Sulfur Nucleophiles

In organic nomenclature, sulfur groups are known as thiols. A thiol is an organic compound that is derived from H₂S. It contains an alkyl or aryl group covalently linked to a sulfhydryl group, ${-}{\rm{SH}}$, through ${\rm{C{-}S}}$ bonds, with ${\rm{R{-}SH}}$ stoichiometry. Thiols interact with carbonyls in the same manner as alcohols; however, they are more nucleophilic than alcohols because sulfur is less electronegative than oxygen and therefore donates its electrons more readily. The nucleophilic addition of thiols to a carbonyl follows the same acid-catalyzed mechanism as that of alcohols but generates thioacetals instead of acetals.

A thioacetal is the sulfur analog of an acetal, an organic compound characterized by the grouping C(SR)₂, where R is an alkyl and is obtained by heating an aldehyde or a ketone with a thiol. Thioacetals are obtained by heating an aldehyde or a ketone with a thiol. A thioacetal formed from a ketone is called a thioketal. The oxygen of the carbonyl donates its electron pair to the acid catalyst (boron trifluoride or BF₃), thus activating the carbonyl. The nucleophilic thiol then donates its electron pair to the electrophilic carbon of the carbonyl. This donation causes the $\pi$ bond between the carbon and the oxygen to break, which results in the shared electrons moving to the oxygen of the carbonyl. The sulfur is now positively charged and needs to lose a proton to yield the hemithioacetal, which is an intermediate in the formation of a thioacetal.

Protonation of the sulfur of the hemithioacetal forms a good leaving group. The leaving group departs, and the sulfur donates its electron pair to form a $\rm\pi$ bond between the sulfur and the carbon. This new carbonyl-like group is already activated because of the positive charge on the sulfur. Another thiol will attack the electrophilic carbon, causing the $\pi$ bond between the carbon and the sulfur to break, which results in the shared electrons moving back to the sulfur. The sulfur of the attacking thiol is now positively charged and needs to lose a proton to yield the final thioacetal. Because all these reaction steps are reversible, the only way to drive the reaction forward and obtain a thioacetal is to use an excess of thiol. In addition to acyclic thioacetals, cyclic thioacetals can also be formed if a dithiol such as ethanedithiol (HSCH₂CH₂SH) is used. Besides being more nucleophilic than alcohols, thioacetals are also more difficult to convert back to carbonyls than acetals. They can only be removed by dilute aqueous acid or Raney nickel under neutral conditions. Raney nickel is a catalyst for the hydrogenation of organic compounds that consists of an alloy of equal parts nickel and aluminum in the form of a pyrophoric powder or crystals or a suspension in alcohol. However, using Raney nickel to remove the thioacetal will also replace the sulfur atoms with hydrogen atoms. This process essentially converts the original carbonyl group into an alkane group. This reduction process is also known as desulfurization. Desulfurization is the removal of sulfur from sulfur-containing compounds.