Ketoximes, reactions with

Vinyl chloride reacts with sulfides, thiols, alcohols, and oximes in basic media. Reaction with hydrated sodium sulfide [1313-82-2] in a mixture of dimethyl sulfoxide [67-68-5] (DMSO) and potassium hydroxide [1310-58-3], KOH, yields divinyl sulfide [627-51-0] and sulfur-containing heterocycles (27). Various vinyl sulfides can be obtained by reacting vinyl chloride with thiols in the presence of base (28). Vinyl ethers are produced in similar fashion, from the reaction of vinyl chloride with alcohols in the presence of a strong base (29,30). A variety of pyrroles and indoles have also been prepared by reacting vinyl chloride with different ketoximes or oximes in a mixture of DMSO and KOH (31). 

Azido derivatives of furazans have proved to be particularly useful for the synthesis of heterocyclic systems. Thus, by 1,3-dipolar addition of l-azido(4-amino-l,2,5-oxadiazol-3-yl)aldoxime 186 to propargyl alcohol and phenylacetyl-ene, bicyclic 4-amino-l,2,5-oxadiazol-3-yl(4-R-l,2,3-triazol-l-yl)ketoximes 187 were obtained (Equation 34) which in reaction with acetic anhydride afforded the corresponding 0-acyl derivatives <2003RJ0574>. 

Unlike the reaction of alkyl aryl ketoximes with tetrasulfur tetranitride <1996CHEC-II(4)355>, the treatment of alkyl methyl ketoximes 189 with tetrasulfur tetranitride antimony pentachloride complex in either benzene or toluene at 50-80°C gave low yields (3-37%) of 3-alkyl-4-methyl-l,2,5-thiadiazoles 190 (Equation 39) <1999H(50)147>. Compounds 190 were volatile and the low yields are in part attributed to their loss as the solvent was removed in vacuo. Suprisingly, only single regioisomers were obtained. 3-Heptanone oxime 191 did, however, give a mixture of two isomers 192 and 193 (Equation 40). 

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. 

The reaction of ketoximes with monoactivated allenes is either slow or complicated. However, the reaction with allene-l,3-carboxylate 476 afforded addition product ( )-527 highly stereoselectively [238]. 

In an attempt to prepare alkylamines by asymmetric reduction of imines with chiral hydride reagents, diphenylphosphinyl imines (38), prepared by reaction of ketoximes (39) with chlorodiphenylphosphine [(Cg 115)2 PCI], were reduced in the presence of a variety of chiral aluminum and boron hydride reagents43. Among the most promising reagents was BINAHL-H44 (40), a chiral hydride compound prepared by the modification of lithium... 

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],... 

Phenyl- and 2-(2-thienyl)-3,3-dimethyl-3//-pyrroles (58) were obtained by the reaction of the corresponding ketoximes 56 with acetylene catalyzed by MOH (M = Na, K) in DMSO. The reaction intermediate observed is the corresponding O-vinyl oxime 57 which undergoes [3,3] sigmatropic rearrangement and cyclization to products 58 (equation 24). The yield of the products obtained strongly depends on the structure of the ketoxime . 

The reaction of ketoximes 235 with dimethyl carbonate in the presence of K2CO3, carried out in an autoclave at 180-190 °C, afforded 3-methyl-4,5-disubstituted 4-oxazolin-2-ones 236 (equation 102). The formation of compounds 236 occurred via [3,3]sigma-tropic rearrangement of intermediates of the oxime methylated with dimethyl carbonate. 

Reaction of ketoxime 336 with 5-aryl-2,3-dihydrofuran-2,3-diones afforded 4-methyl-1,2-dihydroquinazoline 337 in 70-75% yields (equation 146) . ... 

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. 

Ethoxyacetylene reacts with refluxing ethanolic sodium ethoxide to give a 44% yield of triethyl orthoacetate [128], In addition, aldoximes and ketoximes react with ethoxyacetylene to give orthoacetic acid derivatives shown in Eqs. (35) and (36) [129]. More work is required to establish the generality of this reaction. 

Oxidative deoximation/ Ketoximes revert to ketones by reaction with H,0, in an alkaline medium (75 95° yield, five examples). 

This order of base activity corresponds almost exactly to that observed in the formation of pyrroles from ketoximes and acetylene, evidently for the same causes. The failure of trimethylbenzylammonium hydroxide to catalyze the reaction of vinylation is believed (59MI1 66MI1) to be caused by its lack of coordination. Along with inhibition of the reaction with water, pyridine, o-phenanthroline, and diketones, this indicates the reaction occurs by complex ionic mechanisms in which the participation of the complex ion as an intermediate is possible. 

Nonempirical quantum-chemical calculations of acetylide molecules support the ready displacement of alkali metal cations to the bridge position (87IZV2777 88IZV1335, 88IZV1339). This naturally leads to the conclusion that the polarization and deformation of the ir-electronic shell of acetylene must depend on the atomic number of the cation attached to the acetylene anion. However, the acetylene activation in the reaction with ketoximes via acetylides suggests nucleophile attack at a carbanionlike complex, which is of course a week point of the hypothesis. Nevertheless, the electrophilic assistance from the alkali metal cation (Na+) to the... 

Under the conditions favorable for the synthesis of pyrroles from alkyl aryl ketoximes (100°C, 3 hr, 30% KOH of ketoximes mass, DMSO, acetylene under 12-16 atm pressure), the reaction with methyl naphthyl ketoximes is accompanied by considerable resinification to give low yields of pyrroles 14-17. The best results were achieved at 90°C. From methyl 1-naphthyl ketoxime at this temperature (2 hr, KOH), 2-(l-naphthyl)pyrrole (14) and 2-(l-naphthyl)-1-vinylpyrrole (15) are formed in 15 and 48% yield, respectively. 

The experimental conditions for the reaction of alkyl furyl ketoximes (20) with acetylene (Scheme 12) were first described in detail by Trofimov and co-workers (81KGS1058). Under conditions close to those typical of... 

Realization of this reaction with furyl ketoximes opens an easy access to a novel series of furylpyrroles having a reactive vinyl group ready for... 

The oxime 39 bearing a nitroxyl group (X = O) can be converted to the corresponding azaindole 40 without affecting the free-radical center (yield 6S%, nonoptimized conditions). It follows that (i) the presence of the nitroxyl function in ketoximes does not impede their pyrrolization by the reaction with acetylene in a superbase medium, and (ii) the acetylene-involved pyrrolization of ketoximes in the presence of superbase does not show any clearly defined radical stage, otherwise the nitroxyl center would have acted as a spin trap, thus inhibiting the reaction. 

The corresponding 2-hydroxy-2,3-dihydropyrrole (94a), the product of rearrangement of the O-vinyloxime 93a (see Section IV.B), is converted to the 3//-pyrrole 97 under the conditions of the reaction with acetylene (85KGS1573), and this provides more evidence for the O-vinyloxime route to pyrroles from ketoximes and acetylene. 

Reaction of aryl methyl ketoximes (118) with vinylchloride in the KOH (5-fold molar excess)/DMSO system at 120°C and atmospheric pressure gave 2-arylpyrroles (119) and their N-vinyl derivatives (120) (Scheme 58) (84KGS1359, 84MI3 87KGS1486). 

In the preparation of pyrroles and N-vinylpyrroles from ketoximes, along with vinyl halides, dihaloalkanes as acetylene equivalents can also be used. Pyrroles and /V-vinylpyrroles are formed in a yield of about 30% in the reaction of ketoximes with dihaloalkanes in the presence of excess alkali metal hydroxide in DMSO (Scheme 60) (79IZV2840). 

As in the reaction with free acetylene (see Section II.A), acetoxime is least prone to pyrrole formation (the total yield of the pyrroles 126a and 127a is about 30%). The n-alkyl methyl ketoximes 125b,e,f react exclusively via the methylene group of the alkyl radical, whereas ketoxime 134 reacts by the methylene (preferably) and methyl groups to form pyrrole isomers. 

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