The Stevens rearrangement in

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

is an

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, mechanistic organ ...

converting

quaternary ammonium salt In organic chemistry, quaternary ammonium cations, also known as quats, are positively-charged polyatomic ions of the structure , where R is an alkyl group, an aryl group or organyl group. Unlike the ammonium ion () and the primary, secondary, ...

s and sulfonium salts to the corresponding

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

s or

sulfide Sulfide (also sulphide in British English) is an inorganic anion of sulfur with the chemical formula S2− or a compound containing one or more S2− ions. Solutions of sulfide salts are corrosive. ''Sulfide'' also refers to large families o ...

s in presence of a strong base in a

1,2-rearrangement A 1,2-rearrangement or 1,2-migration or 1,2-shift or Frank C. Whitmore, Whitmore 1,2-shift is an organic reaction where a substituent moves from one atom to another atom in a chemical compound. In a 1,2 shift the movement involves two adjacent atom ...

. The reactants can be obtained by

alkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

of the corresponding amines and sulfides. The

substituent In organic chemistry, a substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. The suffix ''-yl'' is used when naming organic compounds that contain a single bond r ...

R next the amine

methylene bridge In chemistry, a methylene bridge is part of a molecule with formula . The carbon atom is connected by single bonds to two other distinct atoms in the rest of the molecule. A methylene bridge is often called a methylene group or simply methylene, ...

is an

electron-withdrawing group An electron-withdrawing group (EWG) is a Functional group, group or atom that has the ability to draw electron density toward itself and away from other adjacent atoms. This electron density transfer is often achieved by resonance or inductive effe ...

. The original 1928 publication by Thomas S. Stevens concerned the reaction of ''1-phenyl-2-(N,N-dimethylamino)ethanone'' with

benzyl bromide Benzyl bromide is an organic compound with the formula . The molecule consists of a benzene ring substituted with a bromomethyl group. It is a colorless liquid with lachrymatory properties. The compound is a reagent for introducing benzyl group ...

to the ammonium salt followed by the rearrangement reaction with

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula . It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly corrosive base (chemistry), ...

in water to the rearranged amine. A 1932 publication described the corresponding sulfur reaction.

Reaction mechanism

The reaction mechanism of the Stevens rearrangement is one of the most controversial reaction mechanisms in organic chemistry. Key in the

reaction mechanism In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical reaction occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage ...

for the Stevens rearrangement (explained for the nitrogen reaction) is the formation of an

ylide An ylide () or ylid () is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both ...

after

deprotonation Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...

of the ammonium salt by a strong base. Deprotonation is aided by electron-withdrawing properties of substituent R. Several reaction modes exist for the actual rearrangement reaction. A

concerted reaction In chemistry, a concerted reaction is a chemical reaction in which all bond breaking and bond making occurs in a single step. Reactive intermediates or other unstable high energy intermediates are not involved. Concerted reaction rates tend not ...

requires an

antarafacial In organic chemistry, antarafacial ( Woodward-Hoffmann symbol a) and suprafacial (s) are two topological concepts in organic chemistry describing the relationship between two simultaneous chemical bond making and/or breaking processes in or around ...

reaction mode but since the migrating group displays

retention of configuration Walden inversion is the inversion of a stereogenic center in a chiral molecule in a chemical reaction. Since a molecule can form two enantiomers around a stereogenic center, the Walden inversion converts the configuration of the molecule from ...

this mechanism is unlikely. In an alternative reaction mechanism the N–C bond of the leaving group is homolytically cleaved to form a di-radical pair (3a). In order to explain the observed retention of configuration, the presence of a solvent cage is invoked. Another possibility is the formation of a cation-anion pair (3b), also in a solvent cage.

Scope

Competing reactions are the Sommelet-Hauser rearrangement and the

Hofmann elimination Hofmann elimination is an elimination reaction of an amine to form alkenes. The least stable alkene (the one with the fewest substituents on the carbons of the double bond), called the Hofmann product, is formed. This tendency, known as the Hofm ...

. In one application a double-Stevens rearrangement expands a

cyclophane In organic chemistry, a cyclophane is a hydrocarbon consisting of an aromatic unit (typically a benzene ring) and a Catenation, chain that forms a bridge (chemical), bridge between two non-adjacent positions of the aromatic ring. More complex der ...

ring.''Macrocycle Ring Expansion by Double Stevens Rearrangement''Keisha K. Ellis-Holder, Brian P. Peppers, Andrei Yu. Kovalevsky, and Steven T. Diver Org. Lett.; 2006; 8(12) pp. 2511–2514; (Letter) The ylide is prepared

in situ is a Latin phrase meaning 'in place' or 'on site', derived from ' ('in') and ' ( ablative of ''situs'', ). The term typically refers to the examination or occurrence of a process within its original context, without relocation. The term is use ...

by reaction of the

diazo In organic chemistry, the diazo group is an organic moiety consisting of two linked nitrogen atoms at the terminal position. Overall charge-neutral organic compounds containing the diazo group bound to a carbon atom are called diazo compounds ...

compound ''ethyl diazomalonate'' with a

catalyzed by dirhodium tetraacetate in

reflux Reflux is a technique involving the condensation of vapors and the return of this condensate to the system from which it originated. It is used in industrial and laboratory distillations. It is also used in chemistry to supply energy to Chemical ...

ing

xylene In organic chemistry, xylene or xylol (; IUPAC name: dimethylbenzene) are any of three organic compounds with the formula . They are derived from the substitution of two hydrogen atoms with methyl groups in a benzene ring; which hydrogens are su ...

. :

Enzymatic reaction

Recently, γ-butyrobetaine hydroxylase, an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that is involved in the human

carnitine biosynthesis Carnitine biosynthesis is a method for the endogenous production of L-carnitine, a molecule that is essential for energy metabolism. In humans and many other animals, L-carnitine is obtained from both diet and by biosynthesis. The carnitine biosynth ...

pathway, was found to

catalyze Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

C-C bond CC, cc, or C-C may refer to: Arts, entertainment, and media Fictional characters * C.C. (''Code Geass''), a character in the ''Code Geass'' anime series, pronounced "C-two" * C.C. Babcock, a character in the American sitcom ''The Nanny'' * Co ...

formation reaction in a fashion analogous to a Stevens type rearrangement. The substrate for the reaction is

meldonium Meldonium (International Nonproprietary Name, INN; trade name Mildronate, among others) is a pharmaceutical developed in 1970 by Ivars Kalviņš at the USSR Latvia Institute of Organic Synthesis. It is now manufactured by the Latvian pharma ...

References

{{DEFAULTSORT:Stevens Rearrangement Rearrangement reactions Name reactions

Reaction mechanism

Scope

Enzymatic reaction

See also

References