Sulfoxide
Table of Contents
A sulfoxide, also spelled as sulphoxide, is an organosulfur compound characterized by a sulfur atom doubly bonded to an oxygen atom and singly bonded to two carbon atoms. Its general formula is R–S(=O)–R′, where R and R′ denote alkyl or aryl groups [1–4].
Sulfoxides serve as important intermediates in organic chemistry because they participate in a variety of oxidation–reduction, and substitution reactions. Among them, dimethyl sulfoxide (DMSO, (CH3)2SO) is the most notable example. DMSO is distinguished by its exceptional ability to dissolve both polar and nonpolar substances, making it a widely used solvent in chemical synthesis, pharmaceuticals, and biological research.
Structure and Bonding
The most distinctive feature of sulfoxides is their highly polar S=O bond, which carries a partial negative charge on the oxygen atom and a corresponding partial positive charge on the sulfur atom. This polarity arises from the significant difference in electronegativity (χ) between sulfur (χ = 2.58) and oxygen (χ = 3.44). [4]
The oxygen and sulfur atoms in a sulfoxide do not form a typical π bond through p-orbital overlap, as such a bond would make the molecule planar. Instead, one of the oxygen’s lone pairs interacts with an empty orbital on the sulfur atom, imparting partial double-bond character to the S=O linkage. This interaction is sometimes described as a d–π or n→σ* interaction. [10]
The sulfur atom adopts a pyramidal geometry, close to sp3 hybridization, with one of its four regions of electron density corresponding to a lone pair. As a result, the bond angles are slightly smaller than the ideal tetrahedral value of 109.5°. For example, in dimethyl sulfoxide (DMSO), the observed C–S–C bond angle is about 98°, indicating a nearly tetrahedral but slightly compressed structure.
Example [5,6]
| Name | Chemical Formula | Physical Properties | Uses |
|---|---|---|---|
| Dimethyl sulfoxide (DMSO) | (CH3)2SO | Colorless, hygroscopic liquid; m.p. ≈ 18 °C; b.p. ≈ 189 °C; highly polar and miscible with water | Used as a solvent, cryoprotectant, and in medicine for its anti-inflammatory properties |
| Methyl phenyl sulfoxide | C6H5SOCH3 | Colorless solid or oily liquid; m.p. ≈ 31 °C; b.p. ≈ 263.5 °C; slightly soluble in water but soluble in organic solvents | Employed in laboratory research and as an intermediate in the synthesis of other sulfur compounds |
Preparation [7,8]
1. Oxidation of Sulfides
The most common method for synthesizing sulfoxides is the oxidation of sulfides:
R2S + [O] → R2SO
In this reaction, the sulfur atom is partially oxidized from an oxidation state of –2 to +4 without breaking the carbon–sulfur bonds. Mild oxidizing agents such as hydrogen peroxide (H2O2) or sodium periodate (NaIO4) are typically used. Strict control of reaction conditions ensures that oxidation stops at the sulfoxide stage and does not proceed to the fully oxidized sulfone (R2SO2).
For example:
(CH3)2S + H2O2 → (CH3)2SO + H2O
Here, dimethyl sulfide is oxidized to yield dimethyl sulfoxide (DMSO).
2. Friedel–Crafts Arylations of Sulfur Dioxide
Sulfoxides, especially diaryl sulfoxides, can also be synthesized via two successive Friedel–Crafts arylations of sulfur dioxide (SO2) in the presence of an acid catalyst:
2 ArH + SO2 → Ar2SO + H2O
In this reaction, two aryl groups (Ar) are introduced onto the sulfur atom of SO2, forming a diaryl sulfoxide along with water as a by-product.
3. Reaction of Arenes with Thionyl Chloride
Another route involves reacting arenes with thionyl chloride (SOCl2) in the presence of Lewis acid catalysts such as lithium perchlorate (LiClO4) or sodium perchlorate (NaClO4). These catalysts facilitate electrophilic substitution, promoting the formation of carbon–sulfur bonds in the product.
For example, diphenyl sulfoxide can be synthesized as follows:
2 C6H6 + SOCl2 → (C6H5)2SO + 2 HCl (in presence of LiClO4)
Reactions [9]
1. Oxidation to Sulfone
Sulfoxides undergo further oxidation to sulfones (R2SO2), with sulfur reaching a +6 oxidation state:
R2SO + [O] → R2SO2
Oxidizing agents such as hydrogen peroxide or organic peroxides are commonly used. For instance:
(CH3)2SO + H2O2 → (CH3)2SO2 + H2O
This reaction converts dimethyl sulfoxide (DMSO) to dimethyl sulfone (DMSO2).
2. Reduction to Sulfide
Sulfoxides can be reduced back to sulfides (R2S), reversing their oxidation. This process converts sulfur from the +4 to the -2 oxidation state:
R2SO + [H] → R2S + H2O
Metal hydrides such as lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) are typical reducing agents.
Example:
(CH3)2SO + LiAlH4 → (CH3)2S + H2O
Here, DMSO is reduced to dimethyl sulfide.
3. Acid-Base Reactions
Sulfoxides contain slightly acidic hydrogen atoms on the carbon adjacent to the S=O group, that is, the α-carbon. The strong polarity of the S=O bond increases the acidity of these α-hydrogens, allowing deprotonation by strong bases.
For example:
CH3S(O)CH3 + NaH → CH3S(O)CH2Na + H2
In this reaction, sodium hydride (NaH) removes an α-hydrogen from DMSO, forming a sodium sulfoxide salt and releasing hydrogen gas.
Sulfoxides are crucial to modern chemistry due to their versatility and reactivity. Their unique polarity and stability make them essential in synthesis, catalysis, and pharmaceutical applications, ensuring their continued importance in advancing sustainable and innovative chemical research.
