Difficulty: Intermediate | Prerequisites: Ethers (Part 1 of Ch. 16), SN2 mechanism, basic understanding of oxidation states.
Sulfides are the sulfur analogues of ethers: replace the oxygen in R–O–R’ with sulfur and you get R–S–R’. This section is shorter than the ether and epoxide material, but it introduces two ideas that come up repeatedly in later courses and in biochemistry: sulfur’s greater polarisability (which lets it form sulfonium salts, R3S+) and sulfur’s ability to expand its oxidation state (giving sulfoxides and sulfones). If you understand ethers and SN2, sulfides will feel familiar, with a few twists.
Sulfides (R–S–R’) are made by SN2 reaction of a thiolate (RS⁻) with an alkyl halide. Because sulfur is larger and more polarisable than oxygen, it readily forms trialkylsulfonium salts (R3S+), which are good alkylating agents. Sulfides can also be oxidised stepwise to sulfoxides and then sulfones, which increases the acidity of adjacent C–H bonds.
Sulfide (thioether)
The sulfur analogue of an ether: R–S–R’. Think of it as an ether where the oxygen has been swapped for sulfur.
Thiolate (RS⁻)
The conjugate base of a thiol (R–SH), formed by deprotonation. Thiolates are excellent nucleophiles, more so than the corresponding alkoxides, because sulfur is larger and more polarisable.
Sulfonium salt (R3S+)
A positively charged sulfur species bearing three organic groups. Formed when a sulfide reacts with an additional alkyl halide. In simple terms, sulfur can carry a third substituent (and a positive charge) in a way that oxygen does much less readily.
Sulfoxide
The product of one-electron oxidation of a sulfide: R–S(=O)–R’. The sulfur bears one oxygen and retains a lone pair, making the molecule chiral when the two R groups differ.
Sulfone
The product of further oxidation: R–S(=O)2–R’. Sulfur now bears two oxygens. Sulfones are strongly electron-withdrawing and increase the acidity of nearby C–H bonds.
Acidity of adjacent C–H bonds
The trend: CH3 attached to a sulfone is more acidic than CH3 on a sulfoxide, which is more acidic than CH3 on a sulfide. Each additional oxygen withdraws more electron density from the C–H bond.
Thiolates (RS⁻) are strong nucleophiles. React a thiolate with a primary or methyl alkyl halide (SN2) to form the sulfide.
RS⁻ + R’–I → R–S–R’ + I⁻
This is directly analogous to the Williamson ether synthesis, but thiolates are more nucleophilic than alkoxides, so the reaction is typically faster and higher-yielding.
Sulfur’s greater polarisability (compared to oxygen) means a sulfide can react with yet another alkyl halide to form a trialkylsulfonium salt.
Example: dimethyl sulfide (CH3–S–CH3) + CH3I gives trimethylsulfonium iodide [(CH3)3S+ I⁻].
Sulfonium salts are potent alkylating agents. They can transfer a methyl group to a nucleophile (e.g. an alcohol), regenerating the sulfide.
Biological relevance: S-adenosylmethionine (SAM) is nature’s sulfonium-based methyl donor in countless biochemical methylation reactions.
Sulfides can be oxidised in a stepwise fashion:
Sulfide → sulfoxide (one oxygen on sulfur)
Sulfoxide → sulfone (two oxygens on sulfur)
Common oxidants include H2O2 (one equivalent for sulfoxide) and further oxidation or a stronger oxidant for the sulfone.
The acidity of a C–H bond adjacent to sulfur increases with the oxidation state of sulfur:
CH3 on a sulfone > CH3 on a sulfoxide > CH3 on a sulfide
Each oxygen added to sulfur withdraws electron density, stabilising the conjugate base formed when that C–H is removed.
This trend matters for reactions that require deprotonation at carbon (carbanion chemistry, which you will encounter later).
Students often assume sulfides behave identically to ethers. Sulfur is larger, more polarisable, and a better nucleophile than oxygen, so sulfides can do things ethers cannot (form sulfonium salts, be oxidised to sulfoxides/sulfones).
A common error is thinking sulfonium salts are unreactive. They are excellent electrophiles and can transfer alkyl groups to nucleophiles.
Students sometimes forget that sulfoxides are chiral when the two R groups differ. The lone pair, the oxygen, and the two R groups create four different substituents around sulfur.
⚠️ Know the sulfide synthesis (thiolate + alkyl halide, SN2). It is a straightforward analogy to the Williamson synthesis and is commonly tested alongside it.
⚠️ The sulfonium salt as an alkylating agent appears in questions bridging to biochemistry (SAM and biological methylation).
⚠️ The acidity trend (sulfone > sulfoxide > sulfide) for adjacent C–H bonds is a conceptual question that tests your understanding of electron-withdrawing effects and conjugate-base stabilisation.
⚠️ Being able to assign oxidation states to sulfur (sulfide = no extra O, sulfoxide = one O, sulfone = two O) is quick marks on naming and identification questions.
True or false: Thiolates are weaker nucleophiles than alkoxides. False. Thiolates are stronger nucleophiles because sulfur is larger and more polarisable.
Fill in the blank: A sulfide can react with an additional alkyl halide to form a ______ salt. Sulfonium salt (R3S+).
True or false: A sulfoxide has two oxygens bonded to sulfur. False. A sulfoxide has one oxygen. A sulfone has two.
Fill in the blank: The acidity of an adjacent C–H bond follows the order sulfone > ______ > sulfide. Sulfoxide.
True or false: Sulfonium salts are poor leaving groups. False. Sulfonium salts are good leaving groups and effective alkylating agents.
Q: Show how you would synthesise methyl phenyl sulfide from thiophenol (PhSH) and an alkyl halide.
A: Deprotonate thiophenol with a base (e.g. NaOH or NaH) to form the thiolate PhS⁻. Then react it with CH3I via SN2 to give PhSCH3 + I⁻.
Q: Explain why dimethyl sulfide can form a trimethylsulfonium salt but dimethyl ether does not readily form a trimethyloxonium salt under the same conditions.
A: Sulfur is larger and more polarisable than oxygen, so it is a better nucleophile. The larger atomic radius also accommodates a third substituent with less steric strain. Oxygen, being smaller and less nucleophilic, does not undergo this alkylation as readily.
Q: Rank the following in order of increasing C–H acidity adjacent to sulfur: methyl phenyl sulfone, methyl phenyl sulfide, methyl phenyl sulfoxide.
A: Sulfide < sulfoxide < sulfone. Each additional oxygen on sulfur withdraws more electron density, stabilising the conjugate base.
Q: Draw the product when methyl phenyl sulfide is treated with one equivalent of H2O2.
A: Methyl phenyl sulfoxide (PhS(=O)CH3). One oxygen is added to sulfur.
Sulfide synthesis reinforces SN2 from your substitution chapter and parallels the Williamson ether synthesis from earlier in this chapter. Sulfonium salts connect forward to biochemistry (S-adenosylmethionine and biological methylation). The acidity trend introduced here (sulfone > sulfoxide > sulfide for adjacent C–H) foreshadows carbanion chemistry and stabilised enolates you will study in later chapters on carbonyl reactions.
Sulfide, thioether, thiol, thiolate, RS⁻, SN2, sulfonium salt, R3S+, trimethylsulfonium, S-adenosylmethionine, SAM, biological methylation, sulfoxide, sulfone, oxidation of sulfur, H2O2 oxidation, polarisability, nucleophilicity of sulfur vs oxygen, C–H acidity adjacent to sulfur, methyl phenyl sulfide, DMSO, dimethyl sulfoxide.