Question

Mustard gas or bis-( $\beta$ -chloroethyl) sulfide, ${\left(\mathrm{C}1{\mathrm{CH}}_2{\mathrm{CH}}_2\right)}_2\mathrm{S}$, is an oily liquid that was used extensively as poison gas in World War I. It is a deadly vesicant that causes blindness and numerous other effects. The active agent is actually the cyclic sulfonium salt which reacts with nucleophilic materials in the body. The formation of the cyclic sulfonium salt can be regarded as an internal or intramolecular ${\mathrm{S}}_{\mathrm{N}}2$ displacement reaction. Write out this reaction mechanism. What mechanism does this process suggest for the subsequent reaction of the cyclic sulfonium salt with nucleophilic reagents?

Short answer

The formation of cyclic sulfonium salt from mustard gas is an intramolecular S_N2 displacement reaction with the mechanism: (CH${}_2$CH${}_2$Cl)${}_2$S $\to$ [CH${}_2$CH${}_2$-S-CH${}_2$CH${}_2$]${}^{+}$Cl${}^{-}$. The subsequent reaction with nucleophilic reagents involves the nucleophile attacking the positively charged sulfur atom in the cyclic sulfonium salt, opening the ring structure, and forming CH${}_2$CH${}_2$-S-Nu + CH${}_2$CH${}_2$Cl.

Step-by-step solution

Identify the structure and break up of mustard gas

The structure of mustard gas is given as ${\left(\mathrm{C}1{\mathrm{CH}}_2{\mathrm{CH}}_2\right)}_2\mathrm{S}$. Before writing the reaction mechanism, we need to understand the structure and breakup of mustard gas. The skeletal structure of mustard gas can be simplified as: (CH${}_2$CH${}_2$Cl)${}_2$S Notice the two identical groups on both sides of the sulfur atom: CH${}_2$CH${}_2$Cl.

Intramolecular S_N2 displacement reaction

In an intramolecular S_N2 displacement reaction, one of the nucleophilic CH${}_2$CH${}_2$Cl groups will attack the electrophilic sulfur, forming a cyclic sulfonium salt and displacing the chloride ion. The reaction mechanism can be written as: (CH${}_2$CH${}_2$Cl)${}_2$S $\to$ [CH${}_2$CH${}_2$-S-CH${}_2$CH${}_2$]${}^{+}$Cl${}^{-}$

Suggest a mechanism for the reaction of cyclic sulfonium salt with nucleophilic reagents

Now that we have the cyclic sulfonium salt formed, we can predict the mechanism for its reaction with nucleophilic reagents. The negative charge of the nucleophile will attack the electrophilic, positively charged sulfur atom in the cyclic sulfonium salt. This will cause the sulfur atom to lose its positive charge and to form a bond with the attacking nucleophile, resulting in the opening of the ring structure. Let's call the nucleophilic reagent Nu${}^{-}$. The mechanism for the reaction of the cyclic sulfonium salt with a nucleophilic reagent can be written as: [CH${}_2$CH${}_2$-S-CH${}_2$CH${}_2$]${}^{+}$Cl${}^{-}$ + Nu${}^{-}$ $\to$ CH${}_2$CH${}_2$-S-Nu +$CH$_{2}$CH$_{2}$Cl In summary, the formation of cyclic sulfonium salt from mustard gas is an intramolecular S_N2 displacement reaction. The subsequent reaction with nucleophilic reagents involves the nucleophile attacking the sulfur atom in the cyclic sulfonium salt, resulting in the opening of the ring structure.

Key concepts

Intramolecular SN2 Displacement

In the context of mustard gas chemistry, intramolecular SN2 displacement is a critical step in understanding how this toxic compound behaves. SN2 stands for 'Substitution Nucleophilic Bimolecular,' and it is a fundamental type of reaction in organic chemistry involving a nucleophile and an electrophile. The 'intramolecular' part means that the reaction occurs within a single molecule, rather than between two different molecules.

The process starts when a nucleophilic group within the molecule, such as the -CH₂CH₂ group in mustard gas, attacks an electrophilic center, like the sulfur atom. This results in the displacement of a leaving group, which is typically a halide such as chlorine. During this movement, there is a simultaneous creation and breaking of bonds, leading to the formation of a new compound. The hallmark of this displacement is that it happens in one concerted step, with the bond formation and bond-breaking processes occurring simultaneously. This contrasts with other mechanisms where these processes happen in distinct steps.

To enhance understanding, visualize an elastic band connecting the incoming nucleophile and the leaving group. As the nucleophile pushes in, the leaving group is pushed out, but both actions occur at once. This sort of 'dance' within the molecule is what defines intramolecular SN2 reactions.

Cyclic Sulfonium Salt Formation

Moving into the specifics of the mustard gas reaction mechanism, cyclic sulfonium salt formation signifies a pivotal stage of transformation. A sulfonium salt is a compound featuring a sulfur atom bonded to three organic groups, carrying a positive charge. When mustard gas undergoes the intramolecular SN2 displacement, one of the two -CH₂CH₂Cl side chains attacks the central sulfur atom and kicks out the chloride ion, ultimately forming the sulfonium salt.

Visualizing the 3D Structure

The sulfur atom in this salt is located at the center of a trigonal pyramidal shape. This 3D geometry is key to understanding the reactivity of cyclic sulfonium salts. When it comes to cyclic sulfonium salt formation from mustard gas, it's an internal process where the attacking group and the leaving group are part of the same original molecule, leading to a cycle or ring structure.

The formation of the cyclic sulfonium salt is not just a neat chemical trick; it sets the stage for the substance's biological activity. Once formed, this cyclic salt is primed as a highly reactive intermediate, ready to interact with nucleophiles present in the body, explaining part of the toxic nature of mustard gas.

Nucleophilic Attack

In a nucleophilic attack, which follows the formation of the cyclic sulfonium salt, a nucleophile, a chemical species rich in electrons, approaches and donates a pair of electrons to an electrophile, an electron-deficient species. In biological systems, common nucleophiles include water, proteins, DNA bases or enzyme active sites.

It's essential to show how this interaction is like a chemical 'tug of war.' The nucleophile, with its surplus of electrons, is attracted to the positively charged electrophilic species. When it encounters a suitable target, like the cyclic sulfonium salt from mustard gas, a bond is formed as the nucleophile shares its electrons.

Biological Relevance of Nucleophilic Attack

After the cyclic sulfonium salt is formed from mustard gas, it is susceptible to nucleophilic attack by various biological molecules. These attacks can lead to the breaking of the sulfur cycle and the binding of the toxic substance to crucial biomolecules, which disrupts normal cellular function and causes the detrimental effects of this chemical warfare agent in the body.

Chemical Warfare Agents

Mustard gas belongs to a class of chemicals known as chemical warfare agents, specifically designed or used to harm or kill in conflict situations. Their insidious nature lies not just in their immediate effect, but in the way they interact with biological organisms on a molecular level.

The Impact of Chemical Warfare Agents

Chemical warfare agents like mustard gas are typically very reactive, due to their ability to form intermediate compounds such as cyclic sulfonium salts which act on nucleophiles in the body. Through nucleophilic attack on these intermediates, they can form covalent bonds with biological molecules, leading to cellular and tissue damage.

Mustard gas, in particular, is notorious for causing blisters, eye damage, and respiratory harm, amongst other effects. Due to this high potential for damage, the use of such agents is heavily restricted under international law by treaties such as the Chemical Weapons Convention. The creation, stockpiling, and use of these substances are subject to strict control, reflecting the global consensus on the need to prevent the horrors associated with chemical warfare.