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بسمه تعالی
Structure, Properties, and Preparation Of Boronic Acid
IN THE NAME OF GOD
Introduction: In 1860 Frankland reported the reaction of pyrophoric diethylzinc with triethyl borate to form anew product,triethylborane,readily oxidized by air to diethylborinic acid.slow oxidation gave a more stable,crystalline product identified as ethylboronic acid.
STRUCTURE Structurally, boronic acids are trivalent boron-containing organic compounds that possess one alkyl substituent and two hydroxyl groups to fill the remaining valences on the boron atom.
R=alkyl, alkene, alkyn, aryl
The CBO2 plane is quite Coplanar with the benzene ring
Structure and Binding
Physical properties & safty:
white crystalline solids
handled in air without special precautions.
low toxicity levels
Acidic Character :
Boronic Acid Derivatives:
Broxines:
Boronic ester:
replacement of the hydroxyl groups of boronic acids by alkoxy or aryloxy groups provides esters
Synthesis of Boronic Acids
Electrophilic Trapping of Arylmetal Intermediates with Borates
By Directed ortho-Metallation
Transmetallation of Aryl Silanes and Stannanes
Coupling of Aryl Halides with Diboronyl Reagents
Direct Boronylation by Transition Metal-catalyzed Aromatic C–H
Functionalization
cheapest and most common way of synthesizing arylboronic acids involves the reaction of a hard organometallic intermediate (i.e.,
lithium or magnesium) with a borate ester at low temperature
Electrophilic Trapping of Arylmetal Intermediates with Borates:
The metallation of arenes functionalized with coordinating ortho-directing groups such as amines, ethers, anilides, esters and amides is yet another popular way to access arylmetal intermediates that can be trapped with borate esters.
By Directed Ortho-Metallation:
Transmetallation of Aryl Silanes and Stannanes:
Miyaura and co-workers found that diboronyl esters suchasB2pin2 undergo a smooth cross-coupling reaction with aryl bromides, iodides,and trif lates under palladium catalysis.
Coupling of Aryl Halides with Diboronyl Reagents :
Direct Boronylation by Transition Metal-catalyzed Aromatic C–H Functionalization :
Catalytic cycles involving Ir(III)-Ir(V) intermediates
Hydroboration of Alkynes :
Mechanism:
Reactions of Boronic Acid
Metallation
Oxidative Replacement of Boron
Halogenation
Palladium-catalyzed Cross-coupling with Carbon Halide s
Alkylation of Carbonyl Compounds
Additions to Imines and Iminiums
Chan-lam coupling
Metallation:
In 1882, Michaelis and Becker described the preparation of phenyl mercuric chloride(119) from the reaction of phenylboronic acid and aqueous mercuric chloride
Catechol and pinacol alkenylboronic esters can also be easily transformed into
the corresponding organomercurial derivative with retention of configuration.
Oxidative Replacement of Boron :
The treatment of arylboronic acids and esters with alkaline hydrogen peroxide to producethe corresponding phenols.
The oxidation of alkyl- and alkenyl- boronic acid derivatives leads to alkanols.
Halogenation :
Arylboronic acids are halodeboronated regioselectively by the action of aqueous chlorine, bromine,and aqueous iodine
treatment of alkenylboronic esters with bromine in ethereal anhydrous solvent, then with sodium hydroxide or alkoxides in a one-pot fashion, provides the corresponding alkenyl bromides with inversion of olefin geometry
Palladium-catalyzed Cross-coupling with Carbon Halides (Suzuki Coupling) :
In1979 discovery by Suzuki and Miyaura that arylboronicacids undergo palladium- catalyzed cross-coupling with aryl halides in the presence of a base providing
arylated alkene products in high yields
Transmetallation :
Mechanism:
AlKylation of Carbonyl Compounds
The addition of allylboronates to aldehydes was first discovered in 1974. One of the most recent developments of this reaction is the discovery that additions of allylboronates to aldehydes can be catalyzed by Lewis acids.
Additions to Imines and Iminiums (Petasis reaction) :
In 1997, Petasis and Zavialov described a novel uncatalyzed three-component reaction between α-keton, amines and boronic acids, providing a novel synthetic route to amiine or α-amino acids.
General mechanism for the condensation of boronic acid with secondary amine and formaldehyde via the additional of an activated tetracoordinate anionic boron species to iminium ions
Petasis reaction Boronic acid Mannich
Chan-lam coupling :
In 1998 Chan, Evans, and Lam reported their observations that copper diacetate of promotes the coupling aryl and heteroaryl boronicacids to moderately acidic heteroatom-containing functionalities like phenols, thiols,amines, amides, and various heterocycles
The reaction with a stoichiometric amount of copper(II) is also facilitated by oxygen, because reductive elimination from a copper(III) species is faster.
Mechanism of the Chan-Lam Coupling :
Use as Reaction Promoters and Catalysts
Use in Neutron Capture Therapy for Cancer
Boronic acid as Agent targeting the Human Immunodeficiency Virus
Use as Antimicrobial Agents and Enzyme Inhibitors
Boronic acid compound as Drug
Applications of Boronic Acid
Use as Receptors and Sensors for Carbohydrates and other Small Molecules
Use as Reaction Promoters and Catalysts
By forming transient esters with alcohols, boronic acids can act as catalysts or templates for directed reactions. In the early 1960s, Letsinger demonstrated that a bifunctional boronic acid, 8-quinoline boronic acid, accelerates the hydrolysis of certain chloroalkanols
1a-oxygen is located in water molecule held between boron and nitrogen.
1b-oxygen is covalently bound to boron and one hydrogen
1c-oxygen is covalently bond to two boron atoms
2-(2-boronophenyl)benzimidazole serve as catalysts for the formation of ether from chloroethanol in butanol solution.
Narasaka and co-workers demonstrated that phenylboronic acid can be employed to hold the diene and dienophile in such a way that the normal regiocontrol of a Diels–Alder reaction can even be inverted
Use as Receptors and Sensors for Carbohydrates and other Small Molecules
The ability of boronic acids to form esters reversibly with cis-diols has been a central theme in the intensive area of sensor and receptor development for oligosaccharides.
The first fluorescent probe for saccharides (anthracene boronic acid ) was described in 1992 by Yoon and Czarnik.
Several boronic acids and esters display potent antifungal activity. For instance, the diazaborine family, exemplified by the thienodiazaborine, has long been known to possesspotent activity against a wide range of bacteria.
Use as Antimicrobial Agents and Enzyme Inhibitors
Boronic acids inhibit hydrolytic enzymes such as serine proteases
The usual mechanism of inhibition is the formation of a tetracoordinate boronatecomplex by coordination of the side chain hydroxyl nucleophile of the active serine residue.
1-(1-(3-phenylpropanoyl)pyrrolidine-2-carboxamido)-3-aminopropylboronic acid hydrochloride
Use in Neutron Capture Therapy for Cancer
Several boronic acids such as 4-boronophenylalanine have been evaluated as sources of boron for their potential use in a form of brain cancer therapy based on the technology of soft neutron capture
Bortezomib was granted by the US Food and Administration in early 2003 as a single agent for the treatment of multiple myeloma and a bond marrow cancer
Us as Agent targeting the Human immunodeficiency Virus
HIV protease is involved in the production of infectious virions of HIV.
Inhibition of HIV protease provides an effective way to develop new agent for therapy of HIV
4-(2,6-dichloro-9H-purin-9-yl)butyl boronic acid
Such properties have been used to develop polymers that respond to glucose constraction by changing their permeability for protein such as insuline .
BORONIC ACID AS DRUG
PBA-NVP
A glucose-sensitive insulin rlease system using boronic acid polymer-complexes
REFERENCES:
Boronic acid preparation,applications in organic synthesis and medicine.Dennis G.Hall .WILEY-VCH.
Boronic acid in saccharide recognition.Tony D James,Seiji Shinkai .RSC Publishing
Boronic acid based probes for microdetermination of saccharides and glycosylated biomolecules. Heike S. Mader, Otto S. Wolfbeis. Microchim Acta (2008) 162: 1–34
Palladium catalyzed ligand-free Suzuki cross-coupling reactions of benzylic halides with aryl boronic acids. B. P. Bandgar,* Sampada V. Bettigeri and Jaywant Phopase Tetrahedron Letters 45 (2004) 6959–6962
A. H. Soloway, J. Am. Chem. Soc. 1960,82, 2442–2444 FluorescentChemosensors ofcarbohydrates. A means of chemically communicating the binding of polyols in water based on chelation-enhanced quenching. Yoon J, Czarnik A W (1992) . J Am Chem Soc 114: 5874.
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