Oxime intermediates protonated

In carbonyl addition reactions, a commonly occurring and important mechanistic step is the transfer of a proton from one site to another in a reactive intermediate (proton switch). If the proton switch occurs sufficiently rapidly compared with the rate of collapse of the intermediate to reactants, the overall reaction may be facilitated by trapping of the unstable intermediate by the proton switch (Jencks, 1976). For example, in the formation of oximes from the reaction of benzaldehyde with O-methylhydroxylamine shown in (87H89) (Sayer and Jencks, 1973 Rosenberg et al., 1974), the first unstable intermediate (It) on the reaction pathway is converted by a proton switch (88) to the intermediate (I2) which has less tendency than It to... 

Nitroalkenes react with benzene derivatives at low temperature in triflic acid to afford a-aryl ketones after quenching with methanol182,183 [Eq. (5.74)]. At higher temperature the 0-protonated oxime intermediate may react further to yield 4//-1,2-benzoxazines (see Section 5.14.1.3). a-Nitrocarbonyl compounds show similar characteristics as alkylating agents to yield oximes with the involvement of the tricationic intermediate 44.181... 

Products isolated from the thermal fragmentation of A-arylbenzamide oximes and A-arylbenzamide O-phenylsulfonyl oximes have been accounted for by invoking a free-radical mechanism which is initiated by the preferential homolysis of the N-O bond." Time-resolved IR spectroscopy has revealed that photolysis of A, A -diphenyl-l,5-dihydroxy-9,10-anthraquinone diimine affords acridine-condensed aromatic products via excited-state intramolecular proton transfer." The absolute and relative rates of thermal rearrangements of substituted benzyl isocyanides have been measured,and it has been found that the relative rates are independent of temperature and exhibit excellent Hammett correlations. Thionitrosoarene (25), thought to be generated by desulfurization of the stable A-thiosulfinylaniline (24), has been established" " as an intermediate in the formation of 3,3a-dihydro-2,l-benzisothiazole (26) from o-alkylthionitrosoarene (24). 

The reduction of aliphatic nitrocompounds in acid solution proceeds in two steps. First the nitrosocompound is formed. A low steady state concen ation of 2-methyl-2-nitrosopropane has been detected during the reduction of 2-methyl-2-nitropropane [13]. At the cathode potential necessary to attach the first electron to a nitro group, the nitroso intermediate undergoes further reduction to the hydroxyla-mine. When the nitrocompound has one a-hydrogen substituent, tautomerism of the nitroso intermediate to an oxime is in competition with further reduction. Both temperature and proton availability affect the rate of this isomerisation. Reduction of aliphatic nitrocompounds to the hydroxylamine is usually carried out in acid solution at 0-5° C to minimise oxime formation [14, 15], The hydroxylamine is stable towards further reduction in acid solution. Oximes in acid solution are reduced... 

In many of these cases, the nucleophile is a C=C double bond (usually an alkenic group and less frequently an aromatic group). Alkenic oxime mesylates enable intramolecular cyclization by an electrophihc addition of the double bond to the electrophilic intermediate. These reactions are terminated by a proton loss. 

A benzofuran ring replaces one of the benzene rings of the biphenyl moiety present in many of the sartans in the rather more complex drug saprisartan (80-10). It is of note, further, that the acidic proton is provided in this case by a trifluorosulfo-namide instead of the more common tetrazole ring. Construction of the imidazole fragment begins by nitrosation of the (3-ketoester (79-1) by means of sodium nitrite in acid to afford the oxime (79-2). Reaction with acetyl chloride leads to the ester (79-3). Reaction of this last intermediate with the iminoether from propionitrile then affords the imidazole (79-4). 

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). 

PET cyclizations of (3,y-unsaturated oximes (27) have been established by Armesto and Horspool [38]. This 9,10-dicyanoanthracene (DCA) sensitized reaction provides an efficient route for the synthesis of dihydroisoxazole derivatives (28) in reasonable to good yields (Sch. 17). Key step in the mechanistic scenario is an electron transfer from the oxime group to DCA in its excited singlet state. The radical cationic intermediate thus generated undergoes subsequent exo-cyclization with the olefinic moiety. Further, proton and electron transfer steps complete the reaction. A major limitation of this process is the restriction to molecules incorporating two aryl groups [38a]. 

The initial step in the reduction of protonated oximes has been shown [146] to be a hydrogenolysis of the oxygen-nitrogen bond in cyclic derivatives of oximes the same occurs. In 4-(4 -methoxyphenyl)-2,3-benzoxazin-l-one (XLV) the reduction proceeds in two steps, and it is possible to isolate the rather stable intermediate ketimine [146] ... 

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