WO1999064428A1 - Synthesis of aryl boronic acids - Google Patents
Synthesis of aryl boronic acids Download PDFInfo
- Publication number
- WO1999064428A1 WO1999064428A1 PCT/US1999/013105 US9913105W WO9964428A1 WO 1999064428 A1 WO1999064428 A1 WO 1999064428A1 US 9913105 W US9913105 W US 9913105W WO 9964428 A1 WO9964428 A1 WO 9964428A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- aryl
- boronic acid
- reaction mixture
- borate
- aryl boronic
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Definitions
- This invention relates to the synthesis of aryl boronic acids .
- Known aryl boronic acid synthesis typically entails concurrent or dual addition of substantially equimolar amounts of a trialkyl borate ester and an aromatic Grignard reagent to a reaction vessel at a temperature of less than -60°C, wherein a reaction mixture containing an aryl boronic acid ester is produced in a 30% to 50% yield. The ester is separated and hydrolyzed to provide the desired aryl boronic acid.
- Aryl boronic acids are now in substantial commercial use to synthesize biaryl compounds by the palladium catalyzed cross-coupling "Suzuki" reaction. See, e.g., A. Suzuki, et al., Syn . Commun .
- aryl borate diesters is accomplished at a temperature of from about -10° to 0°C by direct addition of the Grignard to the trialkyl borate or conversely in any desired mole ratio.
- Hydrolysis of the aryl borate diesters may be accomplished in situ in synthesis reaction mixture with an aqueous mineral, preferably, aqueous sulfuric acid, in known manner .
- This invention typically provides aryl boronic yields approximately 20-40% greater than those achieved by the prior art. More specifically, the invention may provide aryl boronic acid yields of from about 50% to about 70% based on the trialkyl borate reactant.
- the invention may, but need not be, practiced as a one pot method.
- a Grignard reagent is prepared in known manner in an appropriate ethereal solvent, preferably at the greatest concentration resulting in a solution. Any ethereal solvent compatible with
- Useful solvents may be ethers which are cyclic, e.g. , tetrahydrofuran, or which have the formula ROR, in which R is an alkyl group preferably having 2 to 6 carbon atoms .
- an aryl boronic acid triester is synthesized at a temperature of -10°C to
- the Grignard aryl (Ar) groups may be substituted at one, some, or all available positions by any halogen (chlorine, bromine, fluorine or iodine) , or by any straight or branched chain, substituted or unsubstituted alkyl group, or by any functional group compatible with or protected by standard methods to be compatible with the Grignard function.
- Phenyl, 4-fluorophenyl and naphthyl groups are typical Grignard aryl groups .
- the alkyl borate reactant (B (OR 3 ) ) is preferably used in an amount greater than stoichiometric with respect to the ArMgX reagent. For example, from about 1.1 to 2.0, preferably about 1.5 moles, of B(OR 3 ) may be used for each mole of ArMgX.
- Each of the R groups may be any alkyl group.
- Appropriate R groups have one to ten carbon atoms .
- R is preferably methyl .
- the hydrolysis of the aryl boronic acid diester (equation 2) may be performed in known manner, e.g., by combining a mineral acid, preferably aqueous H 2 S0 4 , directly with the Grignard reaction mixture: ArB(OR) 2 +H 2 S0 4(aq) > ArB (OH) 2 +2ROH (2)
- EXAMPLE 1 (General Example) The Grignard reagent is prepared in known manner in an appropriate ethereal solvent, preferably at the greatest concentration resulting in a solution.
- a flask of appropriate size to accommodate the reaction volume as well as the volume of the aqueous acid hydrolysis solution is set up under a sweep of inert atmosphere and equipped for reflux and cooling.
- Trialkyl borate e.g., trimethyl borate diluted with an equal weight of an ethereal solvent, preferably THF, is charged to the lask in an amount to provide a mole ratio of ArMgX:B (0CH 3 ) 3 of 1:1.5.
- the flask is cooled with dry ice:acetone to -10°C and addition of Grignard reagent begun, wherein a reaction mixture containing an aryl borate dialkyl ester is produced.
- the reaction mixture Upon completion of the Grignard addition, the reaction mixture is stirred to room temperature (1-2 hours) .
- the dialkyl ester is hydrolyzed in situ by directly adding a 10% w/v H 2 S0 4 aqueous solution in an amount equal to 2 mole H 2 S0 4 with vigorous stirring for 30 minutes .
- the reaction mixture is then allowed to settle for 30 minutes .
- the hydrolysis reaction mixture forms an upper organic layer and a lower aqueous layer.
- the organic layer is separated, and then dried over sodium sulfate.
- Solvent is distilled until solids begin to precipitate. Hexanes are added, and the precipitated product collected by filtration.
- reaction flask was charged with trimethyl borate (1.5 moles, 155.7g) and tetrahydrofuran (300g) .
- the mixture was cooled to a temperature of -5°C to 0°C.
- One mole of phenyl magnesium bromide was added slowly with maintenance of the temperature between -5°C and 0°C.
- the reaction mixture was stirred for thirty minutes .
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000553436A JP2002517503A (en) | 1998-06-10 | 1999-06-10 | Synthesis of arylboric acid |
CA002297780A CA2297780A1 (en) | 1998-06-10 | 1999-06-10 | Synthesis of aryl boronic acids |
NZ502612A NZ502612A (en) | 1998-06-10 | 1999-06-10 | Synthesis of aryl boronic acids |
EP99930198A EP1064286A1 (en) | 1998-06-10 | 1999-06-10 | Synthesis of aryl boronic acids |
AU46786/99A AU4678699A (en) | 1998-06-10 | 1999-06-10 | Synthesis of aryl boronic acids |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9451198A | 1998-06-10 | 1998-06-10 | |
US09/094,511 | 1998-06-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999064428A1 true WO1999064428A1 (en) | 1999-12-16 |
Family
ID=22245595
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/013105 WO1999064428A1 (en) | 1998-06-10 | 1999-06-10 | Synthesis of aryl boronic acids |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1064286A1 (en) |
JP (1) | JP2002517503A (en) |
AU (1) | AU4678699A (en) |
CA (1) | CA2297780A1 (en) |
NZ (1) | NZ502612A (en) |
WO (1) | WO1999064428A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1285924A1 (en) * | 2001-08-21 | 2003-02-26 | Clariant GmbH | Process for the preparation or aryl and alkyl boron compounds in micro reactors |
GB2415193A (en) * | 2004-06-19 | 2005-12-21 | F2 Chemicals Ltd | Fluorinated arylboronic acids |
US7507262B2 (en) | 2006-03-07 | 2009-03-24 | The Procter & Gamble Company | Compositions for oxidatively dyeing keratin fibers and methods for using such compositions |
WO2010094406A1 (en) | 2009-02-17 | 2010-08-26 | Bayer Cropscience Aktiengesellschaft | Aminopyrimidinamides as pest control agents |
EP2266973A1 (en) | 2009-05-29 | 2010-12-29 | Bayer CropScience AG | Pyrazinylpyrazole |
EP2275422A1 (en) | 2006-12-20 | 2011-01-19 | Bayer CropScience AG | Pyrimidinylpyrazoles as insecticide and parasiticide agents |
EP2374791A1 (en) | 2008-08-14 | 2011-10-12 | Bayer CropScience Aktiengesellschaft | Insecticidal 4-phenyl-1H pyrazoles |
CN104119367A (en) * | 2014-07-09 | 2014-10-29 | 中国科学技术大学苏州研究院 | Preparation method of aryl boric acid |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2898365A (en) * | 1956-12-05 | 1959-08-04 | American Potash & Chem Corp | Process for manufacture of areneboronic acids |
-
1999
- 1999-06-10 WO PCT/US1999/013105 patent/WO1999064428A1/en not_active Application Discontinuation
- 1999-06-10 NZ NZ502612A patent/NZ502612A/en unknown
- 1999-06-10 EP EP99930198A patent/EP1064286A1/en not_active Withdrawn
- 1999-06-10 AU AU46786/99A patent/AU4678699A/en not_active Abandoned
- 1999-06-10 JP JP2000553436A patent/JP2002517503A/en active Pending
- 1999-06-10 CA CA002297780A patent/CA2297780A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2898365A (en) * | 1956-12-05 | 1959-08-04 | American Potash & Chem Corp | Process for manufacture of areneboronic acids |
Non-Patent Citations (1)
Title |
---|
SEAMAN W., JOHNSON J. R.: "DERIVATIVES OF PHENYLBORIC ACID, THEIR PREPARATION AND ACTION UPON BACTERIA.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, US, vol. 53., 1 February 1931 (1931-02-01), US, pages 711 - 723., XP002919981, ISSN: 0002-7863, DOI: 10.1021/ja01353a039 * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1285924A1 (en) * | 2001-08-21 | 2003-02-26 | Clariant GmbH | Process for the preparation or aryl and alkyl boron compounds in micro reactors |
GB2415193A (en) * | 2004-06-19 | 2005-12-21 | F2 Chemicals Ltd | Fluorinated arylboronic acids |
US7507262B2 (en) | 2006-03-07 | 2009-03-24 | The Procter & Gamble Company | Compositions for oxidatively dyeing keratin fibers and methods for using such compositions |
US7678158B2 (en) | 2006-03-07 | 2010-03-16 | The Procter & Gamble Company | Compositions for oxidatively dyeing keratin fibers and methods for using such compositions |
EP2275422A1 (en) | 2006-12-20 | 2011-01-19 | Bayer CropScience AG | Pyrimidinylpyrazoles as insecticide and parasiticide agents |
EP2374791A1 (en) | 2008-08-14 | 2011-10-12 | Bayer CropScience Aktiengesellschaft | Insecticidal 4-phenyl-1H pyrazoles |
WO2010094406A1 (en) | 2009-02-17 | 2010-08-26 | Bayer Cropscience Aktiengesellschaft | Aminopyrimidinamides as pest control agents |
EP2246335A1 (en) | 2009-02-17 | 2010-11-03 | Bayer CropScience AG | Aminopyridineamides as pesticides |
US8202877B2 (en) | 2009-02-17 | 2012-06-19 | Bayer Cropscience Ag | Aminopyrimidinamides as pesticides |
EP2266973A1 (en) | 2009-05-29 | 2010-12-29 | Bayer CropScience AG | Pyrazinylpyrazole |
US8513260B2 (en) | 2009-05-29 | 2013-08-20 | Bayer Cropscience Ag | Pyrazinylpyrazoles |
CN104119367A (en) * | 2014-07-09 | 2014-10-29 | 中国科学技术大学苏州研究院 | Preparation method of aryl boric acid |
Also Published As
Publication number | Publication date |
---|---|
NZ502612A (en) | 2001-06-29 |
EP1064286A1 (en) | 2001-01-03 |
AU4678699A (en) | 1999-12-30 |
CA2297780A1 (en) | 1999-12-16 |
JP2002517503A (en) | 2002-06-18 |
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