Question

Muscalure, cis-9-tricosene, is the sex-attractant insect pheromone of the common housefly. Give a practical synthesis of this compound from acetylene and straight chain alcohols.

Short answer

To synthesize cis-9-tricosene (Muscalure) from acetylene and straight-chain alcohols, use the following steps: 1) Choose a suitable straight-chain alcohol, 1-icosanol. 2) Convert 1-icosanol to its corresponding aldehyde, icosanal, through oxidation using a mild oxidizing agent (e.g., Swern oxidation or PCC). 3) Form 9-hexadecyne via a coupling reaction between icosanal and acetylene, using Corey-Fuchs reaction. 4) Perform cis-hydrogenation on 9-hexadecyne using the Lindlar catalyst (Pd/CaCO3-Pb) to obtain cis-9-tricosene (Muscalure).

Step-by-step solution

Select an appropriate straight-chain alcohol

We must first choose a suitable straight-chain alcohol to use as a starting material. Knowing that Muscalure has 23 carbons, the straight-chain alcohol should contain 22 carbons. Therefore, 1-icosanol (CH3(CH2)19CH2OH), a long-chain primary alcohol, will be utilized.

Convert 1-icosanol to its corresponding aldehyde

Next, we need to convert 1-icosanol to its corresponding aldehyde, icosanal. This can be done through the oxidation of the primary alcohol using a mild oxidizing agent, such as the Swern oxidation or PCC(Pyridinium chlorochromate). Reaction: 1-icosanol + Oxidizing agent -> Icosanal

Formation of 9-hexadecyne

Following this, we need to couple the 8 carbons from acetylene to icosanal. We will form a carbon-carbon triple bond using acetylene and an appropriate coupling agent such as Corey-Fuchs reaction, utilizing diethyl bromomalonate(DEBM) and trimethyl phosphorodithioate(triphenylphosphine(PPh3)-carbon tetrabromide(CBr4)). This will result in the formation of 9-hexadecyne. Reaction: Icosanal + Acetylene + Coupling agent -> 9-hexadecyne

cis-Hydrogenation

In order to convert the triple bond to a cis-double bond, cis-hydrogenation of the alkyne must be performed. This can be done through the Lindlar catalyst (Pd/CaCO3-Pb), which allows for the selective hydrogenation of a carbon-carbon triple bond (alkyne) to a cis carbon-carbon double bond (alkene). Reaction: 9-hexadecyne + H2 + Lindlar catalyst -> cis-9-tricosene (Muscalure) After completing these steps, you should have successfully synthesized the target molecule, cis-9-tricosene (Muscalure), from acetylene and 1-icosanol, using the appropriate reactions and reagents.

Key concepts

Organic Synthesis

Organic synthesis is a fundamental aspect of organic chemistry, focused on constructing organic molecules through a sequence of chemical reactions. The objective is to construct complex and useful chemical compounds from simpler ones. In the context of muscalure synthesis, we start with simple substances like acetylene, a hydrocarbon with a triple bond, and 1-icosanol, a straight-chain alcohol with 22 carbons. Using various reactions and reagents, we methodically build up the carbon chain and introduce functional groups until we acquire the target compound, muscalure.

An effective synthesis must consider the length of the carbon chain and the specific functional groups' position. It often requires a deep understanding of reaction mechanisms and properties of the beginning materials. In addition, it is important to manage factors like reaction conditions and the potential formation of side products, as these can impact the yield and purity of the final product.

Swern Oxidation

Swern oxidation is a well-established method for converting primary alcohols into the corresponding aldehydes, critical for the synthesis of numerous organic compounds, including muscalure. The beauty of this reaction lies in its mildness and high selectivity, which prevent over-oxidation to carboxylic acids.

Typically, the Swern oxidation involves dimethyl sulfoxide (DMSO) and an activating reagent like oxalyl chloride, followed by treatment with a base, such as triethylamine. The reaction conditions for Swern oxidation are also quite essential; it's usually performed at very low temperatures to avoid decomposition of the DMSO-activated intermediate. Swern oxidation is a versatile tool that's particularly valuable for synthesizing sensitive molecules due to its gentle nature. This is why selecting it in the synthesis of muscalure ensures the preservation of the intricate molecular structure.

Corey-Fuchs Reaction

The Corey-Fuchs reaction, named after the chemists E.J. Corey and P.L. Fuchs, is a pivotal transformation in the construction of carbon-carbon triple bonds, integral to the architecture of various complex molecules. This reaction is instrumental in extending carbon chains and transitioning aldehydes to terminal alkynes.

The reaction employs the use of dibromocarbene, generated from triphenylphosphine and carbon tetrabromide. The dibromocarbene intermediate is highly reactive and adds to the aldehyde to form a dibromoalkene. The final phase involves a base-induced elimination, such as with the use of zinc, which results in the expulsion of the two bromide groups, leading to the formation of the alkyne. For muscalure synthesis, the Corey-Fuchs reaction is employed to append an eight-carbon acetylene unit to the icosanal precursor, enabling the assembly of the molecule's full carbon skeleton.

cis-Hydrogenation

cis-Hydrogenation is a catalytic process that allows for the addition of hydrogen to alkynes, resulting in alkenes with cis-stereochemistry. Stereochemistry is a branch of chemistry dealing with the three-dimensional arrangement of atoms in molecules, which significantly affects a compound's physical and chemical properties.

Hydrogenation reactions are ubiquitous in the field of drug manufacture and the production of various organic compounds, including pheromones like muscalure. The success of this step hinges on the selective introduction of hydrogen atoms across the carbon-carbon triple bond. The cis configuration is vital for biological activity in many compounds, and the control over the geometry of the resulting double bond is critical in synthesizing the correct isomer for physiological efficacy.

Lindlar Catalyst

The Lindlar catalyst is a specialized heterogeneous catalyst composed of palladium deposited on calcium carbonate and poisoned with various substances like lead acetate. This catalyst is renowned for its ability to selectively hydrogenate triple bonds (alkynes) to double bonds (alkenes) without further reducing the double bond to a single bond (alkane).

In the muscalure synthesis, the Lindlar catalyst provides specificity in the creation of the cis-9-tricosene molecule. The partial hydrogenation facilitated by this catalyst is essential in transforming 9-hexadecyne into the target molecule without over-reducing it. The careful control of reaction conditions such as pressure and temperature, in conjunction with the use of the Lindlar catalyst, ensures that only the desired cis-hydrogenation occurs, resulting in the synthesis of a biologically active pheromone.