Question

(a) What prediction can be made about the acidity of the \Upsilon-hydrogens of \(\alpha, \beta\) -unsaturated carbony1 compounds? (b) Suggest a pathway for the synthesis of 5-pheny1-2,4-pentadienal, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}=\mathrm{CH}-\mathrm{CH}=\mathrm{CH}-\mathrm{CHO}\).

Short answer

(a) The acidity of the \(\Upsilon\)-hydrogens of \(\alpha, \beta\)-unsaturated carbonyl compounds is generally higher than those in a fully saturated carbon chain without a carbonyl group, because the negatively charged conjugate base formed upon deprotonation can be stabilized by resonance. (b) One synthesis pathway for 5-phenyl-2,4-pentadienal is via the Wittig reaction, starting with benzaldehyde (\(\mathrm{C}_{6} \mathrm{H}_{5}\mathrm{CHO}\)) and a phosphonium ylide derived from n-butyltriphenylphosphonium bromide (\((C_{6}H_{5})_{3}P(+)CH_{2}CH_{2}CH_{3}Br(-)\)). After generating the ylide using sodium amide (NaNH2), it is reacted with benzaldehyde to yield 5-phenyl-2,4-pentadienal and triphenylphosphine oxide.

Step-by-step solution

Understanding acidity of hydrogens in molecules

To predict the acidity of \(\Upsilon\)-hydrogens in \(\alpha, \beta\)-unsaturated carbonyl compounds, we need to understand acidity and what makes a hydrogen atom acidic. In general, the acidity of a hydrogen atom is determined by its ability to be removed as a proton (H⁺) from the molecule, leaving behind a stable conjugate base. The more stable the conjugate base, the more acidic the hydrogen.

Identifying the structure of α, β-unsaturated carbonyl compounds and the position of Υ-hydrogens

An \(\alpha, \beta\)-unsaturated carbonyl compound has a carbon-carbon double bond (\(\beta\)-carbon) adjacent to (or conjugated with) the carbonyl (\(\alpha\)-carbon) functional group. The general structure of such compounds is as follows: \[\text{R}\text{C}(\text{=O})-\text{C}(\text{H})=\text{C}\text{R}'\] Where R and R' are any substituent groups. The \(\Upsilon\)-hydrogen is the hydrogen atom on the carbon that is two carbons away from the carbonyl carbon (\(\beta\)-position).

Predicting the acidity of Υ-hydrogens in α, β-unsaturated carbonyl compounds

Removing a \(\Upsilon\)-hydrogen from an \(\alpha, \beta\)-unsaturated carbonyl compound creates a negatively charged conjugate base (anion), which can be stabilized through resonance structures by leveraging the adjacent carbonyl and the \(\beta\)-carbon (double bond). This stabilization by resonance makes the conjugate base stable and thus increases the acidity of the \(\Upsilon\)-hydrogen. So, we can predict that the acidity of the \(\Upsilon\)-hydrogens in such compounds is generally higher compared to hydrogens in a fully saturated carbon chain without a carbonyl group.

Identifying the target molecule for synthesis

The target molecule for synthesis is 5-phenyl-2,4-pentadienal: \[\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}=\mathrm{CH}-\mathrm{CH}=\mathrm{CH}-\mathrm{CHO}\] We need to identify suitable starting materials and reactions to yield this molecule.

Synthesis of 5-phenyl-2,4-pentadienal using Wittig reaction

One way to synthesize 5-phenyl-2,4-pentadienal is via the Wittig reaction, which involves the reaction of an aldehyde or a ketone with a phosphonium ylide to form an alkene. Based on the structure of the target molecule, we can identify the following suitable starting materials: 1. Benzaldehyde (\(\mathrm{C}_{6} \mathrm{H}_{5}\mathrm{CHO}\)) 2. A phosphonium ylide derived from n-butyltriphenylphosphonium bromide (\((C_{6}H_{5})_{3}P(+)CH_{2}CH_{2}CH_{3}Br(-)\)) To synthesize the phosphonium ylide, you can treat n-butyltriphenylphosphonium bromide with a strong base such as sodium amide (NaNH2) in a suitable solvent: \[((C_{6}H_{5})_{3}P(+)CH_{2}CH_{2}CH_{3}Br(-) + NaNH_{2} \to [(C_{6}H_{5})_{3}P=CHCH_{2}CH_{3}]^{-} + NaBr\] Now that we have the phosphonium ylide, we can perform the Wittig reaction by reacting it with benzaldehyde: \[((C_{6}H_{5})_{3}P=CHCH_{2}CH_{3} + C_{6}H_{5}CHO \to C_{6}H_{5}CH=CH-CH=CH-CHO + (C_{6}H_{5})_{3}P(O)H\] The final product is 5-phenyl-2,4-pentadienal as desired.

Key concepts

Wittig Reaction

The Wittig reaction is an essential tool in organic chemistry for the synthesis of alkenes from ketones or aldehydes. It involves the reaction between a phosphonium ylide and a carbonyl compound. A phosphonium ylide is a type of organophosphorus compound with a positively charged phosphorus atom and a negatively charged carbon atom.

The beauty of this reaction lies in its ability to form double bonds with great precision. To carry out the reaction, a strong base is used to deprotonate a phosphonium salt, generating the ylide, which then reacts with the aldehyde or ketone to form the alkene.

Through the example of synthesizing 5-phenyl-2,4-pentadienal, we can see how effectively this reaction builds complex molecules. The choice of the starting materials is critical, and the reaction conditions must be carefully controlled to ensure the success of the Wittig reaction. Benzaldehyde and a tailored phosphonium ylide combine to form the target alkene, showcasing the Wittig reaction's versatility as a synthetic strategy.

Acidity of Hydrogens

Understanding the acidity of hydrogens is pivotal when predicting reactions involving hydrogen atom removal or exchange, which occurs frequently in organic chemistry.

The acidity of a hydrogen atom is influenced by its environment within a molecule. Hydrogens attached to oxygen or nitrogen, or adjacent to electron-withdrawing groups, are typically more acidic due to the more electronegative atoms' ability to stabilize the resulting negative charge.

In \(\alpha, \beta\)-unsaturated carbonyl compounds, the \Upsilon-hydrogens exhibit increased acidity as they can be removed to form a stable conjugate base. This base is stabilized by resonance, hence these hydrogens are more acidic than those in saturated hydrocarbons. This concept is essential when designing reaction pathways that involve deprotonation steps, particularly in the creation of enolates and other reactive intermediates.

Stable Conjugate Base

A stable conjugate base plays a vital role in the reactivity of molecules, especially in deprotonation events. In the context of acidity, a stable conjugate base is the negatively charged species formed after an acid donates a proton.

The stability of a conjugate base is a critical factor in the acidity of the corresponding acid. Several factors contribute to this stability, including electronegativity, hybridization, and the ability to delocalize charge through resonance.

In the case of \(\alpha, \beta\)-unsaturated carbonyl compounds, when a \Upsilon-hydrogen is removed, the resulting conjugate base is highly stabilized by resonance with the adjacent carbonyl group and the \(\beta\)-carbon double bond. This increased stability makes the \Upsilon-hydrogens more acidic and the deprotonated form a powerful nucleophile in various organic transformations.

Resonance Stabilization

Resonance stabilization is a concept that describes the delocalization of electrons within a molecule, often leading to increased stability. It occurs when a compound has multiple valid Lewis structures—known as resonance structures—that contribute to the overall hybrid structure of the molecule.

The ability of a molecule to resonate among several structures is significant in predicting its reactivity and stability. In \(\alpha, \beta\)-unsaturated carbonyl compounds, resonance stabilization has a profound impact on the acidity of hydrogens. When a \Upsilon-hydrogen is abstracted, the negative charge on the conjugate base can spread out across the carbonyl and adjacent double bonds. This dispersal of charge across multiple atoms reduces the energy of the conjugate base, resulting in heightened acidity of the original hydrogen atom.

Resonance stabilization is a cornerstone of understanding why certain molecules are more reactive than others and is a powerful predictor of the outcomes in organic synthesis.