The
Dowd-Beckwith Ring Expansion Reaction is an
organic reactionOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
in which a cyclic β-
ketoIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
is expanded by up to 4 carbons in a
free radicalIn chemistry, radicals are atoms, molecules, or ions with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions...
ring expansion reactionA ring expansion reaction is a type of organic reaction in which usually a hydrocarbon ring is expanded. Examples of ring expansions are:* the Beckmann rearrangement* the Dowd-Beckwith ring expansion reaction.* the Tiffeneau-Demjanov rearrangement...
through an α-alkylhalo
substituentIn organic chemistry and biochemistry, a substituent is an atom or group of atoms substituted in place of a hydrogen atom on the parent chain of a hydrocarbon...
. The radical initiator system is based on
AIBNAIBN can refer to:* Ain't It Bale News* Azobisisobutyronitrile* Norwegian Accident Investigation Board...
and
tributyltin hydrideTributyltin hydride is an organotin compound. It is a useful reagent in organic synthesis. Combined with azobisisobutyronitrile or by irradiation with light, tributyltin hydride cleaves to form the tributyltin radical , which reacts with substrate by substitution of a halogen atom for a hydrogen...
. The cyclic β-
ketoIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
can be obtained through a
Dieckmann condensationThe Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β-ketoesters. It is named after the German chemist Walter Dieckmann . The equivalent intermolecular reaction is the Claisen condensation....
. The original reaction consisted of a nucleophilic aliphatic substitution of the enolate of ethyl cyclohexanone-2-carboxylate with 1,4-diiodobutane and
sodium hydrideSodium hydride is the chemical compound with the formula NaH. It is primarily used as a strong base in organic synthesis. NaH is representative of the saline hydrides, meaning it is a salt-like hydride, composed of Na+ and H− ions, in contrast to the more molecular hydrides...
followed by ring expansion to ethyl cyclodecanone-6-carboxylate.
The
Dowd-Beckwith Ring Expansion Reaction is an
organic reactionOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
in which a cyclic β-
ketoIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
is expanded by up to 4 carbons in a
free radicalIn chemistry, radicals are atoms, molecules, or ions with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions...
ring expansion reactionA ring expansion reaction is a type of organic reaction in which usually a hydrocarbon ring is expanded. Examples of ring expansions are:* the Beckmann rearrangement* the Dowd-Beckwith ring expansion reaction.* the Tiffeneau-Demjanov rearrangement...
through an α-alkylhalo
substituentIn organic chemistry and biochemistry, a substituent is an atom or group of atoms substituted in place of a hydrogen atom on the parent chain of a hydrocarbon...
. The radical initiator system is based on
AIBNAIBN can refer to:* Ain't It Bale News* Azobisisobutyronitrile* Norwegian Accident Investigation Board...
and
tributyltin hydrideTributyltin hydride is an organotin compound. It is a useful reagent in organic synthesis. Combined with azobisisobutyronitrile or by irradiation with light, tributyltin hydride cleaves to form the tributyltin radical , which reacts with substrate by substitution of a halogen atom for a hydrogen...
. The cyclic β-
ketoIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
can be obtained through a
Dieckmann condensationThe Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β-ketoesters. It is named after the German chemist Walter Dieckmann . The equivalent intermolecular reaction is the Claisen condensation....
. The original reaction consisted of a nucleophilic aliphatic substitution of the enolate of ethyl cyclohexanone-2-carboxylate with 1,4-diiodobutane and
sodium hydrideSodium hydride is the chemical compound with the formula NaH. It is primarily used as a strong base in organic synthesis. NaH is representative of the saline hydrides, meaning it is a salt-like hydride, composed of Na+ and H− ions, in contrast to the more molecular hydrides...
followed by ring expansion to ethyl cyclodecanone-6-carboxylate. A side-reaction is organic reduction of the iodoalkane.
center
Reaction mechanism
The
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
involves a bicyclic intermediate. The reaction is initiated by thermal decomposition of
AIBNAIBN can refer to:* Ain't It Bale News* Azobisisobutyronitrile* Norwegian Accident Investigation Board...
. The resulting
radicalsIn chemistry, radicals are atoms, molecules, or ions with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions...
abstract hydrogen from
tributyltin hydrideTributyltin hydride is an organotin compound. It is a useful reagent in organic synthesis. Combined with azobisisobutyronitrile or by irradiation with light, tributyltin hydride cleaves to form the tributyltin radical , which reacts with substrate by substitution of a halogen atom for a hydrogen...
to a tributyltin radical which in turn abstracts the
halogenThe halogens or halogen elements are a series of nonmetal elements from Group 17 IUPAC Style of the periodic table, comprising fluorine, ; chlorine, ; bromine, ; iodine, ; and astatine,...
atom to form an
alkylIn chemistry, an alkyl group is a hydrocarbon; typically an alkyl is a part of a larger molecule. The term is usually used loosely; there is no general formula for an alkyl group. In structural formulae, an alkyl group is represented with an R. Usually, alkyl groups resemble hydrocarbons, but...
radical. This radical attacks the
carbonylIn organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex In organic chemistry, a carbonyl group is a functional group...
group to an intermediate bicyclic
ketylA ketyl group in organic chemistry is an anion radical with the general structure C-O. in which an oxygen radical is bonded directly to carbon. This radical is very unstable and appears in chemical reactions as a reactive intermediate...
. This intermediate then
rearrangesA 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...
with ring expansion to a new carbon radical species which recombines with a proton radical from tributyltin hydride propagating the
catalytic cycleA catalytic cycle in chemistry is a term for 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, materials science, etc. Often such cycles show the conversion of a...
.
Scope
A side reaction accompanying this ring expansion is organic reduction of the halo alkane to a saturated alkyl group. One study shows that the success depends critically on the accessibility of the carbonyl group.
DeuteriumDeuterium, also called heavy hydrogen, is a stable isotope of hydrogen with a natural abundance in the oceans of Earth of approximately one atom in of hydrogen...
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 posiibility but has an unfavorable
activation energyIn chemistry, activation energy is a term introduced in 1889 by the Swedish scientist Svante Arrhenius, that is defined as the energy that must be overcome in order for a chemical reaction to occur. Arrhenius' research was a follow up of the theories of reaction rate by Serbian physicist Nebojsa...
.