Aryl ketoximes

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). 

In a development on the reaction of monohaloalkyl aryl ketoximes with tetrasulfur tetranitride, the introduction of two halogens such as chlorine, bromine, or fluorine at the a-position of alkyl aryl ketoximes significantly improved the yields of thiadiazoles <1998J(P1)109>. The preferential displacement of chlorine over bromine or fluorine allowed the preparation of monobromo- and monofluoro-3-aryl-thiadiazoles 195 from a,a-chlorobromoalkyl- and a,a-chlorofluoro-alkyl aryl ketoximes 194 (Equation 41). 

Although true for many oximes of aliphatic and alicyclic ketones, the previous sequence is not absolute and can change depending on the reaction conditions and ketoxime type. Tetrabutylammonium hydroxide, for instance, which catalyzes fairly actively in the synthesis of 4,5,6,7-tetrahydroindole from cyclohexanon oxime and acetylene (79KGS197), turned out to be nearly inert with alkyl aryl ketoximes (78ZOR1733). 

Representatives of Arylpyrroles Prepared from Alkyl Aryl Ketoximes... 

The pyrrolization of various alkyl aryl ketoximes (Scheme 6) was also studied [78KGS489 84ZOR1960 90ZOR(ip)], and it was confirmed that the corresponding 2-arylpyrroles (7) could also be obtained successfully in this way (see Table XIII). 

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. 

Enantioselective Hydrosilylation of C=N Double Bonds in Ketoximes and Ketimines. Homogeneous enantioselective hydrosilylation of prochiral alkyl aryl ketoximes has been carried out by using a Rh-(R,R)-NORPHOS catalyst. Thus, hydrosilylation of r-butyl phenyl ketoxime in the presence of [Rh(COD)Cl]2-(R,R)-NORPHOS followed by aqueous acidic work-up afforded the corresponding amine (eq 3) [16.5% ee, (5)], which became inverted to 15.0% ee (R) when this reaction was performed in the presence of added ammonium hexafluo-rophosphate (RhiNHaPF = 1.1, CH2CI2 solvent). ... 

The electrocyclic rearrangement of 0-aryl-ketoximes produces benzofurans. The acid-catalysed rearrangement exactly parallels the rearrangement of phenylhydrazones, which gives indoles - the classical Fischer indole synthesis (20.16.1.1). 

The electrocyclic rearrangement of O-aryl ketoximes produces benzofurans. 

Reactions with alkyl aryl ketoximes are less selective than reactions with diaryl ketoximes. 

Alkali metal hydroxides differ not only in reactivity but also in selectivity of action. For example, LiOH selectively catalyzes the reaction of the pyrrole ring construction from alkyl aryl ketoximes [160,163-165], while it is almost inactive at the stage of vinylation of the pyrrole formed. At the same time, LiOH is ineffective for cycloaliphatic ketoximes at both stages [159] the pyrrole ring formation is accelerated in this case by rubidium and tetrabutylammonium hydroxides [159,161]. 

SCHEME 1.46 Synthesis of 2-aryl-3-alkyl(phenyl)pyrroles from alkyl aryl ketoximes and acetylene. 

This new synthesis of 3-alkyl(phenyl)-2-phenylpyrroles has been extended over alkyl aryl ketoximes (Scheme 1.46) [163,221], As a consequence, earlier unknown or difficult to produce 2-arylpyrroles can be synthesized using this methodology. 

In the conditions developed for alkyl aryl ketoximes (100°C, 3 h, 30% KOH from ketoxime weight, acetylene pressure 12-16 atm), the reaction with acetylnaphthalene oximes is accompanied by considerable resiniflcation, and the yields of pyrrole are low. The best results are attained at 90°C a mixture of 2-(l-naphthyl)pyrrole and 2-(l-naphthyl)-N-vinylpyrrole in 15% and 48% yields, respectively, is formed from 1-acetylnaphthalene oxime (2 h, KOH) [225]. 

A new and efficient microwave induced bismuth trichloride catalyzed Beckmann rearrangement of oximes in the solid state has been achieved by Thakur et al. (2007). Beckmann rearrangement of aryl ketoximes catalyzed by In(OTf)3 gave amides in ionic liquid under microwave irradiation. These aryl ketoximes were converted to corresponding amides in good yields within very short times (10-270 sec). The catalyst and the ionic liquid were easily recovered and reused (Sugamoto et al, 2011). 

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