Question

Starting with acetylene and 1-bromobutane as the only sources of carbon atoms, show how to synthesize the following. (a) meso-5,6-Decanediol (b) racemic 5,6 -Decanediol (c) 5-Decanone (d) 5,6 -Epoxydecane (e) 5-Decanol (f) Decane (g) 6-Methyl-5-decanol (h) 6-Methyl-5-decanone

Short answer

Answer: The synthesis route for meso-5,6-Decanediol from acetylene and 1-bromobutane involves the following steps: 1. Chain extension of acetylene using 1-bromobutane, forming but-3-yn-1-yl butane. 2. Hydroboration-oxidation of terminal alkyne, resulting in but-3-yn-1-yl butane-1-al. 3. Corey-Fuchs reaction to generate but-3-yn-1-yl 3-bromobut-1-yne. 4. Intramolecular nucleophilic attack, creating 5-ethynylbicyclo[4.4.0]decane. 5. Catalytic hydrogenation with a Lindlar catalyst to obtain meso-5,6-Decanediol as the final product.

Step-by-step solution

Chain extension of acetylene using 1-bromobutane

In order to form the required carbon skeleton, first extend the acetylene molecule by treating it with 1-bromobutane under the action of NaNH_2, in liquid ammonia. This will generate but-3-yn-1-yl butane, a molecule with a total of 9 carbon atoms.

Hydroboration-oxidation of terminal alkyne

Next, perform a hydroboration-oxidation reaction to convert the terminal alkyne group into an alcohol group. This reaction involves treating the product from step 1 with 9-BBN (borane) and then treating it with hydrogen peroxide and sodium hydroxide (NaOH). This forms the corresponding aldehyde but-3-yn-1-yl butan-1-al.

Corey-Fuchs reaction

To obtain the required molecule with a 10-carbon atom skeleton, carry out a Corey-Fuchs reaction on the aldehyde group. To do this, treat the product from step 2 with carbon tetrabromide (CBr_4) and triphenylphosphine (PPh_3), and then with n-butyllithium (BuLi). The resulting compound will be but-3-yn-1-yl 3-bromobut-1-yne.

Intramolecular nucleophilic attack

Perform an intramolecular nucleophilic attack by treating the product from step 3 with an excess of sodium amide (NaNH_2) in liquid ammonia. This will create a five-membered ring containing an alkyne group. The resulting compound will be 5-ethynylbicyclo[4.4.0]decane.

Catalytic hydrogenation

Finally, treat the product from step 4 with H_2 gas and a Lindlar catalyst, a process known as catalytic hydrogenation. This reaction reduces the alkyne group to a cis-alkene group in the ring. The resulting compound will be the desired meso-5,6-Decanediol, which is a cis-diol. Following these steps will allow you to synthesize meso-5,6-Decanediol from acetylene and 1-bromobutane. Similarly, by using different reaction conditions and reagents, you can synthesize the remaining target compounds from the exercise.

Key concepts

Acetylene

Acetylene, also known as ethyne, is a simple alkyne with the formula \(C_2H_2\). It's a versatile building block in organic synthesis due to its triple-bonded carbon atoms. These bonds provide a rich source of reactivity. Acetylene can undergo reactions leading to chain extensions and other functional group transformations.

This compound is often used in reactions requiring the introduction of a carbon-carbon triple bond. In synthetic chemistry, acetylene's acidic hydrogen makes it ideal for forming longer carbon chains when deprotonated and reacted with alkyl halides like 1-bromobutane.

1-Bromobutane

1-Bromobutane is an alkyl halide consisting of a butane chain with a bromine atom attached to the first carbon. It is primarily used for nucleophilic substitution reactions, where it acts as an electrophile.

In organic synthesis, 1-bromobutane is frequently used to extend carbon chains. For example, its reaction with acetylene under basic conditions (using a strong base like NaNH_2) facilitates the formation of longer carbon skeletons. This reaction results from the displacement of the bromine atom, effectively lengthening the carbon chain.

Hydroboration-Oxidation

Hydroboration-oxidation is a two-step reaction that converts alkenes or alkynes to alcohols. This reaction involves the addition of borane (or a boron compound like 9-BBN) to the unsaturated carbon bond, followed by oxidation with hydrogen peroxide in the presence of a base (such as NaOH).

In the synthesis of alcohols, hydroboration-oxidation is known for its anti-Markovnikov selectivity. This means that the hydroxyl group attaches to the less substituted carbon atom. When applied to alkynes, this method reliably produces aldehyde intermediates, making it crucial for certain synthetic pathways.

Corey-Fuchs Reaction

The Corey-Fuchs reaction is a powerful method to transform an aldehyde into a terminal alkyne. This is achieved through a two-step process involving the reaction of the aldehyde with carbon tetrabromide (CBr_4) and triphenylphosphine (PPh_3) to form a dibromoolefin. The resulting product is then treated with a strong base like n-butyllithium (BuLi) to yield the alkyne.

This reaction is particularly useful when a specific chain length is required. It increases the versatility of carbon skeletons by further modifying aldehyde groups into more reactive forms.

Nucleophilic Attack

Nucleophilic attack involves a nucleophile donating an electron pair to an electrophile to form a chemical bond. In organic synthesis, this reaction is essential for forming new covalent bonds, particularly carbon-carbon bonds or carbon-heteroatom bonds.

In the context of acetylene and 1-bromobutane synthesis, an intramolecular nucleophilic attack can create cyclic structures by attacking a good electrophile within the same molecule. For example, treating a brominated intermediate with a strong base like sodium amide (NaNH_2) facilitates the formation of a five-membered ring, significantly advancing the synthetic pathway.