Ketoximes, dehydration

For example, the reaction of nitronates (123) with a zinc copper pair in ethanol followed by treatment of the intermediate with aqueous ammonium chloride a to give an equilibrium mixture of ketoximes (124) and their cyclic esters 125. Heating of this mixture b affords pyocoles (126). Successive treatment of nitronates (123) with boron trifluoride etherate and water c affords 1,4-diketones (127). Catalytic hydrogenation of acyl nitronates (123) over platinum dioxide d or 5% rhodium on aluminum oxide e gives a-hydroxypyrrolidines (128) or pyrrolidines 129, respectively. Finally, smooth dehydration of a-hydroxypyrrolidines (128) into pyrrolines (130f) can be performed. 

Aldoximes are normally dehydrated by reaction with dichlorocarbene, produced under soliddiquid two-phase conditions, to yield nitriles in high yield [41, 42], whereas a-hydroxy ketoximes are cleaved with the simultaneous formation of a nitrile and either an aldehyde or ketone (Scheme 7.33). Yields are generally >70% and, in the case of cyclic hydroxy ketoximes, the products are acyclic oxo nitriles [43],... 

Also, chlorosulfonic acid was demonstrated to be an efficient catalyst in the Beckmann rearrangement of a variety of ketoximes in refluxing toluene, and excellent conversion and selectivity was observed . This procedure can also be applied to the dehydration of aldoximes yielding the corresponding nitriles. 

Indium trifluoromethanesulfonate was found to be an effective high-yielding catalyst for the facile dehydration of aldoximes to nitriles and Beckmann rearrangement of ketoximes to anilides. ... 

Sheradsky has found that the hydroxyl function of a ketoxime such as acetophenone oxime can be made to react with DMAD when the reaction is carried out in methanol with a basic catalyst, to give mixture of the fumarate and maleate isomers (164) in the ratio 2 1. This mixture on heating undergoes a hetero-Cope rearrangement followed by cyclization and dehydration to give dimethyl 5-phenylpyrrole-2,3-dicarboxylate (168) (Scheme 25). Similarly, Heindel and Chun have reported that vinyl ether adducts (171), obtained by the condensation of arylamide oximes with DMAD, get thermally converted into oxa-diazolines (172) or imidazolinones (174), depending on the reaction conditions. A similar reaction occurs with aromatic amidoxime-methyl propiolate adducts to give imidazoles (170) (Scheme 26). 1,2,4-Dioxazoles have been reported to be formed in the reaction of hydrox-amic acids with DMAD. - ... 

Surprisingly it was reported that when potassium cyanate is substituted for sodium cyanate the yields of carbamates are reduced to less than 5 %. The reason for this drastic effect is not known at this time. In addition, the use of other alkali or alkaline metal cyanates in this reaction has not been investigated. The Loev [28] procedure appears applicable to the synthesis of carbamates from primary, secondary, and tertiary alcohols (2 hr reaction time affords 60-90% yields), cyclic and acyclic 1,3-diols, phenols, oximes, ald-oximes, and ketoximes, and primary, secondary, and tertiary mercaptans. Carbamates could not be obtained from diphenylethylcarbinol (dehydrated to 1,1-diphenylethylene) or trichloro- and trifluoromethylcarbinols. 

Reduction of ketoximes.1 Ketoximes are reduced by LiAlH4 to a mixture of primary and secondary amines. In contrast, reduction with LiAlH4-HMPT in the molar ratio 1 10 in refluxing THF (130°, 3 hours) results in ketones. HMPT is believed to prevent further reduction of the imine intermediate and to facilitate hydrolysis. This method is not useful for reversion of aldoximes to aldehydes because of dehydration to nitriles. 

By analogy with the dehydration of aldoximes in the KOH/DMSO system, which certainly involves abstraction of the proton nearest to the oxime function, in the case ketoximes, one can expect 1,3-dehydration which leads to unstable intermediates such as the 1,3-dipole 82, azirine 83, vinylnitrene 84 or nitrile, or the stable rearrangement product of one of them (Scheme 42). 

Under the relatively mild conditions of chlorosulfonic acid in toluene, ketoximes undergo Beckmann rearrangement, whereas aldoximes dehydrate to nitriles.90... 

Reaction of oximes. Aldoximes are dehydrated to afford nitriles on treatment with HjSO -SiOj under microwave. Actually it suffices to irradiate the mixtures of aldehydes, NHjOH HCl, and HCOOH with microwave for the direct access to nitriles.- Regeneration of ketones from ketoximes is readily achieved by the same technique, while adding wet NalO orNaBiDOj to drive the reaction. 

With dimethylacetylene dicarboxylate (DMAD) 1-acylimidazoles form novel functionalized derivatives as a consequence of electrophilic attack on the pyridine nitrogen followed by intramolecular transacylation (Scheme 112) <88CC1151,90JCS(P1)1821,92CB1939>. Ketoximes undergo Beckmann rearrangement and primary carboxamides are dehydrated to nitriles on treatment with (170)... 

Ketoximes are readily dehydrated by acetic anhydride to give isoxazolo[4,5-rfjisoxazoles (equation 17) (59G571). 

Dehydration Ketoximes of alkyl aryl ketones afford pynolines on heating with AC2O in dimethylacetamide. CycUzation probably proceeds via H-abstraction after the nitrenium ions are formed. 

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]. 

This new reaction was shown to be applicable to various a,/3-epoxy ketoximes and to other cuprates. The products are easily dehydrated hence this method can be used to effect a-alkylation of a,/3-enones. 

Reaction with Oximes.Oximes are activated for dehydration (aldoximes, with hexamethylsilazane) or Beckmann rearrangement (ketoximes) with TMS-I (eq 37). 

It is not possible to dehydrate ketoximes but some cyclic ketoximes break down under Beckmann rearrangement conditions to give nitriles - a reaction which is sometimes called a Beckmann fragmentation. The oxime of 2-(l-cyclo-hexenyl)cyclohexanone when treated at 0° with phosphorus pentachloride in ether gave the nitrile (16) as the main product [67]. 

Another reaction comprises the interception of intermediate adduct of ketone and hydroxylamine C by acetylene to afford O-vinyl derivative D, further dehydration of which leads to O-vinyl oxime B (Scheme 1.21). Such interception can be more preferable than vinylation of the corresponding ketoxime, since the hydroxyl group is bonded to less electronegative nitrogen atom than nitrogen atom in ketoxime. 

In the case of ketoximes in the system MOH/DMSO, one can expect that in the same conditions, the 1,3-dehydration should occur producing such unstable intermediates as C,0-dianion A, zwitterion B, azirine C, vinylnitrene D, or yielding nitrile, a stable product of one of these intermediate rearrangements (Scheme 1.184). 

The discussion of the mechanism of pyrrole synthesis from ketoximes and acetylene should also account for a possibility of azirine intermediate (or its open-chain forms, zwitterion and vinyl nitrene) participation in the reaction, since ketoximes are known to undergo 1,3-dehydration under the influence of the strong bases to produce azirines (the Hoch-Campbell reaction) (Scheme 1.207) [344-348]. 

Mechanism 3. 1,3-Dehydration of ketoximes and addition of zwitterions (or the corresponding vinyl nitrene) across the triple bond (Scheme 1.210)... 

SCHEME 1.210 Alternative formation of pyrroles via addition of zwitterions, generated by 1,3-dehydration of ketoximes, to acetylene. 

Silica supported dichlorophosphate has been found to be an efficient, recoverable and reusable catalyst for Beckmann rearrangement of a variety of ketoximes and dehydration of various aldoximes in tetrahydrofuran under microwave irradiation (Li and Lu, 2008). This protocol is also advantageous because of high conversion, high selectivity, short reaction time, no environmental pollution and simple work-up procedure. 

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