Alpha position carbonyl compounds

Treatment of 2-arylsemicarbazides with dicarbonyl or alpha-substituted carbonyl compounds is a common method for the formation of 2-aryl-l,2,4-triazin-3-ones (Scheme 1) (2). Reduction and then alkylation in the case of 3 or alkylation in the case of 4 would provide access to compounds with substituents at the 4-, 5- and 6-positions of the heterocyclic ring. Neither approach, however, has been reported to give triazin-3-ones where the heterocyclic ring is unsubstituted at the 5- and 6-positions. 

The third major reaction of carbonyl compounds, alpha substitution, occurs at the position next to the carbonyl group—the alpha (a) position. This reaction, which takes place with all carbonyl compounds regardless of structure, results in the substitution of an a hydrogen by an electrophile through the formation of an intermediate enol or enolcite ion ... 

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

Friedlander synthesis org chem A synthesis of quinolines the method is usually catalyzed by bases and consists of condensation of an aromatic p-amino-carbonyl derivative with a compound containing a methylene group in the alpha position to the carbonyl. fred.lan dar. sin-tha-sas ... 

As previously described, ethers can be alkylated photochemically at the carbon alpha to the ether oxygen. In compounds having both an ether and a carbonyl function a "competitive alkylation process may take place. Tetrahydro-y-pyrone can serve as a good model for this "competitive alkylation between a ketone and an ether. This molecule has a ketone function having two methylene groups at its alpha positions, and an ether function having also two adjacent methylenes. When tetrahydro-y-pyrone was left in sunlight with 1-octene the 1 1 adduct was obtained in about 70 % yield. Alkylation occurred at the carbon alpha to the carbonyl function (24) ... 

Therefore, it is possible to obtain compounds with four different substituents at the 2- and 5-positions of the 4-oxoimidazoli-dine ring by reacting the appropriate carbonyl compound with an alpha aminonitrile formed in a Strecker reaction from a selected ketone. The oxidation of these imidazolidines by hydrogen peroxide in the presence of catalytic amounts of sodium tungstate in acetic acid gave new stable nitroxyl radicals (12) shown in Chart 4. 

Activated hydrogen atoms, prepared to react with formaldehyde to yield C-hydroxymethyl compounds, one finds in nitro-hydrocarbons at the carbon atom adjacent to the nitro group, in ketones at the carbon atom in alpha-position towards the carbonyl group, in certain phenol derivatives. However, the formaldehyde combined in these substances cannot be determined by the Tanenbaum method, as the hydroxymethyl group is fixed to the substances more or lees irreversibly. Accordingly C-hydroxymethyl compounds in general do not exhibit antimicrobial activity with the exception of the hydroxymethylated nitro-hydrocarbons, which under certain conditions (pH >7) release formaldehyde, though very slowly. As C-hydroxymethylated nitro-hydrocarbons... 

The carbon alpha to the carbonyl of aldehydes and ketones can act as a nucleophile in reactions with other electrophilic compounds or intermolecu-larly with itself. The nucleophilic character is imparted via the keto-enol tau-tomerism. A classic example of this reactivity is seen in the aldol condensation (41), as shown in Figure 23. Note that the aldol condensation is potentially reversible (retro-aldol), and compounds containing a carbonyl with a hydroxyl at the (3-position will often undergo the retro-aldol reaction. The aldol condensation reaction is catalyzed by both acids and bases. Aldol products undergo a reversible dehydration reaction (Fig. 23) that is acid or base catalyzed. The dehydration proceeds through an enol intermediate to form the a,(3-unsaturated carbonyl containing compound. 

Similar observations of base catalysis have been used to invoke the ElcB mechanism for elimination from 4,4-dicyano-3-p-nitrophenyl-1 -phenylbutan-1 -one in neutral and acidic methanol (34) , and l,l,l,3-tetranitro-2-phenylpro-pane in methanol in the presence of hydrochloric acid and pyridine-pyridine hydrochloride buffers (36) . In the former reaction, an example of a reverse Michael addition, the carbanion intermediate with the electron pair alpha to the carbonyl rather than in the gamma position is favoured, as the methyl isomer (35) eliminates more rapidly than the parent compound. 

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