Chemistry of Carbonyl Compounds

Carbonyl groups are a key functional group in organic chemistry, with the general formula C=O

Aldehydes and ketones are two main types of carbonyl compounds.

Nucleophilic addition reactions are a common reaction type involving the addition of nucleophiles to the carbonyl group of aldehydes and ketones

Nucleophilic addition reactions involve the addition of a nucleophile to the carbonyl group, resulting in the formation of a new bond between the nucleophile and the carbonyl carbon.

Carbonyl compounds are versatile molecules with a wide range of applications in organic synthesis and biological systems.

Cyanide (CN-) acts as a nucleophile, which is a species that attacks electron-deficient centers. In this reaction, cyanide adds to the carbonyl group of an aldehyde or ketone, forming a cyanohydrin.

Hydride addition reactions involve the addition of a hydride ion (H-) to the carbonyl group of an aldehyde or ketone.

In a reduction reaction, the carbonyl group (C=O) is converted to a hydroxyl group (C-OH). Aldehydes are typically reduced to primary alcohols, while ketones are reduced to secondary alcohols.

Aldehydes and ketones are reactive molecules that undergo various chemical reactions. The carbonyl group is the key site for these interactions.

Nucleophiles can be negatively charged ( : Nu) or neutral ( : NuH) at the reaction site.

The overall charge on the nucleophilic species is not considered when analyzing its behavior.

Nucleophilic attacks occur under either basic or acidic conditions.

In basic conditions, the carbonyl group is activated by the strong nucleophile OH-.

In acidic conditions, the carbonyl group is activated by protonation, making the electrophilic carbon more susceptible to attack.

The Bürgi-Dunitz angle is the optimized angle of approach for nucleophilic attacks on carbonyl groups, around 107 degrees.

In nucleophilic addition reactions, the nucleophile attacks the electrophilic carbon atom of the carbonyl group, forming a tetrahedral intermediate.

Aldehydes and ketones can undergo nucleophilic addition reactions, which often involve the formation of new carbon-carbon bonds, leading to the synthesis of more complex molecules.

The reversibility of nucleophilic addition reactions to carbonyl compounds depends on the strength of the nucleophile and the stability of the resulting tetrahedral intermediate.

The carbonyl group requires activation to be susceptible to nucleophilic attack, which can be achieved by using a strong nucleophile or by protonation under acidic conditions.

Electron-withdrawing groups (EWGs) are atoms or groups of atoms that pull electron density away from a particular location in a molecule. They are often more electronegative than carbon.

Electron-withdrawing groups (EWGs) can increase the acidity of carboxylic acids. This is because they stabilize the negative charge of the carboxylate ion, making it more likely to lose a proton (H+).

When an EWG is attached to a carboxylic acid, it pulls electron density away from the carbonyl group (C=O), making the carbon more positive and the oxygen more negative.

The negative charge on the carboxylate ion (COO-) is delocalized over both oxygen atoms. This is due to resonance, where electrons are spread out over multiple atoms.

EWGs stabilize the negative charge of the carboxylate ion by delocalizing the charge over the EWG. This makes the carboxylate ion more stable, making it more willing to lose a proton.

A more stable carboxylate ion is more likely to lose a proton, leading to a stronger acid. This is because the conjugate base of the acid is more stable.

The more resonance structures a molecule has, the more stable it is. This is because the electrons are delocalized over a larger area, reducing electron density in specific locations.

EWGs increase the acidity of carboxylic acids by making the carboxylate ion more stable through delocalization of the negative charge. This is achieved by pulling electron density away from the carbonyl group and stabilizing the negative charge on the oxygen atoms.

Acid chlorides are highly reactive carbonyl compounds that undergo nucleophilic acyl substitution reactions.

Acid chlorides react with water to form carboxylic acids, a process called hydrolysis. Water acts as a nucleophile, attacking the carbonyl carbon and replacing the chlorine atom.

The carbonyl group in acid chlorides is very electrophilic due to the electron-withdrawing nature of the chlorine atom.

The reactivity of acid chlorides makes them useful in organic synthesis to create other carboxylic acid derivatives such as esters and amides. They are often used as intermediates in drug synthesis.

Acid chlorides are not commonly used as pharmaceutical drugs because they are too reactive and can cause side effects in the body.

The stability of carboxylic acid derivatives is related to the effectiveness of orbital overlap, which contributes to resonance. The more resonance there is, the more stable and less reactive the derivative.

Amides are the least reactive of the carboxylic acid derivatives because they have the most effective resonance.

Acid chlorides can be synthesized by reacting a carboxylic acid with thionyl chloride (SOCl2). The reaction involves the replacement of the -OH group in the carboxylic acid with a chlorine atom.

The mechanism of nucleophilic acyl substitution in acid chlorides involves a two-step process: an addition step where the nucleophile attacks the carbonyl carbon, followed by an elimination step where the chloride ion leaves.

The nucleophile attacks the carbonyl carbon, forming a tetrahedral intermediate. The tetrahedral intermediate then eliminates the chloride ion and loses a proton to regenerate the carbonyl group, yielding the final product.

Sodium borohydride (NaBH4) and lithium aluminium hydride (LiAlH4) are commonly used reducing agents in organic chemistry. They donate hydride ions (H-) to carbonyl compounds, like aldehydes and ketones, to form alcohols.

Aldehydes and ketones are both carbonyl compounds, but aldehydes have a hydrogen atom attached to their carbonyl group, while ketones have two alkyl groups attached.

When an aldehyde is reduced, it forms a primary alcohol, with the alcohol group attached to the end carbon. When a ketone is reduced, it forms a secondary alcohol, with the alcohol group attached to a carbon that has two alkyl groups.

The reduction of carbonyl compounds involves the addition of a hydride ion from a reducing agent like NaBH4 or LiAlH4 to the carbonyl carbon. The reaction proceeds through a tetrahedral intermediate and is followed by protonation to yield the alcohol. This involves the addition of a nucleophile to the carbonyl carbon and the formation of a new carbon-hydrogen bond.

The nucleophile in the carbonyl reduction reaction is the hydride ion (H-) donated by the reducing agent, which attacks the electrophilic carbonyl carbon.

Aldehydes are easily oxidized to carboxylic acids, while ketones are relatively inert to oxidation. This difference in reactivity is due to the presence of a hydrogen atom attached to the carbonyl group in aldehydes, which can be easily abstracted during oxidation.

NADH is a key coenzyme in biological redox reactions, acting as a reducing agent. It plays a crucial role in various metabolic pathways, like glycolysis.

The reduction of ketones by NADH is a key step in many metabolic processes, including the conversion of pyruvate to lactate in the lactic acid fermentation pathway.

Alcoholysis of carbonyl compounds involves the reaction of an alcohol with an aldehyde or ketone, forming a hemiacetal or hemiketal, respectively. This reaction occurs through a nucleophilic addition mechanism, with the alcohol acting as the nucleophile.

The cyclisation of D-glucose involves an intramolecular alcoholysis reaction between the aldehyde group and the hydroxyl group at carbon 5. This process forms a hemiacetal, resulting in the cyclic form of glucose.

The two cyclic forms of D-glucose are the alpha and beta anomers, differing in the configuration of the hydroxyl group at the anomeric carbon, which is the carbon that was originally part of the aldehyde group.

Cyanohydrin formation involves the addition of a cyanide ion (CN-) to a carbonyl compound, forming a cyanohydrin. This is a nucleophilic addition reaction, where the cyanide ion acts as the nucleophile. This reaction is important in organic synthesis, especially as a way to introduce a new carbon chain with specific functional groups.

The stereochemistry of cyanohydrin formation is important because it creates a new chiral center at the carbonyl carbon. The stereochemistry of the cyanohydrin can be controlled by using specific reaction conditions or by using chiral catalysts.

Nucleophilic attack on a carbonyl group often leads to the formation of a tetrahedral intermediate, which is an unstable species with four substituents around the carbonyl carbon.

The leaving group in organic reactions is the group or atom that departs the molecule during a reaction. In the case of nucleophilic addition to a carbonyl, the leaving group is usually a hydroxyl group (OH-) or a hydrogen atom.

Nucleophiles, with their electron-rich nature, readily attack electrophilic centers, which are electron-deficient. In carbonyl compounds, the carbonyl carbon is electrophilic because of the partial positive charge on it.