1,1'-Bi-2-naphthol
Encyclopedia
1,1'-Bi-2-naphthol is an organic compound
that is often used as a ligand
for transition-metal catalysed asymmetric synthesis. BINOL has axial chirality
and the two enantiomer
s can be readily separated and are stable toward racemisation. The specific rotation
of the two enantiomers is +/- 35.5° (c=1 in THF
). BINOL is a precursor for another chiral ligand
called BINAP
.
of BINOL is not a challenge as such but the preparation of the individual enantiomer
s is.
(S)-BINOL can be prepared directly from an asymmetric oxidative coupling of 2-naphthol
with copper(II) chloride
. The chiral ligand
in this reaction is (S)-(+)-amphetamine
.
Racemic BINOL can also be produced using iron(III) chloride
as an oxidant. The mechanism involves complexation of iron(III) into the hydroxyl
, followed by a radical coupling reaction of the naphthol rings initiated by iron(III) reducing into iron(II).
Optically active BINOL can also be obtained from racemic
BINOL by optical resolution. In one method, the alkaloid
N-benzylcinchonidinium chloride form a crystalline inclusion compound
. The inclusion compound of the S-enantiomer is soluble in acetonitrile
but that of the R-enantiomer is not.
In another method BINOL is reacted with the acid chloride pentanoyl chloride to obtain the di-ester compound. The enzyme cholesterol
esterase
is then added in the form of bovine pancreas
acetone powder which is able to hydrolyse
the (S)-di-ester but not the (R)-di-ester. The (R)-dipentanoate is hydrolysed in a second step with sodium methoxide
.
Third method employs HPLC
with chiral stationary phases.
being one of them.
The compound AlLibis(binaphthoxide) (ALB) is prepared by reaction of BINOL with lithium aluminium hydride
.
It has been employed in an asymmetric Michael reaction with cyclohexenone
and dimethyl malonate
:
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
that is often used as a ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
for transition-metal catalysed asymmetric synthesis. BINOL has axial chirality
Axial chirality
Axial chirality is a special case of chirality in which a molecule does not possess a stereogenic center but an axis of chirality – an axis about which a set of substituents is held in a spatial arrangement that is not superposable on its mirror image...
and the two enantiomer
Enantiomer
In chemistry, 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 except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
s can be readily separated and are stable toward racemisation. The specific rotation
Specific rotation
In stereochemistry, the 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. It is the main property used to...
of the two enantiomers is +/- 35.5° (c=1 in THF
ThF
Follicular B helper T cells , are antigen-experienced CD4+ T cells found in the B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5...
). BINOL is a precursor for another chiral ligand
Chiral ligand
In chemistry a chiral ligand is a specially adapted ligand used for asymmetric synthesis. This ligand is an enantiopure organic compound which combines with a metal center by chelation to form an asymmetric catalyst. This catalyst engages in a chemical reaction and transfers its chirality to the...
called BINAP
BINAP
BINAP is an abbreviation for the organophosphorus compound 2,2'-bis-1,1'-binaphthyl. This chiral ligand is widely used in asymmetric synthesis. It consists of a pair of 2-diphenylphosphinonaphthyl groups linked at the 1 and 1´ positions. This C2-symmetric framework lacks stereogenic atom, but...
.
Preparation
The organic synthesisOrganic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
of BINOL is not a challenge as such but the preparation of the individual enantiomer
Enantiomer
In chemistry, 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 except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
s is.
(S)-BINOL can be prepared directly from an asymmetric oxidative coupling of 2-naphthol
2-Naphthol
2-Naphthol, or β-naphthol, is a colorless crystalline solid with the formula C10H7OH. It is an isomer of 1-naphthol, differing by the location of the hydroxyl group on naphthalene. The naphthols are naphthalene homologues of phenol, with the hydroxyl group being more reactive than in the phenols....
with copper(II) chloride
Copper(II) chloride
Copper chloride is the chemical compound with the formula CuCl2. This is a light brown solid, which slowly absorbs moisture to form a blue-green dihydrate. The copper chlorides are some of the most common copper compounds, after copper sulfate....
. The chiral ligand
Chiral ligand
In chemistry a chiral ligand is a specially adapted ligand used for asymmetric synthesis. This ligand is an enantiopure organic compound which combines with a metal center by chelation to form an asymmetric catalyst. This catalyst engages in a chemical reaction and transfers its chirality to the...
in this reaction is (S)-(+)-amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
.
Iron(III) chloride
Iron chloride, also called ferric chloride, is an industrial scale commodity chemical compound, with the formula FeCl3. The colour of iron chloride crystals depends on the viewing angle: by reflected light the crystals appear dark green, but by transmitted light they appear purple-red...
as an oxidant. The mechanism involves complexation of iron(III) into the hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
, followed by a radical coupling reaction of the naphthol rings initiated by iron(III) reducing into iron(II).
Optically active BINOL can also be obtained from racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
BINOL by optical resolution. In one method, the alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
N-benzylcinchonidinium chloride form a crystalline inclusion compound
Inclusion compound
In host-guest chemistry an inclusion compound is a complex in which one chemical compound forms a cavity in which molecules of a second "guest" compound are located. The definition of inclusion compounds is very broad, extending to channels formed between molecules in a crystal lattice in which...
. The inclusion compound of the S-enantiomer is soluble in acetonitrile
Acetonitrile
Acetonitrile is the chemical compound with formula . This colourless liquid is the simplest organic nitrile. It is produced mainly as a byproduct of acrylonitrile manufacture...
but that of the R-enantiomer is not.
In another method BINOL is reacted with the acid chloride pentanoyl chloride to obtain the di-ester compound. The enzyme cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
esterase
Esterase
An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis.A wide range of different esterases exist that differ in their substrate specificity, their protein structure, and their biological function.- EC classification/list...
is then added in the form of bovine pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
acetone powder which is able to hydrolyse
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
the (S)-di-ester but not the (R)-di-ester. The (R)-dipentanoate is hydrolysed in a second step with sodium methoxide
Sodium methoxide
Sodium methoxide is a chemical compound, with formula CH3ONa. This colourless solid, which is formed by the deprotonation of methanol, is a widely used reagent in industry and the laboratory...
.
Third method employs HPLC
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
with chiral stationary phases.
BINOL compounds
Many variations of BINOL exist, BINAPBINAP
BINAP is an abbreviation for the organophosphorus compound 2,2'-bis-1,1'-binaphthyl. This chiral ligand is widely used in asymmetric synthesis. It consists of a pair of 2-diphenylphosphinonaphthyl groups linked at the 1 and 1´ positions. This C2-symmetric framework lacks stereogenic atom, but...
being one of them.
The compound AlLibis(binaphthoxide) (ALB) is prepared by reaction of BINOL with lithium aluminium hydride
Lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...
.
It has been employed in an asymmetric Michael reaction with cyclohexenone
Cyclohexenone
Cyclohexenone is an organic compound which is a versatile intermediate used in the synthesis of a variety of chemical products such as pharmaceuticals and fragrances...
and dimethyl malonate
Dimethyl malonate
Dimethyl malonate is a diester derivative of malonic acid. It is a common reagent for organic synthesis. It is used in the malonic ester synthesis....
: