Question

Which combination of reagents will bring about the following conversion? CC1CCCCC1=O CC1CCC(Br)C(C)C1 (A) (i) \(\mathrm{MeMgBr}\) (ii) \(\mathrm{H}_{2} \mathrm{SO}_{4} / \Delta\) (iii) \(\mathrm{HBr} / \mathrm{H}_{2} \mathrm{O}_{2}\) (B) \(\mathrm{MeMgBr} / \mathrm{H}^{+}, \mathrm{H}_{2} \mathrm{SO}_{4} / \Delta, \mathrm{HBr}\) (C) (i) \(\mathrm{MeMgBr}\) (ii) \(\mathrm{H}^{+}\)(iii) \(\mathrm{HBr} / \mathrm{CCl}_{4}\) (D) (i) \(\mathrm{HBr} / \mathrm{H}_{2} \mathrm{O}_{2}\) (ii) \(\mathrm{MeMgBr} / \mathrm{H}^{+}\)

Short answer

The correct combination of reagents for the conversion is option (A): (i) \(\mathrm{MeMgBr}\) (ii) \(\mathrm{H}_{2} \mathrm{SO}_{4} / \Delta\) (iii) \(\mathrm{HBr} / \mathrm{H}_{2} \mathrm{O}_{2}\).

Step-by-step solution

Identify the required transformation

We need to convert a cyclic ketone (\(CC1CCCCC1=O\)) into a different cyclic compound containing a bromine atom (\(CC1CCC(Br)C(C)C1\)). From the given options, we can see that Grignard reagents (such as \(\mathrm{MeMgBr}\)) and reactions involving acids (\(\mathrm{H}^+\), \(\mathrm{H}_{2} \mathrm{SO}_{4}\), and \(\mathrm{HBr}\)) are involved.

Analyze the available options

Let's analyze each option to see if the combination of reagents will bring about the required conversion: (A) (i) \(\mathrm{MeMgBr}\) (ii) \(\mathrm{H}_{2} \mathrm{SO}_{4} / \Delta\) (iii) \(\mathrm{HBr} / \mathrm{H}_{2} \mathrm{O}_{2}\) (B) \(\mathrm{MeMgBr} / \mathrm{H}^{+}, \mathrm{H}_{2} \mathrm{SO}_{4} / \Delta, \mathrm{HBr}\) (C) (i) \(\mathrm{MeMgBr}\) (ii) \(\mathrm{H}^{+}\)(iii) \(\mathrm{HBr} / \mathrm{CCl}_{4}\) (D) (i) \(\mathrm{HBr} / \mathrm{H}_{2} \mathrm{O}_{2}\) (ii) \(\mathrm{MeMgBr} / \mathrm{H}^{+\)

Review the effect of each reagent

(i) \(\mathrm{MeMgBr}\): Grignard reagents can attack the carbonyl group of a ketone, resulting in the formation of a tertiary alcohol. (ii) \(\mathrm{H}_{2} \mathrm{SO}_{4} / \Delta\): A strong acid with heat can cause dehydration of alcohols to form alkenes. (iii) \(\mathrm{HBr} / \mathrm{H}_{2} \mathrm{O}_{2}\): This combination of reagents can add a bromine atom across a double bond using an anti-Markovnikov addition. (iv) \(\mathrm{H}^+\): Protonation of a tertiary alcohol, facilitating its dehydration. (v) \(\mathrm{HBr}\): Addition of a bromine atom across a double bond (Markovnikov addition). (vi) \(\mathrm{HBr} / \mathrm{CCl}_{4}\): Formation of a bromonium ion and anti-Markovnikov addition of a bromine atom across a double bond.

Evaluate each option based on the effects of reagents

(A) Reaction sequence: Formation of a tertiary alcohol, dehydration to form an alkene, and anti-Markovnikov addition of bromine. This sequence will result in the formation of the desired product. (B) The reaction sequence is similar to option A, but with the reagents combined in one step, which is not the order we need for the desired transformation. (C) The reaction sequence lacks dehydration to form an alkene, so bromine addition will not occur, and the desired product will not form. (D) The reaction sequence starts with the addition of bromine across a double bond, but there is no double bond present in the starting compound, so this sequence does not bring the desired conversion.

Choose the correct combination of reagents

Option (A) is the correct combination of reagents that will bring about the required conversion from \(CC1CCCCC1=O\) to \(CC1CCC(Br)C(C)C1\).

Key concepts

Bromination

Bromination is a crucial reaction in organic chemistry, particularly in the synthesis of certain compounds where bromine atoms need to be added to a molecule. Bromination can be carried out in different ways, often depending on the conditions and the specific functional group being targeted. In the exercise, bromination is the step where bromine (Br) needs to be added to a cyclic compound to transform it into a different structural form.

The process involves two main types of reaction mechanisms:

• Anti-Markovnikov addition: In the presence of peroxides such as hydrogen peroxide (\(\mathrm{H}_{2}\mathrm{O}_{2}\)), bromination of an alkene follows an anti-Markovnikov rule, where the bromine atom is added to the less substituted carbon atom. This is explained by the free radical mechanism where initiation begins with the formation of bromine radicals.
• Markovnikov addition: Without the presence of peroxides, the addition of bromine across a double bond typically follows Markovnikov's rule, where the bromine atom is added to the more substituted carbon atom. This is useful for controlling regioselectivity in reactions.

Understanding these basic concepts of bromination helps predict the outcome of reactions involving bromine and its application in organic synthesis.

Carbonyl Group

The carbonyl group is a pivotal functional group in organic chemistry, denoted by the presence of a carbon atom double-bonded to an oxygen atom (C=O). It is found in various compounds, such as ketones, aldehydes, and carboxylic acids. In the given exercise, a cyclic ketone is converted into another compound by manipulating its structure using a series of reagents.

Carbonyl groups are highly reactive due to the partial positive charge on the carbon atom, making them excellent electrophiles. This makes them susceptible to nucleophilic attacks.

• Nucleophilic addition: A common reaction involving carbonyls where a nucleophile attacks the electrophilic carbon in the carbonyl, forming an intermediate which then rearranges to form a new compound. In the exercise, the Grignard reagent (\(\mathrm{MeMgBr}\)) acts as the nucleophile.
• Grignard reaction: This is an important reaction where Grignard reagents add to the carbonyl carbon, resulting in the formation of an alcohol. In the exercise, this step is necessary to create a tertiary alcohol intermediate.

Understanding the reactivity of carbonyl groups is critical in the design of synthetic pathways, especially in creating complex molecules in organic synthesis.

Organic Synthesis

Organic synthesis refers to the construction of complex organic molecules through a series of chemical reactions. It is a fundamental aspect of organic chemistry that enables the creation of a wide range of compounds, from pharmaceuticals to materials.

In the discussed exercise, organic synthesis is demonstrated by transforming a cyclic ketone into a different brominated compound. This is achieved through multiple reaction steps, showcasing key aspects of synthetic strategy:

• Stepwise transformation: Organic synthesis often requires multiple reaction steps to convert simple molecules into complex structures. Each step is carefully designed to introduce new functional groups or to modify existing ones.
• Use of reagents: Each reagent in a synthetic pathway serves a specific purpose, often:
  1. Creating new bonds (e.g., Grignard reaction forms C-C bonds).
  2. Introducing functional groups (e.g., bromination for adding Br atoms).
  3. Altering existing functional groups to enable further reactions (e.g., dehydration).
• Order of reactions: The sequence of reactions is crucial. Changing the order can lead to different or unintended products, as seen in different options of the exercise.

Organic synthesis is an art that combines creativity and logic, requiring an understanding of the reactivity of functional groups and the strategic use of different reagents to efficiently produce desired compounds.