Activated methylene groups

Barbituric acid can be considered as a cyclized malonic acid diamide (malonyl-urea). It is therefore a cyclic diketone that may be classified, in the sense of the compounds discussed in Section 12.6, as a coupling component with a methylene group activated by two carbonyl groups in the a- and a -positions. The reaction with arenediazonium salts was studied by Nesynov and Besprozvannaya (1971). These authors obtained coupling products (in good yield) that they considered to be arylhydrazones. Coupling with 4-(phenylazo)benzenediazonium chloride was studied by Chandra and Thosh (1991). The lH NMR spectra of these compounds are consistent with the arylhydrazone structure 12.68. 

The Mannich reaction consists in the condensation of formaldehyde with ammonia or a primary or a secondary amine and a compound containing at least one hydrogen atom of pronounced reactivity the active hydrogen atom may be derived from a methylene group activated by a neighbouring keto group, or from a nitroparaffin, or it may be the o- or p-hydrogen atoms in phenols. Thus when acetophenone is boiled in alcoholic solution with formaldehyde and dimethylamine hydrochloride, the Mannich base P-dimethylamino-propiopbenone hydrochloride (I) is readily formed ... 

Typical liquickliquid alkylation of methylene groups activated by a carbonyl or nitrile group... 

In a rather remarkable reaction, methylene groups activated by two electron-withdrawing substituents react with non-activated alkenes under soliddiquid phase-transfer conditions in the presence of a molar equivalent of iodine to yield cyclopropane derivatives (Scheme 6.29) [62, 63], The reaction fails, when the catalyst is omitted or if iodine is replaced by bromine or chlorine. The intermediate iodomethylene systems are unstable in the absence of the reactive alkene and dimerize to produce, for example, ethane-1,1,2,2-tetracarboxylie esters and ethene-1,1,2,2-tetracarboxy lie esters. 

Compounds containing methylene groups activated by both a cationic ring and another electron-withdrawing group easily form stable anhydro-bases, e.g. (636) — (637), (638) — (639). Stabilization is also achieved by utilization of the aromatic character of the cyclopentadiene anion or the pyrrole anion compounds of type (640 Z = NR, O, S) and (643) readily lose protons to give the mesomeric anhydro-bases (as 641 <- 642) which are called pseudoazulenes. 

Imidoylbenzotriazoles 823 are prepared in good yields from amides with benzotriazole and oxalyl chloride in the presence of pyridine <2006JOC3375>. These compounds bring about imidoylation of methylene groups activated by electron-withdrawing substituents, for example, with ester enolates, to give -enaminoesters (Scheme 180). 

In two examples, type 2 reagents produce 4-nitroisoxazoles. Nitro-keteneaminals undergo cycloaddition with nitrile oxides to produce the 4-nitroisoxazoles 61 (10-25%) [(Eq. 19)].30 Substrates possessing a methylene group activated on one side by a nitro group and on the other by either a nitrile or a carbonyl, react with hydroxamoyl chlorides in presence of base to produce the 4-nitroisoxazoles (62) and (63) [Eqs. (20,21)].57... 

Oxidation. DMSO in combination with catalytic amounts of iodine and a strong acid oxidizes methylene groups activated by an adjacent benzoyl group in good yield. The method is only suitable for preparation of diaryl di- and triketones. Examples ... 

Methylene groups activated by only one carbonyl group usually do not react, but j8-aryl ketones are reactive. Side products formed... 

The reactions of methylene groups activated by cyano groups give 5-amino-l,2,3-triazoles. Cyanoacetamide and phenyl azide yielded (88%) the triazole 262 21,... 

A methylene group activated by carbonyl and sulphonamido groups reacts with a neighbouring amino group on heating with orthoformate ester. 

Sulfur dissolved in DMF thionates in the presence of sec-amines methylene groups activated by a captor group. The halogen is then replaced by the amine, the overall sequence leading to thioamides. This is shown below for bromotrifluoro-acetone (Scheme 29, refs. 23, 24). 

Methyl and Methylene Groups Activated by Adjacent Aromatic and... 

TABLE XVmA. METHYL AND METHYLENE GROUPS ACTIVATED BY A FULLY CONJUGATED MONOCYCUC RING... 

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