Phenylboronic acid

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Phenylboronic acid
Phenylboronic-acid-2D-skeletal.png
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Names
Preferred IUPAC name
Phenylboronic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.002.456
EC Number 202-701-9
Properties
C6H7BO2
Molar mass 121.93 g/mol
Appearance white to yellow powder
Odor odorless
Melting point 216 °C (421 °F; 489 K)
0.1 g/mL in MeOH
Solubility soluble in diethyl ether, ethanol
Acidity (pKa) 8.83
Structure
planar
Thermochemistry
-719.6 kJ/mol
Hazards
Safety data sheet [1]
R-phrases (outdated) 22
Lethal dose or concentration (LD, LC):
740 mg/ml (rat, oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

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 acids which are generally stable and easy to handle, making them important to organic synthesis.

Properties[edit]

Phenylboronic acid is soluble in most polar organic solvents and is poorly soluble in hexanes 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 bonding to form units made up of two molecules.[1] 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.[2]

Synthesis[edit]

Numerous methods exist to synthesize phenylboronic acid. One of the most common synthesis uses phenylmagnesium bromide and trimethyl borate to form the ester PhB(OMe)2, which is then hydrolyzed to the product.[3]

PhMgBr + B(OMe)3 → PhB(OMe)2 + MeOMgBr
PhB(OMe)2 + H2O → PhB(OH)2 + MeOH

Other routes to phenylboronic acid involve Electrophilic borates to trap phenylmetal intermediates from phenyl halides or from directed ortho-metalation.[2] Phenylsilanes 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.

Reactions[edit]

The dehydration of boronic acids gives boroxines, the trimeric anhydrides of phenylboronic acid. The dehydration reaction is driven thermally, sometimes with a dehydration agent.[4]

Triphenyl boroxine synthesis01.svg

Phenylboronic acid participates in numerous cross coupling reactions where is serves as a source of a phenyl group. One example is the Suzuki reaction) where, in the presence of a [palladium|Pd(0)]] catalyst and base, phenylboronic acid and vinyl halides are coupled to produce phenyl alkenes.[5] This method was generalized to a route producing biaryls by coupling phenylboronic acid with aryl halides.

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.[6] Heck-type cross coupling of phenylboronic acid and alkenes and alkynes has been demonstrated.[7]

Aryl azides and nitroaromatics can also be generated using phenylboronic acid.[2] Phenylboronic acid can also be regioselectively halodeboronated using aqueous bromine, chlorine, or iodine:[8]

PhB(OH)2 + Br2 + H2O → PhBr + B(OH)3 + HBr

Boronic esters result from the condensation of boronic acids with alcohols. This transformation is simply the replacement of the hydroxyl group by alkoxy or aryloxy groups.[2] This reversible reaction is commonly driven to product by the use of Dean-Stark apparatus or a dehydration agent to remove water.

PhB(OH)2 + 2 ROH ⇌ PhB(OR)2 + 2 H2O

As an extension of this reactivity, PhB(OH)2 can be used as a protecting group for diols and diamines. This reactivity is the basis of the use of phenylboronic acid's use as a receptor and sensor for carbohydrates, antimicrobial agents, and enzyme inhibitors, neutron capture therapy for cancer, transmembrane transport, and bioconjugation and labeling of proteins and cell surface.[2]

See also[edit]

References[edit]

  1. ^ Rettig SJ, Trotter J (1977). "Crystal and molecular structure of phenylboronic acid, C6H5B(OH)2". Can. J. Chem. 55: 3071–3075. 
  2. ^ a b c d e Hall, D. G. Boronic Acids; WILEY-VCH: Edmonton, Canada, 2005. ISBN 3-527-30991-8
  3. ^ Washburn, RM; Levens, E; Albright, CF; Billig, FA (1963). "Benzeneboronic anhydride". Organic Syntheses. ; Collective Volume, 4, p. 68 
  4. ^ Snyder, H. R.; Kuck, J. A.; Johnson, J. R. (1938). "Organoboron Compounds, and the Study of Reaction Mechanisms. Primary Aliphatic Boronic Acids". J. Am. Chem. Soc. 60: 105. doi:10.1021/ja01268a033. 
  5. ^ Miyaura, N.; Suzuki, A. (1979). "Stereoselective synthesis of arylated (E)-alkenes by the reaction of alk-1-enylboranes with aryl halides in the presence of palladium catalyst". J. Chem. Soc., Chem. Commun. (19): 866. doi:10.1039/C39790000866. 
  6. ^ Petasis, N. A.; Xavialov, I. A. (1997). "A New and Practical Synthesis of α-Amino Acids from Alkenyl Boronic Acids". J. Am. Chem. Soc. 119 (2): 445. doi:10.1021/ja963178n. 
  7. ^ Sakai, M.; Hayashi, H.; Miyaura, N. (1998). "Rhodium-Catalyzed Addition of Organoboronic Acids to Aldehydes". Angew. Chem. Int. Ed. 37 (23): 3279. doi:10.1002/(SICI)1521-3773(19981217)37:23<3279::AID-ANIE3279>3.0.CO;2-M. 
  8. ^ Ainley, A. D.; Challenger, F. (1930). "Studies of the boron–carbon linkage. Part I. The oxidation and nitration of phenylboric acid". J. Chem. Soc.: 2171. doi:10.1039/JR9300002171. 

Further reading[edit]

  • Brown, H.C. Organic Synthesis via Boranses, Wiley, New York, 1975.
  • Matteson, D. S. Stereodirected Synthesis with Organoboranes, Springer, Berlin, 1995. ISBN 978-3-540-59182-5
  • Lappert, M. F. (1956). "Organic Compounds Of Boron". Chem. Rev. 56 (5): 959. doi:10.1021/cr50011a002. 
  • 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 3-7186-0113-3