Question

Indicate how you would synthesize each of the following substances from the given organic starting materials and other necessary organic or inorganic reagents. Specify reagents and conditions. (b) \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}-\mathrm{CH}_{2} \mathrm{Br}\) from \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{COH}\) (c) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHO}\) from \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{C}(\mathrm{OH}) \mathrm{CH}_{2} \mathrm{CH}_{3}\) (d) \(\mathrm{CH}_{3} \mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{3}\) from ethylene

Short answer

(b) To synthesize \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}-\mathrm{CH}_{2} \mathrm{Br}\) from \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{COH\), first react with H2SO4 to form \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}-\mathrm{CH}_{2}\), then use NBS in the presence of light to add the bromine, forming the desired compound. (c) To synthesize \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHO}\) from \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{C}(\mathrm{OH}) \mathrm{CH}_{2} \mathrm{CH}_{3}\), first oxidize using PCC to form \(\mathrm{CH}_{3}\mathrm{CH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2}\mathrm{C}=O\), then react with CH3MgBr to form the final product. (d) To synthesize \(\mathrm{CH}_{3} \mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{3}\) from ethylene, first perform epoxidation using m-CPBA, then react with NaOMe in methanol to open the epoxide ring and form the desired compound.

Step-by-step solution

Convert alcohol to alkene

For this conversion, use sulfuric acid (H2SO4) as the reagent. The reaction will undergo dehydration, forming the alkene. \[ \left(\mathrm{CH}_{3}\right)_{3} \mathrm{COH} \xrightarrow[\text{H2SO4}]{\text{Heat}} \left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}-\mathrm{CH}_{2} \]

Add halogen to the alkene

To add a halogen, use N-Bromosuccinimide (NBS) in the presence of light. This will form an allylic bromide by a radical reaction. \[ \left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}-\mathrm{CH}_{2} \xrightarrow[\text{NBS}]{\text{Light}} \left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}-\mathrm{CH}_{2} \mathrm{Br} \] (c) Synthesis of \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHO}\) from \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{C}(\mathrm{OH}) \mathrm{CH}_{2} \mathrm{CH}_{3}\):

Convert alcohol to ketone

To make this conversion, use PCC (Pyridinium Chlorochromate) as the oxidizing agent. The secondary alcohol will be oxidized to a ketone. \[ \left(\mathrm{CH}_{3}\right)_{2} \mathrm{C}(\mathrm{OH}) \mathrm{CH}_{2} \mathrm{CH}_{3} \xrightarrow[\text{PCC}]{\text{CH2Cl2}} \mathrm{CH}_{3}\mathrm{CH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2}\mathrm{C}=O \]

Grignard Reaction to Form Aldehyde

Prepare a Grignard Reagent, Methylmagnesium bromide (CH3MgBr), and use Diethyl ether (Et2O) as a solvent. Then, react with ethanal to form the desired product. \[ \mathrm{CH}_{3}\mathrm{CH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2}\mathrm{C}=O + \mathrm{CH}_{3}\mathrm{MgBr} \rightarrow \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHO} \] (d) Synthesis of \(\mathrm{CH}_{3} \mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{3}\) from ethylene:

Epoxidation of ethylene

To transform ethylene into an epoxide, use a peroxy acid, such as meta-chloroperoxybenzoic acid (m-CPBA) as a reagent. \[ \mathrm{CH}_{2}=\mathrm{CH}_{2} \xrightarrow[\text{m-CPBA}]{} \mathrm{CH}_{2}\mathrm{OCH}_{2} \]

Nucleophilic ring-opening of epoxide

To open the epoxide ring, use Sodium Methoxide (NaOMe). The nucleophile will attack the epoxy carbon and form the new C-O bond. \[ \mathrm{CH}_{2}\mathrm{OCH}_{2} \xrightarrow[\text{NaOMe}]{\text{MeOH}} \mathrm{CH}_{3} \mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{3} \]

Key concepts

Alcohol to Alkene Conversion

In organic chemistry, converting an alcohol to an alkene is a common technique, often achieved through a dehydration process. Here, sulfuric acid (\( \text{H}_2\text{SO}_4 \)) is used as a catalyst. When you heat the alcohol with \( \text{H}_2\text{SO}_4 \), it facilitates the elimination of a water molecule from the alcohol. This leaves a double bond in place, creating an alkene.

• The process is called dehydration because it removes a water molecule.
• This reaction often requires heating to drive off the water as steam, shifting the equilibrium to the product side, enhancing alkene formation.

Understanding this step is crucial for further modifications, as alkenes are reactive intermediates for many synthetic pathways.

Halogenation

Halogenation of alkenes is a useful reaction in organic synthesis, often achieved using N-Bromosuccinimide (NBS) in the presence of light. This process introduces a halogen atom at the allylic position of the alkene. The presence of light induces a radical mechanism:

• NBS generates bromine radicals, which abstract a hydrogen from the allylic position, creating an allylic radical.
• This allylic radical then reacts with another bromine molecule to form the allylic bromide product.

This method selectively brominates the allylic position without adding bromine directly across the double bond, which could occur under different conditions.

Oxidation of Alcohols

Turning an alcohol into a ketone or aldehyde is a fundamental reaction in organic synthesis, using oxidizing agents like Pyridinium Chlorochromate (PCC). The choice of oxidizing agent determines the extent of oxidation:

• PCC is mild and converts primary alcohols to aldehydes and secondary alcohols to ketones.
• Using PCC avoids further oxidation of aldehydes to carboxylic acids, which is possible with stronger oxidants.

In a typical lab procedure, dichloromethane (\( \text{CH}_2\text{Cl}_2 \)) is used as a solvent for these reactions, stabilizing intermediates and aiding efficient electron transfer.

Grignard Reaction

The Grignard reaction is a powerful tool in building carbon-carbon bonds, using Grignard reagents like Methylmagnesium Bromide ( \( \text{CH}_3\text{MgBr} \)). Here's how it works:

• Grignard reagents are formed by reacting an alkyl halide with magnesium shavings in dry ether, creating nucleophilic carbon centers.
• These reagents can add to carbonyl compounds (like ketones and aldehydes), forming alcohols after acid workup.

Using Grignard reagents can help in synthesizing complex alcohols that form the backbone of many bioactive molecules, allowing intricate modifications.

Epoxidation

Epoxidation involves transforming alkenes into epoxides, a three-membered ring with an oxygen atom. This typically uses peroxy acids like meta-chloroperoxybenzoic acid (m-CPBA):

• The peroxy acid transfers an oxygen atom to the alkene, forming a strained epoxide with syn addition.
• Epoxidation is a stereospecific reaction; thus, the stereochemistry of the alkene is preserved in the product.

Epoxides are versatile intermediates that can be transformed into various products, making epoxidation a valuable reaction in organic synthesis.

Nucleophilic Ring-Opening

Opening an epoxide ring with a nucleophile like Sodium Methoxide ( \( \text{NaOMe} \)) is a key step in synthesizing ethers. This ring-opening reaction can lead to useful synthetic intermediates:

• The nucleophile attacks the more electrophilic carbon, opening the epoxide ring and forming a new carbon-oxygen bond.
• The opened product retains the stereochemistry, allowing control over the final product's configuration.

This approach is valuable in creating ethers with specific functional properties, aiding in the design of custom organic compounds.