The Dowd–Beckwith ring-expansion reaction 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, photochemical rea ...
in which a cyclic β-
keto ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
is expanded by up to 4 carbons in a
free radical
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Metabo ...
ring expansion reaction through an α-alkylhalo
substituent
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and '' functional group'', as well as '' ...
. The radical initiator system is based on
AIBN and
tributyltin hydride
Tributyltin hydride is an organotin compound with the formula (C4H9)3SnH. It is a colorless liquid that is soluble in organic solvents. The compound is used as a source of hydrogen atoms in organic synthesis.
Synthesis and characterization
The ...
.
The cyclic β-
keto ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
can be obtained through a
Dieckmann condensation. The original reaction consisted of a
nucleophilic aliphatic substitution
In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...
of the
enolate
In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl () compounds. Rarely isolated, they are widely used as reagents in the synthesis of organic compounds.
Bonding and structure
Enolate anions are electr ...
of ethyl cyclohexanone-2-carboxylate with 1,4-diiodobutane and
sodium hydride
Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in ...
followed by ring expansion to ethyl cyclodecanone-6-carboxylate. A side-reaction is
organic reduction
Organic reductions or organic oxidations or organic redox reactions are redox reactions that take place with organic compounds. In organic chemistry oxidations and reductions are different from ordinary redox reactions, because many reactions car ...
of the iodoalkane.
center, Dowd–Beckwith Ring Expansion.gif
Reaction mechanism
The
reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.
A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage o ...
involves a bicyclic intermediate. The reaction is initiated by thermal decomposition of
AIBN. The resulting
radicals
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abstract hydrogen from
tributyltin hydride
Tributyltin hydride is an organotin compound with the formula (C4H9)3SnH. It is a colorless liquid that is soluble in organic solvents. The compound is used as a source of hydrogen atoms in organic synthesis.
Synthesis and characterization
The ...
to a tributyltin radical which in turn abstracts the
halogen atom to form an
alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloal ...
radical. This radical attacks the
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containin ...
group to an intermediate
bicyclic
In chemistry, a bicyclic molecule () is a molecule that features two joined rings. Bicyclic structures occur widely, for example in many biologically important molecules like α-thujene and camphor. A bicyclic compound can be carbocyclic (a ...
ketyl
A ketyl group in organic chemistry is an anion radical that contains a group R2C−O•. It is the product of the 1-electron reduction of a ketone.
Another mesomeric structure has the radical position on carbon and the negative charge on oxyg ...
. This intermediate then
rearranges with ring expansion to a new carbon radical species which recombines with a proton radical from tributyltin hydride propagating the
catalytic cycle
In chemistry, a catalytic cycle is a multistep reaction mechanism that involves a catalyst. The catalytic cycle is the main method for describing the role of catalysts in biochemistry, organometallic chemistry, bioinorganic chemistry, material ...
.
Scope
A side reaction accompanying this ring expansion is
organic reduction
Organic reductions or organic oxidations or organic redox reactions are redox reactions that take place with organic compounds. In organic chemistry oxidations and reductions are different from ordinary redox reactions, because many reactions car ...
of the halo alkane to a saturated alkyl group. One study shows that the success depends critically on the accessibility of the carbonyl group.
Deuterium
Deuterium (or hydrogen-2, symbol or deuterium, also known as heavy hydrogen) is one of two Stable isotope ratio, stable isotopes of hydrogen (the other being Hydrogen atom, protium, or hydrogen-1). The atomic nucleus, nucleus of a deuterium ato ...
experiments also show the presence of a 1,5 hydride shift. The reaction of the alkyl radical with the ester carbonyl group is also a possibility but has an unfavorable
activation energy
In chemistry and physics, activation energy is the minimum amount of energy that must be provided for compounds to result in a chemical reaction. The activation energy (''E''a) of a reaction is measured in joules per mole (J/mol), kilojoules p ...
.
References
* ''A new tributyltin hydride-based rearrangement of bromomethyl .beta.-keto esters. A synthetically useful ring expansion to .gamma.-keto esters'' Paul Dowd, Soo Chang Choi;
J. Am. Chem. Soc.; 1987; 109(11); 3493–3494
Abstract* ''Free radical ring expansion by three and four carbons'' Paul Dowd, Soo Chang Choi;
J. Am. Chem. Soc.; 1987; 109(21); 6548–6549
Abstract* ''Rearrangement of suitably constituted aryl, alkyl, or vinyl radicals by acyl or cyano group migration'' Athelstan L. J. Beckwith, D. M. O'Shea, Steven W. Westwood;
J. Am. Chem. Soc.; 1988; 110(8); 2565–2575
Abstract* ''Three-Carbon Dowd–Beckwith Ring Expansion Reaction versus Intramolecular 1,5-Hydrogen Transfer Reaction: A Theoretical Study'' Diego Ardura and Tomás L. Sordo
J. Org. Chem.; 2005; 70(23) pp. 9417–9423; (Article)
Abstract
{{DEFAULTSORT:Dowd-Beckwith ring-expansion reaction
Rearrangement reactions
Name reactions