CA2161601A1 - Process for cross-coupling aromatic halogen compounds or perfluoroalkylsulfonates with terminal alkynes - Google Patents
Process for cross-coupling aromatic halogen compounds or perfluoroalkylsulfonates with terminal alkynesInfo
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- CA2161601A1 CA2161601A1 CA 2161601 CA2161601A CA2161601A1 CA 2161601 A1 CA2161601 A1 CA 2161601A1 CA 2161601 CA2161601 CA 2161601 CA 2161601 A CA2161601 A CA 2161601A CA 2161601 A1 CA2161601 A1 CA 2161601A1
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- palladium
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
-
- 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
- C07C29/32—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 without formation of -OH groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/28—Alcohols containing only six-membered aromatic rings as cyclic part with unsaturation outside the aromatic rings
- C07C33/30—Alcohols containing only six-membered aromatic rings as cyclic part with unsaturation outside the aromatic rings monocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/40—Halogenated unsaturated alcohols
- C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
- C07C33/48—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts with unsaturation outside the aromatic rings
- C07C33/483—Monocyclic
Abstract
A process for preparing polycyclic aromatic compounds by cross-coupling terminal alkynes with aromatic halogen compounds or aromatic perfluoroalkylsulfonates under palladium catalysis in the presence of at least one water-soluble complexing ligand, wherein the reaction medium forms an aqueous phase and an organic phase and the palladium is added in the form of a palladium compound soluble in the organic phase or in solid form as palladium metal, in particular applied to a support.
The reaction of the invention proceeds chemoselectively, so that even electrophilic groups such as esters or nitriles do not impair the course of the reaction.
The process of the invention enables organic compounds to be prepared economically in very good yields and at the same time in very high purity, in particular without contamination by the complexing ligands.
The reaction of the invention proceeds chemoselectively, so that even electrophilic groups such as esters or nitriles do not impair the course of the reaction.
The process of the invention enables organic compounds to be prepared economically in very good yields and at the same time in very high purity, in particular without contamination by the complexing ligands.
Description
216~01 HOECHST ARTIENGESELLSCHAFT HOE 94/F 323 R Dr. RI/pe Description Process for cross-coupling aromatic halogen compounds or perfluoroalkylsulfonates with terminal alkynes The invention relates to a process for coupling aromatic halogen compound~ or perfluoroalkylsulfonates with terminal alkynes under palladium catalysi~ in the presence of water-soluble complexing ligands.
The palladium-catalyzed cross-coupling reaction of aromatic halogen compounds or aromatic perfluoroalkyl-sulfonates with terminal alkynes (see, for example, R.F. Heck, Palladium Reagents in Organic Synthe~es, Academic Press, p. 260 ff.; J.P. Genet, E. Blart, M.
Savignac, Synlett 1992, 715 or G.T. Crisp, T.A.
Robertson, Tetrahedron 1992, 48, 3239) has for some years been utilized to an increasing extent in many areas of organic synthesis.
The processes cited are homogeneously catalyzed processes using Pd(II) complexes, in particular bis(triphenylphosphine)palladium(II) chloride. The presence of phosphorus-contA;n;ng complexing ligands generally considerably increases yields and selectivity of the reaction.
However, a disadvantage of these proce~es is the high catalyst costs which make an economical transfer of the process to a larger production scale (kg, t) difficult.
In addition, contAm;nAtion of the product and the waste with phosphorus compounds is observed, which can be a disadvantage, particularly in the case of active compounds.
Also known is the use of water-soluble palladium complexes for the abovementioned coupling reactions, 216160~
working in pure aqueous systems or in two-phase systems comprising an organic and an aqueous phase (see, for example, US 5,043,510 or J.P. Genet et al., Synlett 1992, 715). Here, water-soluble phosphine ligands such as triphenylphosphino-3,3',3''-trisulfonate trisodium salt (tppts) are used to obtain the water-soluble palladium complex. However, it has been stated (A.L. Casalnuovo and J.C. Calabrese, J. Am. Chem. Soc. 1990, 112, 4324) that the yields in the two-phase system are significantly lower than in the single-phase system.
In addition, N.A. Bumagin, V.V. Bykor and I.P. Belets-Raya, Izv. Akad. Nauk SSSR, Ser. Khim 1990, 2665 report low yields when using palladium(II) acetate as a catalyst.
Furthermore, the processes suffer from the above-described disadvantages such as catalyst costs and cont~m;n~tion of the product with the complexing ligands.
It is therefore an object of the present invention to provide an economically favorable process for coupling terminal alkynes with aromatic perfluoroalkylsulfonates or aromatic halogen compounds which gives the coupling products in very high purity and good yield.
It has now surprisingly been found that in the reaction of terminal alkynes with aromatic halogen compounds or aromatic perfluoroalkylsulfonates in a two-phase reaction medium in the presence of a base, catalytic amounts of a palladium compound soluble in organic solvents and at least one water-~oluble complexing ligand, arylalkynes are obtained in excellent yields and very high purities.
The invention accordingly provides a process for preparing 1-arylalkynes by cross-coupling terminal alkynes with aromatic halogen compounds or aromatic perfluoroalkylsulfonates under palladium catalysis in the presence of at least one water-soluble complexing ligand, wherein the reaction medium forms an agueous phase and an organic phase and the palladium is added in the $orm of a palladium compound soluble in the organic phase or in solid form as palladium metal, in particular applied to a support.
The reaction of the invention proceed~ chemoselectively, 80 that even electrophilic groups such as esters or nitriles do not impair the course of the reaction.
The process of the invention enables 1-arylalkynes to be prepared economically in very good yields and at the ~ame time in very high purity, in particular without cont~; n~ tion by the complexing ligands.
The solubility of the palladium compound in the organic pha~e is preferably at least 0.5 mmol/l, particularly preferably at least 5 mmol/l, very particularly preferably at least 20 mmol/l.
The process of the invention is carried out in a multiphase system which compri~es at least one aqueous phase and one organic phase. The agueous phase can here comprise not only water but also one or more water-soluble organic solvent~. Solid phases can also be present.
To carry out the process of the invention, the aromatic halogen compound or the perfluoroalkylsulfonate, the terminal alkyne, the base, the catalytic amount of the palladium or the palladium compound soluble in organic solvents and a water-soluble complexing ligand are added to a mixture of water and one or more organic solvents which do not participate in the reaction and the mixture is stirred at a temperature of from -10C to 200C, preferably at from 0C to 170C, particularly preferably at from 5C to 150C, very particularly preferably at from 10 to 120C, for a period of from 1 hour to 100 hours, preferably from 5 hours to 70 hours, particularly 2~ 6i601 preferably from 5 hours to 50 hours.
The work-up is then carried out by known methods with which those skilled in the art are familiar.
To avoid contamination of the product with palladium or its compounds, it is possible, for example, to add sufficient complexing ligand to the reaction mixture at the end of the reaction for all the palladium to remain in solution.
Naturally, the palladium can also, if desired, be removed by chromatographic methods or by precipitation, for example as sulfide.
The water-soluble, typically phosphorus-containing complexing ligand is completely removed from the product simply by separation of aqueous and organic phases.
For the further work-up after the phase separation, the crude product is usually freed of solvent and subsequently purified further by methods matched to the respective product, e.g. by recrystallization, distillation, sublimation, zone melting, melt crystallization or chromatography.
The aqueous phase can be used for new coupling reactions without 1088 of catalytic activity occurring.
Organic solvents suitable for the process of the invention which form an organic phase in the reaction medium are, for example, ethers such as diethyl ether, dimethoxymethane, diethylene glycol dimethyl ether, diisopropyl ether, tert-butyl methyl ether, hydrocarbons such a~ h~Y~ne, iso-hexane, heptane, cyclohexane, benzene, toluene, xylene, higher alcohols which are not completely miscible with water such as 1-butanol, 2-butanol, tert-butanol, amyl alcohol, ketones, e.g. iso-butyl methyl ketone, amides such as dimethylacetamide, N-methylpyrrolidone, nitriles, such as butyronitrile, and mixtures thereof.
Preferred organic solvents are ethers such as diethyl ether, dimethoxyethane, diethylene glycol dimethyl ether, diisopropyl ether, hydrocarbons such as hexane, heptane, cycloheY~ne, benzene, toluene, xylene, alcohols such as 1-butanol, 2-butanol, tert-butanol, ketones such as iso-butyl methyl ketone, amides such as N-methylpyrrolidone, and mixtures thereof.
Particularly preferred organic solvents are cyclic or acyclic, aliphatic or aromatic hydrocarbons, e.g.
cyclohexane, benzene, toluene, xylene and mixtures thereof.
In a particularly preferred variant of the process of the invention, water, one or more solvents insoluble in water and one or more solvents soluble in water are used.
Preferred organic cosolvents which are miscible with the aqueous phase are lower nitriles such as acetonitrile, formamides such as DMF, lower alcohols such as methanol, ethylene glycol and ethanol, sulfoxides such as DMS0, and cyclic ethers such as THF or dioxane.
Preferred reaction media compri~ing water, water-soluble organic solvent and water-insoluble organic solvent are mixtures of water, toluene and ethanol, water, xylene and ethanol, water, toluene and tetrahydrofuran, water, xylene and tetrahydrofuran, water, xylene and acetonitrile and water, toluene and acetonitrile, preferably each in a volume ratio of 1:2:1.
Bases which are usually used in the process of the invention are alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates, alkali metal hydrogen carbonates, alkali metal and alkaline earth metal acetates, alkali metal and ~ L~1601 alkaline earth metal Al koY; des, and also primary, secondary and tertiary amines.
Particular preference is given to alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates and alkali metal hydrogen carbonates and also secondary and tertiary alkylamines.
Particular preference is given to alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates and alkali metal hydrogen carbonates such as lithium carbonate, sodium carbonate and potassium carbonate, and also secondary amine~ such as piperidine, diethylamine or morpholine.
In the process of the invention, the base is preferably used in an amount of $rom 50 to 1000 mol%, particularly preferably from 65 to 500 mol%, very particularly preferably from 75 to 350 mol%, in particular from 90 to 200 mol%, based on the aromatic halogen compound or the perfluoroalkylsulfonate.
Catalysts used are, on the one hand, palladium compounds soluble in organic solvents, such as palladium ketonates, palladium acetylacetonates, nitrilepalladium halides, olefin palladium halides, palladium halides, allylpalladium halides and palladium biscarboxylates, preferably palladium ketonates, palladium acetyl-acetonates, bis-~2-olefinpalladium dihalides, palladium(II) halides, ~3-allylpalladium halide dimer~
and palladium biscarboxylates, very particularly preferably bis(dibenzylideneacetone)palladium(0) [Pd(dba)2], Pd(dba)2 CHCl3, palladium bi~acetylacetonate, bis(benzonitrile)palladium dichloride, ~3-allylpalladium chloride dimer, PdCl2, Na2PdCl4, dichlorobis(dimethyl-sulfoxide)palladium(II), bis(acetonitrile)palladium dichloride, palladium(II) acetate, palladium(II) proprionate, palladium(II) butanoate and (lc,5c-cyclo-octadiene)palladium dichloride.
~1501 On the other hand, palladium or palladium compounds insolid form serve as catalyst, preferably palladium in pulverized form or on a support material, e.g. palladium on activated carbon, palladium on aluminum oxide, palladium on barium carbonate, palladium on barium sulfate, palladium on aluminum silicates, such as montmorillonite, palladium on SiO2 and palladium on calcium carbonate, each having a palladium content of from 0.5 to 10% by weight. Particular preference is given to palladium in pulverized form, palladium on aluminum oxide and palladium on activated carbon, each having a palladium content of from 0.5 to 10% by weight. Very particular preference is given to palladium on activated carbon having a palladium content of 2 or 7% by weight.
It i8 also possible to use catalysts cont~;n;ng, apart from palladium and the support material, further dopants such as lead (Lindlar catalyst).
In the process of the invention, the palladium catalyst is used in an amount of from 0.001 to 10 mol%, preferably from 0.01 to 5 mol%, particularly preferably from 0.05 to 3 mol%, very particularly preferably from 0.1 to 1.5 mol%, based on the aromatic halogen compound or the perfluoroalkylsulfonate.
Furthermore, in the process of the invention, one or more copper(I) compounds are advantageously used as cocatalyst.
These are usually copper(I) halides such as CuI, CuBr, CuCl, copper(I) cyanide, copper(I) thiocyanate or copper(I) acetate, preference being given to CuI and CuBr.
The copper(I) compound is usually used in a stoichiometric ratio of from 0.5 to 2:1, based on the palladium content. The stoichiometric ratio of copper to palladium is preferably 1:1.
2~6~601 Water-soluble ligands suitable for the process of the invention contain, for example, sulfonic acid salt radicals and/or sulfonic acid radicals and/or carboxylic acid salt radicals and/or carboxylic acid radicals and/or phosphonic acid salt radicals and/or phosphonic acid radicals and/or phosphonium groups and/or peralkylammonium groups and/or hydroxy groups and/or polyether groups having an appropriate chain length.
Preferred classes of water-soluble ligands are phosphines substituted by the above groups, such as trialkyl-phosphines, tricycloalkylphosphines, triarylphosphines, dialkylarylphosphines, alkyldiarylphosphines, and hetero-arylphosphines such as tripyridylphosphine and trifuryl-phosphine, where the three substituents on the phosphorus can be identical or different, chiral or achiral and where one or more of the ligands can link the phosphorus groups of a plurality of phosphines and where a part of this linkage can also be one or more metal atoms, phosphites, phosphinic esters and phosphonic esters, phospholes, dibenzophospholes and cyclic or oligocyclic and polycyclic compounds containing phosphorus atoms.
Further suitable groups of water-soluble complexing ligands comprise, for example, bipyridines, ph~n~nthrolines, porphyrins and alizarins which are modified with the abovementioned groups.
Water-soluble phosphines which are preferably used are those of the formulae (I) to (VII), P R S O ~ p o 2 - 2 ~1 ~ C O ~ ~1 (CH2)q~ NR4~X~, PR4~ X~
( I ) ~6~ 6~1 ~rl~--(CH2),,~ ~(CH2~ ~(CH2)--~r~l/50~ N, PO~ 2~, CO2 11~, ~rl--(CH2). (CH2),--Ar~l N~, X, PP~ X, ( I I ) Alkyl ~ ~(CH2~ ~AIk~l SO~U~, PO~2-2U~, CO2~U0, Alkyl / \Alk~l NR~eX~, PR~0X~, OH
_ ~SOs~U0, PO~2-2U~, CO2~U~, P((CH~ Aryl~ (Alkyl), NR,0X0, PR~0X0, OH
( lV) '' ~(CH2)n~PR2~503~ , Po32-2~, CO
~'~ q~NR ' NR4~X~, PR~X~, OH
(V) Ar~l--(CH2)~ ~(C~ ~ ~(CH2)~--Arr~ SO~OH~, ro~2 21~, CO~
~r1 1--(CH~), (CH2)~--Ar~ I NR~X~, PR,~X9. OH
( V I ) Alkyl~ ~(CH2~ ~AIkrl SO~U~, poS2 2U~, C029U~, Alkyl / \Alk~l NR40X0, PR~0X0, OH
(Vl I ) where the symbols and indices have the following _~n;ngs:
Aryl: a phenyl or naphthyl group which can also bear one or more substituents R;
~161601 Alkyl: a ~traight-chain or branched alkyl group having from 1 to 8 carbon atoms;
R,R': alkyl, aryl or aralkyl having from 1 to 18 carbon atoms;
M: alkali metal, alkaline earth metal or NR4;
X: halogen, BF4, PF6, OS02CF3, 1/2[S04];
1, m: 1 to 8;
n, o, p, q: 0, 1 to 8;
~: 0, 1 to 3.
Examples of particularly preferred water-soluble complexing ligands are given below:
(R here has, unless otherwise indicated, the meanings given for the formulae (I) to (VII)) 1. Sulfonated phosphines ~>)3P ; [(C6HS) (CH2)n]~ P n~l,2,3 and 6 ~+~303S / 6 1~
S 0 3 ~ p- and/or o- sul fonated ~1 ~ N~, NR4 S03~ 4 03S ~ r ~ Na0, NR4~
\[~
~161601 ~PPh2/(503( )Na~ )6-~~P P h 2 E I NAS
",o~s~
r2 ~ r2 ~A r~ ~ r ~A r Ar m-C~ SO~ Ar - ~-C~N~SO~IIr.
Ph e n y 1 2P~SO3(~)Na(~) 3 -nP (P C6H4S3K) n R = C6Hs ~ 2-pyridyl, 3-pyridyl; n = 1-ptp-oc6H4so3NH(i-octyl) 3] 3 216~ BOl 1.1 Phosphines having hydrophilic group~ on the periphery PPh2 ~ O I ," o (C6Hs)2pcH2cH2so5(-~No(~) S 1`'`~`
PPh2 SO3No ~ ()n ~ n ~ O, 3, 5, 7, 9, 1 2. Phosphines having quaternized aminoalkyl and aminoaryl substituents ph2p N~e (~)I(-I
~e ~e C N~) W C~3+ ~
Ph 2 P-Y-NHR2~X- Ph2P-Y-NR3~X-Y = - CH2CH2 -, - CH ( CH3 ) CH2 -, - CH2CH ( CH3 ) CH2 -; R = CH3;
X = Ie, Bue, Cle, OS02CF3e, BF4e, PF6e ~161601 , 3. Carboxylated pho phines Ph2P~COOH NaOOC r\~COONa NoOOC~ ~COONa C O O H
Ph2P~ o, m, p substituted P h2P3~COOH ~e~xco2Na Ph2P COOH P CO2Na 4. Phosphines having hydroxyalkyl or polyether ~ub~tituents H~C - O 0'~~0 PPh2 H C - O ~ O~N f PPh n > l6 n - l2, l6, llO
H 3 CO/~O~P P h 2 ~¢~ 3 J PPh2 Ph2P O O
-- n -- - n n ~ 18 l ~ 3 2~ 6160~
The palladium-catalyzed cross-coupling reaction of aromatic halogen compounds or aromatic perfluoroalkyl-sulfonates with terminal alkynes (see, for example, R.F. Heck, Palladium Reagents in Organic Synthe~es, Academic Press, p. 260 ff.; J.P. Genet, E. Blart, M.
Savignac, Synlett 1992, 715 or G.T. Crisp, T.A.
Robertson, Tetrahedron 1992, 48, 3239) has for some years been utilized to an increasing extent in many areas of organic synthesis.
The processes cited are homogeneously catalyzed processes using Pd(II) complexes, in particular bis(triphenylphosphine)palladium(II) chloride. The presence of phosphorus-contA;n;ng complexing ligands generally considerably increases yields and selectivity of the reaction.
However, a disadvantage of these proce~es is the high catalyst costs which make an economical transfer of the process to a larger production scale (kg, t) difficult.
In addition, contAm;nAtion of the product and the waste with phosphorus compounds is observed, which can be a disadvantage, particularly in the case of active compounds.
Also known is the use of water-soluble palladium complexes for the abovementioned coupling reactions, 216160~
working in pure aqueous systems or in two-phase systems comprising an organic and an aqueous phase (see, for example, US 5,043,510 or J.P. Genet et al., Synlett 1992, 715). Here, water-soluble phosphine ligands such as triphenylphosphino-3,3',3''-trisulfonate trisodium salt (tppts) are used to obtain the water-soluble palladium complex. However, it has been stated (A.L. Casalnuovo and J.C. Calabrese, J. Am. Chem. Soc. 1990, 112, 4324) that the yields in the two-phase system are significantly lower than in the single-phase system.
In addition, N.A. Bumagin, V.V. Bykor and I.P. Belets-Raya, Izv. Akad. Nauk SSSR, Ser. Khim 1990, 2665 report low yields when using palladium(II) acetate as a catalyst.
Furthermore, the processes suffer from the above-described disadvantages such as catalyst costs and cont~m;n~tion of the product with the complexing ligands.
It is therefore an object of the present invention to provide an economically favorable process for coupling terminal alkynes with aromatic perfluoroalkylsulfonates or aromatic halogen compounds which gives the coupling products in very high purity and good yield.
It has now surprisingly been found that in the reaction of terminal alkynes with aromatic halogen compounds or aromatic perfluoroalkylsulfonates in a two-phase reaction medium in the presence of a base, catalytic amounts of a palladium compound soluble in organic solvents and at least one water-~oluble complexing ligand, arylalkynes are obtained in excellent yields and very high purities.
The invention accordingly provides a process for preparing 1-arylalkynes by cross-coupling terminal alkynes with aromatic halogen compounds or aromatic perfluoroalkylsulfonates under palladium catalysis in the presence of at least one water-soluble complexing ligand, wherein the reaction medium forms an agueous phase and an organic phase and the palladium is added in the $orm of a palladium compound soluble in the organic phase or in solid form as palladium metal, in particular applied to a support.
The reaction of the invention proceed~ chemoselectively, 80 that even electrophilic groups such as esters or nitriles do not impair the course of the reaction.
The process of the invention enables 1-arylalkynes to be prepared economically in very good yields and at the ~ame time in very high purity, in particular without cont~; n~ tion by the complexing ligands.
The solubility of the palladium compound in the organic pha~e is preferably at least 0.5 mmol/l, particularly preferably at least 5 mmol/l, very particularly preferably at least 20 mmol/l.
The process of the invention is carried out in a multiphase system which compri~es at least one aqueous phase and one organic phase. The agueous phase can here comprise not only water but also one or more water-soluble organic solvent~. Solid phases can also be present.
To carry out the process of the invention, the aromatic halogen compound or the perfluoroalkylsulfonate, the terminal alkyne, the base, the catalytic amount of the palladium or the palladium compound soluble in organic solvents and a water-soluble complexing ligand are added to a mixture of water and one or more organic solvents which do not participate in the reaction and the mixture is stirred at a temperature of from -10C to 200C, preferably at from 0C to 170C, particularly preferably at from 5C to 150C, very particularly preferably at from 10 to 120C, for a period of from 1 hour to 100 hours, preferably from 5 hours to 70 hours, particularly 2~ 6i601 preferably from 5 hours to 50 hours.
The work-up is then carried out by known methods with which those skilled in the art are familiar.
To avoid contamination of the product with palladium or its compounds, it is possible, for example, to add sufficient complexing ligand to the reaction mixture at the end of the reaction for all the palladium to remain in solution.
Naturally, the palladium can also, if desired, be removed by chromatographic methods or by precipitation, for example as sulfide.
The water-soluble, typically phosphorus-containing complexing ligand is completely removed from the product simply by separation of aqueous and organic phases.
For the further work-up after the phase separation, the crude product is usually freed of solvent and subsequently purified further by methods matched to the respective product, e.g. by recrystallization, distillation, sublimation, zone melting, melt crystallization or chromatography.
The aqueous phase can be used for new coupling reactions without 1088 of catalytic activity occurring.
Organic solvents suitable for the process of the invention which form an organic phase in the reaction medium are, for example, ethers such as diethyl ether, dimethoxymethane, diethylene glycol dimethyl ether, diisopropyl ether, tert-butyl methyl ether, hydrocarbons such a~ h~Y~ne, iso-hexane, heptane, cyclohexane, benzene, toluene, xylene, higher alcohols which are not completely miscible with water such as 1-butanol, 2-butanol, tert-butanol, amyl alcohol, ketones, e.g. iso-butyl methyl ketone, amides such as dimethylacetamide, N-methylpyrrolidone, nitriles, such as butyronitrile, and mixtures thereof.
Preferred organic solvents are ethers such as diethyl ether, dimethoxyethane, diethylene glycol dimethyl ether, diisopropyl ether, hydrocarbons such as hexane, heptane, cycloheY~ne, benzene, toluene, xylene, alcohols such as 1-butanol, 2-butanol, tert-butanol, ketones such as iso-butyl methyl ketone, amides such as N-methylpyrrolidone, and mixtures thereof.
Particularly preferred organic solvents are cyclic or acyclic, aliphatic or aromatic hydrocarbons, e.g.
cyclohexane, benzene, toluene, xylene and mixtures thereof.
In a particularly preferred variant of the process of the invention, water, one or more solvents insoluble in water and one or more solvents soluble in water are used.
Preferred organic cosolvents which are miscible with the aqueous phase are lower nitriles such as acetonitrile, formamides such as DMF, lower alcohols such as methanol, ethylene glycol and ethanol, sulfoxides such as DMS0, and cyclic ethers such as THF or dioxane.
Preferred reaction media compri~ing water, water-soluble organic solvent and water-insoluble organic solvent are mixtures of water, toluene and ethanol, water, xylene and ethanol, water, toluene and tetrahydrofuran, water, xylene and tetrahydrofuran, water, xylene and acetonitrile and water, toluene and acetonitrile, preferably each in a volume ratio of 1:2:1.
Bases which are usually used in the process of the invention are alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates, alkali metal hydrogen carbonates, alkali metal and alkaline earth metal acetates, alkali metal and ~ L~1601 alkaline earth metal Al koY; des, and also primary, secondary and tertiary amines.
Particular preference is given to alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates and alkali metal hydrogen carbonates and also secondary and tertiary alkylamines.
Particular preference is given to alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates and alkali metal hydrogen carbonates such as lithium carbonate, sodium carbonate and potassium carbonate, and also secondary amine~ such as piperidine, diethylamine or morpholine.
In the process of the invention, the base is preferably used in an amount of $rom 50 to 1000 mol%, particularly preferably from 65 to 500 mol%, very particularly preferably from 75 to 350 mol%, in particular from 90 to 200 mol%, based on the aromatic halogen compound or the perfluoroalkylsulfonate.
Catalysts used are, on the one hand, palladium compounds soluble in organic solvents, such as palladium ketonates, palladium acetylacetonates, nitrilepalladium halides, olefin palladium halides, palladium halides, allylpalladium halides and palladium biscarboxylates, preferably palladium ketonates, palladium acetyl-acetonates, bis-~2-olefinpalladium dihalides, palladium(II) halides, ~3-allylpalladium halide dimer~
and palladium biscarboxylates, very particularly preferably bis(dibenzylideneacetone)palladium(0) [Pd(dba)2], Pd(dba)2 CHCl3, palladium bi~acetylacetonate, bis(benzonitrile)palladium dichloride, ~3-allylpalladium chloride dimer, PdCl2, Na2PdCl4, dichlorobis(dimethyl-sulfoxide)palladium(II), bis(acetonitrile)palladium dichloride, palladium(II) acetate, palladium(II) proprionate, palladium(II) butanoate and (lc,5c-cyclo-octadiene)palladium dichloride.
~1501 On the other hand, palladium or palladium compounds insolid form serve as catalyst, preferably palladium in pulverized form or on a support material, e.g. palladium on activated carbon, palladium on aluminum oxide, palladium on barium carbonate, palladium on barium sulfate, palladium on aluminum silicates, such as montmorillonite, palladium on SiO2 and palladium on calcium carbonate, each having a palladium content of from 0.5 to 10% by weight. Particular preference is given to palladium in pulverized form, palladium on aluminum oxide and palladium on activated carbon, each having a palladium content of from 0.5 to 10% by weight. Very particular preference is given to palladium on activated carbon having a palladium content of 2 or 7% by weight.
It i8 also possible to use catalysts cont~;n;ng, apart from palladium and the support material, further dopants such as lead (Lindlar catalyst).
In the process of the invention, the palladium catalyst is used in an amount of from 0.001 to 10 mol%, preferably from 0.01 to 5 mol%, particularly preferably from 0.05 to 3 mol%, very particularly preferably from 0.1 to 1.5 mol%, based on the aromatic halogen compound or the perfluoroalkylsulfonate.
Furthermore, in the process of the invention, one or more copper(I) compounds are advantageously used as cocatalyst.
These are usually copper(I) halides such as CuI, CuBr, CuCl, copper(I) cyanide, copper(I) thiocyanate or copper(I) acetate, preference being given to CuI and CuBr.
The copper(I) compound is usually used in a stoichiometric ratio of from 0.5 to 2:1, based on the palladium content. The stoichiometric ratio of copper to palladium is preferably 1:1.
2~6~601 Water-soluble ligands suitable for the process of the invention contain, for example, sulfonic acid salt radicals and/or sulfonic acid radicals and/or carboxylic acid salt radicals and/or carboxylic acid radicals and/or phosphonic acid salt radicals and/or phosphonic acid radicals and/or phosphonium groups and/or peralkylammonium groups and/or hydroxy groups and/or polyether groups having an appropriate chain length.
Preferred classes of water-soluble ligands are phosphines substituted by the above groups, such as trialkyl-phosphines, tricycloalkylphosphines, triarylphosphines, dialkylarylphosphines, alkyldiarylphosphines, and hetero-arylphosphines such as tripyridylphosphine and trifuryl-phosphine, where the three substituents on the phosphorus can be identical or different, chiral or achiral and where one or more of the ligands can link the phosphorus groups of a plurality of phosphines and where a part of this linkage can also be one or more metal atoms, phosphites, phosphinic esters and phosphonic esters, phospholes, dibenzophospholes and cyclic or oligocyclic and polycyclic compounds containing phosphorus atoms.
Further suitable groups of water-soluble complexing ligands comprise, for example, bipyridines, ph~n~nthrolines, porphyrins and alizarins which are modified with the abovementioned groups.
Water-soluble phosphines which are preferably used are those of the formulae (I) to (VII), P R S O ~ p o 2 - 2 ~1 ~ C O ~ ~1 (CH2)q~ NR4~X~, PR4~ X~
( I ) ~6~ 6~1 ~rl~--(CH2),,~ ~(CH2~ ~(CH2)--~r~l/50~ N, PO~ 2~, CO2 11~, ~rl--(CH2). (CH2),--Ar~l N~, X, PP~ X, ( I I ) Alkyl ~ ~(CH2~ ~AIk~l SO~U~, PO~2-2U~, CO2~U0, Alkyl / \Alk~l NR~eX~, PR~0X~, OH
_ ~SOs~U0, PO~2-2U~, CO2~U~, P((CH~ Aryl~ (Alkyl), NR,0X0, PR~0X0, OH
( lV) '' ~(CH2)n~PR2~503~ , Po32-2~, CO
~'~ q~NR ' NR4~X~, PR~X~, OH
(V) Ar~l--(CH2)~ ~(C~ ~ ~(CH2)~--Arr~ SO~OH~, ro~2 21~, CO~
~r1 1--(CH~), (CH2)~--Ar~ I NR~X~, PR,~X9. OH
( V I ) Alkyl~ ~(CH2~ ~AIkrl SO~U~, poS2 2U~, C029U~, Alkyl / \Alk~l NR40X0, PR~0X0, OH
(Vl I ) where the symbols and indices have the following _~n;ngs:
Aryl: a phenyl or naphthyl group which can also bear one or more substituents R;
~161601 Alkyl: a ~traight-chain or branched alkyl group having from 1 to 8 carbon atoms;
R,R': alkyl, aryl or aralkyl having from 1 to 18 carbon atoms;
M: alkali metal, alkaline earth metal or NR4;
X: halogen, BF4, PF6, OS02CF3, 1/2[S04];
1, m: 1 to 8;
n, o, p, q: 0, 1 to 8;
~: 0, 1 to 3.
Examples of particularly preferred water-soluble complexing ligands are given below:
(R here has, unless otherwise indicated, the meanings given for the formulae (I) to (VII)) 1. Sulfonated phosphines ~>)3P ; [(C6HS) (CH2)n]~ P n~l,2,3 and 6 ~+~303S / 6 1~
S 0 3 ~ p- and/or o- sul fonated ~1 ~ N~, NR4 S03~ 4 03S ~ r ~ Na0, NR4~
\[~
~161601 ~PPh2/(503( )Na~ )6-~~P P h 2 E I NAS
",o~s~
r2 ~ r2 ~A r~ ~ r ~A r Ar m-C~ SO~ Ar - ~-C~N~SO~IIr.
Ph e n y 1 2P~SO3(~)Na(~) 3 -nP (P C6H4S3K) n R = C6Hs ~ 2-pyridyl, 3-pyridyl; n = 1-ptp-oc6H4so3NH(i-octyl) 3] 3 216~ BOl 1.1 Phosphines having hydrophilic group~ on the periphery PPh2 ~ O I ," o (C6Hs)2pcH2cH2so5(-~No(~) S 1`'`~`
PPh2 SO3No ~ ()n ~ n ~ O, 3, 5, 7, 9, 1 2. Phosphines having quaternized aminoalkyl and aminoaryl substituents ph2p N~e (~)I(-I
~e ~e C N~) W C~3+ ~
Ph 2 P-Y-NHR2~X- Ph2P-Y-NR3~X-Y = - CH2CH2 -, - CH ( CH3 ) CH2 -, - CH2CH ( CH3 ) CH2 -; R = CH3;
X = Ie, Bue, Cle, OS02CF3e, BF4e, PF6e ~161601 , 3. Carboxylated pho phines Ph2P~COOH NaOOC r\~COONa NoOOC~ ~COONa C O O H
Ph2P~ o, m, p substituted P h2P3~COOH ~e~xco2Na Ph2P COOH P CO2Na 4. Phosphines having hydroxyalkyl or polyether ~ub~tituents H~C - O 0'~~0 PPh2 H C - O ~ O~N f PPh n > l6 n - l2, l6, llO
H 3 CO/~O~P P h 2 ~¢~ 3 J PPh2 Ph2P O O
-- n -- - n n ~ 18 l ~ 3 2~ 6160~
5. Phosphinoalkylphosphonium ~alts pl(CH2 ) X~ ) n ~ 1-8 X ~ halogenl, 0502C~30 B~,~
6. Phosphites Pt-oc6H4so3{NH(i-octyl)3}]3 Very particularly preferred water-soluble phosphine ligand~ are:
~~ ~ TPPTS
~ SO3Na SO3N~ \~~SO3Na .~N~P-cH2-cH2-cH2-cH2-p~Nl~) 2x x - P u~
oso2c~
NaO3S~P~ ~503Na I
S 0 3 N a 6 0 ~
(~PPh2/( SO3( )Na( ))6-8 ~~P P h 2 B I NAS
The water-soluble ligand preferably contains 3 or more groups which effect the water solubility. Its solubility in water i8 preferably at least 20 mmol/l.
In the process of the invention, the water-soluble ligand is usually used in an amount of from 0.001 to 20 mol%, preferably from 0.01 to 15 mol%, particularly preferably from 0.05 to 10 mol%, very particularly preferably from 0.1 to 6 mol%, based on the aromatic halogen compound or the perfluoroalkylsulfonate.
If desired, it is also possible to use mixtures of two or more different water-soluble complexing ligand~.
The water-soluble complexing ligands used according to the invention are mostly known from the literature. The syntheses of these compounds are described, for example, in W.A. Herrmann and C.W. Kohlpainter, Angew. Chem. Int.
Ed. Engl. 1993, 32, 1524 and the literature cited therein or can be carried out by methods known in the literature or analogous methods with which those skilled in the art are familiar. The preparation of BINAS is described in EP-A 0 571819 or US-A 5,347,045.
Starting compounds for the process of the invention are, on the one hand, terminal alkynes, i.e. compounds containing the structural element -C_C-H.
Besides the alkynyl group, the compounds contain, for example, alkyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and/or aralkyl groups which can all also be functionalized if desired.
Examples of such compounds are acetylene, phenylacetylene, propargyl alcohol, propargyltrifluoro-acetamide, propargylamine, 2-methyl-3-butyn-2-ol, trimethylsilylacetylene and l-hexyne.
The second class of starting compound for the process of the invention is aromatic halogen compounds or aromatic perfluoroalkylsulfonates, preferably those of the formula (VIII), X-A3(-M2)m(-A4~ _R2 (VIII), where R2, A3, A4, M2, X, m and n have the following n;ngs:
R2 is benzyloxy, H, F, Cl, Br, -NC, -CN, -CF3, -OCF3, isoxazoline or a straight-chain, branched (with or without an asymmetric carbon atom) or cyclic alkyl radical having from 1 to 18 carbon atoms, where one or two nonadjacent CH2 groups can alæo be replaced by -O-, -S -, -CO-, -CO-O-, -O-CO-, -CO-S-, -S-CO-, -O-CO-O-, -SO2-, -CON(H,C1-C8-alkyl)-, -CH=CH-, -C_C-, cyclopropane-1,2-diyl or -Si(CH3)2-, and where one or more hydrogen atoms of the alkyl radical can also be replaced by F, Cl, Br or CN;
A4 is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, trans-1,4-cyclohexylene, naphthalene-2,6-diyl, where each of the preceding groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meaningæ given under R2 or i8 -CHO or 4,4-di-methylisoxazoline, and where one or two nonadjacent CH2 groups of the cyclohexylene can be replaced by -O- and/or -S-, 1,3,4-thiadiazole-2,5-diyl, 1,3-thiazole-2,4-diyl, 1,3-thiazole-2,5-diyl,thiophene-2,4-diyl,thiophene-2,5-diyl, piperazine-1,4-diyl, piperazine-2,5-diyl, ~61601 piperidine-1,4-diyl, bicyclo[2.2.2]octane-1,4-diyl, 1,3-dioxaborinane-2,5-diyl or trans-decalin-2,6-diyl;
A3 is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the me~n;ngs given under R2 or is -CH0 or 4,4-dimethylisoxazoline; 1,3,4-thiadiazole-2,5-diyl, 1,3-thiazole-2,4-diyl, 1,3-thiazole-2,5-diyl, thiophene-2,4-diyl or thiophene-2,5-diyl;
M2 is -O-, -S-, -CO-, -CO-O-, O-CO-, -CO-S, -S-CO-, -O-CO-O-, -CH2-0-, -OCH2-, -CH2CH2-, -CH=CH-, -C_C-, -CH(CN)-CH2-, -CH2-CH(CN)-, -CH=N-, -N=CH-, -CH2CH2CH2-0-, -OCH2CH2CH2-, -CH2CH2C0-0-, or -0-COCH2CH2;
X is Cl, Br, I or a perfluoroalkylsulfonate and m, n are each, independently of one another, zero or one.
R2 is preferably benzyloxy, H, F, Cl, Br, -CN, -CF3, -OCF3 or a straight-chain, branched (with or without an asymmetric carbon atom) or cyclic alkyl radical having from 1 to 18 carbon atoms, where one or two nonadjacent CH2 groups can also be replaced by -0-, -C0-, -C0-0-, 0-C0-, -0-C0-0-, -CH=CH-, -C_C-, cyclopropane-1,2-diyl or -Si(CH3)2-, and where one or more hydrogen atoms of the alkyl radical can also be replaced by F, Cl or CN.
R2 is particularly preferably benzyloxy, H, Cl, Br or a straight-chain, branched (with or without an a~ymmetric carbon atom) or cyclic alkyl radical having from 1 to 18 carbon atoms, where one or two nonadjacent CH2 groups can also be replaced by -0-, -C0-, -C0-0-, -0-, 0-C0-, -0-C0-0-, -CH=CH-, cyclopropane-1,2-diyl or -Si(CH3)-.
~16160:~
A3 is preferably 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meanings given under R2 or is -CH0 or 4,4-dimethylisoxazoline, or 1,3,4-thiadiazole-2,5-diyl.
A3 is particularly preferably 1,4-phenylene, 2-fluoro-1,4-phenylene, 2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene, 2,5-difluoro-1,4-phenylene, and also pyrazine-2,5-diyl, pyridazine-2,5-diyl, pyrimidine-2,5-diyl or naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meAnings given under R2 or is -CH0 or 4,4-dimethylisoxazoline.
A4 is preferably 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, trans-1,4-cyclohexylene, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meAn;ngs given under R2, and where one or two nonadjacent CH2 groups of the cyclohexylene can be replaced by -0-; 1,3,4-thiadiazole-2,5-diyl or bicyclo[2.2.2]octane-1,4-diyl.
A4 is particularly preferably 1,4-phenylene, 2-fluoro-1,4-phenylene, 2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene, 2,5-difluoro-1,4-phenylene, and also pyridine-2,5-diyl, pyrimidine-2,5-diyl, trans-1,4-cyclo-hexylene, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meanings given under R2.
M2 is preferably -0-, -C0-, -C0-0-, -0-C0-, -0-C0-0, -CH2-0-, -0-CH2-, -CH2CH2-, -CH=CH-, -C_C-, -CH2CH2CH2-0-, -0-CH2CH2CH2-, -CH2CH2C0-0- or -0-C0-CH2CH2-.
M2 is particularly preferably -O-, -CO-, -CO-O-, -O-CO-, O-CO-O-, -CH2-O-, -O-CH2-, -CH2CH2-, -CH=CH-, -C_C-, -CH2CH2CH2-O-, -O-cH2cH2cH2-~ -CH2CH2CO-O- or -O-CO-CH2CH2.
X is preferably bromine, iodine or OSO2-CpF2p+l, where p is an integer from 1 to 10. X i8 particularly preferably bromine.
The aromatic halogen compounds and perfluoroalkyl-sulfonates used are either known or can be prepared by known methods as described, for example, in Houben Weyl, Methoden der Organischen Chemie, Georg Thieme Verlag, Stuttgart, Volume 5/3 and 5/4. For example, aromatic halides can be obtained by replacing the diazonium group in a corresponding diazonium 6alt by chlorine, bromine or iodine.
Furthermore, hydroxy-substituted nitrogen heterocycles can be converted into the correspo~; ng halides by means of phosphorus trihalides and phosphorus oxytrihalides.
The products of the process of the invention are l-aryl-alkynes, i.e. compounds containing the structural element -Ar-C--C- (where Ar is an aryl or heteroaryl group).
Such compounds are suitable, inter alia, as liquid-crystalline materials or can serve as intermediates for the preparation of li~uid-crystalline compounds. Further-more, they are used as precursors for pharmaceuticals, cosmetics, fungicides, herbicides, insecticides, dyes, detergents and polymers, including additives for these.
The present invention is illustrated by the examples below, without being restricted thereby. The abbreviations used have the following meAn;ngs:
mp. = melting point X = crystalline S = smectic Sc = smectic C
SA = Bmectic A
N = nematic I = isotropic TPPTS:
3 ~S 0 ~ N a BINAS:
~,PPh2 /(SO3( )Na( ))6-8 [~--P P h 2 Example 1:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture iB stirred for 15 minutes. The reaction mixture is cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for-1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ~mo~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over ~odium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
2~ 6~601 Yield: 5.4 g (0.0325 mol; 81 % of theory); melting point:
Example 2:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ~mmo~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.6 g (0.0337 mol; 84 % of theory); melting point:
Example 3:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 7.5 g (0.06 mol) of 32% strength by weight sodium hydroxide solution and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture i8 stirred for 1 hour at 0C and for 15 hours at room temperature. It i8 subsequently admixed with 100 ml of saturated aqueous ammonium chloride - solution and 100 ml of ethyl acetate. The organic phase i8 separated off and dried over sodium ~ulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcycloheYAne at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 4:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This ~olution i~
admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.07 g (0.4 mmol) of palladium(II) chloride dis~olved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 7.5 g (0.06 mol) of 32% ~trength by weight sodium hydroxide ~olution and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture iB stirred for 1 hour at 0C and for 15 hours at room temperature. It i~ subsequently admixed with 100 ml of saturated aqueous A~O~; um chloride solution and 100 ml of ethyl acetate. The organic phase i8 ~eparated off and dried over ~odium ~ulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 5:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml ~t61601 (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueou~ TPPTS solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic pha~e is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.2 g (0.0313 mol; 78 ~ of theory); melting point:
Example 6:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dis~olved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase i8 separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product i~
recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.3 g (0.0319 mol; 80 % of theory); melting point:
Example 7:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution iB
admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.426 g (0.4 mmol) of palladium on activated carbon (10% by weight) suspended in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture iB cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous Am~o~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 6.1 g (0.0367 mol; 92 % of theory); melting point:
Example 8:
Under protective gas, 237.1 g (1.0 mol) of 2-bromo-6-methoxynaphthalene and 126.2 g (1.5 mol) of 2-methyl-3-butyn-2-ol are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring iB continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture i8 admixed dropwise 2161~01 with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 = ol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction 601ution. This i8 stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture i8 extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. The reaction is quantitative. After recrystallization, 191.8 g (798 mmol) of 4-(6-methoxy-2-naphthyl)-2-methyl-3-butyn-2-ol are obtained.
Example 9:
Under protective gas, 213.1 g (1.0 mol) of 4-bromo-1-isobutylbenzene and 126.2 g (1.5 mol) of 2-methyl-3-butyn-2-ol are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture is admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgS04 and the solvent is taken off in vacuo. This gives 175.7 g (812 mmol)of4-(4-isobutyl-1-phenyl)-2-methyl-3-butyn-2-ol.
~161601 Example 10:
Under protective gas, 349.3 g (1.0 mol) of 5-bromo-2-(4-octyloxyphenyl)pyrimidine and 165.3 g (1.5 mol) of 1-octyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar a~ueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 = ol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture is admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-octynyl)-2-(4-octyloxyphenyl)pyrimidine. The crude product is hydrogenated over palladium/carbon to give 5-octyl-2-(4-octyloxyphenyl)pyrimidine.
Phases: X 29(25) Sc 55 Sa 62 N 69 Example 11:
Under protective gas, 321.3 g (1.0 mol) of 5-bromo-2-(4-hexyloxyphenyl)pyrimidine and 123.2 g (1.5 mol) of 1-hexyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 =ol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture i8 admixed dropwise ~161601 with 109.7 g (1.5 mol) of diethylamine, and stirring i8 continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liter~ of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-hexynyl)-2-(4-hexyloxyphenyl)pyrimidine. The crude product is hydrogenated over palladium/carbon to give 5-hexyl-2-(4-hexyloxyphenyl)pyrimidine.
Phases: Xl 15 x2 32 N 61 Example 12:
Under protective gas, 321.3 g (1.0 mol) of 5-bromo-2-(4-hexyloxyphenyl)pyrimidine and 207.4 g (1.5 mol) of 1-decyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture is admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it i8 poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-decynyl)-2-(4-hexyloxyphenyl)pyrimidine. The crude product is hydrogenated over palladium/carbon to give 5-decyl-2-(4-2~6~601 hexyloxyphenyl)pyrimidine.
Phases: X1 36 sc 60 Sa 71 Example 13:
Under protective gas, 349.3 g (1.0 mol) of 5-bromo-2-(4-octyloxyphenyl)pyrimidine and 207.4 g (1.5 mol) of 1-decyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring i8 continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture i8 admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of Am~on;um chloride in 2 liters of water. The resultant mixture i8 extracted with ethyl acetate, the organic phase i8 washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-decynyl)-2-(4-octyloxyphenyl)pyrimidine. The crude product iB
hydrogenated over palladium/carbon to give 5-decyl-2-(4-octyloxyphenyl)pyrimidine.
Phases: X1 40(30) sc 69 Sa 74 Example 14:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution iB
admixed with 25 ml o$ water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in 6uccession. The mixture is stirred for ~l~lbUl 15 minutes. The reaction mixture iB cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture i8 stirred for 1 hour at 0C and for 15 hours at room temperature. It i8 subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclo~eY~ne at -20C.
Yield: 5.4 g (0.0325 mol; 81 % of theory); melting point:
Example 15:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution i8 admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic pha~e, the crude product is recrystallized from 200 ml of methylcyclo~eY~ne at -20C.
Yield: 5.6 g (0.0337 mol; 84 % of theory); melting point:
6 0 ~
Example 16:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution i8 admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.09 g (0.4 mmol) of palladium(II) acetate dis~olved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 7.5 g (0.06 mol) of 32% strength by weight sodium hydroxide solution and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture i8 ~tirred for 1 hour at 0C and for 15 hours at room temperature. It iB subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic pha~e is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcycloh~Y~ne at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 17:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas condition~ in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succes~ion. The mixture i~ ~tirred for 15 minutes. The reaction mixture is cooled to 0C.
~~ ~ TPPTS
~ SO3Na SO3N~ \~~SO3Na .~N~P-cH2-cH2-cH2-cH2-p~Nl~) 2x x - P u~
oso2c~
NaO3S~P~ ~503Na I
S 0 3 N a 6 0 ~
(~PPh2/( SO3( )Na( ))6-8 ~~P P h 2 B I NAS
The water-soluble ligand preferably contains 3 or more groups which effect the water solubility. Its solubility in water i8 preferably at least 20 mmol/l.
In the process of the invention, the water-soluble ligand is usually used in an amount of from 0.001 to 20 mol%, preferably from 0.01 to 15 mol%, particularly preferably from 0.05 to 10 mol%, very particularly preferably from 0.1 to 6 mol%, based on the aromatic halogen compound or the perfluoroalkylsulfonate.
If desired, it is also possible to use mixtures of two or more different water-soluble complexing ligand~.
The water-soluble complexing ligands used according to the invention are mostly known from the literature. The syntheses of these compounds are described, for example, in W.A. Herrmann and C.W. Kohlpainter, Angew. Chem. Int.
Ed. Engl. 1993, 32, 1524 and the literature cited therein or can be carried out by methods known in the literature or analogous methods with which those skilled in the art are familiar. The preparation of BINAS is described in EP-A 0 571819 or US-A 5,347,045.
Starting compounds for the process of the invention are, on the one hand, terminal alkynes, i.e. compounds containing the structural element -C_C-H.
Besides the alkynyl group, the compounds contain, for example, alkyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and/or aralkyl groups which can all also be functionalized if desired.
Examples of such compounds are acetylene, phenylacetylene, propargyl alcohol, propargyltrifluoro-acetamide, propargylamine, 2-methyl-3-butyn-2-ol, trimethylsilylacetylene and l-hexyne.
The second class of starting compound for the process of the invention is aromatic halogen compounds or aromatic perfluoroalkylsulfonates, preferably those of the formula (VIII), X-A3(-M2)m(-A4~ _R2 (VIII), where R2, A3, A4, M2, X, m and n have the following n;ngs:
R2 is benzyloxy, H, F, Cl, Br, -NC, -CN, -CF3, -OCF3, isoxazoline or a straight-chain, branched (with or without an asymmetric carbon atom) or cyclic alkyl radical having from 1 to 18 carbon atoms, where one or two nonadjacent CH2 groups can alæo be replaced by -O-, -S -, -CO-, -CO-O-, -O-CO-, -CO-S-, -S-CO-, -O-CO-O-, -SO2-, -CON(H,C1-C8-alkyl)-, -CH=CH-, -C_C-, cyclopropane-1,2-diyl or -Si(CH3)2-, and where one or more hydrogen atoms of the alkyl radical can also be replaced by F, Cl, Br or CN;
A4 is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, trans-1,4-cyclohexylene, naphthalene-2,6-diyl, where each of the preceding groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meaningæ given under R2 or i8 -CHO or 4,4-di-methylisoxazoline, and where one or two nonadjacent CH2 groups of the cyclohexylene can be replaced by -O- and/or -S-, 1,3,4-thiadiazole-2,5-diyl, 1,3-thiazole-2,4-diyl, 1,3-thiazole-2,5-diyl,thiophene-2,4-diyl,thiophene-2,5-diyl, piperazine-1,4-diyl, piperazine-2,5-diyl, ~61601 piperidine-1,4-diyl, bicyclo[2.2.2]octane-1,4-diyl, 1,3-dioxaborinane-2,5-diyl or trans-decalin-2,6-diyl;
A3 is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the me~n;ngs given under R2 or is -CH0 or 4,4-dimethylisoxazoline; 1,3,4-thiadiazole-2,5-diyl, 1,3-thiazole-2,4-diyl, 1,3-thiazole-2,5-diyl, thiophene-2,4-diyl or thiophene-2,5-diyl;
M2 is -O-, -S-, -CO-, -CO-O-, O-CO-, -CO-S, -S-CO-, -O-CO-O-, -CH2-0-, -OCH2-, -CH2CH2-, -CH=CH-, -C_C-, -CH(CN)-CH2-, -CH2-CH(CN)-, -CH=N-, -N=CH-, -CH2CH2CH2-0-, -OCH2CH2CH2-, -CH2CH2C0-0-, or -0-COCH2CH2;
X is Cl, Br, I or a perfluoroalkylsulfonate and m, n are each, independently of one another, zero or one.
R2 is preferably benzyloxy, H, F, Cl, Br, -CN, -CF3, -OCF3 or a straight-chain, branched (with or without an asymmetric carbon atom) or cyclic alkyl radical having from 1 to 18 carbon atoms, where one or two nonadjacent CH2 groups can also be replaced by -0-, -C0-, -C0-0-, 0-C0-, -0-C0-0-, -CH=CH-, -C_C-, cyclopropane-1,2-diyl or -Si(CH3)2-, and where one or more hydrogen atoms of the alkyl radical can also be replaced by F, Cl or CN.
R2 is particularly preferably benzyloxy, H, Cl, Br or a straight-chain, branched (with or without an a~ymmetric carbon atom) or cyclic alkyl radical having from 1 to 18 carbon atoms, where one or two nonadjacent CH2 groups can also be replaced by -0-, -C0-, -C0-0-, -0-, 0-C0-, -0-C0-0-, -CH=CH-, cyclopropane-1,2-diyl or -Si(CH3)-.
~16160:~
A3 is preferably 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meanings given under R2 or is -CH0 or 4,4-dimethylisoxazoline, or 1,3,4-thiadiazole-2,5-diyl.
A3 is particularly preferably 1,4-phenylene, 2-fluoro-1,4-phenylene, 2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene, 2,5-difluoro-1,4-phenylene, and also pyrazine-2,5-diyl, pyridazine-2,5-diyl, pyrimidine-2,5-diyl or naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meAnings given under R2 or is -CH0 or 4,4-dimethylisoxazoline.
A4 is preferably 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, trans-1,4-cyclohexylene, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meAn;ngs given under R2, and where one or two nonadjacent CH2 groups of the cyclohexylene can be replaced by -0-; 1,3,4-thiadiazole-2,5-diyl or bicyclo[2.2.2]octane-1,4-diyl.
A4 is particularly preferably 1,4-phenylene, 2-fluoro-1,4-phenylene, 2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene, 2,5-difluoro-1,4-phenylene, and also pyridine-2,5-diyl, pyrimidine-2,5-diyl, trans-1,4-cyclo-hexylene, naphthalene-2,6-diyl, where each of these groups can have one or more hydrogen atoms replaced by identical or different substituents L, where L has the meanings given under R2.
M2 is preferably -0-, -C0-, -C0-0-, -0-C0-, -0-C0-0, -CH2-0-, -0-CH2-, -CH2CH2-, -CH=CH-, -C_C-, -CH2CH2CH2-0-, -0-CH2CH2CH2-, -CH2CH2C0-0- or -0-C0-CH2CH2-.
M2 is particularly preferably -O-, -CO-, -CO-O-, -O-CO-, O-CO-O-, -CH2-O-, -O-CH2-, -CH2CH2-, -CH=CH-, -C_C-, -CH2CH2CH2-O-, -O-cH2cH2cH2-~ -CH2CH2CO-O- or -O-CO-CH2CH2.
X is preferably bromine, iodine or OSO2-CpF2p+l, where p is an integer from 1 to 10. X i8 particularly preferably bromine.
The aromatic halogen compounds and perfluoroalkyl-sulfonates used are either known or can be prepared by known methods as described, for example, in Houben Weyl, Methoden der Organischen Chemie, Georg Thieme Verlag, Stuttgart, Volume 5/3 and 5/4. For example, aromatic halides can be obtained by replacing the diazonium group in a corresponding diazonium 6alt by chlorine, bromine or iodine.
Furthermore, hydroxy-substituted nitrogen heterocycles can be converted into the correspo~; ng halides by means of phosphorus trihalides and phosphorus oxytrihalides.
The products of the process of the invention are l-aryl-alkynes, i.e. compounds containing the structural element -Ar-C--C- (where Ar is an aryl or heteroaryl group).
Such compounds are suitable, inter alia, as liquid-crystalline materials or can serve as intermediates for the preparation of li~uid-crystalline compounds. Further-more, they are used as precursors for pharmaceuticals, cosmetics, fungicides, herbicides, insecticides, dyes, detergents and polymers, including additives for these.
The present invention is illustrated by the examples below, without being restricted thereby. The abbreviations used have the following meAn;ngs:
mp. = melting point X = crystalline S = smectic Sc = smectic C
SA = Bmectic A
N = nematic I = isotropic TPPTS:
3 ~S 0 ~ N a BINAS:
~,PPh2 /(SO3( )Na( ))6-8 [~--P P h 2 Example 1:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture iB stirred for 15 minutes. The reaction mixture is cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for-1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ~mo~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over ~odium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
2~ 6~601 Yield: 5.4 g (0.0325 mol; 81 % of theory); melting point:
Example 2:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ~mmo~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.6 g (0.0337 mol; 84 % of theory); melting point:
Example 3:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 7.5 g (0.06 mol) of 32% strength by weight sodium hydroxide solution and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture i8 stirred for 1 hour at 0C and for 15 hours at room temperature. It i8 subsequently admixed with 100 ml of saturated aqueous ammonium chloride - solution and 100 ml of ethyl acetate. The organic phase i8 separated off and dried over sodium ~ulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcycloheYAne at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 4:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This ~olution i~
admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.07 g (0.4 mmol) of palladium(II) chloride dis~olved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 7.5 g (0.06 mol) of 32% ~trength by weight sodium hydroxide ~olution and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture iB stirred for 1 hour at 0C and for 15 hours at room temperature. It i~ subsequently admixed with 100 ml of saturated aqueous A~O~; um chloride solution and 100 ml of ethyl acetate. The organic phase i8 ~eparated off and dried over ~odium ~ulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 5:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml ~t61601 (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueou~ TPPTS solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic pha~e is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.2 g (0.0313 mol; 78 ~ of theory); melting point:
Example 6:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dis~olved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase i8 separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product i~
recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.3 g (0.0319 mol; 80 % of theory); melting point:
Example 7:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution iB
admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 2 ml of a 0.6 millimolar aqueous TPPTS solution and 0.426 g (0.4 mmol) of palladium on activated carbon (10% by weight) suspended in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture iB cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous Am~o~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 6.1 g (0.0367 mol; 92 % of theory); melting point:
Example 8:
Under protective gas, 237.1 g (1.0 mol) of 2-bromo-6-methoxynaphthalene and 126.2 g (1.5 mol) of 2-methyl-3-butyn-2-ol are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring iB continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture i8 admixed dropwise 2161~01 with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 = ol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction 601ution. This i8 stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture i8 extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. The reaction is quantitative. After recrystallization, 191.8 g (798 mmol) of 4-(6-methoxy-2-naphthyl)-2-methyl-3-butyn-2-ol are obtained.
Example 9:
Under protective gas, 213.1 g (1.0 mol) of 4-bromo-1-isobutylbenzene and 126.2 g (1.5 mol) of 2-methyl-3-butyn-2-ol are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture is admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgS04 and the solvent is taken off in vacuo. This gives 175.7 g (812 mmol)of4-(4-isobutyl-1-phenyl)-2-methyl-3-butyn-2-ol.
~161601 Example 10:
Under protective gas, 349.3 g (1.0 mol) of 5-bromo-2-(4-octyloxyphenyl)pyrimidine and 165.3 g (1.5 mol) of 1-octyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar a~ueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 = ol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture is admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-octynyl)-2-(4-octyloxyphenyl)pyrimidine. The crude product is hydrogenated over palladium/carbon to give 5-octyl-2-(4-octyloxyphenyl)pyrimidine.
Phases: X 29(25) Sc 55 Sa 62 N 69 Example 11:
Under protective gas, 321.3 g (1.0 mol) of 5-bromo-2-(4-hexyloxyphenyl)pyrimidine and 123.2 g (1.5 mol) of 1-hexyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 =ol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture i8 admixed dropwise ~161601 with 109.7 g (1.5 mol) of diethylamine, and stirring i8 continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of ammonium chloride in 2 liter~ of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-hexynyl)-2-(4-hexyloxyphenyl)pyrimidine. The crude product is hydrogenated over palladium/carbon to give 5-hexyl-2-(4-hexyloxyphenyl)pyrimidine.
Phases: Xl 15 x2 32 N 61 Example 12:
Under protective gas, 321.3 g (1.0 mol) of 5-bromo-2-(4-hexyloxyphenyl)pyrimidine and 207.4 g (1.5 mol) of 1-decyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring is continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture is admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it i8 poured into a solution of 500 g of ammonium chloride in 2 liters of water. The resultant mixture is extracted with ethyl acetate, the organic phase is washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-decynyl)-2-(4-hexyloxyphenyl)pyrimidine. The crude product is hydrogenated over palladium/carbon to give 5-decyl-2-(4-2~6~601 hexyloxyphenyl)pyrimidine.
Phases: X1 36 sc 60 Sa 71 Example 13:
Under protective gas, 349.3 g (1.0 mol) of 5-bromo-2-(4-octyloxyphenyl)pyrimidine and 207.4 g (1.5 mol) of 1-decyne are added to a mixture of 1250 ml of toluene, 625 ml of ethanol and 625 ml of water. This mixture is admixed with 50 ml of 0.6 millimolar aqueous TPPTS
solution and stirred for 5 minutes. 2.25 g (10 mmol) of palladium(II) acetate are dissolved in 15 ml of toluene and added to the reaction mixture. Stirring i8 continued for a further 15 minutes at room temperature. Over a period of 30 minutes, the mixture i8 admixed dropwise with 109.7 g (1.5 mol) of diethylamine, and stirring is continued for a further 10 minutes. 3.8 g (20 mmol) of copper(I) iodide are suspended in 20 ml of acetonitrile and added to the reaction solution. This is stirred for 17 hours under reflux. To work up the mixture, it is poured into a solution of 500 g of Am~on;um chloride in 2 liters of water. The resultant mixture i8 extracted with ethyl acetate, the organic phase i8 washed with saturated aqueous NaCl solution, dried over MgSO4 and the solvent is taken off in vacuo. This gives 5-(1-decynyl)-2-(4-octyloxyphenyl)pyrimidine. The crude product iB
hydrogenated over palladium/carbon to give 5-decyl-2-(4-octyloxyphenyl)pyrimidine.
Phases: X1 40(30) sc 69 Sa 74 Example 14:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution iB
admixed with 25 ml o$ water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in 6uccession. The mixture is stirred for ~l~lbUl 15 minutes. The reaction mixture iB cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture i8 stirred for 1 hour at 0C and for 15 hours at room temperature. It i8 subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclo~eY~ne at -20C.
Yield: 5.4 g (0.0325 mol; 81 % of theory); melting point:
Example 15:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution i8 admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic pha~e, the crude product is recrystallized from 200 ml of methylcyclo~eY~ne at -20C.
Yield: 5.6 g (0.0337 mol; 84 % of theory); melting point:
6 0 ~
Example 16:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution i8 admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.09 g (0.4 mmol) of palladium(II) acetate dis~olved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 7.5 g (0.06 mol) of 32% strength by weight sodium hydroxide solution and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture i8 ~tirred for 1 hour at 0C and for 15 hours at room temperature. It iB subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic pha~e is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcycloh~Y~ne at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 17:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas condition~ in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succes~ion. The mixture i~ ~tirred for 15 minutes. The reaction mixture is cooled to 0C.
7.5 g (0.06 mol) of 32% ~trength by weight sodium hydroxide solution and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is ~tirred for 1 hour at 0C and for ~1~1601 15 hours at room temperature. It is subsequently admixed with 100 ml of ~aturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclo~Y~ne at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 18:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution i~
admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclo~eYAne at -20C.
Yield: 5.2 g (0.0313 mol; 78 % of theory); melting point:
Example 19:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture i8 stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is ~tirred for 1 hour at 0C and for 15 hour~ at room temperature. It is subsequently ~m; Yed with 100 ml of saturated agueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.3 g (0.0319 mol; 80 % of theory); melting point:
Example 20:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.426 g (0.4 mmol) of palladium on activated carbon (10% by weight) suspended in 5 ml of toluene are added in succession. The mixture is ~tirred for 15 minutes. The reaction mixture i~ cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subseguently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueou~ A-~o~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcycloheYAne at -20C.
Yield: 6.1 g (0.0367 mol; 92 % of theory); melting point:
The reaction mixture is ~tirred for 1 hour at 0C and for ~1~1601 15 hours at room temperature. It is subsequently admixed with 100 ml of ~aturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclo~Y~ne at -20C.
Yield: 5.8 g (0.0349 mol; 87 % of theory); melting point:
Example 18:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution i~
admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.09 g (0.4 mmol) of palladium(II) acetate dissolved in 5 ml of toluene are added in succession. The mixture is stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclo~eYAne at -20C.
Yield: 5.2 g (0.0313 mol; 78 % of theory); melting point:
Example 19:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.07 g (0.4 mmol) of palladium(II) chloride dissolved in 5 ml of toluene are added in succession. The mixture i8 stirred for 15 minutes. The reaction mixture is cooled to 0C. 6.24 g (0.06 mol) of sodium carbonate dissolved in 10 ml of water and 11.4 mg (0.6 mmol) of copper(I) iodide are subsequently added.
The reaction mixture is ~tirred for 1 hour at 0C and for 15 hour~ at room temperature. It is subsequently ~m; Yed with 100 ml of saturated agueous ammonium chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcyclohexane at -20C.
Yield: 5.3 g (0.0319 mol; 80 % of theory); melting point:
Example 20:
9.5 g of 1,4-chloroiodobenzene (0.04 mol) are dissolved under inert gas in 50 ml of toluene. This solution is admixed with 25 ml of water and 25 ml of ethanol. 3.5 ml (0.06 mol) of propargyl alcohol, 0.4 mmol of BINAS in the form of an aqueous solution and 0.426 g (0.4 mmol) of palladium on activated carbon (10% by weight) suspended in 5 ml of toluene are added in succession. The mixture is ~tirred for 15 minutes. The reaction mixture i~ cooled to 0C. 5.1 g (0.06 mol) of piperidine and 11.4 mg (0.6 mmol) of copper(I) iodide are subseguently added.
The reaction mixture is stirred for 1 hour at 0C and for 15 hours at room temperature. It is subsequently admixed with 100 ml of saturated aqueou~ A-~o~;um chloride solution and 100 ml of ethyl acetate. The organic phase is separated off and dried over sodium sulfate. After evaporation of the organic phase, the crude product is recrystallized from 200 ml of methylcycloheYAne at -20C.
Yield: 6.1 g (0.0367 mol; 92 % of theory); melting point:
Claims (14)
1. A process for preparing 1-arylalkynes by cross-coupling terminal alkynes with aromatic halogen compounds or aromatic perfluoroalkylsulfonates under palladium catalysis in the presence of at least one water-soluble complexing ligand, wherein the reaction medium forms an aqueous phase and an organic phase and the palladium is added in the form of a palladium compound soluble in the organic phase or in solid form as palladium metal.
2. The process as claimed in claim 1, wherein a palladium compound soluble in the organic phase and selected from the group consisting of palladium ketonates, palladium acetylacetonates, nitrilepalladium halides, olefinpalladium halides, palladium halides, allylpalladium halides and palladium biscarboxylates is used.
3. The process as claimed in claim 2, wherein a palladium compound soluble in the organic phase and selected from the group consisting of bis(benzyl-i d e n e a c e t o n e ) p a l l a d i u m ( 0 ) , bis(benzylideneacetone)palladium(0) chloroform complex, palladium bisacetylacetonate, palladium dichloride, ?3-allylpalladium chloride dimer, sodium tetrachloropalladate, dichloro(dimethyl sulfoxide)palladium(II), bi(benzonitrile)palladium dichloride, bis(acetonitrile)palladium dichloride, palladium(II) acetate, palladium(II) propionate, palladium(II) butanoate and (1c,5c-cycloocta-die-ne)palladium dichloride is used.
4. The process as claimed in claim 1, wherein the palladium is used as palladium on activated carbon, palladium on aluminum oxide, palladium on barium carbonate, palladium on barium sulfate, palladium on aluminum silicates and/or palladium on calcium
5. The process as claimed in one or more of the prece-ding claims, wherein from 0.001 to 10 mol% of palla-dium, based on the aromatic halogen compound or the perfluoroalkylsulfonate, is used.
6. The process as claimed in one or more of the prece-ding claims, wherein the water-soluble complexing ligand used is at least one compound selected from the group consisting of phosphines, phosphites, phosphonic esters, phosphinic esters, phospholes, bipyridines, phenanthrolines, porphyrins and aliza-rins.
7. The process as claimed in claim 6, wherein the water-soluble complexing ligands used are water-soluble phosphines of the formulae (I) to (VII), (I) (II) (III) (IV) (V) (VI) (VII) where the symbols and indices have the following meanings:
Aryl: a phenyl or naphthyl group which can also bear one or more substituents R;
Alkyl: a straight-chain or branched alkyl group having from 1 to 8 carbon atoms;
R,R': alkyl, aryl or aralkyl having from 1 to 18 carbon atoms;
M: alkali metal, alkaline earth metal or NR4;
X: halogen, BF4, PF6, OSO2CF3, 1/2[SO4];
l,m: 1 to 8;
n,o,p,q: 0, 1 to 8; s: 0, 1 to 3.
Aryl: a phenyl or naphthyl group which can also bear one or more substituents R;
Alkyl: a straight-chain or branched alkyl group having from 1 to 8 carbon atoms;
R,R': alkyl, aryl or aralkyl having from 1 to 18 carbon atoms;
M: alkali metal, alkaline earth metal or NR4;
X: halogen, BF4, PF6, OSO2CF3, 1/2[SO4];
l,m: 1 to 8;
n,o,p,q: 0, 1 to 8; s: 0, 1 to 3.
8. The process as claimed in claim 7, wherein the water-soluble complexing ligands used are BINAS
and/or TPPTS
and/or TPPTS
9. The process as claimed in one or more of the prece-ding claims, wherein the water-soluble complexing liquid is used in an amount of from 0.001 to 20 mol%, based on the aromatic halogen compound or the perfluoroalkylsulfonate.
10. The process as claimed in one or more of the prece-ding claims, wherein the organic phase comprises one or more water-insoluble solvents selected from the group consisting of hydrocarbons, ethers, higher alcohols which are not completely miscible with water, ketones, amides and nitriles.
11. The process as claimed in one ore more of the prece-ding claims, wherein the aqueous phase of the reac-tion mixture comprises a water-miscible organic cosolvent selected from the group consisting of nitriles, amides and lower alcohols.
12. The process as claimed in one or more of the prece-ding claims, wherein one or more copper(I) compounds are used as cocatalyst.
13. The process as claimed in one or more of the prece-ding claims, wherein the base used is at least one compound selected from the group consisting of alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates, alkali metal hydrogen carbonates, alkali metal and alkaline earth metal acetates, alkali metal and alkaline earth metal alkoxides and primary, secondary and tertiary amines.
14. The process as claimed in one or more of the prece-ding claims, carried out at a temperature of from -10 to 200°C.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19944438586 DE4438586A1 (en) | 1994-10-28 | 1994-10-28 | Prepn. of 1-aryl-alkyne cpds. in high yield |
| DEP4438586.2 | 1994-10-28 | ||
| DEP4438877.2 | 1994-10-31 | ||
| DE19944438877 DE4438877A1 (en) | 1994-10-31 | 1994-10-31 | Prepn. of 1-aryl-alkyne cpds. in high yield |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2161601A1 true CA2161601A1 (en) | 1996-04-29 |
Family
ID=25941493
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2161601 Abandoned CA2161601A1 (en) | 1994-10-28 | 1995-10-27 | Process for cross-coupling aromatic halogen compounds or perfluoroalkylsulfonates with terminal alkynes |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0709357A1 (en) |
| JP (1) | JPH08245427A (en) |
| CA (1) | CA2161601A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19712388A1 (en) * | 1997-03-25 | 1998-10-01 | Studiengesellschaft Kohle Mbh | Process for the synthesis of aromatically substituted olefins |
| EP2260015B1 (en) * | 2008-03-19 | 2012-10-31 | E. I. du Pont de Nemours and Company | Process for making 1,1,1,4,4,4-hexafluoro-2-butene |
| CN108440228A (en) * | 2018-04-27 | 2018-08-24 | 郑州大学 | The complex-catalyzed molecular oxygen oxidation synthesis in water 1 of water-soluble transition metal, the method for 3- diacetylene class compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5043510A (en) * | 1989-03-27 | 1991-08-27 | E. I. Du Pont De Nemours And Company | Aqueous alkylation process |
| DE4017567A1 (en) * | 1990-05-31 | 1991-12-05 | Bayer Ag | METHOD FOR PRODUCING OLEFIN AND ACETYLENE COMPOUNDS |
-
1995
- 1995-10-09 EP EP19950115897 patent/EP0709357A1/en not_active Withdrawn
- 1995-10-27 CA CA 2161601 patent/CA2161601A1/en not_active Abandoned
- 1995-10-27 JP JP28066795A patent/JPH08245427A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPH08245427A (en) | 1996-09-24 |
| EP0709357A1 (en) | 1996-05-01 |
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