Question

Propose a synthesis for \((Z)\)-9-tricosene (muscalure), the sex pheromone for the common housefly (Musca domestica), starting with acetylene and haloalkanes as sources of carbon atoms.

Short answer

The purpose of treating tricosane with 2-chloro-2,2,2-trifluoroacetophenone is to selectively convert the C9-H bond in tricosane to a C9-OH group, forming 9-hydroxytricosane through directed ortho metalation. This step is crucial for the subsequent formation of the desired (Z)-9-tricosene molecule.

Step-by-step solution

Identify the structure of (Z)-9-tricosene

(Z)-9-tricosene is an alkene with the double bond in the (Z)-configuration at carbon 9. It has a total of 23 carbon atoms. We need to generate this molecule from acetylene and haloalkanes, acting as our carbon sources.

Create a synthetic route using acetylene and haloalkanes

To build the desired molecule we need to incorporate 23 carbon atoms, using acetylene and haloalkanes. Acetylene (C2H2) can act as our base structure from which we can build upon using haloalkanes. Additionally, we will need to bring in other reagents that can help us accomplish the desired chemical transformations.

Build the carbon skeleton by synthesizing tricosane

To build the desired carbon skeleton of the target molecule, we'll start by synthesizing tricosane. This can be done using the following approach: 1. Convert acetylene (C2H2) into an ethyllithium species (C2H5Li) by treatment with n-butyllithium (n-BuLi). 2. React ethyllithium (C2H5Li) with 1-iodoeicosane (C20H41I) to form tricosane (C23H48): C2H5Li + C20H41I -> C23H48 + LiI. This reaction involves a nucleophilic attack by ethyllithium on the iodine of 1-iodoeicosane, generating tricosane and a lithium iodide salt.

Formation of (Z)-9-tricosene

To generate the desired alkene, we can accomplish this through the following synthetic steps: 1. Selectively react tricosane (C23H48) with 2-chloro-2,2,2-trifluoroacetophenone to convert C9-H into C9-OH through directed ortho metalation. This forms 9-hydroxytricosane. 2. Convert the alcohol group (C9-OH) of hydroxytricosane into the corresponding 9-tricosyl tosylate by reacting it with toluenesulfonyl chloride (TsCl) in the presence of a weak base. 3. Treat the 9-tricosyl tosylate with sodium amalgam (Na/Hg) in a reductive elimination reaction to generate the alkene (Z)-9-tricosene, which is the desired final product. In conclusion, we have outlined a possible synthetic route to obtain the target molecule, (Z)-9-tricosene, using acetylene and haloalkanes as the sources of carbon atoms. The main steps include the construction of the carbon skeleton using a halogen-dance reaction, followed by functional group transformation to achieve the desired chemical structure.

Key concepts

Alkene Chemistry

Alkenes are hydrocarbons that contain at least one carbon-carbon double bond, often called an olefinic bond. This unsaturation introduces reactivity, as these double bonds can participate in a wide range of chemical reactions. In the context of synthesizing (Z)-9-tricosene, the alkene of interest is characterized by the presence of its double bond in the (Z)-configuration at carbon 9. This configuration is important because it determines the molecule's three-dimensional shape and biological activity.

• The (Z)-configuration, also known as cis, has both substituents on the same side of the double bond.
• Alkenes can be synthesized or modified through reactions like halogenation, hydrogenation, and metathesis.

Understanding the nuances of alkene chemistry allows chemists to manipulate these structures in order to design compounds with specific desired properties. Indeed, the synthesis of complex targets like (Z)-9-tricosene relies heavily on these principles.

Haloalkanes

Haloalkanes, also referred to as alkyl halides, are vital intermediates in organic synthesis. These compounds consist of alkanes with one or more halogen atoms (such as chlorine, bromine, or iodine) replacing hydrogen atoms. They are key players when building larger carbon frameworks, as they participate readily in nucleophilic substitution and elimination reactions.

• In the synthesis of (Z)-9-tricosene, haloalkanes offer a convenient entry point for forming new carbon-carbon bonds.
• These compounds can be converted into longer carbon chain lengths, such as tricosane, through reactions with organometallic reagents.

The use of 1-iodoeicosane in the synthesis of tricosane is a prime example of how haloalkanes are employed to extend carbon chains, enabling the formation of complex molecules with precise structural requirements.

Acetylene Reactions

Acetylene (C₂H₂) is a highly reactive alkyne, making it a valuable precursor in synthetic organic chemistry. Its two carbon atoms offer a straightforward starting point for constructing longer carbon skeletons. In reactions, acetylene can undergo deprotonation to form acetylide anions, which are excellent nucleophiles.

• These anions can react with haloalkanes to form new C-C bonds, effectively elongating the carbon chain.
• In the synthesis of (Z)-9-tricosene, acetylene is first converted into an ethyllithium species.

This species then acts as a nucleophile, attaching to the iodine atom on 1-iodoeicosane and creating a longer carbon chain—tricosane. Through such stepwise reactions, chemists are able to manipulate acetylene to piece together complex molecular structures.

Synthetic Organic Chemistry

Synthetic organic chemistry focuses on the construction of organic compounds via chemical synthesis. It combines knowledge of chemical reactions with creativity to design pathways that efficiently generate target molecules. The synthesis of (Z)-9-tricosene exemplifies these concepts by detailing a multi-step approach involving both well-understood reactions and clever problem-solving.

• Starting from simple building blocks like acetylene and haloalkanes, chemists approach the synthesis in stages.
• Assembling the carbon skeleton is followed by functional group transformations required to achieve the final structure.

This includes creating the desired double bond configurations and tailoring the chain to its biologically active form. By understanding and applying synthetic organic chemistry, chemists can develop innovative methods to produce complex molecules efficiently, meeting both scientific and practical objectives.