Question

Using your reaction roadmaps as a guide, show how to convert (2-methylpropyl) benzene into 4 -phenyl-3-buten-2-one.You must use (2-methylpropyl)benzene as the source of all carbon atoms in the target molecule. Show all reagents and all molecules synthesized along the way.

Short answer

Question: Convert (2-methylpropyl) benzene into 4-phenyl-3-buten-2-one using the given starting material as the source of all carbon atoms. Provide the reaction sequence. Answer: The reaction sequence is as follows: 1. Bromination: (2-methylpropyl) benzene + NBS → 1-bromo-2-methylpropyl benzene 2. Formation of Grignard reagent: 1-bromo-2-methylpropyl benzene + Mg (ether) → (2-methylpropyl)phenylmagnesium bromide 3. Addition of carbon: (2-methylpropyl)phenylmagnesium bromide + ethyl formate → 1-phenyl-2-methyl-3-hydroxybutan-1-one (acidification with HCl) 4. Dehydration: 1-phenyl-2-methyl-3-hydroxybutan-1-one + H2SO4 (heat) → 4-phenyl-3-buten-2-one

Step-by-step solution

Formation of Grignard Reagent

Firstly, we need to convert the (2-methylpropyl) benzene into a Grignard reagent, which will enable us to further manipulate the carbon skeleton. To do this, brominate the (2-methylpropyl) benzene using N-bromosuccinimide (NBS) as a brominating agent to form 1-bromo-2-methylpropyl benzene. Then, treat the halide with magnesium in an ether solvent, such as diethyl ether or tetrahydrofuran (THF), to produce the Grignard reagent: (2-methylpropyl)phenylmagnesium bromide.

Addition of Carbon

Next, react the Grignard reagent with ethyl formate (HCOOEt) in order to add an additional carbon to the molecule. The Grignard reagent will attack the carbonyl group of ethyl formate, forming a new carbon-carbon bond and generating an alkoxide intermediate. Subsequently, acidify the reaction mixture with dilute hydrochloric acid (HCl) to protonate the alkoxide, yielding 1-phenyl-2-methyl-3-hydroxybutan-1-one.

Dehydration

Now it's time to remove the hydroxy group from our intermediate compound in order to form the desired product. Treat 1-phenyl-2-methyl-3-hydroxybutan-1-one with sulfuric acid (H2SO4) under heating conditions to effect an E1 dehydration. This will generate 4-phenyl-3-buten-2-one as the final product. In summary, the full reaction sequence is as follows: 1. Bromination: (2-methylpropyl) benzene + NBS → 1-bromo-2-methylpropyl benzene 2. Formation of Grignard reagent: 1-bromo-2-methylpropyl benzene + Mg (ether) → (2-methylpropyl)phenylmagnesium bromide 3. Addition of carbon: (2-methylpropyl)phenylmagnesium bromide + ethyl formate → 1-phenyl-2-methyl-3-hydroxybutan-1-one (acidification with HCl) 4. Dehydration: 1-phenyl-2-methyl-3-hydroxybutan-1-one + H2SO4 (heat) → 4-phenyl-3-buten-2-one

Key concepts

Grignard Reagent Formation

Grignard reagents are pivotal in the synthesis of organic compounds because they open up pathways for creating new carbon-carbon bonds. To form a Grignard reagent, a halogenated organic precursor reacts with magnesium metal in an ether solvent, such as diethyl ether or tetrahydrofuran (THF).

For instance, when we consider the step-by-step solution provided, converting (2-methylpropyl) benzene into a Grignard reagent is the initial focus. The process starts with bromination, introducing a bromine atom in place of a hydrogen atom to yield 1-bromo-2-methylpropyl benzene. This compound then reacts with magnesium in ether to form (2-methylpropyl)phenylmagnesium bromide. During this reaction, the magnesium inserts itself between the carbon and bromine atoms, forming a carbon-magnesium bond, thus establishing the Grignard reagent.

Key Points to Remember:

• A halogen (such as bromine) must be present in the organic compound to react with magnesium.
• Ether solvents stabilize the Grignard reagent by coordinating with the magnesium atom.
• Grignard reagents are sensitive to moisture and must be handled under anhydrous (water-free) conditions.

Carbon-Carbon Bond Formation

A core objective of many synthetic organic reactions is the formation of carbon-carbon bonds, which is central to building complex organic structures from simpler ones. The step-by-step solution given demonstrates the utility of Grignard reagents in this endeavor. Here, the Grignard reagent, (2-methylpropyl)phenylmagnesium bromide, attacks the carbonyl carbon of ethyl formate (HCOOEt), leading to the formation of a new carbon-carbon bond.

This reaction proceeds through a nucleophilic addition mechanism where the nucleophilic Grignard reagent donates electrons to the electrophilic carbonyl carbon. An alkoxide intermediate forms, which is then protonated upon treatment with dilute hydrochloric acid, ultimately yielding 1-phenyl-2-methyl-3-hydroxybutan-1-one.

Critical Concepts:

• The Grignard reagent acts as a nucleophile and seeks electrophilic carbon atoms.
• Carbonyl compounds such as aldehydes, ketones, and esters are common electrophiles in these reactions.
• Protonation of the resulting alkoxide intermediate is an essential step to obtain the final alcohol product.

Organic Reaction Mechanisms

Understanding the sequence of steps that define how a reaction occurs at the molecular level is fundamental to mastering organic chemistry. Organic reaction mechanisms provide a detailed description of the breaking and forming of bonds, along with the movement of electrons that facilitate these changes.

For example, in the dehydration step of the given solution, an E1 mechanism is employed to remove a hydroxy group from our intermediate compound. In an E1 dehydration, the reaction proceeds through the formation of a carbocation intermediate, followed by the loss of a water molecule to create a double bond, resulting in the alkene 4-phenyl-3-buten-2-one.

Key Mechanistic Elements:

• E1 reactions typically involve the formation of a carbocation intermediate.
• Dehydration steps often require an acid catalyst; in this instance, sulfuric acid is used.
• Heat helps in shifting the equilibrium towards the elimination product—here, the formation of the alkene.