Ketoximes, ©-substituted

The rearrangement of oximes 1 under the influence of acidic reagents to yield A -substituted carboxylic amides 2, is called the Beckmann rearrangement. The reaction is usually applied to ketoximes aldoximes often are less reactive. 

Tables XXVIII and XXIX, respectively. Excellent correlations were obtained for all three sets. The stereochemistry of the sy -methyl ketoximes is discussed by Charton and Charton (73). The values of pj obtained for the trans-heterovinylene sets are not in good agreement with each other. Two sets gave values of 54 and 55, respectively, and the third set gave a value of 35. The difference in pj values cannot be accounted for. A value of 54 to 55 for pj suggests the possibility of some exaltation between substituent and reaction site such as that which occurs in para-substituted phenols and anilines. To demonstrate this with certainty requires that the value of pj be determined for a set of imines bearing a reaction site on the nitrogen which will not interact strongly with substituents. No such set of data is extant in the literature at the present time.

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. 

Ketoximes and aldoximes Ketoximes and aldoximes are uniquely substituted C=N systems that react differently with titanocene and zirconocene. Aliphatic and alicyclic O-silylated ketoximes R2C=N OSiMe3 react with complex 1 with elimination of the alkyne and N—O bond cleavage to give imido-silanolates 85 [45],... 

The pKi, values of a series of para- and meffl-substituted benzaldoximes and phenyl methyl ketoximes, ArCR=NOH (R=H, Me), have been measured in DMSO. The aldoximes exhibit pK. = 20.05 + 3.21ap. The homolytic bond dissociation energy of the O-H bond has been estimated as 88.3 (aldoximes) and 89.2kcal mol" (ketoximes) by relating the pK to the oxidation potential of the conjugate base (i.e. ox for ArCR=NO- ArCR=NO ). 

The Ponzio reaction provides a useful route to gem-dinitro compounds and involves treating oximes with a solution of nitrogen dioxide or its dimer in diethyl ether or a chlorinated solvent. The Ponzio reaction works best for aromatic oximes where the synthesis of many substituted aryldinitromethanes have been reported. Compound (56), an isomer of TNT, is formed from the reaction of dinitrogen tetroxide with the oxime of benzaldehyde (55) followed by mononitration of the aromatic ring with mixed acid. Yields are usually much lower for aliphatic aldoximes and ketoximes. " The parent carbonyl compound of the oxime is usually the major by-product in these reactions. 

An efficient synthesis of 2Ff-azirines 6 substituted with a phosphate group is described. Its key step is an alkaloid catalyzed Neber reaction of -ketoxime tosylates 5 (equation 3) . Similarly, azirines containing an ester group in position 2 were obtained from tosy-lated oximes . A novel approach to substituted 2Ff-azirines using benzotriazole (Bt) methodology was recently presented. The reaction of benzotriazole oxime tosylates formed from the oxime 7 and TsCl with aqueous KOH yielded 2-(benzotriazol-l-yl)-2H-azirines. 

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. 

Alternatively, oximes may be converted to O-substituted oximes (typically O-tosyl oximes) making the rearrangement much easier. Sometimes, these oxime derivatives rearrange spontaneously under the condition of their formation and cannot be isolated. Usually, O -tosyl ketoximes rearrange smoothly with exclusive anti migration. Relative to the acid-promoted Beckmann rearrangement, the rearrangement of O -tosyl oximes is much milder and specific. 

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. 

Aryl alkyl ketoximes also react with aryl or alkyl Grignard reagents to give substituted ethylenimines [44, 45]. Additional methods for the synthesis of ethylenimines (aziridines) is found in Dermer and Ham [lb]. 

Extention of the reaction of ketoximes with acetylene to oximes of hydroxyalkyl ketones can lead to the synthesis of inaccessible, functionally substituted pyrroles and A-vinyl derivatives. However, the methyl a- and /3-hydroxyalkyl ketoximes used by Trofimov et al. (80ZOR410) appeared to react with acetylene in the KOH/DMSO system in an abnormal way. 

This process, likely based on vinyl chloride, is simple, efficient, safe, and convenient for engineering (it can easily be realized in the simplest conventional reactor at atmospheric pressure), and uses cheap and accessible raw material (dihaloethane and ketoximes). As stated previously, the interaction of ketoximes with dihaloethanes may also lead to N-vinylpyrroles. Occasionally the nucleophilic substitution of halogen by oximate anions, leading to ethyleneglycol diethers of ketoximes, becomes noticeable (see following). 

In brief communications concerning the use of dialkyl ketoximes (79IZV2840 81MI7, 81MI8) in this reaction, no comprehensive synthetic procedures are described. The experimental details for the synthesis of 2,3-dialkyl-substituted pyrroles from symmetrical and unsymmetrical dialkyl ketoximes and dichloroethane in the KOH/DMSO system (Scheme 63) were first discussed by Trofimov et al. (85KGS59). 

The l,2-bis(alkylideniminoxy)ethanes 128 formed in minor quantities (Table XXVIII) are side products. The 128 content of the reaction mixture increases in the case of a one-batch addition of alkali and dichloroethane to the ketoxime solution in DMSO. So, in order to suppress the substitution reaction, this operation should be performed batchwise. 

Detection of the Ovinyloximes 136a,d (Scheme 66) and the 0(2-chloroethyl)oxime 137 (Scheme 67) suggests two possible pathways for the formation of pyrroles from ketoximes and dichloroethane [89KGS901]. First, in a strongly basic medium, dichloroethane may act as an acetylene supplier (Scheme 66). Second, nucleophilic substitution of one chlorine atom in dichloroethane by the oximate-anion may lead to the 0(2-... 

A synthetic route to substituted a-methyl pyrroles (141) from ketoximes and 1,2-dibromopropane has been developed (Scheme 69) (88IZV2175). 

The addition of ZnBi 2 to die tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones.79 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material.80 The cycloaddition of thiophene-2 -carbaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, substituted isoxazolidines, and not the previously reported 4 + 2-adducts.81 Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines.82 The 3 + 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-l,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22).83... 

Falbe and co-workers have studied carbonylation of unsaturated amides to give imides (34), unsaturated amines to give lactams (37), and unsaturated alcohols to give lactones (38). Rosenthal and co-workers studied carbonylation of aromatic ketoximes, (127), phenylhydrazones (131), semicarbazones (129), azines (129), and nitriles (128) to produce phthalimidines. Horiie (65) has described the carbonylation of azobenzenes to give indazolones or 2,4-dioxo-l,2,3,4-tetrahydroquinazolines. Pritchard (121) and Murahashi et al. (103) have described the carbonylation of Schiff s bases to yield substituted phthalimidines. 

The observed substituent effect on the reaction rate in the oxidation of substituted aliphatic ketoximes by /V-bromosaccharin has been rationalized in terms of a mechanism.126 The oxidation of acetophenones with N-bromophthalimidc exhibited a linear correlation with Brown s a+ with reaction constant p = —0.52. An Exner plot gave an isokinetic temperature p = 263 K. A mechanism consistent with the kinetic data has been proposed.127... 

Ketoximes from some aromatic ketones (benzophenone and substituted acetophenones) underwent deoximation, at room temperature, in 65-80% yield [56]. 

Ketoximes give 3-substituted derivatives in the same manner.9 Thio-ethers undergo a similar reaction, the extra alkyl group on the sulfur... 

The synthesis of NH- and Af-vinylpyrroles from ketones (ketoximes) and acetylenes has stimulated physicochemical and theoretical studies of ketoximes as well as pyrroles and N-vinylpyrroles. The easy access to diversely substituted representatives of pyrrole series made it possible to systematically examine the structural effect on their reactivity and spectral properties. This section is a concise account on the research related to NH- and N-vinylpyrroles originated from the reaction of ketones with acetylenes along with investigation of stereoelectronic properties of intermediate ketoximes. 

Unsubstituted ketoximes undergo rearrangement in nonacidic media also. Thus, both geometric isomers of cholest-4-en-3-one oxime (12) rearranged to (13) in the presence of triphenylphosphine in refluxing tetrachloromethane (equation 8) 7 the apparent reluctance to migrate of endocyclic unsaturated substituents has also been observed for 0-substituted oximes (vide infra). 

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