Ketoximes, Isomerism

When treated with certain reagents, the ketoximes in particular undergo the Beckmann rearrangement to isomeric acid amides (p. 227). 

Trofimov has extended his previously reported heterocyclization of ketoximes 39 with acetylene to propyne or its isomer allene in superbase systems (MOR/DMSO M = K, Cs, R = H, t-Bu) to afford a facile synthesis of substituted pyrroles 40 and 41 . Due to a fast propyne to allene protropic isomerization under the reaction conditions, the product is the same regardless of which species is employed. 

This is the first example of a direct coupling of a diazo compound in a / position of the thiophene nucleus. The Beckmann rearrangement with the ketoxime of 2-thienylketone was found to give poor yields of the aceto-2-thiopheneamide. Furthermore, the Schmidt reaction using hydrazoic and sulphuric acids was investigated and did give rise to aceto-2-thiopheneamide but probably as an eutectic with the isomeric 2-thenoylmethylamide. 

Beckmann rearrangement org chem An intramolecular change of a ketoxime into its isomeric amide when treated with phosphorus pentachloride. bek-man re-g ranj-mont ... 

We will look at three pairs of syn and anti aldoxime isomers, 9A and 9B, corresponding to R = CH3 (acetaldoxime), R = CH2CI (chloroacetaldoxime) and R = CgH5 (benzal-doxime). We will also consider the two isomeric forms lOA and lOB of acetophenone oxime, a ketoxime in which R = CH3 and R" = CeHs. 

In Table 4 are the computed AE, AG and for the aldoxime isomerization equihbria syn anti, and also for the ketoxime equilibrium lOA lOB. It should be kept in mind that all of these results come from single-molecule calculations, and do not include any intermolecular interactions. 

In Table 2 are listed the hydroxylamines, oximes and hydroxamic acids for which we have determined the gas phase structures. We tried to select a representative group in each category. There are two types of oximes, as indicated, aldoximes and ketoximes. Due to restricted rotation around the C=N double bond, these can exist in two isomeric forms (except when R = H for an aldoxime and R = R" for a ketoxime). We have investigated both isomers in nearly every instance. For aldoximes, they are generally labeled syn when the H and OH are on the same side of the double bond and anti when on opposite sides. Note that the ketoximes in Table 2 contain one pair of isomers in which the >C=NOH group is not bonded to two carbons instead one bond is to a chlorine. One of these isomers wiU be of interest in Section B.D in the context of hydrogen bonding vi lone pair—lone pair repulsion. 

Carbon chemical shifts were employed in studies of conformational effects on aldoximes and ketoximes. They appear in the region 145 to 163 ppm and several values are illustrated in Table 2. Such resonances are some 50 ppm to higher field relative to the corresponding carbonyl resonance. Where substimtion is asymmetrical, differences in oxime carbon chemical shifts are observed, depending upon the conformation of the oxime N—OH. Such conformational isomerism also has a profound effect upon the chemical shift of the a-carbon. 

Hydrogenated isoxazole derivatives were obtained by single electron transfer (SET) cyclization of /9,y-unsaturated oximes , by thermal [4- -2] cycloaddition of aldox-imes or ketoximes to conventional dienophiles or isomerization/cyclization of an ortho halogeno or nitro-substituted amidoximes. Preparation of 1,4-disubstituted 3-hydroximino-2-nitro-l-butenes and their oxidative cyclization to 4-nitroisoxazoles are reported " . Synthesis of fluorine-containing substituted isoxazolidines as well as isoxazoles by ultrasonic methods has been also described. 

Enehydroxylamines (102) are invoked as intermediates in the rearrangement of O-vinyl, acyl or aryl oximes (101) (equation 31). Varlamov and coworkers demonstrated that the heterocyclization of ketoximes (103) with acetylene in snper basic medium and in the presence of metal hydroxides proceeds by a [3,3]-sigmatropic rearrangement of the enehydroxylamine 105 of the corresponding oxime vinyl ethers 104 (equation 32). The unreactivity of 3-methyl-2-azabicyclo[3.3.1]nonan-9-one oxime (106) in the same reaction conditions was explained by its inability to isomerize to the corresponding enehydroxylamine. 

The formation of a very electrophilic intermediate 258 from 256 and 257 is proposed (equation 78). The hydroxyl group of the oxime adds to 259, giving a reactive cationic species 260 that rearranges and affords the nitrile 261 (in the case of aldoxime, equation 79), or the amide 262 upon hydrolytic workup (equation 80). The conversion of 260 to the nitrilium ion should occur through a concerted [1,2]-intramolecular shift. This procedure can be applied in the conversion of aldoximes to nitriles. It was observed that the stereochemistry of the ketoximes has little effect on the reaction, this fact being explained by the E-Z isomerization of the oxime isomers under the reaction conditions. 

The isomerization of the (Z)-isomer into the ( )-isomer promoted by the iridium complex explains the lack of stereospecificity of the transformation. O-Alkylated oximes and ketoximes do not react and this fact suggests that the presence of both hydrogen and a hydroxyl group is required for the success of the transformation. The authors proposed that the initial displacement of a chloride ion of the iridium complex by the oxime allows the iridium to remove both the oxygen and the hydride from the initial oxime. Swapping places of both substituents produces the amide. 

Grigg and co-workers (310) recently examined the 1,3-APT reaction of various aldoximes (270) (R or R = H) with divinyl ketone (Scheme 1.56). While ketoximes 270 (R = R) form a mixture of adducts, 271 and 272 via nitrone 273, the aldoximes selectively afford 272 (as a mixture of endo and exo diastereoisomers). Under the thermal reaction conditions, the oxime starting materials can undergo ( /Z) isomerization, while the nitrone intermediate was expected to be unaffected and the isolated cycloadducts showed no interconversion via cycloreversion. Thus, the increasing selectivity for endo-212 [via ( )-273, R = H] over exo-212 [via (Z)-273, R = H] with the increasing size of the aldoxime substituent was attributed primarily to the inhibition of oxime isomerization by steric clash between R or R and the oxime OH. In contrast, Lewis acid catalysis, in particular by hafnium (iv) chloride, of the cycloaddition of various aldoximes with this dipolarophile gave exo-271 exclusively (216). 

Acetoxime is the simplest ketoxime. It occurs in two isomeric forms ... 

The one-stage transformation of 3-butenyl-l-methyl ketoxime (63) to 2-methyl-3-(2-propenyl-l)pyrrole (64) and 2-methyl-3-(l-propenyl-l)-l-vinylpyrrole (65) (Scheme 34) (82TL5063) is typical and demonstrates two essential features of this version of the reaction the reaction either can be stopped selectively at the stage of pyrrole ring formation without vi-nylation onto the N—H bond and prototropic isomerization of the alkenyl, or it can form an N-vinylpyrrole in which the double bond of the alkenyl is shifted into conjugation with the pyrrole ring. 

During the interaction of benzyl methyl and benzyl ethyl ketoximes with acetylene, one can expect in each case the formation of two isomeric... 

Comparison of IR Spectra of Isomeric Pyrroles Obtained from Benzyl Methyl Ketoxime"... 

Under appropriate conditions, ketones may be converted directly to amides. The facility of ketoxime formation from ketones strongly suggests that the former are reactive intermediates in these processes. Treatment of the strained bicyclic ketone (25) with 0-(mesitylsulfonyl)hydroxylamine gave a mixture of the isomeric lactams (26) and (27) in good yield, and with moderate stereoselectivity (equation 15). ... 

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