The Dowd–Beckwith ring-expansion reaction is an organic reaction 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 a ...

is expanded by up to 4 carbons in a

free radical A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing. Ageing Ailments of unknown cause Biogerontology Biological processes Causes of death Cellular processes Gerontology Life extension Metabo ...

ring expansion reaction Ring expansion and ring contraction reactions in the course of organic synthesis refer to a set of reactions which can lead to the expansion or contraction of an existing Ring (chemistry), ring. This often makes it possible to access structures ...

through an α-alkylhalo substituent. 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 c ...

. The cyclic β- keto

can be obtained through a

Dieckmann condensation The Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β-keto esters. It is named after the German chemist Walter Dieckmann (1869–1925). The equivalent intermolecular reaction is the Claisen condensat ...

. 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). Th ...

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 co ...

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 involves a bicyclic intermediate. The reaction is initiated by thermal decomposition of AIBN. The resulting radicals abstract hydrogen from

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 cycloa ...

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 containi ...

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 (all ...

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 oxyge ...

. 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, materials s ...

Scope

A side reaction accompanying this ring expansion is

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 isotopes of hydrogen (the other being protium, or hydrogen-1). The nucleus of a deuterium atom, called a deuteron, contains one proton and one ...

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. The ''Journal of the American Chemical Society'' is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the ''Journal of Analytic ...

; 1987; 109(11); 3493–3494
Abstract
* ''Free radical ring expansion by three and four carbons'' Paul Dowd, Soo Chang Choi;

; 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;

; 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. ''The Journal of Organic Chemistry'', colloquially known as ''JOC'', is a peer-reviewed scientific journal for original contributions of fundamental research in all branches of theory and practice in organic and bioorganic chemistry. It is publ ...

; 2005; 70(23) pp. 9417–9423; (Article)
Abstract
{{DEFAULTSORT:Dowd-Beckwith ring-expansion reaction Rearrangement reactions Name reactions