was wondering if someone could help me write a mechanism for the synthesis of methyl E-4-methoxycinnamate from p-anisaldehyde. and suggest a reason why the cyclic intermediate might have two important groups in a trans relationship that could favor the E-alkene.
Have you tried to draw a mechanism on one of these help boards. Tough to do. Actually, almost impossible to do.
How are you making it?
MeOAr-CHO + wittig -> MeOAr-CH=CHCOOMe
or a Wadsworth Emmons?
If it is a Wittig you should get the Z product unless it is the Schlosser Modification which gives the E product.
There is a good description of the Wittig mechanism on the Wikipedia page
http://en.wikipedia.org/wiki/Wittig_reaction
Which shows the cyclic transition state.
Sure, I can help you with that! The synthesis of methyl E-4-methoxycinnamate from p-anisaldehyde can be achieved through a two-step process: first, you need to convert p-anisaldehyde into p-anisalacetophenone, and then you can use an esterification reaction to obtain methyl E-4-methoxycinnamate.
Here's a step-by-step explanation of the synthesis:
Step 1: Conversion of p-anisaldehyde to p-anisalacetophenone:
To achieve this conversion, you can use a crossed aldol condensation reaction. Here's how you can do it:
1. React p-anisaldehyde (p-methoxybenzaldehyde) with acetophenone in the presence of a base such as sodium hydroxide (NaOH) or potassium hydroxide (KOH).
2. The base deprotonates the alpha-hydrogen of p-anisaldehyde, creating a stabilized enolate ion.
3. The enolate ion undergoes a nucleophilic attack on the carbonyl carbon of the acetophenone, forming an alkoxide intermediate.
4. The alkoxide intermediate undergoes intramolecular proton transfer and elimination of water, resulting in the formation of the beta-diketone compound, p-anisalacetophenone.
Step 2: Esterification to obtain methyl E-4-methoxycinnamate:
Once you have obtained p-anisalacetophenone, you can now perform an esterification reaction to convert it into methyl E-4-methoxycinnamate. Here's how you can do it:
1. React p-anisalacetophenone with methanol (CH3OH) and a strong acid catalyst such as sulfuric acid (H2SO4) or hydrochloric acid (HCl).
2. The acid catalyst protonates the carbonyl oxygen of p-anisalacetophenone, making it more susceptible to a nucleophilic attack.
3. Methanol (CH3OH) acts as the nucleophile and attacks the carbonyl carbon, resulting in the formation of a tetrahedral intermediate.
4. The tetrahedral intermediate loses a water molecule and rearomatizes to form the desired product, methyl E-4-methoxycinnamate.
Now, let's discuss why the cyclic intermediate might favor the E-alkene configuration:
The E-alkene configuration refers to the arrangement where the substituents on the double bond are placed on opposite sides of the molecule. In the synthesis of methyl E-4-methoxycinnamate, the cyclic intermediate is likely to favor the E-alkene due to two important factors:
1. Steric hindrance: If the cyclic intermediate had the two important substituents (methoxy and carbonyl) in a cis relationship, there would be significant steric hindrance between these groups. This would result in a higher energy state and decreased stability. On the other hand, in the trans relationship, the steric hindrance is minimized, leading to a more stable cyclic intermediate.
2. Conjugation: The trans relationship between the two substituents allows for optimal conjugation along the double bond. Conjugation is an electronic effect that stabilizes the molecule by delocalizing electrons over a larger area. In the case of methyl E-4-methoxycinnamate, the trans relationship allows the carbonyl group to conjugate with the aromatic ring, resulting in increased stability and a lower energy state.
These two factors contribute to the preference for the trans relationship of the two important groups in the cyclic intermediate, favoring the formation of the E-alkene configuration in the final product, methyl E-4-methoxycinnamate.