted oxime intermediates were found to be active, and this led to an examination of their precursor ortho-substituted ketones, again within the context of simple aryl systems like that present in practolol and its para-substituent [132]. This gradual accumulation of SAR data further demonstrates propranolol s key role as a pioneer drug during ABDD, as well as practolol s key role as an early offspring that prompted so much interest in... 

Various a,/3-unsaturated ketones were used as versatile synthons in heterocyclizations with hydroxylamine hydrochloride, probably through oxime intermediates, RCOCH=C(Cl)CH2Br (R = alkyl, aryl, furyl), affording 3-substituted 5-bromomethylisoxazoles <2005RJ01192>, and l-bis(methoxy)-4-bis(methylthio)-3-buten-2-one led to isoxazoles with a masked aldehyde functionality <2003T2631>. 

The N-hydroxylation reaction is not restricted to o-substi-tuted primary amines such as phentermine. Amphetamine has been observed to undergo some N-hydroxylation in vitro to (V-hydroxyamphetamine.- - /V-Hydroxyamphetamine is, however, susceptible to further conversion to the imine or oxidation to the oxime intermediate. Note that the oxime intermediate arising from this N-oxidation pathway can undergo hydrolytic cleavage to yield phenylacetone. the same product obtained by the a-carbon hydroxylation (carbi-... 

The synthesis of the bisbenzannelated spiroketal core of the y-rubromycins was achieved by the research team of C.B. de Koning." The key step was the Nef reaction of a nitroolefin, which was prepared by the Henry reaction between an aromatic aldehyde and a nitroalkane. The nitroolefin was a mixture of two stereoisomers, and it was subjected to catalytic hydrogenation in the presence of hydrochloric acid. The hydrogenation accomplished two different tasks it first converted the nitroalkene to the corresponding oxime and removed the benzyl protecting groups. The oxime intermediate was hydrolyzed to a ketone that underwent spontaneous spirocyclization to afford the desired spiroketal product. 

Aerothionin (809), homoaerothionin (810) and aerophobin-1 (811), metabolites of sponges such as Aplysia flstularis and Veronia thionia, have a unique spiroisoxazohne framework. These metabolites must be biosynthesized in nature from a common phenylpyruvate oxime intermediate. 

Perfluorination. Ketoximes are converted to gcm-difluorides and diary-lacetylenes to 1,2-diaryltetrafluoroethanes with this combination of reagents. The latter transformation is actually initiated by nitrosofluorination to generate fluori-nated oxime intermediates. 

Sarodnick and Linker developed an onc-pot synthesis of quinoxaline 254 from 1,2-phenylenediamine (242) and 23-butancdione monoxime 252 via oxime intermediate 253 < 01JHC829>. Yields were only moderate. 

The synthesis of etoxazoie is shown in Scheme 26.2.3 [19, 26]. Starting from 2-ethoxy-4- butyl acetophenone standard procedures lead to an oxime intermediate, which is reduced to the corresponding amino alcohol. Acylation of this amino alcohol with 2,6-difluorobenzoyl chloride and subsequent base-catalyzed cydization after activation of the hydroxy group leads to etoxazoie (4). An alternative route starts with the amino acid ester, which is first acylated using 2,6-difluorobenzoyl chloride and then reduced with sodium borohydride to the same final intermediate. 

In 1986, Boyd et al. [93] disclosed an elegant strategy allowing the preparation of homocarbapenems with a C-3 electron-withdrawing substituent. The amino side-chain was introduced by stereoselective hydrogenation of the oxime intermediate 175. The key-step was a [3 + 2] cyclisation of the... 

An improved synthesis of the oximino-lactone derivative 63 ( PUGNAc ) in five steps from 2-acetamido-2-deoxy-a-D-glucopyranose tetraacetate has been described, the critical step being a low temperature oxidation of an acyclic aldose oxime intermediate to a cyclic oximino-lactone with NCS and DBU. " The D-xylono-l,5-lacatam oxime derivative 64 has been synthesized from an L-serinal derivative as a potential A-acetylglucosaminyl transferase inhibitor. ... 

From this key intermediate (78), the steps required to effect its subsequent conversion into 21 proceeded smoothly. Thus, partial reduction of the cyanide to its aldehyde counterpart in CH2CI2 at —78°C was followed by reaction with H2NOH HCl to afford oxime intermediate 80. With this new functional group appended in proper relation to the disubstituted C—C double bond, tiie stage was set to attempt ring formation through a nitrile oxide-based... 

When the Beckmann reaction was performed with mesylated oxime intermediate 113, lactam 112, from the Beckmann rearrangement, was obtained as the sole product tScheme 5.261. thus shutting down the Beckmann fragmentation pathway.This reaction is similar to what White and coworkers observed during their morphine synthesis. Beckmann reaction of an intermediate brosylated oxime in acetic acid provided the desired lactam, whereas the reaction of the corresponding oxime under acidic conditions did not yield any lactam... 

Isatins are indole derivatives with broad use in synthetic dye production and are intermediates in the synthesis of other heterocyclic molecules/ They also possess a variety of biological activities/ Aksenov et al. reported a one-pot synthesis of isatins using ethyl nitroacetate with substituted benzenes such as anisole (159) in polyphosphoric acid fScheme 5.38)/ The process for isatin formation likely includes a hybrid between the Nef and Vilsmeier reactions of anisole 159 and nitro ester 160 to form the oxime intermediate 161, which then undergoes a Beckmann rearrangement to give the anilide 162. Subsequent intramolecular acylation yields isatin 163. 

In the CPL production through the cyclohexanone oxime intermediate, the large byproduction of ammonium sulfate is a critical environmental and economic issue associated with the process, due in part to possible problems related to the disposal of ammonium sulfate. 

Treatment of the oxime intermediate with alcoholic KOH causes an elimination reaction that yields the target nitrile product, piperonylonitrile ... 

The generation of the oxime intermediate involves a nucleophilic addition of the amine group of the hydroxylamine to the carbonyl carbon, followed by a dehydration to form the carbon-nitrogen double bond (and the oxime group). A general mechanism for the reaction is given here. 

Purpose. Tbe piperonal 0-(2,4-dinitropbenyl)oxime intermediate, prepared in the previous experiment (Experiment [E2]), is converted into the target molecule, piperonylonitrile. This completes the set of Sequence E reactions for the conversion of a substituted benzyl alcohol into an aromatic nitrile. You will investigate the use of a novel elimination reaction to convert an oxime derivative to a nitrile. 

Among the industrially produced lactams, e-caprolactam has by far the highest production capacity due to its important role as monomer in the polyamide business. There exist several synthetic routes to produce e-caprolactam. The most important one starts from benzene (Scheme 5.3.7). Benzene is hydrogenated in a first step to cyclohexane, followed by oxidation of the latter to a mixture of cyclohexanone and cydohexanol. This mixture is then reacted with NH2OH to give cyclohexanone oxime, which is converted under add catalysis in a so-called Beckmann rearrangement reaction to e-caprolactam. Alternative routes try to avoid the oxime intermediate (UCC peracetic add process via e-caprolactone), try to avoid the cydohexanone intermediate (e.g., DuPont process converting cydohexane directly into the oxime intermediate by reaction with nitric add), or start from toluene (Snia-Viscosa process). 

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