Isomerism aldoximes

Anacardic acid similarly forms an isomeric aldoxime and a polymer with formaldehyde. 

In an alternative approach, the isomeric unsaturated pyrrolidine or piperidine aldoximes 245 a and 245b were prepared and subjected to lOOC reaction affording 246a and 246b, respectively (Eq. 28). Esterification of 240 followed by N-tert-BOC protection and DIBALH reduction provided aldehyde 244 (X = 0) which was subjected to Wittig olefination. Introduction of a two carbon aldoxime chain on N in 244 (X = CH2) was carried out by alkylation with Et a-bromoacetate after deprotection of the N atom in 244. Reduction and oxima-tion led to 245. 

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. 

Rare-earth exchanged [Ce ", La ", Sm"" and RE (RE = La/Ce/Pr/Nd)] Na-Y zeolites, K-10 montmorillonite clay and amorphous silica-alumina have also been employed as solid acid catalysts for the vapour-phase Beckmann rearrangement of salicylaldoxime 245 to benzoxazole 248 (equation 74) and of cinnamaldoxime to isoquinoline . Under appropriate reaction conditions on zeolites, salicyl aldoxime 245 undergoes E-Z isomerization followed by Beckmann rearrangement and leads to the formation of benzoxazole 248 as the major product. Fragmentation product 247 and primary amide 246 are formed as minor compounds. When catalysts with both Br0nsted and Lewis acidity were used, a correlation between the amount of Br0nsted acid sites and benzoxazole 248 yields was observed. 

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. 

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). 

For a time, considerable attention was focussed on stereoisomeric changes about the C=N double bond in substituted benz-syn-aldoximes, e.g., the partial isomerization of methyl ethers of m-and p-nitrobenz-spn-aldoximes and the complete conversion of the a-O-p-nitrobenzyl ethers of o-, m-, and p-aldoximes.26 In the case of the semicarbazones, the isomeric changes can be attributed to tautomerism in the urea portion of the molecule without the necessity of considering stereisom-erism about the double bonds in other portions of the molecule.266,310... 

To ascertain the structure of the above aldoximes, various substituted pyridazine A-oxides have been treated with amyl nitrite and sodium amide in liquid ammonia. The products were the unstable a- or syn-aldoximes, which are readily isomerized to the stable /3 or anti isomers under the influence of heat or hydrochloric acid. ... 

Reaction with (172) and other aldoximes may require oxime activation, which can be achieved with the addition of 1 equiv. of BF3-OEt2." " Yields in the addition of organometallic reagents to substituted aldoximes are modest and are a function of the isomeric composition of the oxime ethers, as the (Z)-oxime isomers are reported to preferentially react with organolithium reagents (entries 1 and 2, Table 13). ° The reaction has been employed for the preparation of 6-aminoalkyl-substituted pencillins (entry 3, Table 13)."° Cyclic oxime ether additions have also been evaluated (entries 4 and 5, Table 13). ° With the lability of the nitrogen-oxygen bond, addition to S-substituted isoxazolines provides a potential avenue for stereospecific synthesis of substituted 3-aminoalcohols (entry 5, Table 13). 

Aldoximes Amides. The isomerization of piperonaldoxime to piperonylamide is accomplished by refluxing a solution in xylene with catalytic amounts of nickel... 

The small amount of benzamide was considered to arise from isomerization of oxime before rearrangement, rather than from migration of a syn methyl group. Aldoximes (R2 = H) dehydrate to the nitrile under conditions causing ketoximes to rearrange to the corresponding lactams [29]. 

When aldoximes 309 reacted with dimedone 58 in the presence of ammonium acetate under MWI, they gave acridines 308 in 80 92% yields within 5 min. These reactions may occur through a Michael addition of dimedone 58 to 309 to give the intermediate 310, which on elimination of hydroxylamine gave 313. Then Michael addition between 311 and 312, resulting from dimedone 58 and ammonium acetate, produced 313, which isomerized and cyclodehydrated to give 308 (Scheme 63) (04SC1289). 

Thus it has been possible to separate a mixture of isomeric benz-aldoximes, benzoin oximes and anisoin oximes on 200 p.m silica gel layers, using benzene-ethyl acetate (83 + 17) chamber saturation [192]. o-, m-and p-Nitrobenzaldoxime isomers have been separated in the same way. The a-isomers always migrate further than the j8-isomers. 

Aldoximes can be isomerized to corresponding amides in dry toluene with silica gel... 

Table 3.20 Silica-gel induced isomerization of aldoximes to amides...

Field L, Hughmark PB, Shumaker SH, Marshall WS (1961) Isomerization of aldoximes to amides under substantially neutral conditions. J Am Chem Soc 83 1983... 

---