CN1307137C - Preparation of substituted indenes - Google Patents
Preparation of substituted indenes Download PDFInfo
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- CN1307137C CN1307137C CNB2003801018106A CN200380101810A CN1307137C CN 1307137 C CN1307137 C CN 1307137C CN B2003801018106 A CNB2003801018106 A CN B2003801018106A CN 200380101810 A CN200380101810 A CN 200380101810A CN 1307137 C CN1307137 C CN 1307137C
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
- C07C1/24—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms by elimination of water
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/325—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom
- C07C1/326—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom the hetero-atom being a magnesium atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/14—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the side-chain of aromatic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/20—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms
- C07C17/202—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction
- C07C17/208—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction the other compound being MX
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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Abstract
The present invention relates to a simple process for preparing specifically substituted indenes of formula (I) or (Ia) to compounds of formula (II) serving as starting materials and to the use of the compounds of formula (II) as starting materials for the synthesis of substituted indenes.
Description
The present invention relates to a kind of indenes that the preparation shown in the formula (I) specifically replaces or their simple but effective method of double bond isomer shown in the formula (1a) of being used for
Relate to the compound shown in the formula (II) as raw material
Wherein
R
1Be C
1-C
40-alkyl,
R
2For replacing or unsubstituted C
6-C
40-aryl, wherein the substituting group of this aryl is the alkyl that does not wherein comprise hydrogen atom with respect to the alpha position of aryl or vinyl,
R
3-R
5Identical or different, respectively for hydrogen or wherein at the C that does not comprise hydrogen atom with respect to the alpha position of aryl or vinyl
1-C
40-alkyl, perhaps R
2With R
3Form loop systems together, and
X is a halogen atom,
And the purposes that relates to the raw material of the synthetic indenes that replaces of formula (II) compound.
The indenes that replaces is to be used to prepare pharmacy (Negwer, VCH 1987, p.1703 ff.), plant protection, fine chemicals, liquid crystal and the important intermediate that is used for metallocene catalyst (Chem.Rev.2000, number 4) the field active compound of alpha-olefin polymerization.
The indenes that replaces can be used for preparing the chirality ansa-metallocene as the transition metal component of the effective catalyst of important stereospecific olefinic polymerization.
The variation of ligand system for example replaces, and can influence the character of catalyzer in the target mode.This may change the productive rate that makes polymkeric substance, molecular weight distribution, and tacticity and fusing point make it reach desirability (Chem.Rev.2000, number 4).As US 5,770,753 and US5,723,640 is described, comprise as the π ligand, wherein 1 have abutment in the position, 2 preferably have alkyl, particularly alkyl in the position, and 4 further have alkyl in the position, particularly replace or the luxuriant zirconium (zirconocenes) of the bridging of the indenyl of unsubstituted aryl has been considered to efficient especially and stereoselective catalyst system.Be used for of the indenes preparation of the ligand system of these efficient metallocenes by corresponding replacement.
The cost of the indenes that the synthetic metallocene of preparation needs is an integral part of synthetic metallocene total cost.The whole bag of tricks that is used to prepare the indenes that 2-alkyl-4-aryl replaces is disclosed, and for example US 5,770,753, and US 5,723,640, WO 98/40331 and US 5,789,634.Aryl in the position 4 is usually by introducing by the mode of transition metal-catalyzed aryl-aryl coupling, both can introduce when synthesis program begins also and can be just to have introduced after indone or indenyl skeleton have been set up.In aforesaid method, 2 alkyl on the indenyl skeleton were always introduced before 1-indone system forms.Organometallics 1993,12,4391-4401 discloses the synthetic of biindyl metallocene, this biindyl metallocene bridge joint is unsubstituted at 2 and six-ring, wherein directly pass through α in two indenyl ligands of 2 position bridge joints, the bis-Grignard reagent of α-two chloro-o-Xylol and suitable bridge joint reagent react form.Organometallics1999,18,4147-4155 disclose that 2 big aryl of quilt replace and six-ring on unsubstituted indenes synthetic, equally by α, α-two chloro-o-Xylol is synthetic with the reaction of the methyl benzoate that suitably replaces.
So far knownly be used for preparing last 2 of handle-metallocene indenyl system and change and indenyl system last 4 or 7 has that fixing substituent 2-alkyl-4-aryl-or the method for the indenes that replaces of 2-alkyl-7-aryl is still too time-consuming, thus too expensive.
An object of the present invention is to find simple, flexibly, fast and the 2-alkyl-4-aryl indenes that replaces of cheap preparation or the method for 2-alkyl-7-aryl indenes, this method can avoid currently known methods shortcoming and, particularly, the group in 2 in the endenyl system is provided the variation of plain mode.
We have found that and to realize this purpose by following method, comprising the indenes of the replacement shown in the preparation formula (I)
And their double bond isomer shown in the formula (1a)
Comprising transformation formula (II) compound
Become two organometallic compound compounds shown in the formula (III)
And itself and formula (IV) compound are reacted:
Obtain the formula V indanol
And by dehydration these are transformed into formula (I) or indenes (1a),
Wherein
R
1Be C
1-C
40-alkyl,
R
2For replacing or unsubstituted C
6-C
40-aryl, wherein the substituting group of this aryl is the alkyl that does not wherein comprise hydrogen atom with respect to the alpha position of aryl or vinyl,
R
3-R
5Identical or different, respectively for hydrogen or wherein at the C that does not comprise hydrogen atom with respect to the alpha position of aryl or vinyl
1-C
40-alkyl, perhaps R
2With R
3Form loop systems together, wherein do not comprise hydrogen atom with respect to aryl or vinyl α position, or R
2With R
3Obtain ring together,
X is a halogen atom,
M is a lithium, sodium, and potassium or magnesium monohalide or two group M represent a magnesium atom together, and
Y is the leading group of nucleophilic.
In addition, we go back discoverable type (II) compound.
Work as R
2, R
3, R
4, R
5Each defines as above with X, and these compounds are as the purposes of the raw material of the synthetic indenes that replaces.
For example, R
1Be C
1-C
20-alkyl, C
6-C
18-aryl, C
7-C
40-aralkyl or C
7-C
40-alkylaryl.R
1Be preferably C
1-C
20-alkyl, particularly straight chain, side chain or cyclic C
1-C
10-alkyl.
R
2For replacing or unsubstituted C
6-C
40-aryl, wherein the substituting group of this aryl is the alkyl that does not wherein comprise hydrogen atom with respect to the alpha position of aryl or vinyl, R
2Be preferably and replace or unsubstituted C
6-C
18-aryl, as phenyl, the 1-naphthyl, phenanthryl, the 3-tert-butyl-phenyl, the 4-tert-butyl-phenyl, 3,5-two (tertiary butyl) phenyl, 4,4 '-biphenyl or 3,5-two (phenyl) phenyl.
R
3-R
5Identical or different, respectively for hydrogen or wherein at the C that does not comprise hydrogen atom with respect to the alpha position of aryl or vinyl
1-C
40-alkyl.The example of such alkyl is the tertiary butyl, tert-pentyl, and 1-adamantyl (adamanty1), phenyl, the 1-naphthyl, phenanthryl, the 3-tert-butyl-phenyl, the 4-tert-butyl-phenyl, 3,5-two (tertiary butyl) phenyl, 4,4 '-biphenyl or 3,5-two (phenyl) phenyl.R
3-R
5Be preferably hydrogen.
Radicals R
2And R
3May form ring together, wherein the alpha position with respect to aryl or vinyl does not comprise hydrogen atom, R
2And R
3Particularly preferably form replacement or unsubstituted 1,3-butadiene-1,4-two bases with the atom that connects them.R
2And R
3Particularly preferably form unsubstituted 1,3-butadiene-1,4-two bases with the atom that connects them.
X is halogen atom such as chlorine, bromine or iodine, preferred chlorine.
M is preferably the magnesium monochloride.
Y is nucleophilic leavings group such as halogen, R
6CO
2Or OR
6Group.Y is preferably OR
6Group, wherein R
6Be C
1-C
40Alkyl is C in this way
1-C
20-alkyl, C
6-C
18-aryl, C
7-C
40-aralkyl or C
7-C
40-alkylaryl.R
6Be preferably C
1-C
10-alkyl.
The hydrogen atom that is present in aryl or vinyl α position is, for example, and the methyl (CH of toluene
3-C
6H
5) or the methyne ((CH of isopropyl benzene
3)
2CH-C
6H
5) in the benzylic hydrogens atom, the perhaps methylene radical (CH of 1-butylene
2=CHCH
2-CH
3In allylic hydrogen atom.
Unless otherwise defined, alkyl is a straight chain, side chain or cyclic group such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, n-pentyl, n-hexyl, cyclohexyl, n-heptyl or n-octyl.
Above-mentioned disclosed the inventive method is preferably used for the indenes of preparation formula (I) or replacement (1a), wherein
R
1Be straight chain, side chain or cyclic C
1-C
10-alkyl,
R
2For replacing and unsubstituted C
6-C
18-aryl is selected from and comprises phenyl, the 1-naphthyl, and phenanthryl, the 3-tert-butyl-phenyl, the 4-tert-butyl-phenyl, 3,5-two (tertiary butyl) phenyl, 4,4 '-biphenyl and 3,5-two (phenyl) phenyl groups.
R
3-R
5Respectively be hydrogen,
X is the chlorine atom,
M is preferably the magnesium monochloride, and
Y is OR
6, R wherein
6Be straight chain, side chain or cyclic C
1-C
10-alkyl.
In preferred version, can disclosed in more detail group and substituting group as follows:
R
1Be straight chain, side chain or cyclic C
1-C
10-alkyl.Radicals R
1Example be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, n-pentyl, cyclopentyl, n-hexyl, cyclohexyl, n-heptyl, n-octyl and positive decyl.
R
2For replacing and unsubstituted C
6-C
18-aryl is selected from and comprises phenyl, the 1-naphthyl, and phenanthryl, the 3-tert-butyl-phenyl, the 4-tert-butyl-phenyl, 3,5-two (tertiary butyl) phenyl, 4,4 '-biphenyl and 3,5-two (phenyl) phenyl groups.R
2Particularly preferably be phenyl, 1-naphthyl, 4-tert-butyl-phenyl or 3,5-two (tertiary butyl) phenyl.
Y is OR
6, R wherein
6Be straight chain, side chain or cyclic C
1-C
10-alkyl, for example methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, n-pentyl, cyclopentyl, n-hexyl, cyclohexyl, n-heptyl, n-octyl or positive decyl.R
6Be preferably methyl or ethyl.
In particularly preferred the inventive method, formula (II) compound
Radicals X wherein, R
2, R
3, R
4And R
5Define as above,
By in the presence of transition-metal catalyst, coupling formula (VI) compound
With formula (VII) compound
R
2-X
2 (VII)
Both but formula (VI) compound or formula (VII) compound at first became corresponding organometallic compound, particularly lithium or Grignard compound, then formula (VIII) coupled product
With the halogenating agent reaction, if desired, the halogen atom that will introduce like this replaces with other halogen atoms subsequently, obtains formula (II) compound
Wherein
X
1Be halogen, particularly chlorine, bromine or iodine, preferred chlorine, and
X
2Be halogen, particularly chlorine, bromine or iodine, preferred bromine.
Formula (VI) and (VII) compound can buy from the market.Formula (VI) or (VII) compound can the known method of document become corresponding organolithium compound or Grignard compound, some organometallic compound also can have been bought from the market.Such the synthetic of Grignard reagent is disclosed in, for example, and Holm, Torkil, J.Chem.Soc.PerkinTrans.2.1981,464-467.With formula (VI) and (VII) compound be that the synthetic of other organometallic compound of raw material can carry out according to the standard method of organometallic chemistry, for example, can be with reference to March, Advanced Organic Chemistry, 4thedition, 1992, and the reference of wherein quoting.
For the aryl-aryl coupling of synthesis type (VIII) compound in the presence of transition-metal catalyst is known, can be according to known document, for example, Synthesis 1990, and the 147-148 disclosed method is carried out.The transition-metal catalyst that is preferably used for linked reaction also is that document is known, can buy from the market usually.
Transition-metal catalyst uses the periodic table of elements 8 to 10 families, particularly 10 group 4 transition metal complexes in principle.Useful especially catalyzer is the title complex of the title complex of nickel or palladium, particularly nickel, nickelous chloride (II) for example, [1,3-two (diphenylphosphine) propane] nickel (II) muriate (NiCl
2[dppp]
2), [1,2-two (diphenylphosphine) ethane] nickel (II) muriate (NiCl
2[dppe]
2), two (triphenylphosphine) nickel (II) muriate, [1,1 '-two (diphenylphosphine) ferrocene] nickel (II) muriate methylene dichloride adducts.Replace lithium aryl or aryl magnesium compound to be used under the linked reaction situation at aryl boric acid, preferred especially the use as palladium complex as described in WO 98/40331 and the reference quoted thereof as catalyzer.
The linked reaction that is used for preparation formula (VIII) is carried out in the shielding gas environment at inert solvent that is suitable for special reagent or solvent mixture, and the example of solvent is an ether, tetrahydrofuran (THF), and toluene, or the like.
Two methyl in formula (VIII) compound are that document is known to the conversion of two monochloromethyls (formula (II)) in principle, usually by using bromizating agent such as elemental bromine or N-bromine succinimide or using chlorination reagent such as elemental chlorine or SULPHURYL CHLORIDE free group side chain halogenation to carry out (with reference to March, Advanced Organic Chemistry, 4th edition, 1992, and the reference of quoting).
Halogen group X is similarly the known method of document by the replacement of other halogen groups X in formula (II) compound, be disclosed in, for example, and March, Advanced OrganicChemistry, 4th edition, 1992, and in the reference of quoting.
The preparation of formula (III) compound can be according to as Organometallics1993, and the known method of 12,4398 described documents is carried out.If suitable, may be corroded the magnesium of activatory smear metal or powder type by glycol dibromide except the surface, also can use other highly active magnesium sources, as magnesium-anthracene, by formula (II) compound production formula (III) compound.
On the reaction principle of formula (III) compound and formula (IV) compound formation formula V compound is the known method of document, can use Organometallics 1993,12,4398 or Organometallics 1999,18, the 4147-4155 disclosed method is carried out.Indane-2-the alcohol that forms can be by standard method, and for example US 5,770,753 described methods, and dehydration forms formula (I) or indenes (Ia).May use acid catalyst to be, for example, tosic acid, sulfuric acid, hydrochloric acid or strong acid ion-exchanger.
The present invention illustrates with following non-restrictive example:
General method:
Unless otherwise noted, the preparation of organometallic compound and processing are under the secluding air and moisture condition of argon gas as shielding gas (Schlenk technology or glove box).Before the use, required whole anhydrous solvents are with argon purge and at the molecular sieve inner drying.
1H NMR spectrum is at CDCl
3In with the frequency measurement of 400MHz.Chromatogram purification uses Fluka silica gel 60 (230-400 orders) to carry out.
Embodiment 1:
The 4-tertiary butyl-2 ', 3 '-dimethyl diphenyl
23.8 gram (1.1eq.) magnesium (being used for the Grignard reaction of Aldrich) are suspended in 95 milliliters of tetrahydrofuran (THF)s (THF) and pass through to add a small amount of iodo activation.Add 62.7 gram (0.45 moles) 2 subsequently, the 3-dimethylated chlorobenzene.In order to cause the Grignard reaction, add several glycol dibromides carefully.After successfully inducing reaction, drip 62.7 gram (0.45 moles) 2 with 380 milliliters of THF dilutions, the 3-dimethylated chlorobenzene leniently seethes with excitement reaction soln.Reaction mixture refluxed is reacted (2 hours) up to most of magnesium subsequently.Behind the reaction mixture cool to room temperature, 95 milliliters of other THF are added viscous mixture.-tertiary butyl bromobenzene right with 190.0 grams (0.89 mole) of 190 milliliters of THF dilutions placed other reaction flask.Add 1.0 gram (1mol%) nickelous chlorides (II), then add Grignard solution carefully.Temperature rises to 80 ℃ rapidly.This reaction mixture was stirred 2 hours at 50-55 ℃.Behind the cool to room temperature, add 190 milliliters 2 moles hydrochloric acid carefully.With ether (3 * 200 milliliters) aqueous phase extracted, with organic phase dried over mgso and the decompression separation solvent that merges.With the resistates recrystallization, obtain two crystallising parts (first part: 139.3 grams, according to GC100%/second section: 20.5 grams, according to GC 96.2%) with ebullient ethanol.The productive rate that merges: 159.8 grams (0.67 mole/75%).
1H NMR (400MHz, CDCl
3: δ=7.41 (" d ", 2H, aromatics), 7.21 (" d "＜2H, aromatics), 7.14-7.07 (m, 3H, aromatics), 2.33 (s, 3H, CH
3), 2.16 (s, 3H, CH
3), 1.36 (s, 9H, the tertiary butyl) ppm.
Embodiment 2
The 4-tertiary butyl-2 ', 3 '-two (brooethyl) biphenyl
With 0.58 mole of 137.2 gram) the 4-tertiary butyl-2 ', 3 '-dimethyl diphenyl is dissolved in 576 milliliters of tetracol phenixin.Add 205.1 gram (1.15 moles) N-bromine succinimides and 1.37 gram (8.3 mmole) AIBN and this mixture promptly is heated to reflux temperature.React completely after (according to tlc 3 hours), with reaction mixture cool to room temperature and the sedimentary succinimide of filtering separation.Further use the tetracol phenixin washing leaching cake.The filtrate that reduction vaporization merges removing desolvated.Obtain the thick product of 259.5 grams.Add 550 milliliters of ethanol, this mixture is placed the crystallization of spending the night.If there is not crystalline deposit, the small-crystalline of the product of experiment before then in this solution, adding.Product promptly crystallizes out, filtering separation crystallization and use washing with alcohol.Productive rate: 179.8 grams (0.45 mole/79%/84.4%, pass through GC).
1H NMR (400MHz, CDCl
3): δ=7.45,7.38,7.31,7.21 (4 * m, 7H, aromatic bases), 4.78,4.61 (2 * s, 2 * 2H, CH
2Br), 1.36 (s, 9H, the tertiary butyl) ppm.
Embodiment 3
The 4-tertiary butyl-2 ', 3 '-two (chloromethyl) biphenyl
With 40.0 gram (101.0 mmole) tertiary butyls-2,3-two (bromotrifluoromethane) biphenyl is dissolved in 660 milliliters of DMF.Adding 25.7 restrains (6eq.) lithium chlorides and this reaction mixture was at room temperature stirred 24 hours.Add 500 ml waters and 300 milliliters of ether subsequently and with ether (2 * 200 milliliters) aqueous phase extracted.The organic phase water (3 * 150 milliliters) and the saturated nacl aqueous solution (1 * 100 milliliter) that merge are washed and use dried over mgso.Removal of solvent under reduced pressure obtains yellow oil.With 200 milliliters of alcohol crystals, obtain 17.9 gram white crystals.Concentrating under reduced pressure mother liquor and crystallization.Obtain other 5.5 gram second section crystallizations.Merge productive rate: 23.4 grams (76 mmoles/75%/89.5% passes through GC).
1H NMR (400MHz, CDCl
3): δ=7.46-7.26 (m, 7H, aromatic base), 4.86,4.67 (2 * s, 2 * 2H, CH
2Cl), 1.36 (s, 9H, the tertiary butyls).
Embodiment 4
4-(4-tert-butyl-phenyl)-2-methyl isophthalic acid H-indenes and 7-(4-tert-butyl-phenyl)-2-methyl isophthalic acid H-indenes
8.4 gram (20.0 mmole) magnesium-anthracene 3THF are dissolved in 100 milliliters of THF.Under 0 ℃, in 30 minutes, drip 3.07 gram (10.0 mmole) tertiary butyls-2, the solution of 3-two (chloromethyl) biphenyl in 20 milliliters of THF.This reaction mixture was at room temperature stirred other 30 minutes.(GC analyzes: 60% 2 Grignard form+oligopolymer form) to obtain sample and hydrolysis.Under 0 ℃, in 30 minutes, drip 741 milligrams of (1eq.) methyl acetates in 30 milliliters of THF solution and this reaction mixture at room temperature stirred spends the night.Subsequently reaction mixture is added the ammonium chloride saturated solution.With ether (3 * 100 milliliters) aqueous phase extracted.Merge organic phase, the dry and filtration with magnesium chloride, solvent evaporated under reduced pressure.Indanol and anthracene that the GC of thick product (7.28 gram) analyzes demonstration 15% to be needed are in the same place with other by product.By column chromatography, use heptane as elutriant, remove anthracene, and use 1: 1 methylene dichloride/alcohol mixture wash-out indanol.To be dissolved in 40 milliliters of toluene and in the presence of the 5mol% tosic acid, on water trap, reflux 1.5 hours except that the yellow oil that obtains after desolvating (2.3 gram, 64.4% indanol is according to GC).Wash organic phase and use dried over mgso with saturated sodium bicarbonate solution (1 * 40 milliliter).Removing desolvates and obtain 0.72 by column chromatography purification restrains 1: 1 mixture (935, according to GC) that (2.8mmol/28%) needs indenes.
1H NMR (400MHz, CDCl
3): δ=7.48-7.14 (m, aromatic base), 6.72,6.54 (2 * s ,=C-H), 3.42,3.38 (2 * s, CH
3), 2.16 (" s ", CH
2), 1.39 (" s ", the tertiary butyl) ppm.
Embodiment 5
4-(4-tert-butyl-phenyl)-2-methyl dihydro indenes-2-alcohol
By means of dry 633 milligrams down of hair drier decompressions (26 mmoles, 4eq.) Mg powder (50 orders/Aldrich).Add 10 glycol dibromides of 10 milliliters of THF peace morals.This mixture of reflux is up to gas evolution, and activation fully.Removal of solvent under reduced pressure adds 10 milliliters of fresh THF.Add 2.0 gram (6.5 mmole) tertiary butyls-2,3-two (chloromethyl) biphenyl in 120 milliliters of THF solution and this suspension at room temperature effectively stirred 3 hours.Continue to stir and spend the night, filter the light jade-green turbid solution that obtains and remove excessive magnesium.Filtrate is cooled to-78 ℃, in 1 hour, drips the solution of 482 milligrams of (6.51 moles) methyl acetates in 60 milliliters of THF.In 2 hours, reaction soln is warming to 0 ℃.Add 80 ml waters subsequently, this solution decompression is concentrated.In order to dissolve magnesium salts, add 3 milliliters of concentrated hydrochloric acids, with methylene dichloride (3 * 50 milliliters) dichloromethane extraction water.Merge organic phase, use sal epsom, subduction is subsequently desolvated.The column chromatography purification product uses heptane/dichloromethane mixture to separate nonpolar by product, obtains product with the absolute dichloromethane wash-out, is yellow product.Productive rate: 0.64 gram (2.28 mmoles/35%/94.5% passes through GC).
1H NMR (400MHz, CDCl
3): δ=7.43-7.22 (m, 7H, aromatic base), 3.08 (m, 4H, CH
2), 1.48 (s, 3H, CH
3), 1.35 (s, 9H, the tertiary butyl) ppm.
Embodiment 6
4-(4-tert-butyl-phenyl)-2-sec.-propyl dihydro indenes-2-alcohol
By means of dry 633 milligrams down of hair drier decompressions (26 mmoles, 4eq.) Mg powder (50 orders/Aldrich).Add 10 glycol dibromides of 10 milliliters of THF peace morals.This mixture of reflux is up to gas evolution, and activation fully.Removal of solvent under reduced pressure adds 10 milliliters of fresh THF.Add 2.0 gram (6.5 mmole) tertiary butyls-2,3-two (chloromethyl) biphenyl in 120 milliliters of THF solution and this suspension at room temperature effectively stirred 3 hours.Continue to stir and spend the night, filter the light jade-green turbid solution that obtains and remove excessive magnesium.Filtrate is cooled to-78 ℃, in 1 hour, drips the solution of 665 milligrams of (6.51 moles) methyl isobutyrates in 60 milliliters of THF.In 2 hours, reaction soln is warming to 0 ℃.Add 80 ml waters subsequently, this solution decompression is concentrated.In order to dissolve magnesium salts, add 3 milliliters of concentrated hydrochloric acids, with methylene dichloride (3 * 50 milliliters) dichloromethane extraction water.Merge organic phase, use sal epsom, subduction is subsequently desolvated.The column chromatography purification product uses heptane/dichloromethane mixture to separate nonpolar by product, obtains product with the absolute dichloromethane wash-out, is yellow product.Productive rate: 0.66 gram (2.14 mmoles/33%/96% passes through GC).
1H NMR (400MHz, CDCl
3): δ=7.41-7.21 (m, 7H, aromatic base), 3.18-2.91 (m, 4H, CH
2), 1.92 (m, 1H, CH), 1.36 (s, 9H, the tertiary butyls), 1.02 (t, 6H, CH
3) ppm.
Claims (3)
1. the replacement indenes shown in the preparation formula (I)
And their double bond isomer shown in the formula (1a)
Method, comprising transformation formula (II) compound
Become two organometallic compounds shown in the formula (III)
And itself and formula (IV) compound are reacted
Obtain the formula V indanol
And by dehydration these are transformed into formula (I) or indenes (1a),
Its Chinese style (II) compound
By coupling formula (VI) compound in the presence of transition-metal catalyst
With formula (VII) compound
R
2-X
2 (VII)
Both can make formula (VI) compound also can make formula (VII) compound at first become corresponding organometallic compound, make formula (VIII) coupled product then
With the halogenating agent reaction, obtain formula (II) compound,
Wherein
R
1Be straight chain, side chain or cyclic C
1-C
10-alkyl,
R
2For replacing and unsubstituted C
6-C
10Aryl is selected from and comprises phenyl, the 1-naphthyl, and phenanthryl, the 3-tert-butyl-phenyl, the 4-tert-butyl-phenyl, 3,5-two (tertiary butyl) phenyl, 4,4 '-biphenyl and 3,5-two (phenyl) phenyl groups,
R
3-R
5Respectively be hydrogen,
X is the chlorine atom,
X
1And X
2Be halogen,
M is the magnesium monochloride, and
Y is OR
6, R wherein
6Be straight chain, side chain or cyclic C
1-C
10-alkyl.
2. formula (II) compound
R wherein
2, R
3, R
4, R
5With the definition of X with definition in the claim 1.
3. the formula in the claim 2 (II) compound is used for the purposes of formula (I) that synthetic claim 1 limits or the raw material of the indenes that (Ia) replaces.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10249325.1 | 2002-10-22 | ||
| DE10249325A DE10249325A1 (en) | 2002-10-22 | 2002-10-22 | Production of substituted indene for use e.g. as pharmaceutical intermediate, involves reaction of a 1,2-bis-halomethylbenzene as a bis-organometallic derivative with a carboxylate ester followed by dehydration of indanol |
| US60/425,445 | 2002-11-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1705626A CN1705626A (en) | 2005-12-07 |
| CN1307137C true CN1307137C (en) | 2007-03-28 |
Family
ID=32087114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2003801018106A Expired - Fee Related CN1307137C (en) | 2002-10-22 | 2003-10-18 | Preparation of substituted indenes |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1307137C (en) |
| DE (1) | DE10249325A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110078604B (en) * | 2019-05-08 | 2021-12-03 | 台州学院 | Preparation method of indeno-indanone derivative |
| CN110183298B (en) * | 2019-05-10 | 2021-09-17 | 台州学院 | Preparation method of dibenzopentene derivative |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE618638A (en) * | 1961-06-09 | 1962-12-14 | Hoffmann La Roche | Process for the preparation of substituted hydrazine derivatives |
| US5789634A (en) * | 1997-02-05 | 1998-08-04 | Boulder Scientific Company | Coupling reactions of 2-substituted, 7-haloindenes with aryl substituents to produce metallocene catalyst intermediates |
-
2002
- 2002-10-22 DE DE10249325A patent/DE10249325A1/en not_active Withdrawn
-
2003
- 2003-10-18 CN CNB2003801018106A patent/CN1307137C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE618638A (en) * | 1961-06-09 | 1962-12-14 | Hoffmann La Roche | Process for the preparation of substituted hydrazine derivatives |
| US5789634A (en) * | 1997-02-05 | 1998-08-04 | Boulder Scientific Company | Coupling reactions of 2-substituted, 7-haloindenes with aryl substituents to produce metallocene catalyst intermediates |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1705626A (en) | 2005-12-07 |
| DE10249325A1 (en) | 2004-05-06 |
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