The
Brook rearrangement in
organic chemistryOrganic chemistry is a discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation of chemical compounds that contain carbon...
is a
rearrangement reactionA 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...
in which a organosilyl group switches position with a
hydroxylIn chemistry, hydroxyl is composed of molecules consisting of an oxygen atom and a hydrogen atom connected by a covalent bond . The neutral form is a hydroxyl radical. The hydroxyl anion is called hydroxide; it is a diatomic ion with a charge of negative one...
proton over a carbon to oxygen
covalent bondA covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms, or between atoms and other covalent bonds...
under the influence of a
baseIn chemistry, a base is most commonly thought of as an aqueous substance that can accept hydrogen ions. Bases are also the oxides or hydroxides of metals. A soluble base is also often referred to as an alkali if hydroxide ions are involved. This refers to the Brønsted-Lowry theory of acids and bases...
. It is named for the Canadian chemist Adrian Gibbs Brook (b. 1924). The reaction product is a
silyl etherSilyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group. The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. Silyl ethers are usually used as protecting...
.
The silyl substituents can be aliphatic (methyl) or aromatic (phenyl) and the alcohol is secondary or tertiary with aliphatic or aryl groups.
The
Brook rearrangement in
organic chemistryOrganic chemistry is a discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation of chemical compounds that contain carbon...
is a
rearrangement reactionA 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...
in which a organosilyl group switches position with a
hydroxylIn chemistry, hydroxyl is composed of molecules consisting of an oxygen atom and a hydrogen atom connected by a covalent bond . The neutral form is a hydroxyl radical. The hydroxyl anion is called hydroxide; it is a diatomic ion with a charge of negative one...
proton over a carbon to oxygen
covalent bondA covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms, or between atoms and other covalent bonds...
under the influence of a
baseIn chemistry, a base is most commonly thought of as an aqueous substance that can accept hydrogen ions. Bases are also the oxides or hydroxides of metals. A soluble base is also often referred to as an alkali if hydroxide ions are involved. This refers to the Brønsted-Lowry theory of acids and bases...
. It is named for the Canadian chemist Adrian Gibbs Brook (b. 1924). The reaction product is a
silyl etherSilyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group. The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. Silyl ethers are usually used as protecting...
.
The silyl substituents can be aliphatic (methyl) or aromatic (phenyl) and the alcohol is secondary or tertiary with aliphatic or aryl groups. The base is an
amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
,
sodium hydroxideSodium hydroxide , also known as lye and caustic soda, is a caustic metallic base. It is used in many industries, mostly as a strong chemical base in the manufacture of pulp and paper, textiles, drinking water, soaps and detergents and as a drain cleaner. Worldwide production in 1998 was around...
, an organolithium reagent or an
alkali metalThe alkali metals are a series of chemical elements forming Group 1 of the periodic table: lithium , sodium , potassium , rubidium , caesium , and francium ....
alloyAn alloy is a partial or complete solid solution of one or more elements in a metallic matrix. Complete solid solution alloys give single solid phase microstructure, while partial solutions give two or more phases that may be homogeneous in distribution depending on thermal history...
such as Na/K. When the reactant is a silylmethanol the reaction is a 1,2-brook rearrangement but rearrangements over larger carbon skeletons are also possible.
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...
for this rearrangement starts with proton abstraction of the
hydroxylIn chemistry, hydroxyl is composed of molecules consisting of an oxygen atom and a hydrogen atom connected by a covalent bond . The neutral form is a hydroxyl radical. The hydroxyl anion is called hydroxide; it is a diatomic ion with a charge of negative one...
group by base to the
alkoxideAn alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They can be written as RO–, where R is the organic substituent. Alkoxides are strong bases and, when R is not bulky, good nucleophiles and good...
anion. This
nucleophileIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
attacks the silicon atom in a nucleophilic displacement with the methylene group as the
leaving groupIn 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,...
. The proposed
transition stateThe transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate...
for this reaction step is a three-membered ring with the degree of Si-O bond making in step with the Si-C bond breaking process. The additional electron pair is now transferred from oxygen to a
carbanionA carbanion is an anion in which carbon has an unshared pair of electrons and bears a negative charge usually with three substituents for a total of eight valence electrons . The carbanion exists in a trigonal pyramidal geometry. Formally a carbanion is the conjugate base of a carbon acid.where B...
which quickly abstracts a proton from a proton source such as solvent to form the final
silyl etherSilyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group. The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. Silyl ethers are usually used as protecting...
.
When the reactant is (triphenylsilyl)methylphenylmethanol the
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...
is found to be relatively low but that the entropy of activation has a large negative value which supports the cyclic transition state structure. The
HammettThe Hammett equation in organic chemistry describes a linear free-energy relationship relating reaction rates and equilibrium constants for many reactions involving benzoic acid derivatives with meta- and para-substituents to each other with just two parameters: a substituent constant and a...
results for a group of
para-substitutedArene substitution patterns are part of organic chemistry IUPAC nomenclature and pinpoint the position of substituents other than hydrogen in relation to each other on an aromatic hydrocarbon.- Ortho, meta, and para substitution :...
phenyl methanols conform that electron withdrawing groups help to stabilize the negative charge built up in the carbanionic intermediate.
The thermodynamic driving force for this reaction is the formation of a silicon oxygen bond. The cleavage of the Si-C bond and O-H bond costs in terms of
bond dissociation energyIn chemistry, bond dissociation energy, D0 or BDE, is one measure of the bond strength in a chemical bond. It is defined as the standard enthalpy change when a bond is cleaved by homolysis, with reactants and products of the homolysis reaction at 0 K...
are 451 + 427 = 878
kJThe joule , named for James Prescott Joule, is the derived unit of energy in the International System of Units. It is the energy exerted by a force of one newton acting to move an object through a distance of one metre...
/
molThe mole is a unit of amount of substance: it is an SI base unit, and one of the few units used to measure this physical quantity. The name "mole" was coined in German by Wilhelm Ostwald in 1893, although the related concept of equivalent mass had been in use at least a century earlier...
and the gains are 809 (Si-O) + 338 (C-H) = 1147 kJ/mol.
The Brook rearrangement occurs with retention of configuration as demonstrated in a Walden cycle:
The (+)-
silyl hydrideSilicon hydrides are chemical compounds which contain a silicon-hydrogen bond. The silicon to hydrogen bond is longer than the C–H bond and weaker . Hydrogen is more electronegative than silicon hence the naming convention of silyl hydrides. The parent compound SiH
4 is called silane,...
enantiomerIn stereochemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are "non-superposable" , much as one's left and right hands are "the same" but opposite....
reacts with
chlorineChlorine Chlorine Chlorine ( , from the Greek word 'χλωρóς' (khlôros, meaning 'pale green'), is the chemical element with atomic number 17 and symbol Cl. It is a halogen, found in the periodic table in group 17 (formerly VII, VIIa, or VIIb). As the chloride ion, which is part of common salt and...
to the corresponding silyl chloride with retention of the stereocenter. The subsequent nucleophilic displacement of chlorine with diphenylmethyl lithium occurs with inversion. The next two steps convert the diphenylmethine group through bromination with
NBSNBS can stand for:*The National Broadcasting Society, Alpha Epsilon Rho is the National Honor Society for Electronic Media Students in the United States of America.*N-Bromosuccinimide, a chemical reagent...
(or N-bromosuccinimide) and
hydrolysisHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
with
silver acetateSilver acetate is a photosensitive, white crystalline substance commonly used as a pesticide. It also produces a repulsive taste when combined with cigarette smoke, so it is used in chewing gum and lozenges to aid the cessation of smoking....
into a diphenylmethanol group without any change in configuration. The subsequent Brook rearrangement to the silyl ether and reduction with
lithium aluminium hydrideLithium aluminium hydride , commonly abbreviated to LAH, is a reducing agent used in organic synthesis. It is more powerful than the related reagent sodium borohydride due to the weaker Al-H bond compared to the B-H bond...
occur with retention so that the final reaction product is the opposite enantiomer of the starting material with opposite sign for
specific rotationThe specific rotation of a chemical compound [α] is defined as the observed angle of optical rotation α when plane-polarized light is passed through a sample with a path length of 1 decimeter and a sample concentration of 1 gram per 1 millilitre. The specific rotation of a pure material is an...
.
Scope
Brook rearrangements are known in
acylsilaneAcylsilanes are a group of chemical compounds sharing a common functional group with the general structure R-SiR3. Acylsilanes are starting compounds in the Brook rearrangement with vinyl lithium compounds to silyl enol ethers ....
s and with special silyl ethers
retro-brook rearrangements are also possible . An analogous phospha-Brook rearrangement of 1-hydroxyphosphonates has also been reported.