A-Carbonyl groups

A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

This oxidation proceeds readily if the methylene group is activated by linkage to (a) a carbonyl group, (b) an aromatic ring (c) an olefine link also activates adjacent CH2 and CH groups. 

When camphor (I) is heated with selenium dioxide in acetic acid, the methylene group next to the carbonyl group is oxidised also to a carbonyl group, to form camphorquinone (II). Note that the compound (II) is not a true quinone but a 1,2-diketone ... 

Reagent A is particularly useful for the treatment of the lower aliphatic aldehydes and ketones which are soluble in water cf. acetaldehyde, p. 342 acetone, p. 346). The Recent is a very dilute solution of the dinitrophenylhydrazine, and therefore is used more to detect the presence of a carbonyl group in a compound than to isolate sufficient of the hydrazone for effective recrystallisation and melting-point determination. 

Coulombic Terms. Coulombie energy of interaetion arises from permanent dipoles within the molecule to be modeled, for example, the partial - - and — charges within a carbonyl group... 

By the ketonic hydrolysis of substituted acetoacetic esters this is brought about by the action of dilute alkali in the cold, followed by acidification and boiling. The free substituted acetoacetic acid is produced, which readily undergoes decarboxylation (since it has a carboxyl and a carbonyl group on the same carbon atom) to give a ketone, for example ... 

CgHjCOCHj + SeOa —> CgHgCOCHO + Se + H O This is one example of the oxidation by selenium dioxide of compounds containing a methylene group adjacent to a carbonyl group to thecorresponding a-ketoaldehyde or a-diketone (see also Section VII,23). 

The Stobbe condensation thus provides a method for introducing a propionic acid residue at the site of a carbonyl group. 

Analysis The first step is to put in a carbonyl group next to nitrogen and then reverse the acylation ... 

The discormection corresponding to this reaction is again of the C-N bond, writing an amine and a carbonyl group in the right places ... 

Analysis Since there is one CH2 group next to the nitrogen atom, this might be a carbonyl group in our usual method of amine synthesis (frame 237). 

Diazo compoimds are partieularly easy to make with the diazo group next to a carbonyl group by this reaction ... 

The carbene synthon might be difficult, but since the olefin is conjugated with a carbonyl group we could try a sulphur ylid as a nucleopliilic carbene equivalent (as in frame 283). Synthesis The diene could be made by this route ... 

The obvious ones are a carbonyl group next to the anion and an OH group (which can easily be converted into a leaving group) for the cation giving two possibilities ... 

The isopropyl group could be derived from a carbonyl group and a Grignard reagent in two ways ... 

Analysis This is a 1,6-dicarbonyl compound so a recormection is called for. The next obvious series (frames 36-8) of discormections ends up at 382B - not an easy compound to make. Where could we put a carbonyl group in 382A to allow some more helpfiil discormections ... 

Though you can in principle add a carbonyl group anywhere in a target molecule, remember it means extra steps in the synthesis so use it only as a last resort. 

After the umpolung of an aldehyde group by conversion to a l,3 dithian-2-ide anion (p. 17) it can be combined with a carbonyl group (D. Seebach, 1969, 1979 B.-T. GrO-bel, 1977 B). Analogous reagents are tosylmethyl isocyanide (TosMIC), which can be applied in the nucleophilic formylation of ketones (O.H. Oldenziel, 1974), and dichloromethyl lithium (G. KObrich, 1969 P. Blumbergs, 1972 H. Taguchi, 1973),... 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

The reaction of Grignard reagents with a carbonyl group can be understood as an insertion reaction of an unsaturated C=0 bond of the carbonyl group into... 

As expected, the formation of a carbonyl group is not possible with tert-allylic alcohols. Although the aromatic ring bears electron-donating groups, the 2,2-disubstituted chromene 119 was formed smoothly with the tert-allylic alcohol 118[100]. 

Each carbon of the double bond becomes the carbon of a carbonyl group... 

As Table 12 2 indicates a variety of substituent types are meta directing and strongly deactivating We have already discussed one of these the trifluoromethyl group Several of the others have a carbonyl group attached directly to the aromatic ring... 

To understand the effect of a carbonyl group attached directly to the ring consider Its polarization The electrons m the carbon-oxygen double bond are drawn toward oxy gen and away from carbon leaving the carbon attached to the nng with a partial posi tive charge Using benzaldehyde as an example... 

Because the carbon atom attached to the ring is positively polarized a carbonyl group behaves m much the same way as a trifluoromethyl group and destabilizes all the cyclo hexadienyl cation intermediates m electrophilic aromatic substitution reactions Attack at any nng position m benzaldehyde is slower than attack m benzene The intermediates for ortho and para substitution are particularly unstable because each has a resonance structure m which there is a positive charge on the carbon that bears the electron withdrawing substituent The intermediate for meta substitution avoids this unfavorable juxtaposition of positive charges is not as unstable and gives rise to most of the product... 

The induced field of a carbonyl group (C=0) deshields protons in much Ihe same way lhal a carbon-carbon double bond does and Ihe presence of oxygen makes il even more eleclron wilhdrawmg Thus protons attached to C=0 m aldehydes are Ihe leasl shielded of any protons bonded to carbon They have chemical shifts m Ihe range 8 9-10... 

Protons on carbons adjacent to a carbonyl group are deshielded slightly more than allyhc hydrogens... 

Electronegativity and hybridization effects combine to make the carbon of a carbonyl group especially deshielded Normally the carbon of C=0 is the least shielded one m... 

Neither sodium borohydride nor lithium aluminum hydride reduces isolated carbon-carbon double bonds This makes possible the selective reduction of a carbonyl group m a molecule that contains both carbon-carbon and carbon-oxygen double bonds... 

The reaction of alcohols with acyl chlorides is analogous to their reaction with p toluenesulfonyl chloride described earlier (Section 8 14 and Table 15 2) In those reactions a p toluene sulfonate ester was formed by displacement of chloride from the sulfonyl group by the oxygen of the alcohol Carboxylic esters arise by displacement of chlonde from a carbonyl group by the alcohol oxygen... 

The various ways of representing the polarization m a carbonyl group include... 

Alkyl substituents stabilize a carbonyl group m much the same way that they sta bilize carbon-carbon double bonds and carbocations—by releasing electrons to sp hybridized carbon Thus as then heats of combustion reveal the ketone 2 butanone is more stable than its aldehyde isomer butanal... 

Under conditions of acid catalysis the nucleophilic addition step follows protonation of the carbonyl oxygen Protonation increases the carbocat ion character of a carbonyl group and makes it more electrophilic... 

Increased single bond character in a carbonyl group is associated with a decreased carbon—oxygen stretching frequency Among the three compounds benzaldehyde 2 4 6 trimethoxybenzaldehyde and 2 4 6 trinitrobenzaldehyde which one will have the lowest frequency carbonyl absorption" Which one will have the highest" ... 

A compound has the molecular formula C4HgO and contains a carbonyl group Identify the compound on the basis of its H NMR spectrum shown in Figure 17 20... 

In the preceding chapter you learned that nucleophilic addition to the carbonyl group IS one of the fundamental reaction types of organic chemistry In addition to its own reactivity a carbonyl group can affect the chemical properties of aldehydes and ketones m other ways Aldehydes and ketones having at least one hydrogen on a carbon next to the carbonyl are m equilibrium with their enol isomers... 

As an electron withdrawing group on a carbon-carbon double bond a carbonyl group renders the double bond susceptible to nucleophilic attack... 

Normally carbon-carbon double bonds are attacked by electrophiles a carbon-carbon double bond that is conjugated to a carbonyl group is attacked by nucleophiles... 

The presence of a carbonyl group in a molecule makes possible a number of chemical reactions that are of great synthetic biochemical and mechanistic impor tance This chapter is complementary to the preceding one the two chapters taken together demonstrate the extraordinary range of chemical reactions available to aide hydes and ketones... 

Both enols have their carbon-carbon double bonds conjugated to a carbonyl group and can form an intramolecular hydrogen bond They are of comparable stability... 

---