Phenylboronic acid
Encyclopedia
Phenylboronic acid or benzeneboronic acid, abbreviated as PhB(OH)2 where Ph is the phenyl group
C6H5-, is a boronic acid
containing a phenyl substituent
and two hydroxyl
groups attached to boron
. Phenylboronic acid is white powder and is commonly used in organic synthesis
. Boronic acids are mild Lewis acid
s which are generally stable and easy to handle, making them important to organic synthesis.
s and carbon tetrachloride
. This planar compound has idealized C2V molecular symmetry
. The boron atom is sp2-hybridized
and contains an empty p-orbital
. The orthorhombic crystals use hydrogen bond
ing to form units made up of two molecules. These dimeric units are combined to give an extended hydrogen-bonded network. The molecule is planar with a minor bend around the C-B bond of 6.6o and 21.4o for the two PhB(OH)2 molecules.
In 1860, the first borane
synthesized was ethylboronic acid. Edward Frankland
was the first to prepare and isolate this boronic acid using diethylzinc
and triethylborate to produced triethylborane
, which oxidized
in air to ethylboronic acid.
and trimethyl borate
to form the ester
PhB(OMe)2, which is then hydrolyzed
to the product.
The trimeric
anhydrides of phenylboronic acid are called boroxine
s. The dehydration
of boronic acids creates boroxines by the thermal removal of water or the use of a dehydration agent. Boroxines are isoelectronic
to benzene
.
Boronic esters result from the condensation
of boronic acids with alcohol
s. This transformation is simply the replacement of the hydroxyl group by alkoxy or aryloxy groups. This reversible reaction
is commonly driven to product by the use of Dean-Stark apparatus
or a dehydration agent to remove water.
Since boronic acids have become important synthetic intermediates, a wide variety of methods are available to form boronic acids. Electrophilic
borates can be used to trap phenylmetal intermediates from aryl halides or from directed ortho-metallation. Phenylsilane
s and phenylstannanes transmetalate
with BBr3, followed by hydrolysis
form phenylboronic acid. Aryl halides or triflates can be coupled with diboronyl reagents using transition metal catalysts. Aromatic C-H functionalization can also be done using transition metal catalysts.
. In 1979, Miyarura and Suzuki found a carbon-carbon bond
forming reaction (now called a Suzuki reaction
) using alkenyl boranes, aryl halides, catalytic Pd(0)
, and base to produce arylated alkene
products. This method was generalized to a route producing biaryls by coupling phenylboronic acid with aryl halides.
More C-C bond forming processes commonly use phenylboronic acid as a reagent. Alpha-amino acids can be generated using the uncatalyzed reaction between alpha-ketoacids, amines, and phenylboronic acid. Heck-type cross coupling of phenylboronic acid to alkenes and alkynes. This unique C-C bond forming reaction has the ability to couple a terminal olefin with boronic acid using a transition metal
catalyst. Aryl azides and nitroaromatics can also be generated using phenylboronic acid. PhB(OH)2 can be used as a protecting group for diol
s and diamine
s. Phenylboronic acid can also be regioselectively
halodeboronated using aqueous bromine
, chlorine
, or iodine
.
Phenylboronic acid is used in biology schemes as receptors and sensors for carbohydrates, antimicrobial
agents and enzyme inhibitor
s, neutron capture therapy for cancer
, transmembrane transport, and bioconjugation and labeling of protein
s and cell surface.
Phenyl group
In organic chemistry, the phenyl group or phenyl ring is a cyclic group of atoms with the formula C6H5. Phenyl groups are closely related to benzene. Phenyl groups have six carbon atoms bonded together in a hexagonal planar ring, five of which are bonded to individual hydrogen atoms, with the...
C6H5-, is a boronic acid
Boronic acid
A boronic acid is an alkyl or aryl substituted boric acid containing a carbon–boron bond belonging to the larger class of organoboranes. Boronic acids act as Lewis acids. Their unique feature is that they are capable of forming reversible covalent complexes with sugars, amino acids, hydroxamic...
containing a phenyl substituent
Substituent
In 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...
and two 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...
groups attached to boron
Boron
Boron is the chemical element with atomic number 5 and the chemical symbol B. Boron is a metalloid. Because boron is not produced by stellar nucleosynthesis, it is a low-abundance element in both the solar system and the Earth's crust. However, boron is concentrated on Earth by the...
. Phenylboronic acid is white powder and is commonly used in organic synthesis
Organic 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...
. Boronic acids are mild Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
s which are generally stable and easy to handle, making them important to organic synthesis.
Properties
Phenylboronic acid is soluble in most polar organic solvents and is poorly soluble in hexaneHexane
Hexane is a hydrocarbon with the chemical formula C6H14; that is, an alkane with six carbon atoms.The term may refer to any of four other structural isomers with that formula, or to a mixture of them. In the IUPAC nomenclature, however, hexane is the unbranched isomer ; the other four structures...
s and carbon tetrachloride
Carbon tetrachloride
Carbon tetrachloride, also known by many other names is the organic compound with the formula CCl4. It was formerly widely used in fire extinguishers, as a precursor to refrigerants, and as a cleaning agent...
. This planar compound has idealized C2V molecular symmetry
Molecular symmetry
Molecular symmetry in chemistry describes the symmetry present in molecules and the classification of molecules according to their symmetry. Molecular symmetry is a fundamental concept in chemistry, as it can predict or explain many of a molecule's chemical properties, such as its dipole moment...
. The boron atom is sp2-hybridized
Orbital hybridisation
In chemistry, hybridisation is the concept of mixing atomic orbitals to form new hybrid orbitals suitable for the qualitative description of atomic bonding properties. Hybridised orbitals are very useful in the explanation of the shape of molecular orbitals for molecules. It is an integral part...
and contains an empty p-orbital
Atomic orbital
An atomic orbital is a mathematical function that describes the wave-like behavior of either one electron or a pair of electrons in an atom. This function can be used to calculate the probability of finding any electron of an atom in any specific region around the atom's nucleus...
. The orthorhombic crystals use hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
ing to form units made up of two molecules. These dimeric units are combined to give an extended hydrogen-bonded network. The molecule is planar with a minor bend around the C-B bond of 6.6o and 21.4o for the two PhB(OH)2 molecules.
In 1860, the first borane
Borane
In chemistry, a borane is a chemical compound of boron and hydrogen. The boranes comprise a large group of compounds with the generic formulae of BxHy. These compounds do not occur in nature. Many of the boranes readily oxidise on contact with air, some violently. The parent member BH3 is called...
synthesized was ethylboronic acid. Edward Frankland
Edward Frankland
Sir Edward Frankland, KCB, FRS was a chemist, one of the foremost of his day. He was an expert in water quality and analysis, and originated the concept of combining power, or valence, in chemistry. He was also one of the originators of organometallic chemistry.-Biography:Edward Frankland was born...
was the first to prepare and isolate this boronic acid using diethylzinc
Diethylzinc
Diethylzinc 2Zn, or DEZn, is a highly pyrophoric organozinc compound consisting of a zinc center bound to two ethyl groups. This colourless liquid is an important reagent in organic chemistry and available commercially as a solution in hexanes, heptane, or toluene.-Synthesis:Edward Frankland first...
and triethylborate to produced triethylborane
Triethylborane
Triethylborane , also called triethylborine and triethylboron, is an organoborane , a near-colorless to yellowish transparent liquid with pungent ether-like odor. Its chemical formula can be written as C6H15B, or 3B, or 3B, or Et3B.Triethylborane is strongly pyrophoric, igniting spontaneously in...
, which oxidized
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
in air to ethylboronic acid.
Synthesis
There are numerous methods to synthesize phenylboronic acid. One of the most common synthesis uses phenylmagnesium bromidePhenylmagnesium bromide
Phenylmagnesium bromide, with the simplified formula , is a magnesium-containing organometallic compound. It is so commonly used that it is commercially available as a solution in diethyl ether or tetrahydrofuran . Phenylmagnesium bromide is a Grignard reagent...
and trimethyl borate
Trimethyl borate
Trimethyl borate, or boron trimethoxide, has formula B3. It is a clear liquid. It melts at −34 °C and boils at 68-69 °C. It decomposes in contact with water...
to form the ester
Ester
Esters 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...
PhB(OMe)2, which is then hydrolyzed
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...
to the product.
- PhMgBr + B(OMe)3 → PhB(OMe)2 + MeOMgBr
- PhB(OMe)2 + H2O → PhB(OH)2 + MeOH
The trimeric
Trimer (chemistry)
In chemistry, a trimer is a product derived from three identical precursors. Trimers are typically cyclic. Chemical compounds that often trimerise are aliphatic isocyanates and cyanic acids. Often, trimerization competes with polymerization....
anhydrides of phenylboronic acid are called boroxine
Boroxine
Boroxine is a 6-membered, heterocyclic compound composed of alternating oxygen and singly-hydrated boron atoms. Boroxine derivatives such as trimethylboroxine and triphenylboroxine also make up a broader class of compounds called boroxines. These compounds are solids that are usually in...
s. The dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
of boronic acids creates boroxines by the thermal removal of water or the use of a dehydration agent. Boroxines are isoelectronic
Isoelectronicity
Two or more molecular entities are described as being isoelectronic with each other if they have the same number of electrons or a similar electron configuration and the same structure , regardless of the nature of the elements involved.The term valence isoelectronic is used when these molecular...
to benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
.
Boronic esters result from the condensation
Condensation reaction
A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...
of boronic acids with alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s. This transformation is simply the replacement of the hydroxyl group by alkoxy or aryloxy groups. This reversible reaction
Reversible reaction
A reversible reaction is a chemical reaction that results in an equilibrium mixture of reactants and products. For a reaction involving two reactants and two products this can be expressed symbolically as...
is commonly driven to product by the use of Dean-Stark apparatus
Dean-Stark apparatus
For the video game character, see Wild Arms 5thumb|right|A Dean-Stark apparatus in use; aluminum foil is used to reduce radiative heat lossesThe Dean-Stark apparatus or Dean-Stark receiver or distilling trap is a piece of laboratory glassware used in synthetic chemistry to collect water from a...
or a dehydration agent to remove water.
- PhB(OH)2 + 2 ROH PhB(OR)2 + 2 H2O
Since boronic acids have become important synthetic intermediates, a wide variety of methods are available to form boronic acids. Electrophilic
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...
borates can be used to trap phenylmetal intermediates from aryl halides or from directed ortho-metallation. Phenylsilane
Phenylsilane
Phenylsilane, also known as silylbenzene, a colorless liquid, is one of the simplest organosilanes with the formula C6H5SiH3. It is structurally related to toluene, with a silyl group replacing the methyl group. Both of these compounds have similar densities and boiling points due to these...
s and phenylstannanes transmetalate
Transmetalation
Transmetalation is a general chemical reaction type in organometallic chemistry describing the exchange of ligands between two metal centers....
with BBr3, followed by hydrolysis
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...
form phenylboronic acid. Aryl halides or triflates can be coupled with diboronyl reagents using transition metal catalysts. Aromatic C-H functionalization can also be done using transition metal catalysts.
Applications
Phenylboronic acid is used in numerous cross coupling reactionsCoupling reaction
A coupling reaction in organic chemistry is a catch-all term for a variety of reactions where two hydrocarbon fragments are coupled with the aid of a metal catalyst...
. In 1979, Miyarura and Suzuki found a carbon-carbon bond
Carbon-carbon bond
A carbon–carbon bond is a covalent bond between two carbon atoms. The most common form is the single bond: a bond composed of two electrons, one from each of the two atoms. The carbon–carbon single bond is a sigma bond and is said to be formed between one hybridized orbital from each...
forming reaction (now called a Suzuki reaction
Suzuki reaction
The Suzuki reaction is the organic reaction of an aryl- or vinyl-boronic acid with an aryl- or vinyl-halide catalyzed by a palladium complex. It is widely used to synthesize poly-olefins, styrenes, and substituted biphenyls, and has been extended to incorporate alkyl bromides...
) using alkenyl boranes, aryl halides, catalytic Pd(0)
Palladium
Palladium is a chemical element with the chemical symbol Pd and an atomic number of 46. It is a rare and lustrous silvery-white metal discovered in 1803 by William Hyde Wollaston. He named it after the asteroid Pallas, which was itself named after the epithet of the Greek goddess Athena, acquired...
, and base to produce arylated alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
products. This method was generalized to a route producing biaryls by coupling phenylboronic acid with aryl halides.
More C-C bond forming processes commonly use phenylboronic acid as a reagent. Alpha-amino acids can be generated using the uncatalyzed reaction between alpha-ketoacids, amines, and phenylboronic acid. Heck-type cross coupling of phenylboronic acid to alkenes and alkynes. This unique C-C bond forming reaction has the ability to couple a terminal olefin with boronic acid using a transition metal
Transition metal
The term transition metal has two possible meanings:*The IUPAC definition states that a transition metal is "an element whose atom has an incomplete d sub-shell, or which can give rise to cations with an incomplete d sub-shell." Group 12 elements are not transition metals in this definition.*Some...
catalyst. Aryl azides and nitroaromatics can also be generated using phenylboronic acid. PhB(OH)2 can be used as a protecting group for diol
Diol
A diol or glycol is a chemical compound containing two hydroxyl groups A geminal diol has two hydroxyl groups bonded to the same atom...
s and diamine
Diamine
A diamine is a type of polyamine with exactly two amino groups. Diamines are mainly used as monomers to prepare polyamides, polyimides and polyureas. In terms of quantities produced, 1,6-diaminohexane, a precursor to Nylon 6-6, is most important, followed by ethylenediamine...
s. Phenylboronic acid can also be regioselectively
Regioselectivity
In chemistry, regioselectivity is the preference of one direction of chemical bond making or breaking over all other possible directions. It can often apply to which of many possible positions a reagent will affect, such as which proton a strong base will abstract from an organic molecule, or where...
halodeboronated using aqueous bromine
Bromine
Bromine ") is a chemical element with the symbol Br, an atomic number of 35, and an atomic mass of 79.904. It is in the halogen element group. The element was isolated independently by two chemists, Carl Jacob Löwig and Antoine Jerome Balard, in 1825–1826...
, chlorine
Chlorine
Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
, or iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
.
- PhB(OH)2 + Br2 + H2O → PhBr + B(OH)3 + HBr
Phenylboronic acid is used in biology schemes as receptors and sensors for carbohydrates, antimicrobial
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
agents and enzyme inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
s, neutron capture therapy for cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, transmembrane transport, and bioconjugation and labeling of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s and cell surface.
Further reading
- Brown, H.C. Organic Synthesis via Boranses, Wiley, New York, 1975.
- Matteson, D. S. Stereodirected Synthesis with Organoboranes, Springer, Berlin, 1995. ISBN 9783540591825
- Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents, Academic Press, New York, 1988.
- Mikhailov, B. M.; Bubnov, Y. N. Organoboron Compounds in Organic Synthesis, Harwood Academics, Glasgow, 1984. ISBN: 3718601133