Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
  • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
  • C07D493/04—Ortho-condensed systems
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
  • C07D209/56—Ring systems containing three or more rings
  • C07D209/80—[b, c]- or [b, d]-condensed
  • C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
  • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
  • C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
  • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
  • C07D495/04—Ortho-condensed systems

Definitions

• the present invention relates to a process for the preparation of cyclopentadiene derivatives of formula
• T 1 is oxygen, sulphur or a nitrogen radical
• W represents a 3 or 4 membered rest that forms a 5 or 6 membered ring.
• WO 98/22486 relates to a class of cyclopentadiene compounds containing heteroatoms used as ligands for metallocene complexes.
• WO 99/24446 describes bridged and unbridged metallocenes comprising at least a heterocyclic cyclopentadiene group of one of the following fomiulae:
• X or Y is a single bond, the other being O, S, NR or PR, R being hydrogen or an hydrocarbon group;
• R 2 , R 3 and R 4 are hydrogen, halogen, -R, -OR, -OCOR, -SR, -NR 2 or -PR 2 ;
• a is 0-4.
• CuCl 2 mediated cyclization of organocopper(I), or organozinc intermediates prepared from dilithio-derivatives with CuCN or ZnCl 2 .
• An object of the present invention is a process for preparing cyclopentadiene derivatives having formula (I)
• T 1 is selected from the group consisting of oxygen (O), sulphur (S) and NR, wherein R is a linear or branched saturated or unsaturated C 1 -C 2 o-alkyl, C 3 -C 20 -cycloalkyl, C 6 -C2o-aryl, C 7 -C 2 o-alkylaryl or C 7 -C 2 o-arylalkyl radical, optionally containing heteroatoms belonging to groups 13-17 of the Periodic Table of the Elements;
• R 1 , R 2 are hydrogen or a linear or branched saturated or unsaturated C 1 -C 20 -alkyl, C 3 -C 2 o-cycloalkyl, C 6 -C 2 o-aryl, C 7 -C 2 o-alkylaryl or C 7 -C 20 -arylalkyl radical, optionally containing heteroatoms belonging to groups 13-17 of the Periodic Table of the Elements; or they can form a C 4 -C 7 ring optionally containing O, S, N, P or Si atoms that can bear substituents;
• W is a moiety (a) or (b)
• T 2 , T 3 , T 4 , T 5 are selected from the group consisting of nitrogen (N) and CR 3 wherein R 3 is hydrogen or a linear or branched saturated or unsaturated C 1 -C 20 -alkyl, C 3 -C 2 o-cycloalkyl, C 6 -C 2 o-aryl, C 7 -C 2 o-alkylaryl or C 7 -C 2 o-arylalkyl radical, optionally containing heteroatoms belonging to groups 13-17 of the Periodic Table of the Elements; or two adjacent groups R 3 can form a C 4 -C 7 ring optionally containing O, S, N, P or Si atoms, said ring can bear substituents; preferably not more than two groups selected from T 2 , T 3 , T 4 , T 5 are nitrogen at the same time; fi 1
• T has the same meaning as T ;
• T 7 and T 8 are selected from N and CR 3 wherein R is hydrogen or a linear or branched saturated or unsaturated C 1 -C 2 o-alkyl, C -C 20 -cycloalkyl, C 6 -C 20 -aryl, C 7 -C 2 o-alkylaryl or C 7 -C 2 o-arylalkyl radical, optionally containing heteroatoms belonging to groups 13-17 of the Periodic Table of the Elements; optionally two adjacent group R 3 can form a C 4 -C 7 ring optionally containing O, S, N, P or Si atoms, said ring can bear substituents; with the proviso that when T 6 is different from NR, T 7 and T 8 are both CR 3 ; preferably when T 6 is NR, at least one group between T 7 and T 8 is CR 3 ; said process compres the following steps: a) reacting a compound of formula (II)
• the coupling system is a reagent or a series of reagents that in one or more steps can couple the two compounds of steps a) in order to form the compound of formula (IV).
• Examples of coupling systems can be found in "Comprehensive Organic Transformations” ed. 1989 VCH Publishers pages 45-70. Below is an illustrative non limiting list of coupling systems and relevant references.
• the amount of the coupling system used depends obviously on the type. Generally it is used at least one equivalent of coupling system.
• a prefened step a) comprises the following substeps: i) contacting the compound of formula (II) with magnesium to form the conespondent Grignard reagent; ii) contacting the Grignard reagent formed in step i) with the compound of formula (ffl) in the presence of a compounds selected from the group consisting of [1,3- bis(diphenylphosphino)propane]dichloronickel (dpppNiCl2), [l, -bis(diphenylphosphino)fenocene]dichloropalladium (dppfPdCl 2 ), tetrakis(triphenylphosphino)palladium; preferably with dpppNiCl 2 .
• step a) comprises the following substeps i) contacting the compound of formula (HI) with magnesium to form the conespondent Grignard reagent; ii) contacting the Grignard reagent formed in step i) with the compound of formula (II) in the presence of a compounds selected from the group consisting of [1,3- bis(diphenylphosphino)propane]dichloronickel (dpppNiCl 2 ), [ 1 , 1 ' -bis(diphenylphosphino)fenocene] dichloropalladium (dppfPdC ;), tetrakis(triphenylphosphino)palladium; preferably with dpppNiCl 2 .
• a further prefened step a) comprises contacting two equivalents of the compound of formula (II) with a coupling system comprising i) an alkali or alkaline earth-metal, preferably zinc (zinc powder or granules (mossy zinc)); ii) a compound of formula QG 3 or a compound of formula G 2 Q-A-QG 2 wherein Q is a phosphorus or nitrogen atom, G equal to or different from each other are selected from the group consisting of linear or branched saturated or unsaturated C 1 -C 20 -alkyl, C 3 -C 2 o-cycloalkyl, C 6 -C 20 -aryl, C 7 -C 2 o-alkylaryl, C 7 -C 2 o-arylalkyl radical, optionally containing heteroatoms belonging to groups 13-17 of the Periodic Table of the Elements and A is a coupling system comprising i) an alkali or alkaline earth-metal, preferably zinc
• Step a) is carried out at a temperature range of from -78 C to 100°C, preferably from 10°C to 60°C.
• aprotic solvents such as toluene, diethyl ether, hexane, tetrahydrofuran, dimethyl formamide, etc.
• the product obtained from step a) is purified by process known in the art such as filtration, crystallization, chromatography, distillation; otherwise it is used as such.
• the carbonylating system is defined as reagent or a series of reagents that in one or more steps can close the five membered ring in order to obtain compound of formula (PVa).
• Carbonylating step b) depends from the carbonyl system used.
• a prefened step b) comprises the following substeps: i) contacting the compound of formula (IV) obtained from step a) with two equivalents of a base; and ii) treating the dianionic compound obtained from step i) with a compound of formula (EX)
• step b) wherein R and R 5 equal to or different from each other are selected from the group consisting of hydrogen, chlorine, bromine, iodine, OR and NR 2 , wherein R is described above; preferably R 4 is chlorine bromine, iodine CF 3 , Cl 3 or OR, more preferably chlorine or OCH 2 CH 3 ; preferably R 5 is selected from the group consisting of CF 3 , Cl 3 , OR and NR 2 , wherein R is described above, more preferably R 5 is NR 2 , even more preferably R 5 is N(CH 3 ) 2 ;
• An alternative embodiment for carrying out step b) comprises the following substeps: i) contacting the compound of formula (IV) obtained from step a) with two equivalents of a base and subsequently with one equivalent of a compound selected from chlorine, bromine or iodine in order to obtain an anionic monohalogenated derivative; and ii) treating the an anionic monohalogenated compound obtained from step i) with a
• M is a transition metal of groups 4-11 of the periodic table
• L is a ligand that coordinates the metal M that can be neutral or with a positive or negative charge
• a ranges from -4 to +4 it represents the charge of the complex when a is 0 the complex is neutral
• m ranges from 1 to 20
• j ranges from 0 to 30
• n ranges from 1 to 50; preferably a ranges from -2 to +2
• m ranges from 1 to 10
• j ranges from 0 to 5 and n ranges from 1 to 20.
• a further alternative embodiment for carrying out step b) comprises the following substeps: i) contacting the compound of formula (IV) obtained from step a) with a halogenating compound and subsequently with one equivalent of a base in order to obtain an anionic monohalogenated derivative; and ii) treating the an anionic monohalogenated compound obtained from step i) with' a compound of formula (LXa) wherein M is a transition metal of groups 4-11 of the periodic table; L is a ligand that coordinates the metal M that can be neutral or with a positive or negative charge; a ranges from -4 to +4, it represents the charge of the complex when a is 0 the complex is neutral; m ranges from 1 to 20; j ranges from 0 to 30; and n ranges from 1 to 50; preferably a ranges from -2 to +2; m ranges from 1 to 10; j ranges from 0 to 5 and n ranges from 1 to 20.
• the base used in step b) is preferably selected from hydroxides and hydrides of alkali- and alkaline-earth metals, metallic sodium and potassium and organometallic lithium compounds. Most preferably, said bases are methyllithium, n-butyllithium, or tertbutyUithium optionally activated with tetramethylethylene diamine (TMEDA).
• TEDA tetramethylethylene diamine
• halogenating compounds are described in "Comprehensive Organic Transformations” ed. 1989 VCH Publishers pages 315-318, such as for example chlorine, bromine, iodine CuCl 2 , CBr 4 , N-bromo-succinimide, N-chloro-succinimide.
• Non limitative example of compounds of formula (IX) are: carbethoxyimidazole, triphosgene, ethyl N,N-dimethylcarbamate, chloride of N,N- dimethylcarbamic acid.
• ligands L are; halogen, hydrogen, nitrogen, amines, phosphine, cyclopentadienyl derivatives, octadienes.
• Step b) is carried out to a temperature range of from -78 C to 100°C preferably from -20°C to
• step b) is purified by process known in the art such as filtration, recrystallization, chromatography, distillation; or alternatively is used as such.
• step c) various reducing agent known in the art can be used.
• Example of suitable reducing agent used in step c) are described in "Comprehensive Organic transformations” ed. 1989
• Prefened reducing agents are LiAlH 4 /AlCl and N 2 H 4 /base, such as NaOH and KOH.
• the solvent for carrying out step c) depends upon the reducing agent used. For example when
• LiAlH 4 /AlCl is used the reaction is carried out is an aprotic solvent either polar or apolar such as tetrahydrofuran, dimethoxyethane, diethyl ether, toluene, pentane, hexane.
• polar or apolar such as tetrahydrofuran, dimethoxyethane, diethyl ether, toluene, pentane, hexane.
• N 2 H 4 /base is used a protic solvent such as water or diethylene glycol can also be used, optionally in the presence of a phase transfer agent.
• the temperature depends from the reducing agent used, it generally ranges from -80 C to 300 C, preferably from 0°C to 150 C.
• the step c) comprises the following substeps: i) contacting the compound of formula (Via) with N 2 H 4 ; ii) adding a solution of KOH in water; and iii) filtering the solid and recovering the product.
• Step i) is preferably carried out in water, toluene or diethylene glycol; step ii) is preferably carried out in the presence of a phase transfer agent, preferably diethylene glycol.
• step c) The product obtained from step c) is purified by process known in the art such as filtration, crystallization, column chromatography, preferably by filtration.
• T 1 is preferably sulphur or oxygen, more preferably is sulphur;
• T 2 is NCH 3 or CH, more preferably CH;
• T 3 , T 4 , T 5 are preferably CH;
• R 1 and R 2 are preferably hydrogen methyl, ethyl, phenyl, trimethylsilyl group or together form a benzene ring; more preferably R 1 is methyl and R 2 is hydrogen or together form a benzene ring;
• Ln the compound of formula (lb) preferably:
• T 1 and T 6 are the same and they are sulfur or oxygen, more preferably they are sulfur;
• T 7 and T 8 equal to or different from each other are preferably CR 3 ; more preferably T is CH or form with T a benzene ring;
• T 7 is preferably hydrogen C-CH 3 , C-CH 2 CH 3 , C-C 6 H 5 , Csi(CH 3 ) 3 or form with T 8 a benzene ring, more preferably T 7 is C-CH 3 or form with T 8 a benzene ring;
• R 1 and R 2 are preferably hydrogen methyl, ethyl, phenyl, trimethylsilyl group or together form a benzene ring; more preferably R 1 is methyl and R 2 is hydrogen or together form a benzene ring;
• Non limitative examples of compounds of formula (I) are:
• Compounds of formula (I) can be used as ligands for the synthesis of metallocene complexes, such as those described in WO 98/22486 WO 99/24446 and PCT/EP00/13191. These complexes are useful as catalyst components for polymerizing alpha-olefins.
• the syntheses of the metallocene compounds starting from the compounds of the present invention are described in the above mentioned applications.
• the compounds of formula (I) can be treated with a base and then contacted with a compound of formula YL'Cp wherein Y is halogen, preferably chlorine, L' is a suitable bridge and Cp is a substituted or unsubstituted cyclopentadienyl radical.
• a further object of the present invention is a compound of formula (X)
• R 3 is different from hydrogen.
• a still further object of the present invention is a compound of formula (XI)
• a mixture of 119 g (892 rnmol) of A1C1 3 was suspended into 150 mL of dichloromethane. To this mixture was added 66.6 g (595 mmol) of 2-thiophenecarboxaldehyde in a way the temperature raised to reflux. After addition the mixture was stined for 30 minutes at room temperature. Then 33.8 mL (654.5 mmol) of Br 2 was added and the mixture was stined overnight and poured into a mixture of 250 g of ice and 50 mL of concentrated HC1. The organic layer was isolated and washed subsequently with 300 mL of 5w% NaHCO 3 and 300 mL of 5 w% aqueous KOH.
• step a) l-methyl-3-(4-methylphenyl)-lH-indole
• NiCl 2 dppp was added to a solution of p-TolylMgBr in ether (prepared from 0.6 g of Mg
• the hexane solution was concentrated to a volume of 10 mL and kept 10 hours at r.t.
• the crystalline product was separated from mother solution, wished twice with cold pentane and dried. Yield 0.48 g (20%) of orange crystals.

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• Chemical & Material Sciences (AREA)
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• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
• Plural Heterocyclic Compounds (AREA)
• Furan Compounds (AREA)
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• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

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• 2002
  • 2002-05-08 US US10/477,315 patent/US7253292B2/en not_active Expired - Fee Related
  • 2002-05-08 EP EP02742976A patent/EP1387827B1/en not_active Expired - Lifetime
  • 2002-05-08 AT AT02742976T patent/ATE409180T1/de not_active IP Right Cessation
  • 2002-05-08 DE DE60229054T patent/DE60229054D1/de not_active Expired - Lifetime
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  • 2002-05-08 WO PCT/EP2002/005094 patent/WO2002092564A2/en not_active Ceased
• 2007
  • 2007-06-27 US US11/819,560 patent/US7635781B2/en not_active Expired - Fee Related

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