Pummerer rearrangement
Encyclopedia
The Pummerer rearrangement is an organic reaction
whereby an alkyl sulfoxide
rearranges
to an α-acyloxy–thioether
in the presence of acetic anhydride
. In this reaction, sulfur
is reduced while adjacent carbon is oxidized.
Several reviews have been published.
The usage of α-acyl sulfoxides and Lewis acid
s, such as TiCl4
and SnCl4, allow the reaction to proceed at lower temperatures (0 °C).
Common activators besides acetic anhydride
are trifluoroacetic anhydride
and trifluoromethanesulfonic anhydride. Common nucleophiles besides acetates are arenes, alkenes, amides, and phenols.
of the sulfoxide
(1 and 2). Compound 3 undergoes elimination to produce the thionium ion 4. Acetate adds to the sulfonium ion to give the final product 5.
Other anhydrides and acyl halides can give similar products. Inorganic acids can also give this reaction.This product can be converted to aldehyde
or ketone
by hydrolysis
.
s forming carbon
-carbon bonds and carbon-heteroatom bonds. For example, thionyl chloride
can be used to generate and trap the sulfonium ion:
Likewise, nucleophiles (such as veratrole can also be used.
this group and not the α-hydrogen atom will eliminate in the intermediate step in a Pummerer fragmentation . This reaction type is demonstrated below with a set of sulfoxides and trifluoroacetic anhydride
(TFAA):
The organic group on the right is the moderately methyl violet
carbocation
with pKR+ = 9.4 leading to a classical Pummerer rearrangement. The reaction on the left is a fragmentation because the leaving group with pKR+ = 23.7 is particularly stable.
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
whereby an alkyl sulfoxide
Sulfoxide
A sulfoxide is a chemical compound containing a sulfinyl functional group attached to two carbon atoms. Sulfoxides can be considered as oxidized sulfides...
rearranges
Rearrangement reaction
A rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. Often a substituent moves from one atom to another atom in the same molecule...
to an α-acyloxy–thioether
Thioether
A thioether is a functional group in organosulfur chemistry with the connectivity C-S-C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors. A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen...
in the presence of acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
. In this reaction, sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
is reduced while adjacent carbon is oxidized.
Several reviews have been published.
The usage of α-acyl sulfoxides and Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
s, such as TiCl4
Titanium tetrachloride
Titanium tetrachloride is the inorganic compound with the formula TiCl4. It is an important intermediate in the production of titanium metal and the pigment titanium dioxide. TiCl4 is an unusual example of a metal halide that is highly volatile...
and SnCl4, allow the reaction to proceed at lower temperatures (0 °C).
Common activators besides acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
are trifluoroacetic anhydride
Trifluoroacetic anhydride
Trifluoroacetic anhydride is the acid anhydride of trifluoroacetic acid. In particular, trifluoroacetic anhydride is the perfluorinated derivative of acetic anhydride. Like many acid anhydrides, it may be used to introduce the corresponding trifluoroacetyl group. The corresponding trifluoroacetyl...
and trifluoromethanesulfonic anhydride. Common nucleophiles besides acetates are arenes, alkenes, amides, and phenols.
Mechanism
The mechanism of the Pummerer rearrangement begins with the acylationAcylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
of the sulfoxide
Sulfoxide
A sulfoxide is a chemical compound containing a sulfinyl functional group attached to two carbon atoms. Sulfoxides can be considered as oxidized sulfides...
(1 and 2). Compound 3 undergoes elimination to produce the thionium ion 4. Acetate adds to the sulfonium ion to give the final product 5.
Other anhydrides and acyl halides can give similar products. Inorganic acids can also give this reaction.This product can be converted to aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
or ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
by hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
.
Variations
The thionium ion can be trapped by both intramolecular and intermolecular nucleophileNucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
s forming carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
-carbon bonds and carbon-heteroatom bonds. For example, thionyl chloride
Thionyl chloride
Thionyl chloride is an inorganic compound with the formula SOCl2. It is a reactive chemical reagent used in chlorination reactions. It is a colorless, distillable liquid at room temperature and pressure that decomposes above 140 °C. Thionyl chloride is sometimes confused with sulfuryl...
can be used to generate and trap the sulfonium ion:
Likewise, nucleophiles (such as veratrole can also be used.
Pummerer fragmentation
When the α-organic residue can form a very good leaving groupLeaving group
In chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters, such as para-toluenesulfonate...
this group and not the α-hydrogen atom will eliminate in the intermediate step in a Pummerer fragmentation . This reaction type is demonstrated below with a set of sulfoxides and trifluoroacetic anhydride
Trifluoroacetic anhydride
Trifluoroacetic anhydride is the acid anhydride of trifluoroacetic acid. In particular, trifluoroacetic anhydride is the perfluorinated derivative of acetic anhydride. Like many acid anhydrides, it may be used to introduce the corresponding trifluoroacetyl group. The corresponding trifluoroacetyl...
(TFAA):
The organic group on the right is the moderately methyl violet
Methyl violet
Methyl violet is a family of organic compounds that are mainly used as dyes. Depending on the amount of attached methyl groups, the color of the dye can be altered. Its main use is as a purple dye for textiles and to give deep violet colors in paint and ink...
carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
with pKR+ = 9.4 leading to a classical Pummerer rearrangement. The reaction on the left is a fragmentation because the leaving group with pKR+ = 23.7 is particularly stable.