WO2008037440A1 - Process for the synthesis of 2,2',6-tribromobiphenyl - Google Patents
Process for the synthesis of 2,2',6-tribromobiphenyl Download PDFInfo
- Publication number
- WO2008037440A1 WO2008037440A1 PCT/EP2007/008357 EP2007008357W WO2008037440A1 WO 2008037440 A1 WO2008037440 A1 WO 2008037440A1 EP 2007008357 W EP2007008357 W EP 2007008357W WO 2008037440 A1 WO2008037440 A1 WO 2008037440A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- iodobenzene
- butyllithium
- tribromobiphenyl
- dibromo
- organometallic compound
- Prior art date
Links
- KGVYWUFWUAWULV-UHFFFAOYSA-N Brc(cccc1)c1-c(c(Br)ccc1)c1Br Chemical compound Brc(cccc1)c1-c(c(Br)ccc1)c1Br KGVYWUFWUAWULV-UHFFFAOYSA-N 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
- C07C17/2632—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions involving an organo-magnesium compound, e.g. Grignard synthesis
Definitions
- the invention is directed to a process for the synthesis of 2,2',6-tribromobiphenyl.
- 2,2',6-Tribromobiphenyl has turned out to be a suitable starting material for the synthesis of several biphenyl compounds. Such compounds are valuable precursors for example in the materials sciences and the preparation of ligands for the use in the synthesis of chiral compounds for the pharmaceutical industry.
- a synthesis of this compound is known: the first step consists of an Ullmann coupling of l,3-dibromo-2-iodobenzene which affords 2,2',6,6'-tetrabromobiphenyl.
- debromination by halogen/metal exchange and hydrolysis gives 2,2',6-tribromobiphenyl in an overall yield of 30 % according to WO-A-2006/002731.
- said process comprising the steps of a) mixing an organometallic compound with l ,3-dibromo-2-iodobenzene at a molar ratio of at least 1 : 1, and b) adding 1 ,2-dibromobenzene to the mixture in a molar ratio, based on 1,3-dibromo- 2-iodobenzene, of 0.9:1 to 1.1 : 1, to obtain 2,2',6-tribromobiphenyl which is subsequently subjected to standard work-up procedures.
- the ratio of the organometallic compound to l,3-dibromo-2-iodobenzene is in the range of 1 : 1 to 3 : 1. More preferably the range is 1.5:1 to 2.5 : 1 , most preferably it is 2: 1.
- the organometallic compound is added very slowly to 1,3-di- bromo-2-iodobenzene.
- a suitable addition time depends on the dilution and molar amount of the organometallic compound to be added.
- organometallic compound suitable for the present process must be able to undergo a halogen-metal exchange with l,3-dibromo-2-iodobenzene forming a compound of the formula
- M represents a monovalent metal atom like lithium (Li) or in case of a polyvalent metal like magnesium (Mg) the metal atom including any substituents which are not involved in the halogen-metal exchange.
- Suitable organometallic compounds comprise a metal atom and at least one organic moiety having a carbon-metal bond. Optionally each organic moiety comprises one or more halogen atoms.
- the organometallic compound is a Grignard reagent or a lithiation reagent.
- Grignard reagents examples include ethylmagnesium chloride, ethylmagnesium bromide, isopropylmagnesium chloride, isopropylmagnesium bromide and "magnesate" complexes.
- Magnesate complexes are for example lithium tri-tt-butylmagnesate, [2-(N,N-dimethylaminomethyl)ferrocenyl]magnesium compounds like Li 2 Mg(FcN) 2 Br 2 *(OEt 2 ) 2 , wherein Fc is ferrocenyl or halophthalocyaninato magnesate complex salts like [Mg(X)Pc 2 XH-Bu 4 N) or [Mg(X)Pc 2" ] '(PNP), wherein Pc is phthalo- cyanin and X is F, Cl or Br.
- Said magnesate complex salts can be obtained for example by reacting magnesium phthalocyanine with tetra( «-butyl)ammonium halide ((H-Bu 4 N)X, wherein X is F, Cl or Br) or with bis(triphenylphosphine)iminium halide ((PNP)X, wherein X is F, Cl or Br).
- the organometallic compound is a lithiation reagent, preferably is H-butyllithium, fert-butyllithium or phenyllithium, more preferably is tert-butyllithium.
- the temperature control is not very important and the reaction can be carried out at temperatures up to room temperature.
- lithiation reagents and especially H-butyllithium, sec-butyllithium, te/Y-butyllithium or phenyllithium a good temperature control throughout the whole step a) is important.
- the temperature in step a) is maintained at or below -75 0 C, more preferably at or below -90 0 C and even more preferably at or below -100 0 C.
- reaction step a) is carried out in a non-polar solvent.
- the solvent is selected from the group consisting of tetrahydrofuran, 1,4-dioxane, cyclohexane, diethyl ether, tert-buty ⁇ methyl ether, diisopropyl ether, benzene, toluene, and mixtures thereof.
- reaction step b) is carried out in a non-polar solvent.
- the solvent is selected from the group consisting of tetrahydrofuran, 1 ,4-dioxane, cyclohexane, diethyl ether, tert-butyl methyl ether, diisopropyl ether, benzene, toluene, and mixtures thereof.
- both steps are carried out in the same solvent.
- Polar or protic solvents like chloroform, dichloromethane, all kind of alcohols and acetonitrile are not suitable to perform the reaction.
- Example 1 l,3-Dibromo-2-iodobenzene 1,3-Dibromobenzene (47.2 g, 24.2 mL, 200 mmol, 1 eq) was added dropwise to a solution of lithium diisopropylamide (LDA, 200 mmol, 1 eq) in tetrahydrofuran (400 mL) at -78 °C. After 2 h, a solution of iodine (50.8 g, 200 mmol, 1 eq) in tetrahydrofuran (200 mL) was added and the reaction mixture was then allowed to reach 25 0 C. The solvent was evaporated and the residue was taken up in diethyl ether.
- LDA lithium diisopropylamide
- tetrahydrofuran 400 mL
- iodine 50.8 g, 200 mmol, 1 eq
- tetrahydrofuran 200 mL
- butyllithium (100 mmol) in hexanes (52 niL) was added to a solution of 2,2' ; 6,6'-tetrabromobiphenyl (47 g, 100 mmol) in tetrahydrofuran (500 mL).
- methanol (10 mL) was added and, after addition of water (200 mL), the organic phase was separated and the aqueous layer was extracted with diethyl ether (2> ⁇ 100 mL). The combined organic layers were dried over sodium sulfate before being evaporated.
- the comparative examples 2 and 3 show a total yield of about 30% based on 1 ,3-dibromo- 2-iodobenzene.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/442,237 US20100137659A1 (en) | 2006-09-26 | 2007-09-26 | Process for the synthesis of 2,2',6-tribromobiphenyl |
EP07818441A EP2069272A1 (en) | 2006-09-26 | 2007-09-26 | Process for the synthesis of 2,2',6-tribromobiphenyl |
JP2009529597A JP2010504365A (en) | 2006-09-26 | 2007-09-26 | Method for synthesizing 2,2 ', 6-tribromobiphenyl |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EPEP06020111 | 2006-09-26 | ||
EP06020111A EP1905755A1 (en) | 2006-09-26 | 2006-09-26 | Process for the synthesis of 2,2 ,6-tribromobiphenyl |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008037440A1 true WO2008037440A1 (en) | 2008-04-03 |
Family
ID=37772969
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2007/008357 WO2008037440A1 (en) | 2006-09-26 | 2007-09-26 | Process for the synthesis of 2,2',6-tribromobiphenyl |
Country Status (5)
Country | Link |
---|---|
US (1) | US20100137659A1 (en) |
EP (2) | EP1905755A1 (en) |
JP (1) | JP2010504365A (en) |
CN (1) | CN101516815A (en) |
WO (1) | WO2008037440A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11261198B2 (en) | 2016-06-20 | 2022-03-01 | Shionogi & Co., Ltd. | Process for preparing substituted polycyclic pyridone derivative and crystal thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6357190B2 (en) * | 2016-05-30 | 2018-07-11 | 株式会社神鋼環境ソリューション | Coupling method of halogenated pyridine compound and halogenated aromatic compound |
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US3710279A (en) * | 1969-12-15 | 1973-01-09 | Bell Telephone Labor Inc | Apparatuses for trapping and accelerating neutral particles |
JPS55141417A (en) * | 1979-04-24 | 1980-11-05 | Ube Ind Ltd | Production of biphenyls |
US4523682A (en) * | 1982-05-19 | 1985-06-18 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Acoustic particle separation |
US4465879A (en) * | 1983-08-19 | 1984-08-14 | Fmc Corporation | Process to insecticide intermediate |
JPH0780789B2 (en) * | 1988-03-02 | 1995-08-30 | 三菱化学株式会社 | Dimerization method of aromatic halogen compounds |
US5245466A (en) * | 1990-08-15 | 1993-09-14 | President And Fellows Of Harvard University And Rowland Institute | Optical matter |
US6216538B1 (en) * | 1992-12-02 | 2001-04-17 | Hitachi, Ltd. | Particle handling apparatus for handling particles in fluid by acoustic radiation pressure |
US6797942B2 (en) * | 2001-09-13 | 2004-09-28 | University Of Chicago | Apparatus and process for the lateral deflection and separation of flowing particles by a static array of optical tweezers |
US5938904A (en) * | 1996-03-27 | 1999-08-17 | Curagen Corporation | Separation of charged particles by a spatially and temporally varying electric field |
US6548124B1 (en) * | 2000-03-20 | 2003-04-15 | Paul Brumer | Nanometric scale coherently controlled molecular deposition |
US20020160470A1 (en) * | 2000-11-13 | 2002-10-31 | Genoptix | Methods and apparatus for generating and utilizing linear moving optical gradients |
US6833542B2 (en) * | 2000-11-13 | 2004-12-21 | Genoptix, Inc. | Method for sorting particles |
US6416190B1 (en) * | 2001-04-27 | 2002-07-09 | University Of Chicago | Apparatus for using optical tweezers to manipulate materials |
US6639208B2 (en) * | 2001-06-06 | 2003-10-28 | University Of Chicago | Optical peristaltic pumping with optical traps |
JP2003021100A (en) * | 2001-07-06 | 2003-01-24 | Tokico Ltd | Ejector and negative pressure supply device |
FR2833716B1 (en) * | 2001-12-13 | 2004-01-30 | Commissariat Energie Atomique | OPTICAL DEVICE AND OPTICAL METHOD FOR MOVING PARTICLES |
US6774333B2 (en) * | 2002-03-26 | 2004-08-10 | Intel Corporation | Method and system for optically sorting and/or manipulating carbon nanotubes |
BR0309112A (en) * | 2002-04-10 | 2005-06-28 | Arryx Inc | Apparatus, system and method for generating and controlling optical traps for handling small particles. |
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GB0618605D0 (en) * | 2006-09-21 | 2006-11-01 | Univ St Andrews | Optical sorting |
-
2006
- 2006-09-26 EP EP06020111A patent/EP1905755A1/en not_active Ceased
-
2007
- 2007-09-26 US US12/442,237 patent/US20100137659A1/en not_active Abandoned
- 2007-09-26 JP JP2009529597A patent/JP2010504365A/en active Pending
- 2007-09-26 WO PCT/EP2007/008357 patent/WO2008037440A1/en active Application Filing
- 2007-09-26 EP EP07818441A patent/EP2069272A1/en not_active Withdrawn
- 2007-09-26 CN CN200780035526.1A patent/CN101516815A/en active Pending
Non-Patent Citations (2)
Title |
---|
BECHT J-M ET AL: "A straightforward anionic coupling for the synthesis of ortho-bromobiaryls", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 60, no. 32, 2 August 2004 (2004-08-02), pages 6853 - 6857, XP004522088, ISSN: 0040-4020 * |
LEROUX ET AL: "THE ARYNE ROUTE TO BIARYLS FEATURING UNCOMMON SUBSTITUENT PATTERNS", ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, WILEY VCH VERLAG, WEINHEIM, DE, vol. 41, no. 22, 2002, pages 4272 - 4274, XP009079350, ISSN: 1433-7851 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11261198B2 (en) | 2016-06-20 | 2022-03-01 | Shionogi & Co., Ltd. | Process for preparing substituted polycyclic pyridone derivative and crystal thereof |
US11807648B2 (en) | 2016-06-20 | 2023-11-07 | Shionogi & Co., Ltd. | Process for preparing substituted polycyclic pyridone derivative and crystal thereof |
Also Published As
Publication number | Publication date |
---|---|
EP1905755A1 (en) | 2008-04-02 |
JP2010504365A (en) | 2010-02-12 |
EP2069272A1 (en) | 2009-06-17 |
US20100137659A1 (en) | 2010-06-03 |
CN101516815A (en) | 2009-08-26 |
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