Question

Using your roadmaps as a guide, show how to convert 2-methylpropylbenzene into 4-phenyl-3-buten-2-one. You must use 2-methylpropylbenzene as the source of all carbon atoms in the target molecule. Show all reagents and all molecules synthesized along the way. CC(=O)C=Cc1ccccc1 (2-Methylpropyl)benzene \(\quad\) 4-Phenyl-3-buten-2-one \((E, Z\) mixture \()\)

Short answer

Question: Describe the synthesis of 4-phenyl-3-buten-2-one starting from 2-methylpropylbenzene, including all the necessary reagents and reactions. Answer: The synthesis involves the following steps: 1. Bromination of 2-methylpropylbenzene with N-bromosuccinimide (NBS) and AIBN to form 2-bromo-2-methylpropylbenzene. 2. E2 elimination with t-butoxide to form 2-phenyl-1-butene. 3. Ozonolysis using ozone (O3) and dimethyl sulfide (DMS) to cleave the double bond and produce benzaldehyde and acetone. 4. Aldol condensation between benzaldehyde and acetone using NaOH to form the final product, 4-phenyl-3-buten-2-one (a mixture of E and Z isomers).

Step-by-step solution

Bromination of 2-methylpropylbenzene

React 2-methylpropylbenzene with N-bromosuccinimide (NBS) in the presence of a radical initiator like AIBN (Azobisisobutyronitrile) to selectively form 2-bromo-2-methylpropylbenzene. \[ \text{2-methylpropylbenzene}\ +\ \text{NBS}\ \xrightarrow{\text{AIBN}}\ \text{2-bromo-2-methylpropylbenzene} \]

E2 Elimination

Perform an E2 elimination reaction on the product obtained in Step 1 by treating it with a strong base like t-butoxide to form 2-phenyl-1-butene. \[ \text{2-bromo-2-methylpropylbenzene}\ +\ \text{t-BuO}^{-}\ \rightarrow\ \text{2-phenyl-1-butene} \]

Ozonolysis of double bond

Perform ozonolysis of 2-phenyl-1-butene by treating it with ozone (O3), followed by the addition of a reducing agent like a dimethyl sulfide (DMS) or zinc/acetic acid. This reaction will cleave the double bond and result in the formation of benzaldehyde and acetone. \[ \text{2-phenyl-1-butene}\ \xrightarrow{\text{O}_3}\ \text{Intermediary Ozonide}\ \xrightarrow{\text{DMS}}\ \text{Benzaldehyde} +\ \text{Acetone} \]

Aldol Condensation

Perform an aldol condensation by treating the benzaldehyde with acetone in the presence of a base like NaOH. This will yield the desired product, 4-phenyl-3-buten-2-one (a mixture of E and Z isomers). \[ \text{Benzaldehyde}\ +\ \text{Acetone}\ \xrightarrow{\text{NaOH}}\ (E,\ Z)\text{-4-Phenyl-3-buten-2-one} \] In summary, the synthesis of 4-phenyl-3-buten-2-one from 2-methylpropylbenzene involves the following key steps: 1. Bromination of 2-methylpropylbenzene 2. E2 elimination to form 2-phenyl-1-butene 3. Ozonolysis to form benzaldehyde and acetone 4. Aldol condensation between benzaldehyde and acetone to form the final product, 4-phenyl-3-buten-2-one.

Key concepts

Bromination Reaction

In organic chemistry, the bromination reaction is a critical transformation which involves adding a bromine atom to organic compounds. The reaction of 2-methylpropylbenzene with N-bromosuccinimide (NBS), typically in the presence of a radical initiator like azobisisobutyronitrile (AIBN), leads to the selective bromination at the benzylic position. This process forms 2-bromo-2-methylpropylbenzene, setting the stage for subsequent transformations.

The role of NBS is to provide a stable source of bromine, while AIBN generates radicals needed for the reaction to proceed. The bromination is highly selective because the benzylic position is particularly reactive in free radical halogenation, due to the stabilization of the benzylic radical through resonance.

E2 Elimination Reaction

Following bromination, an E2 elimination reaction is performed to create a double bond in the molecule. This is a type of elimination reaction where both the leaving group (in this case, a bromide ion from 2-bromo-2-methylpropylbenzene) and a β-hydrogen atom are removed simultaneously, leading to the formation of a double bond.

For the E2 reaction, a strong base like t-butoxide is used. This base abstracts a proton from a carbon atom adjacent to the carbon bearing the bromine, resulting in the elimination of HBr and the formation of 2-phenyl-1-butene. The E2 mechanism is bimolecular, involving the base and substrate coming together in a concerted process with no intermediate formation.

Ozonolysis Reaction

Ozonolysis is a powerful reaction used to cleave double bonds in alkenes, and it is particularly useful in determining the structure of the double-bonded compounds. In this synthesis, ozonolysis is applied to 2-phenyl-1-butene. When treated with ozone (O3), the double bond in 2-phenyl-1-butene splits, forming an intermediary ozonide. This intermediate is then reduced to simpler aldehydes or ketones; in this case, benzaldehyde and acetone, by using a reducing agent like dimethyl sulfide (DMS) or zinc/acetic acid.

The ozonolysis step is pivotal in the overall synthesis because it provides the necessary building blocks for the subsequent aldol condensation, paving the way towards the target molecule, 4-phenyl-3-buten-2-one.

Aldol Condensation

Aldol condensation is a fundamental carbon-carbon bond-forming reaction in organic synthesis. This reaction often involves an enolate ion attacking an aldehyde or ketone, leading to the formation of a β-hydroxy aldehyde or ketone, which can then dehydrate to give a conjugated enone.

In the final step to synthesize 4-phenyl-3-buten-2-one, benzaldehyde reacts with acetone in the presence of a base like NaOH. Here, the base generates an enolate from acetone, which then attacks the carbonyl carbon of the benzaldehyde. The product of this reaction is a β-hydroxy ketone, which upon dehydration gives the desired enone, 4-phenyl-3-buten-2-one, which exists as a mixture of E and Z isomers. This final step exemplifies the significance of aldol condensation in building complex organic structures from simpler precursors.