The –ic in the name of the acid is then replaced by aldehyde to get the name of the aldehyde. On the other hand, ketones are named by using the names of the groups attached to the carbonyl group and then adding ketone after the name of groups. The name of the parent hydrocarbon (alkane or alkene or alkyne) is determined while the carbonyl carbon is counted as a methyl group for aldehydes and as a methylene group for ketones.
The position of the keto group is indicated by a numerical prefix and is indicated by use of the word oxo. The reaction probably proceeds through the rate-limiting formation of a chromate ester followed by decomposition of the ester to give the products. In the case of primary alcohol, this process can lead to oxidation of the alcohol to carboxylic acid.
The ozonolysis of alkenes of the type RCH=CHR1 leads to the formation of aldehydes while the tetrasubstituted alkenes will give ketones as a product. The nucleophilic addition to the carbonyl group is the most important reaction of aldehydes and ketones.
Reduction
Several reducing agents are known tailored to suit the purpose of selectively reducing one group while leaving the other unaffected. In the above reduction protocols, the transfer of the hydride ion is irreversible, but a reversible hydride transfer to a carbonyl compound is also possible.
Carbonyl Compounds Lecture 14 Aldehydes and Ketones I
Condensation
The aldehydes and ketones undergo a different class of reactions which can be called addition-elimination reactions or condensation reactions. Thus, it can be expected that in basic and neutral solutions, the elimination of water is the rate-limiting slow step, while in an acidic solution, the attack of the nucleophile is the rate-limiting step. The table below gives the names of the products of some common ammonia derivatives and ketones.
The protocol involves the synthesis of the corresponding hydrazone from the ketone followed by reduction. Another type of reactions is the reaction of aldehydes and ketones with substituted amines (Scheme 10). As shown above, the initial addition of the amine generates a carbinolamine which then undergoes β-elimination to give the imine as product.
However, the pH of the solution must be properly maintained, as a very low pH will result in protonation of the nucleophilic amine. They add to aldehydes and ketones to form a carbinolamine, which on dehydration leads to the formation of an enamine. The reaction pathway is similar to the reaction pathway shown above for the reaction of ketones with primary amines.
The reaction of carbonyl compounds with organometallic reagents is of great importance in organic chemistry. Although almost all classes of carbonyl compounds react with aldehydes and ketones with varying results, only the reactions of aldehydes and ketones are discussed in this section. Formaldehyde forms a primary alcohol as a result of this reaction, while all other aldehydes form secondary alcohols.
The actual composition of Grignard reagents and the reaction pathway is a controversial issue, but it is clear that Grignard reagents usually form linked structures with each other (Scheme 16). The reaction is believed to proceed through a cyclic transition state involving a Grignard reagent, a carbonyl compound, and solvent molecules. However, if the hydrogen atoms are on the β-carbon of the Grignard reagent, then they tend to reduce the carbonyl compound, and they themselves are oxidized to alkenes.
Carbonyl Compounds Lecture 15 Aldehydes and Ketones II
Aldol Reactions
It apparently requires a base to withdraw a proton from the carbonyl compound to generate the carbanion. The carbanion thus generated can now attack another molecule of aldehyde or ketone to generate a β-hydroxycarbonyl compound which can be dehydrated under suitable conditions to generate an α,β-unsaturated carbonyl compound (Scheme 2). The reason for such an observation lies in the reversibility of the formation of the carbanion.
In such cases, when the attack of the carbanion carbonyl compound is slower than the reprotonation of the carbonyl compound, the product will be formed only in small amounts. The reaction can be made to proceed quantitatively if one of the products is continuously removed pulling the reaction to the right. The β-hydroxy compound thus formed can undergo elimination in the presence of excess base to generate an α,β-unsaturated carbonyl compound.
The reaction is clearly dependent on both the concentration of the base and the β-hydroxycarbonyl compound and appears to proceed via the E1cB pathway. The reaction now follows a completely different path and almost always leads to the formation of the dehydrated product. Here the carbonyl compound forms an equilibrium concentration of enol which then attacks the protonated form of the carbonyl compound to give the "aldol" which can be eliminated via the E1 pathway to give the α,β-unsaturated carbonyl compound (Scheme 3).
However, when one of the coupling partners is only capable of enolization and is more electrophilic than the other partner, the aldol reaction can be prolific in giving only one preferential product. In the first step, the enolizable partner undergoes enolization in the presence of the base. The reaction is kinetically controlled and therefore converted quickly enough to prevent the enolate from reacting with a molecule of unenolized carbonyl compound.
Now, if a second carbonyl compound is added, then it also complexes with the lithium cation allowing the aldol reaction to proceed from a six-membered transition state. But it should be noted that the reaction is actually carried out in two steps. The silylenol ether can be prepared from its parent carbonyl compound by forming a small equilibrium concentration of a weakly basic enolate ion such as a tertiary amine and blocking the enolate with the highly efficient oxygen electrophile (CH3)3SiCl.
Benzoin Condensation
In this reaction, the aldehyde is assumed to coordinate to the Lewis acid TiCl4, which then undergoes nucleophilic attack by the silylenol ether to form the aldol product (Scheme 8). Aromatic aldehydes in the presence of catalytic amount of cyanide as nucleophile can undergo benzoin condensation where cyanide first attacks an aldehyde molecule to form an intermediate. When benzaldehyde is used as a reactant in the above reaction, the product is called benzoin and hence the reaction is called benzoin condensation.
These α-hydroxy ketones can be easily oxidized to the 1,2-diketones which undergo rearrangement under the influence of the hydroxyl base to form benzilic acid (Scheme 11).
Wittig Reaction
Baeyer Villiger Oxidation
Carboxylic acids are named by first finding the name of the parent alkane and counting the carboxyl carbon. In the anhydride of an acid, when both acyl groups are the same, the word acid in the carboxylic acid is replaced by anhydride, but when the acyl groups are different, the names of the carboxylic acids are written in alphabetical order. First write the name of the alkyl group, followed by the name of the acyl group.
When naming amides, the -oic in the name of the acid is replaced by -amide. In case of substitution on the nitrogen atom, they are prefixed to the name as N-.
Reactions
Carboxylic Acid Synthesis .1 Oxidation of Alcohols
- Hydrolysis of Nitriles
- Grignard Reaction
Acid Chloride Synthesis
Ester Synthesis
Amide Synthesis
Reactions .1 Reduction
- Halogenation
- Arndt Eistert Synthesis
- Hoffman Rearrangement
- Lossen, Curtius and Schimdt Rearrangements
- Knoevenagel Reaction
- Stobbe Condensation
- Claisen Condensation
The carboxylic acids can be halogenated in α-position by treatment with red phosphorus and halogens (Scheme 9). This is usually called Hell-Vollhard-Zelinsky reaction, which is an important process from the perspective of synthetic chemistry. The role of phosphorus is to eventually convert some of the acid to acid chloride which then undergoes halogenation at α-position.
The resulting α-haloacids can be used as intermediates for the preparation of α-amino acids, α-hydroxy acids and α,β-unsaturated acids (Scheme 11). To move up one carbon in a linear carboxylic acid chain, we can use a protocol called the Arndt Eistert synthesis (Scheme 12). In this protocol, homologation of the carboxylic acid is achieved by first converting the acid to the acyl chloride, which is then treated with diazomethane.
The diazoketene thus formed is treated with moist silver oxide to form a ketene, which can be readily hydrolyzed to give the next higher carboxylic acid. The reaction is carried out by treating the amide with an alkaline solution of sodium hypobromite. The isocyanate formed in this reaction is a key intermediate and can be found in other related rearrangement reactions of the carboxylic acid and its derivatives.
This isocyanate intermediate undergoes the addition of water to form a hydroxamic acid which decomposes under the reaction conditions to give an amine. This reaction involves a concerted debromination step along with migration of the R group which migrates with retention of configuration. In the Knoevenagel reaction, the carbanion generated from an ester can attack an aldehyde or a ketone to undergo a condensation reaction to form an α,β-unsaturated acid or ester ( Scheme 15 ).
Knoevenagel reactions can be extended to other compounds containing active methylene groups, such as nitroalkanes. When an active methylene group is sandwiched between carboxylic acid groups, it often undergoes decarboxylation, as shown in Scheme 16. The reaction is usually carried out using bases such as sodium ethoxide and sodium hydride.
