CN1918110A - Hydroaminomethylation of olefins - Google Patents
Hydroaminomethylation of olefins Download PDFInfo
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- CN1918110A CN1918110A CN 200580004602 CN200580004602A CN1918110A CN 1918110 A CN1918110 A CN 1918110A CN 200580004602 CN200580004602 CN 200580004602 CN 200580004602 A CN200580004602 A CN 200580004602A CN 1918110 A CN1918110 A CN 1918110A
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Abstract
The present invention relates to a method comprising the step of contacting under hydroaminomethylation conditions, an olefin, an amine, a rhodium-phosphorous ligand, and synthesis gas (syngas). In particular, it has been discovered that, under some circumstances, a neutral rhodium-monodentate phosphite ligand is prescribed. The invention provides a simple way of making, in high yields and regiospecificity, a variety of products, including pharmacologically active products such as ibutilide, terfenadine, and fexofenadine, and derivatives thereof.
Description
Background of invention
The present invention relates to the hydrogen aminomethylation (hydroaminomethylation) of alkene.Aliphatic amine is used for various application, comprises agrochemicals and medicament production and intermediate, and as the polymer precursor of urethane.Homogeneous phase hydrogen aminomethylation reaction by the Reppe of BASF use homogeneous cobalt carbonylic catalyst report (Liebigs Ann.Chem.1953,582,133-161).This reaction is made up of series connection, single stage method olefin hydroformylation/reduction amination sequence, and wherein the reaction of intermediate aldehydes and primary amine or secondary amine is to form imines or enamine intermediate, and its experience hydrogenation is to form secondary amine or tertiary amine.US3,513,200 have reported homogeneous phase rhodium triphenylphosphine catalyzer is used for synthesizing tertiary amine by the hydrogen aminomethylation purposes.The hydrogen aminomethylation that adopts ethene with the purposes that forms Tri N-Propyl Amine by Jones at J.Organomet.Chem.1989,366, report among the 403-408.Because the ethylene hydrogenation formylation can only be produced the single area isomer of intermediate propionic aldehyde, this reaction is complete selectivity for the synthetic of Tri N-Propyl Amine.People such as Eilbracht are at Tetrahedron 1999,55, and report pharmacological activity amine can use homogeneous phase [Rh (cod) Cl] by the hydrogen aminomethylation among the 9801-9816
2Preparation of Catalyst, however the selectivity of the required branching regional isomer of this reaction pair is low.People such as Beller are at J.Am.Chem.Soc.2003, and 125, reported the rhodium catalyst that adopts the Xantphos diphosphine ligand by using among the 10311-10318, terminal olefin can adopt the very high selectivity of linear amines isomer is carried out the hydrogen aminomethylation.At Science 2002,297,1676-1678, people such as Seayad have described at synthetic gas, phosphine part and positively charged ion procatalyst [Rh
+(ring suffering-1,5-diene)
2] [BF
4 -] (be also referred to as [Rh
+(cod)
2BF
4] procatalyst) exist down by the prepared in reaction aliphatic amine of internal olefin (as 2-butylene, 2-amylene, or 2-octene) with amine (as piperidines, dimethylamine or two normal hexyl Amines).The researchist is test monodentate phosphite ligands but find that the amine selectivity of difference-and not change into their conclusion that draws of required linear amines-therefrom be that " because the hydrolysis problem that runs into, phosphite ester ligand not too is suitable for required reaction in the presence of water and amine under same reaction conditions also." the same at 1677 pages.The shortcoming of the phosphite ester ligand of this report in the hydrogen aminomethylation is significant, and this is that it is the first step of hydrogen aminomethylation sequence because the rhodium phosphite catalysts is highly suitable for the hydroformylation of alkene.Pruett (J.Org.Chem.1969,34,327) has reported homogeneous phase rhodium triphen phosphite catalysts and has obtained higher linear selectivity than rhodium triphenylphosphine.The large volume monodentate phosphite ligands, (Organometallics 1995,14,34-43) find to obtain under mild conditions very high hydroformylation speed by people such as van Leeuwen as three (the 2-tertiary butyl-4-aminomethyl phenyl) phosphorous acid ester.The bidentate bisphosphite ligands can obtain the very high selectivity to linear aldehyde from the rhodium shortening formylation of terminal olefin.The functional group of the anti-wide region of these catalyzer height, this make they to the synthetic of title complex organic molecule use become possible (J.Am.Chem.Soc.1993,115,2066-2068).The intramolecularly example of the hydrogen aminomethylation of unsaturated amine is seen people such as Bergmann (Tetrahedron.Lett.1997,38, the 4315-4318) report of use height regioselectivity bisphosphite ligands.
For guaranteeing the hydrogenation of enamine intermediate to required amine, people such as Seayad report " need reach 120 ℃ temperature of reaction " is the same 1677.On the other hand, and in the publication document afterwards (Angew.Chem.Int.Ed.2003,42,5615-5619), identical study group's report uses [Rh (CO)
2(acac)] selectivity of procatalyst and phosphine part enamine intermediate under 65 ℃-125 ℃ temperature preparation.
Although can use the method for being described by people such as Seayad to adopt reasonable high yield and selectivity to prepare alkylamine, pyritous requires to make this method only be suitable for alkene stable under these high-temperatures, amine, catalyzer and product.Equally, the long reaction times requires to prolong uses processing unit, and it causes tooling cost to increase.Therefore, need to find the mode of more efficient and more effective alkene amino methylization.
Summary of the invention
In first aspect, the present invention is the method that comprises the steps: make a) alkene under hydrogen aminomethylation condition; B) primary amine or secondary amine or ammonia; C) neutral rhodium-monodentate phosphite ligands title complex and d) synthetic gas contacts.
In second aspect, the present invention is the method that comprises the steps: make a) classification ArXCR=CR under hydrogen aminomethylation condition
2Alkene; B) secondary amine; C) rhodium-Ya phosphorus (phosphorous) ligand-complexes; With d) synthetic gas contacts; Wherein Ar is aryl or substituted aryl, and each R is H, alkyl, cycloalkyl, aryl, aralkyl, substituted alkyl, substituted cycloalkyl, substituted aryl or contains heteroatomic group and X is a linking group that condition is to be-CH as X independently
2-or-OCH
2In-time, nickel/phosphorous ligand is a phosphite ester ligand.
Detailed Description Of The Invention
In first aspect, the present invention is by making alkene, amine, neutral rhodium-monodentate phosphite ligands title complex contact the method for preparing alkylamine with synthetic gas under hydrogen aminomethylation condition.Alkene can be terminal (as ethene, propylene, 1-butylene, the 1-amylene, 4-methyl-1-pentene, 1-hexene, 1-decene, 1-dodecylene, vinyl cyclohexane, the polypropylene of ethenyl blocking, allyl benzene, chavicol, vinylbenzene, iso-butylene, 2-Methyl-1-pentene, the methylene radical hexanaphthene, norbornylene, alpha-methyl styrene, α-phenylcyclohexane ethene, the end capped polypropylene of vinylidene, vinylidene end capped poly-(4-methyl-1-pentene)) or inner (as 2-butylene, the 2-amylene, 2-hexene, 3-hexene, the 2-octene, 3-octene, tetrahydrobenzene, Stilbene and Witconol 2301 and derivative thereof).Olefin addition can comprise ethylenic group more than one (as divinyl, isoprene, piperylene, 1,7-octadiene, propadiene, norbornadiene, Dicyclopentadiene (DCPD), methyl linoleate, Linolenic acid methylester, oleic acid triglyceride level, polyhutadiene, and polyhutadiene-altogether-vinylbenzene), it also can comprise the alkene (as the tetrahydrochysene phenyl aldehyde) that contains ketone or aldehyde, for purpose of the present invention, thinks that it is a diene.
Amine can be primary amine (as methylamine, ethamine, Tri N-Propyl Amine, n-Butyl Amine 99, Isopropylamine, isobutylamine, TERTIARY BUTYL AMINE, normal hexyl Amine, normal hexyl Amine, n-octyl amine, benzylamine, allyl amine, the 1-phenyl-ethyl amine, 2-phenyl-ethyl amine, neopentyl amine, hexahydroaniline, thanomin) or secondary amine (as dimethylamine, ethyl dimethylamine, butyl methylamine, two normal hexyl Amines, piperidines, tetramethyleneimine, morpholine, aniline, dibenzylamine, n-monomethylaniline, diethanolamine, N-methylbenzylamine, N-methylcyclohexylamine, N-methacrylic amine, and indoles) and can comprise amino more than one (as quadrol, 1, the 2-diaminopropanes, 1,3-diaminopropanes, hexamethylene-diamine, piperazine, N methyl piperazine, 1-(2, the 3-dichlorophenyl) piperazine, 1, the 4-diamino-cyclohexane, hydrazine, and N, N '-dimethylpropane diamines).Amine also can comprise one or more non-amine functional groups, and this functional group does not participate in reaction (as 3-methylamino-propionitrile).The N-H group of amine preferably is not less than 0.5: 1 to the mole of the ethylenic group of alkene to molar ratio, more preferably is not less than 0.7: 1; Most preferably be not less than 0.9: 1; Preferably be not more than 2: 1, more preferably no more than 1.5: 1 with most preferably be not more than 1.1: 1.By example, three moles 1-butylene can with one mole ammonia react, two moles 1-butylene can react with diethylamine with the 1-butylene of the reaction of one mole ethamine and a mole.
Neutral rhodium-monodentate phosphite ligands title complex (following title complex) is prepared at an easy rate by following mode usually: the excessive monodentate phosphite ligands that makes neutral rhodium procatalyst and preferred stoichiometry in the presence of solvent such as diox, THF, hexanaphthene, toluene, acetone or o-Xylol contacts and prepares.Monodentate phosphite ligands can be by general formula P (OR)
3Characterize, wherein each R is the carbon containing substituting group independently.Monodentate is expressed as follows the fact: part only comprises a phosphorous acid ester group.Preferably, each R comprises alkyl, aryl, aralkyl, alkoxy aryl or carbonyl aryl independently.The example of representative monodentate phosphite comprises the triphenyl phosphorous acid ester, three (2, the 4-di-tert-butyl-phenyl) phosphorous acid ester, the tri-o-tolyl phosphorous acid ester, three p-methylphenyl phosphorous acid esters, trimethyl phosphite, triethyl phosphorite, three n-propyl phosphorous acid esters, three normal-butyl phosphorous acid esters, tri-tert phosphorous acid ester, three-1-naphthyl phosphorous acid ester, three-2-naphthyl phosphorous acid ester, 2,2 '-the bis-phenol phenyl phosphites, 2,2 ', 4,4 '-tetra-tert-2,2 '-bis-phenol 2,4-di-tert-butyl-phenyl phosphorous acid ester and tribenzyl phosphorous acid ester.
The neutral rhodium procatalyst is rhodium (I) catalyst precursor, and the positive charge that it is characterized by it is by the negative charge balance that supports binding partner.For example, dicarbapentaborane acetonyl rhodium acetate (is also referred to as [Rh (CO)
2(acac)] procatalyst) be the neutral rhodium procatalyst, therefore, be suitable for the method for first aspect present invention, this is because the acetonyl acetate moiety is that Chemical bond arrives the cationic electronegative part of rhodium.On the other hand, because the tetrafluoroborate negatively charged ion can not Chemical bond arrive rhodium positively charged ion, [Rh (cod)
2BF
4] be the cationic rhodium procatalyst.
Other suitable example that is used to prepare the neutral rhodium procatalyst of title complex comprises [Rh
4(CO)
12], [Rh
2(OAc)
4], [Rh (C
2H
4)
2(acac)], [Rh (cyclooctadiene) (acac)], [(Rh (norbornylene)
2(acac)), [(Rh (norbornadiene) (acac)) and [Rh (acac)
3] procatalyst.
Monodentate phosphite ligands preferably is not less than 2: 1 and more preferably is not less than 4: 1 molar ratio the mole of the neutral rhodium catalyzer that is used to prepare title complex; Preferably be not more than 30: 1 and more preferably no more than 20: 1 moles to molar excess.Alkene and amine are preferably with for the excessive use of the stoichiometry of title complex.Title complex preferably is not more than 1: 500 to the mole of the ethylenic group of the amino of amine or alkene to molar ratio and more preferably no more than 1: 200 with preferably be not less than 1: 10 and more preferably be not less than 1: 40.
With alkene, amine and title complex and randomly solvent advantageously adopt excessive CO of stoichiometry and H
2Mixture (following synthetic gas) is saturated and carry out heat and pressure adjusting time enough reactant is changed into required amino methyl product.Perhaps, for the alkene that is obstructed as 1,1 '-pattern that disubstituted olefin (as α-phenylcyclohexane ethene) may be favourable in, amine or ammonia are sequentially added into, promptly after conversion of olefines becomes the hydroformylation intermediate product.H
2: the mole of CO depends on application to molar ratio, but preferably is not less than 1: 1, more preferably is not less than 1.5: 1 and most preferably is not less than 1.8: 1 and preferably is not more than 4: 1, more preferably no more than 3: 1 with most preferably be not more than 2.2: 1.Preferably, be reflected at and be not less than 200psi (1380kPa), more preferably be not less than 500psi (3450kPa) and most preferably be not less than 800psi (5510kPa); Preferably be not more than 3000psi (20700kPa), more preferably no more than 2000psi (13800kPa) with most preferably be not more than under the pressure of 1500psi (10340kPa) and carry out.Preferably, temperature of reaction remains on and is not higher than 140 ℃, more preferably no higher than 120 ℃ with most preferably be not higher than 100 ℃; Preferably be not less than 20 ℃, more preferably be not less than 40 ℃ and most preferably be not less than 60 ℃.
Although synthetic gas presumably forms identical product with the reaction of inferring of title complex, and no matter use neutrality or cationic rhodium procatalyst, phase believer in a certain religion's synthetic gas and derived from the formation of strong acid in the reaction of the title complex of cationic rhodium procatalyst (as from [Rh (cod)
2BF
4] HBF
4) suppress of the hydrogenation of enamine intermediate to the amino methyl product.Owing to this reason, the neutral rhodium procatalyst is to select to be used to prepare precursor of complex.
Be surprisingly found out that the amino methyl product can adopt high yield, under relative low temperature (＜100 ℃) with in the relative short period of time (＜5 hours), prepare.
In second aspect, the present invention is the method for preparing the amino methyl product, and this method comprises the steps: to make a) classification ArXCR=CR under hydrogen aminomethylation condition
2Alkene; B) secondary amine; C) rhodium procatalyst; D) contain the phosphorous part; With e) synthetic gas contacts; Wherein Ar is aryl or substituted aryl, each R is H, alkyl, cycloalkyl, aryl, aralkyl, substituted alkyl, substituted cycloalkyl, substituted aryl independently or contains heteroatomic group, as methoxyl group, oxyethyl group, primary amino and uncle's amino and X is linking group, and condition is to be-CH as X
2-or-OCH
2In-time, nickel/phosphorous ligand is a phosphite ester ligand.Term " nickel/phosphorous ligand " expression contains the phosphorous part as used herein.
Ar is replacement or unsubstituted phenyl, naphthyl, anthryl, phenanthryl or heteroaryl preferably, more preferably replaces or unsubstituted phenyl, most preferably substituted-phenyl.The example of preferred substituted-phenyl comprises p-Y-phenyl or methanesulfonamido phenyl, and wherein Y is C (CH
3)
2R ", wherein R " is methyl, cyano group, hydroxyl methylene radical, alkoxyl group methylene radical, carbonyl hydroxyl, carbo methoxy group, carbonyl oxyethyl group, carbonyl benzyloxy, amido, ortho-formiate, formyl radical, 2-oxazoline or 2-benzoxazole.Preferred substituted-phenyl comprises to tert-butyl-phenyl, to the methanesulfonamido phenyl or to (α-carbo methoxy group-α '-methyl) ethylphenyl.X preferably-CHOH ,-CHOSi (CH
3)
3, or-C=O, more preferably-CHOH.
Although the neutral rhodium procatalyst is preferred for this second aspect, also can use the cationic rhodium procatalyst as [Rh (cod)
2BF
4], [Rh (cod)
2CF
3SO
3], [Rh (cod)
2PF
6], [Rh (cod)
2BPh
4], [Rh (quadrol)
3NO
3], [Rh (dipyridyl)
3Cl]
3[Rh (norbornylene)
2ClO
4].Nickel/phosphorous ligand is phosphine or phosphite ester ligand preferably.If X is-CH
2-or-OCH
2-, nickel/phosphorous ligand is a phosphite ester ligand; For all other X, nickel/phosphorous ligand is unrestricted.Preferably, X is-CR ' OR ', C=O, S or NR-C=O, wherein each R ' is alkyl, cycloalkyl, aryl, arylalkyl, trialkylsilkl or H independently.More preferably, X be-CHOH ,-CHOSi (CH
3)
3, or-C=O; Most preferably-CHOH.
The example that is used for the suitable phosphine of this second aspect comprises 2,2 '-two (diphenylphosphine ylmethyls)-1,1 '-dinaphthalene (NAPHOS), 2,2 '-two [two (3, the 5-trifluoromethyl) phosphinomethyl]-1,1 '-dinaphthalene (IPHOS), 2,2 '-two [two (4-trifluoromethyl) phosphinomethyl]-1,1 '-dinaphthalene and 9,9-dimethyl-4, two (diphenylphosphino) xanthenes (XANTPHOS) of 5-.
The example of suitable phosphorous acid ester comprises above-described monodentate phosphite and multiple tooth, preferred bidentate phosphite ester ligand, and their example comprises the part 2 of following explanation:
Part 2
Other example of bitooth ligand is disclosed in U.S.4, and 748,261, its instruction is hereby incorporated by.
The method of this second aspect of the present invention is provided in the one step reductibility coupling amine and alkene to prepare various useful compounds, as the plain mode of medical compounds, this medical compounds comprises ibutilide, terfenadine and fexofenadine and derivative thereof.For such process application, some olefin substrate is novel composition.
Following embodiment only is used for illustrative purposes and is not intended to limit the scope of the invention.Unless otherwise indicated, synthetic gas obtains from Matheson or Airgas, refers to H
22: 1 moles of/CO to molar mixture.
Embodiment 1-prepares the dimethylaminomethyl paraffins mixture
In 1-gal (4-L) reactor Neodene alkene blend (10/1112/13/12,319g obtains from Shell Chemical) the olefin substrate adding THF (680g).In this solution, add dimethylamine (222g) and from [Rh (CO)
2(acac)] solution of title complex among THF (374g) that (3.7g) (46.2g is from Aldrich Chemical acquisition) prepares with three (2, the 4-di-tert-butyl-phenyl) phosphorous acid ester.Final rhodium concentration is about 900ppm by weight.With this mixture heating up to 80 ℃ with adopt synthetic gas to be pressurized to 600psi (4140kPa) and stirred under these conditions 7 hours.Reactor cooling to 21 ℃ is spent the night and is discharged gas phase.Stir about 1 hour is poured out reactor content to remove after most of excessive dimethylamine under nitrogen gas stream, and stripping goes out THF and uses the distillation of Kugelrohr equipment to obtain colourless fluxion (427g, 99% yield).
The hydrogen aminomethylation of embodiment 2-oleic acid diethyl amide and diethanolamine
The reactor that amine hydroxybenzene (13.49g), diethanolamine (4.51g) and THF solvent (20mL) is added nitrogen purge by syringe.Reactor is stirred with saturated solution under about 200psi (1380kPa) synthetic gas.After exhaust, with [Rh (CO)
2(acac)] (press Rh weight 5351ppm) and the aliquots containig (10.4g) of the pre-preparation catalyst solution of three (2, the 4-di-tert-butyl-phenyl) phosphite ester ligand (5.00 moles of part/mole Rh) in THF adds reactor.With reactor sealing with adopt the synthetic gas pressurization and be heated to 80 ℃.Adopt other synthetic gas to be increased to 600psi (4140kPa) and charging under this pressure in entire reaction on demand then pressure.After 4.5 hours, with reactor cooling, exhaust and discharge reactor content.Amber solution is adopted hexanaphthene, toluene extraction then, abandon supernatant liquid.Acetonitrile is added the brown layer in bottom, and simple agitation.When stopping to stir, separate viscosity, Honey color lower layer (16.7g) by decantation (decantation).H-1 and C-13 NMR spectrum show that the product that has excessive diethanolamine is required.Mass spectrum (adopting the CI of Trimethylmethane) is presented at 489 (M+H)
+Peak and at 545 (M+H+ iso-butylene)
+Molecular weight is confirmed at the peak.
The hydrogen aminomethylation of different polypropylene of embodiment 3-terminal unsaturation and dibenzylamine
Weight-average molecular weight Mw is dissolved in toluene (70mL) for the end capped polypropylene of vinylidene of about 1800g/mol (5.43g is from Baker-Hughes Corporation acquisition).This solution of a part (65mL) is transferred to 100mL Parr reactor, and (2mL is 9.8mmols) with the solution that the comprises title complex (stoste that 20mL is prepared by following mode: dissolving [Rh (CO) in enough THF to add dibenzylamine thus
2(acac)] (2.56g), 2,4-di-tert-butyl-phenyl phosphorous acid ester (32.09g) is to obtain total solution quality 200.73g).With reactor sealing and be pressurized to 600psi (4140kPa) synthetic gas and be heated to 80 ℃ following 130 minutes.After reaction, relief pressure and open the reactor simultaneous temperature still at 60 ℃ enters glass beaker with content.By adding methyl alcohol (about 2 * volume) precipitation polymers product.Leach and adopt methanol wash colourless solid material up to washes.Material is dry in a vacuum to obtain 5.31 gram products, by C-13 and H-1 NMR spectral characterization.
The hydrogen aminomethylation of embodiment 4-tetrahydrobenzene and ammonia
With the title complex stoste (10mL) described in a part of embodiment 3, THF (10mL), tetrahydrobenzene (0.93g., 11.07mmols) and ammonia (the 0.5M solution in the 30mL Zai diox) add 100ml Parr reactor.Reactor adopted 400psi (2760kPa) synthetic gas pressurization and be heated to 80 ℃ following 220 minutes, cool off then and gas chromatographic analysis is carried out in sampling.The result indicates and has consumed 94% tetrahydrobenzene and primary product is three (cyclohexyl methyl) amine (90%), two (cyclohexyl methyl) amine (3%) and hexahydrobenzyl alcohol (7%).
The hydrogen aminomethylation of embodiment 5-ethylidene norbornene and morpholine
To add 100-mL Parr autoclave from the aliquots containig (9.81g) of the catalyzer stoste of embodiment 3 and THF (36.54g) and morpholine (2.02g).Reactor 200psi (1380kPa) synthetic gas was stirred 15 minutes down.Blowdown presssure adds ethylidene norbornene (0.96g) thus.Adopt synthetic gas to be pressurized to 400psi (2760kPa) reactor and be heated to 80 ℃ following 150 minutes.Cooling reactor by the gas chromatography/mass spectrometry analysis, shows that parent material almost completely changes into molecular weight corresponding to the monoamine of structure 1 (46%) and 2 (54%) and the mixture of isomers of diamine with content then.
The hydrogen aminomethylation of embodiment 6-poly-(1) and diethanolamine
Solution poly-(1) (obtaining Mw～100,000,93% vinyl, 7%1,4-cis, 5.1 weight % in 50mL THF from Scientific Design Company) and 9.45g diethanolamine are added 100-mL Parr reactor.Reactor is adopted purified synthesis gas and exhaust, add solution (157.6g, the title complex stoste for preparing from following mode: in THF (157.6g), mix [Rh (CO) of title complex thus
2(acac)] (2.52g), 2,4-di-tert-butyl-phenyl phosphorous acid ester (31.06g)).Adopt synthetic gas to be pressurized to 400psi (2760kPa) reactor and be heated under 80 ℃ almost 4 hours.Cooling reactor and discharge content.Insoluble brown polymkeric substance is dissolved in methyl alcohol, adopts the acetone redeposition, form the product that illustrates with proof by centrifugal recovery with by H-1 and C-13NMR spectroscopic analysis then.
The hydrogen aminomethylation of embodiment 7-vinylbenzene and morpholine
With [Rh (CO)
2(acac)] (0.100g), 2,4-di-tert-butyl-phenyl phosphorous acid ester (1.355g), tetrahydrofuran (THF) (50mL), morpholine (14.62g) and vinylbenzene (8.81g) add 100-mL Parr reactor and be pressurized to 380psi (2620kPa) then and be heated to 80 ℃ following 4 hours.Cooling reactor and with content by GC mass spectrum/Infrared spectroscopy.The distribution of finding product is as follows:
2-phenylpropionaldehyde-6%
2-phenyl propanol-2%
1-morpholino-2-phenyl-propane-40%
1-morpholino-3-phenyl-propane-40%
2-phenylpropionaldehyde morpholine enamine-10%
1-2/3-dimorpholino-3-phenyl-propane-2%
The hydrogen aminomethylation of embodiment 8-tetrahydrochysene phenyl aldehyde and morpholine
In 100mL Parr reactor, add [Rh (CO)
2(acac)] (127.1mg), ligand 1 (2.84g), diox (50mL), hexane (mark in the GC, 1223.5mg), tetrahydrochysene phenyl aldehyde (5.52g) and morpholine (9.08g).Reactor is adopted 1: 1 H of 1000psi (6890kPa)
2/ CO pressurization and be heated to 90 ℃ following 4 hours.After 90 minutes, be 94% to the selectivity of diamines, do not detect enamine.
Ligand 1
The hydrogen aminomethylation of embodiment 9-polyhutadiene and dimethylamine
The aliquots containig (23.31g) that to gather the stoste (19.47g in 376.1g THF) of (cis-1,4-divinyl) adds 100-mL Parr reactor, pressurizes with this reactor sealing with 300psi (2070kPa) synthetic gas then.After exhaust, (9.73g is from [Rh (CO) with complex solution
2(acac)] (3.0001g), 2, the stoste of 4-di-tert-butyl-phenyl phosphorous acid ester (37.77g) and THF (229.2g)) add, add dimethylamine (3.13g) subsequently.Reactor adopts synthetic gas to be pressurized to 600psi (4140kPa), is heated to 80 ℃ then.After about 135 minutes, with reactor cooling and blowdown presssure.Open reactor and content is transferred to flask.Add 1 weight %Ionol (oxidation inhibitor) solution, but do not form throw out.Solvent is removed in a vacuum, product is dissolved in ether and adopts acetone precipitation to obtain cream-coloured elastomeric material.With product dried overnight and by H-1 NMR spectral characterization in a vacuum.H-1 spectrum shows that olefinic C-H resonates almost totally not existing at about 5.4ppm.(CH is appointed as at new peak 2.145 and 2.064 respectively
3)
2NCH
2-and (CH
3)
2NCH
2-.In addition, also exist in the resonance of 1.1-1.6 owing to the saturated polymer chain.
The hydrogen aminomethylation of embodiment 10-vinylidene end capped poly-(4-methyl-1-pentene) and 3-amino methyl-propionitrile
In 1 gallon of stainless steel autoclave, add poly-(4-methyl-1-pentene) (76.04g, 3.5mmol alkene is functionalized, Mn is～22000), 1.5L toluene and 3-amino methyl-propionitrile (20mL, 215.6mmol).Autoclave is carried out pressure test, adopt N
2The simple purification adopted synthetic gas (2: 1H
2/ CO) purify, with content at 400psi synthetic gas (2: 1 H
2/ CO) stir down 20min.Reactor slowly is heated to 60 ℃, exhaust and (the 80psi N by pressurization
2) the Whitey cylinder is added in and comprises Rh (CO) in the 250mL toluene
2(acac) (4.42g, 17.1mmol) with three-2,4-di-tert-butyl-phenyl phosphorous acid ester (23.34g, catalyst solution 36.1mmol).Reactor is heated to 80 ℃ then, adopts synthetic gas (2: 1 H
2/ CO) be pressurized to 400psi and stir 14h.Be cooled to after 60 ℃ reactor to be adopted N
2Purify and the material that inclines.The MeOH adding of equal volume is precipitated with induced polymer.With the solid filtering that obtains and adopt washing with acetone up to filtrate colourless (～2L).With filter cake dried overnight and sample carried out in vacuum drying oven
1H NMR analyzes.The analysis of NMR data discloses the incomplete conversion of parent material, is 65-70% to the transformation efficiency of required product.(20mL 215.6mmol) adds identical stainless steel autoclave together with in addition 1.5L toluene and 3-amino methyl-propionitrile with isolating polymeric blends (vide infra) 68.75g.As mentioned above after purifying and under synthetic gas, stirring, reaction mixture is heated to 60 ℃ and be added in and comprise Rh (CO) among the 250mL THF
2(acac) (4.31g, 16.7mmol) with three-2,4-di-tert-butyl-phenyl phosphorous acid ester (22.99g, catalyst solution 35.5mmol).Reaction mixture is heated to 80 ℃, is pressurized to 400psi synthetic gas (2: 1 H
2/ CO) and stir other 14h.The separation of above-described product obtains the 63.58g colourless powder.Sample is carried out
1HNMR analyzes.The analysis of NMR data shows that this material changes into required amino methyl product fully.
The hydrogen aminomethylation of embodiment 11-α-phenylcyclohexane ethene and piperidines
A. synthetic α-phenylcyclohexane ethene
α-phenylcyclohexane ethene uses standard Wittig chemical preparation (Gupta, P. from cyclohexyl-phenyl ketone; Fernandes, R.A.; Kumar, P.Tet.Lett.2003,44,4231-4232.).With methyl triphenyl phosphorus bromide (29.57g, 82.77mmol) in 600mL THF in glove box slurryization.Mixture is cooled to 2 ℃ and add nBuLi in 15min (1.6M is in hexane, 52mL).After 1h, (15.18g 80.63mmol), slowly is warmed up to ambient temperature overnight with solution to add the solid cyclohexyl-phenyl ketone.Add entry (200mL).Solution is adopted Et
2O (3 * 150mL) extractions.The organic extract that merges adopts salt water washing, drying (MgSO
4) and vaporising under vacuum to obtain tawny liquid.Ph
3PO crystallization and by filtering and removing with adopt hexane (200mL) washing when leaving standstill.Hexane solution is filtered by 2in natural alumina post, adopt other 200mL hexane wash.Filtrate is evaporated to colourless liquid, distills this liquid (46-49 ℃/0.1mm Hg) to obtain 13.72g colourless liquid (89% yield).
B. general hydroformylation process
Hydroformylation solution is prepared by following mode: with part and Rh (CO)
2(acac) stoste adds the THF solvent, adds olefin solution subsequently.The total quantity of liquid is 4mL in each reactor cell.Compound ligand solution (for the 0.11M of unidentate ligand) and Rh (CO) by in toluene, at room temperature dissolving proper amt in loft drier
2(acac) (0.05M).Olefin solution prepares by mixing 2.3493g α-phenylcyclohexane ethene and 0.6444g dodecane (as marking in the GC) (1: 0.3 mol ratio).Hydrogenation formyl reaction is being arranged in the Argonaut Endeavor of inert-atmosphere glove box
Carry out in the reactor assembly.Reactor assembly is made up of eight parallel connections, churned mechanically pressure reactor, and this reactor has one temperature and pressure control.When adding catalyst solution, reactor is adopted synthetic gas (CO: H
2-1: 1) pressurization and be heated to temperature requiredly then, under 800rpm, stir simultaneously.After 16hrs by system exhaust is stopped the test.When opening reactor, each reaction mixture of 0.1mL is taken out and adopts the 1.6mL dilution with toluene, with this solution by gas chromatographic analysis.All GC analyzes and carries out according to following temperature program(me) on the DB-5 post: 100 ℃ of following 5min, 10 ℃ then/min to 250 ℃ and keep 5min then.
C. order adds the hydrogen aminomethylation that piperidines carries out
The Rh (CO) that adds 0.085mL to reactor
2(acac) the 0.11M solution of 0.05M solution and the Doverphos of 0.085mL (part: the Rh ratio is 2.2), add 3.2mL THF subsequently, 0.6mL olefin solution (1: 0.3 solution of α-phenylcyclohexane ethene and dodecane, 500: 1 ratios of olefin substrate: Rh).Reaction mixture is being heated 18hr under 90 ℃ under 300psi synthetic gas pressure.Analyzing α-phenylcyclohexane ethene according to GC is 96.5% to the transformation efficiency of needed 3-cyclohexyl-3-phenyl-propionic aldehyde.After cool to room temperature, open reactor and add the 0.25mL piperidines (piperidines of 1.2: 1 ratios: the aldehyde substrate).After the off-response device, reaction mixture is being heated 18hr under 90 ℃ under 300psi synthetic gas pressure.GC analyzes demonstration and forms required amine with 95% yield, 1-(3-cyclohexyl-3-phenyl-propyl group)-piperidines.Reaction mixture is taken out and under reduced pressure removes solvent from reactor, stay oil.Adding～13mL acetonitrile in this resistates uses hot rifle heated solution.Solution is put into refrigerator (～5 ℃).After 2 days, with the solution decantation and with remaining light yellow oil adopt the washing of cold acetonitrile (2 * 3mL) and then drying under reduced pressure to obtain 150mg cleaning product.
1H(C
6D
6)：δ0.65-1.66(m，1?7H)，1.83(m，1H)，1.92-2.31(m，7H)，2.36(m，1H)，7.04(m，3H)，7.13(m，2H)。
13C{
1H} and APT (C
6D
6): δ 25.30 (CH
2), 26.84 (CH
2), 27.09 (CH
2), 27.15 (CH
2), 30.75 (CH
2), 31.58 (CH
2), 31.93 (CH
2), 43.79 (CH), 50.49 (CH), 55.09 (CH
2), 58.06 (CH
2), 126.09 (CH), 128.30 (CH), 128.86 (CH), 144.82 (C).GC-MS(m/e)：285
D. Comparative Examples: be not sequentially added into the hydrogen aminomethylation of piperidines
The Rh (CO) that adds 0.085mL to reactor
2The 0.11M solution of three (the 2-tertiary butyl-4-aminomethyl phenyl) phosphorous acid ester (part: the Rh ratio is 2.2) of 0.05M solution (acac) and 0.085mL, add 3.2mL THF, 0.6mL olefin solution (1: 0.3 solution of α-phenylcyclohexane ethene and dodecane, 500: 1 ratios of olefin substrate: Rh) and the 0.25mL piperidines (piperidines of 1.2: 1 ratios: olefin substrate) subsequently.Reaction mixture is being heated 18hr under 90 ℃ under 300psi synthetic gas pressure.Analyzing the cinnamic transformation efficiency of α-cyclohexyl according to GC is 11.7%.
Embodiment 12-prepares ibutilide
Ibutilide
A. prepare 4-methanesulfonamido phenyl aldehyde
4-methanesulfonamido phenyl aldehyde
(6.60g, 43.67mmol) (153mg, solution 0.804mmol) is dissolved in 150mL toluene with the tosic acid monohydrate with the 4-nitrobenzaldehyde.Add ethylene glycol (5mL), solution is refluxed with Dean-Stark water trap removes water with azeotropic.After 1 hour, will react cooling, add the 100mL diethyl ether thus.Solution is adopted saturated NaHCO
3Solution washing and adopt saturated NaCl solution washing then.Solution is passed through MgSO
4Dry and evaporation is the 4-nitrobenzaldehyde ethylene glycol ethyl ethers acetal (8.13g, 95% yield) of yellow solid to obtain.
With PtO
2(502mg, 2.21mmol) and MgSO
4(7.34g 61.0mmol) adds 4-nitrobenzaldehyde ethylene glycol ethyl ethers acetal (5.93g, 30.4mmol) solution in 60mL THF.With the suspension that obtains at 70psi H
2Under stir 5h.By the filtering and removing solid, evaporated filtrate is to obtain the 4-aminobenzaldehyde ethylene glycol ethyl ethers acetal for golden liquid.
(1.793g 10.86mmol) is dissolved in 25mLCH with 4-aminobenzaldehyde ethylene glycol ethyl ethers acetal
2Cl
2Be cooled to 0 ℃.Add pyridine (925mg, 11.7mmol), in 30min, drip subsequently methylsulfonyl chloride (1.369g, 11.9mmol).Adopting to stir allows solution be warmed up to room temperature.After 16h, 6M NaOH (5mL) is added, add 150mL water subsequently.Water layer is separated, adopt 50mL CH
2Cl
2The washing and adopt 2M HCl to be acidified to pH 1 then.With the suspension that obtains be extracted into ethyl acetate (4 * 50mL), it is passed through MgSO
4Dry and evaporation is 4-methylsulfonyl phenyl aldehyde (920mg, 42% yield of orange solids to obtain.
B. prepare 4-MeSO
2N (H) C
6H
4[C (H) is (CH=CH (OH)
2)]
4-MeSO
2N(H)C
6H
4[C(H)(OH)(CH＝CH
2)]
(834mg, 4.19mmol) solution in 13mL THF adds the 8.5mL 1.0M (H among the THF with 4-methylsulfonyl phenyl aldehyde
2C=CH
2) MgBr.The suspension that obtains is stirred 3.5h and adopts the saturated NH of 10mL then
4The quenching of Cl solution.With solution adopt diethyl ether (2 * 20mL) extraction and separate.The organic extract that merges is adopted water and saturated NaCl solution washing.Passing through MgSO
4After the drying, evaporating solns is the 4-MeSO of orange liquid to obtain
2N (H) C
6H
4[C (H) is (CH=CH (OH)
2)] (1.036g).
C. prepare ethyl-normal heptane
(10.31g is 89.4mmol) at 100mL CH with positive heptyl amice
2Cl
2In solution in ice bath, cool off.The adding pyridine (7.5mL, 92.7mmol).2min add gradually in the time acetyl muriate (8.0mL, 11mmol).Remove ice bath and allow solution be warmed up to room temperature.After 1h, add entry (100mL), and separate organic layer.Water layer is adopted 100mL CH
2Cl
2Extraction.The organic extract that merges is adopted the 10%HCl aqueous solution, saturated NaHCO
3Solution and saturated then NaCl solution washing.Solution is passed through MgSO
4Dry and evaporation is n-heptyl ethanamide (13.73g, 98% yield of colourless liquid to obtain.
(6.076g, 38.63mmol) drips of solution in the 6mL diethyl ether is added in LiAlH4 (4.60g, 0.121mol) last suspension in the 150mL diethyl ether with the n-heptyl ethanamide.With suspension returning 8h, cooling and employing 4mL H in ice
2O, 4mL 2M NaOH and 12mLH
2The O quenching.Pass through Na with the suspension filtered of acquisition with filtrate
2SO
4Dry.Solvent evaporation is obtained (n-C into colourless liquid
7H
15) N (H) C
2H
5(5.29g, 95% yield).
D. prepare ibutilide
Under nitrogen with Rh (CO)
2(acac) (6.9mg, 27 μ mol) and part 2 (25.0mg, 29.8 μ mol) are dissolved in 3mL THF.Solution transferred to churned mechanically autoclave and at 1: 1 H of 400psi (2760kPa)
2/ CO stirs 30min down.With 4-MeSO
2N (H) C
6H
4[C (H) is (CH=CH (OH)
2)] (438mg is 1.93mmol) with (n-C
7H
15) N (H) C
2H
5(283mg, 1.97mmol) the contrary H of the solution in 3mL THF
2The mobile injecting reactor of/CO.Reactor is being heated under 1: 1 H2/CO of 400psi (2760kPa) under 75 ℃.After 18h, reactor cooling is arrived envrionment temperature and exhaust.Reaction mixture is evaporated and is dissolved in CH
2Cl
2(20mL).Product is extracted into 2M NaOH (2 * 15mL).Then water layer is adopted the 10%HCl neutralization and adopt CH then
2Cl
2(3 * 10mL) extractions.With organic layer at MgSO
4Middle drying and evaporation are the product (410mg) of orange liquid to obtain.GC-MS indication product is formed (linearity: branching=25: 1) by the mixture of ibutilide and branched isomer.
Part 2
Embodiment 13-prepares Aripiprazole
Under nitrogen with Rh (CO)
2(acac) (4.7mg 18pmol) is dissolved in 3mL THF with part 2 (19.7mg, 23 μ mol).Solution transferred to churned mechanically autoclave and at 1: 1 H of 400psi (2760kPa)
2/ CO stirs 30min down.With 1-(2, the 3-dichlorophenyl) piperazine (616mg, 2.66mmol it can wait the people according to Morita, Tetrahedron 1998,54,4811 process prepares) and 7-(allyloxy)-3,4-dihydro-2 (1H)-quinoline (547mg, 2.69mmol it can be according to the process preparation of describing in WO 96/02508) the contrary H of solution in 7mL THF
2The mobile injecting reactor of/CO.With reactor under 75 ℃ at 1 of 400psi (2760kPa): 1H
2/ CO is heating down.After 16h, reactor cooling is arrived envrionment temperature and exhaust.Reaction mixture is evaporated and is dissolved in 10mL CHCl
3Solution is adopted 10%HCl solution, saturated NaHCO
3Solution and saturated then NaCl solution washing.By after the MgSO4 drying, solution evaporation is become orange oil.
Embodiment 14-prepares terfenadine
Terfenadine
A. prepare p-t-BuC
6H
4[C (H) is (CH=CH (OH)
2)]
(1.0M in THF 38mmol) is added drop-wise to p-t-BuC with BrMg (vinyl) under nitrogen
6H
4CHO (4.199g, 25.88mmol) solution in 15mL THF.Solution is at room temperature stirred 18h and the 2h that refluxes then.Add saturated aqueous NH
4Cl (50mL) and with solution adopt diethyl ether (2 * 75mL) extraction.The organic extract that merges is adopted the washing of saturated aqueous sodium-chlor and passes through MgSO
4Dry.Evaporating solns yellowly oil (5.24g).
B. prepare terfenadine
Under nitrogen with Rh (CO)
2(acac) (5.4mg, 21 μ mol) and part 2 (23.9mg, 28 μ mol) are dissolved in 3mL THF.Solution transferred to the mechanical stirring autoclave and at 1: 1 H of 250psi
2/ CO stirs 2h down.With p-t-BuC
6H
4[C (H) is (CH=CH (OH)
2)] (676mg, 3.55mmol) and α, the solution of α-phenylbenzene-4-piperidines and methyl alcohol (950mg, 3.55mmol is available from Acros) prepares in 7mL THF.Pressure is discharged into autoclave and with substrate solution contrary 1: 1H
2The mobile injecting reactor of/CO.With reactor 1: 1 H at 400psi (2760kPa) under 75 ℃
2/ CO is heating down.After 18h, reactor cooling is arrived envrionment temperature and exhaust.The reaction mixture evaporation is to obtain 1.82g viscosity orange liquid, and this liquid is slow crystallization when leaving standstill.
Embodiment 15-prepares terfenadine in addition
A. prepare p-t-BuC
6H
4[C (H) (OSiMe
3) (CH=CH
2)]
p-t-BuC
6H
4[C(H)(OSiMe
3)(CH＝CH
2)]
(5.0mL 37.7mmol) adds p-t-BuC under nitrogen with TMSA
6H
4[C (H) is (CH=CH (OH)
2)] (5.24g is 27.5mmol) at the anhydrous CH of mL
3Solution among the CN.Solution was stirred 3 days at ambient temperature.Removing solvent to obtain in a vacuum is the product (6.27g, 23.9mmol, 87% yield) of yellow liquid.
B. synthetic O-trimethyl silyl terfenadine.
O-trimethyl silyl terfenadine
Under nitrogen with Rh (CO)
2(acac) (9.3mg, 36 μ mol) and part 2 (37.5mg, 44.7 μ mol) are dissolved in 3mL THF.Solution transferred to the mechanical stirring autoclave and at 400psi1: 1 H
2/ CO stirs 15min down.With p-t-BuC
6H
4[C (H) (OSiMe
3) (CH=CH2)] (1.212g, 4.618mmol) and α, α-phenylbenzene-4-piperidines and methyl alcohol (1.240g, 4.638mmol is available from Acros Organics) are dissolved in 10mL THF.Pressure exhaust is arrived autoclave, with contrary 1: 1 H of substrate solution
2The mobile injecting reactor of/CO.With reactor 1: 1 H at 400psi (2760kPa) under 75 ℃
2/ CO is heating down.After 18h, reactor cooling is arrived envrionment temperature and exhaust.Evaporation reaction mixture is to obtain 2.29g viscosity orange liquid.
C. synthetic terfenadine
Will (2.29g 4.21mmol) be dissolved in the anhydrous THF of 20mL from the crude reaction product of B.Add solid [(PhCH
2) NMe
3]
+F
-(870mg, 1.20 equivalents) stirred the suspension that obtains 3 days at ambient temperature.Add entry, solution is adopted diethyl ether (2 * 20mL) extractions.The organic extract that merges is adopted H
2O (10mL) extraction is extracted by salt solution (10mL) subsequently.Solution is passed through MgSO
4Drying and evaporation are to obtain 2.146g viscosity orange liquid, and this liquid slowly is solidified into required product when leaving standstill.
Embodiment 16-prepares the fexofenadine methyl ester
The fexofenadine methyl ester
A. prepare p-[Me
2(CO
2Me) C] C
6H
4CHO
P-[Me
2(CO
2Me) C] C
6H
4CHO (p-(α-carbo methoxy group-α '-methyl) ethylbenzene formaldehyde))
(15.4g, 83.2mmol) (200mg, solution 1.05mmol) is dissolved in 300mL toluene with the tosic acid monohydrate with p-bromobenzaldehyde.Add ethylene glycol (10mL), adopt Dean-Stark water trap to reflux solution and remove water with azeotropic.After 4 hours, add the 100mL ethyl acetate.Solution is adopted frozen water, saturated NaHCO
3Solution and adopt saturated NaCl solution washing then.Solution is passed through MgSO
4Dry and evaporation is the p-bromobenzaldehyde ethylene glycol ethyl ethers acetal of water white oil to obtain, its crystallization when leaving standstill (18.02g, 95% yield).
(10.717g 57.23mmol) is dissolved in 90mL toluene under nitrogen with dicyclohexyl acid amides lithium.Add methyl isobutyrate (4.962g, 48.60mmol), with the solution stirring that obtains 10 minutes.(10.101g is 44.09mmol) with two palladiums three (benzylidene-acetone) (408mg, 0.891mmol Pd) then this solution to be added solid p-bromobenzaldehyde ethylene glycol ethyl ethers acetal.Add solid tri-butyl phosphine (186.4mg) and the solution stirring that obtains is spent the night.Add methylene dichloride (400mL) and 5%HCl solution (400mL).Filter reaction mixture is to remove cotton-shaped gray solid.Organic layer is separated, adopt 200mL 5%HCl solution, water (200mL) and saturated nacl aqueous solution washing.The solution that obtains is evaporated in a vacuum to obtain yellow liquid, this yellow liquid is dissolved in 2: 1 acetone-H of 150mL
2O.Add tosic acid pyridine (478mg) and solution stirring is spent the night.Remove acetone and product is extracted into diethyl ether by rotary evaporation.Solution is adopted the 45mL water washing twice and adopt the saturated nacl aqueous solution washing then.Solution is passed through MgSO
4Dry and evaporation is the product of light yellow oil to obtain.(silica gel, the purification of 9: 1 hexanes-EtOAc) obtains the required product (7.27g, 80% yield) into light yellow liquid by column chromatography.
B. prepare p-[Me
2(CO
2Me) C] C
6H
4[C (H) is (CH=CH (OH)
2)]
p-[Me
2(CO
2Me)C]C
6H
4[C(H)(OH)(CH＝CH
2)]
(1.0M in THF 14mmol) is added drop-wise to p-t-BuC with BrMg (vinyl) under nitrogen
6H
4CHO (2.896g, 14.04mmol) solution in 5mL THF.Feeding in raw material causes a large amount of heat releases, makes the solution boiling.Solution is at room temperature stirred 1.5h.Add saturated aqueous NH
4Cl (30mL) and with solution adopt diethyl ether (2 * 50mL) extraction.The organic extract that merges is adopted the washing of saturated aqueous sodium-chlor and passes through MgSO
4Dry.The required product (5.24g) of evaporating solns yellowly oil.
C. prepare the fexofenadine methyl ester
Under nitrogen with Rh (CO)
2(acac) (5.7mg, 22 μ mol) and part 2 (23.5mg, 28 μ mol) are dissolved in 3mL THF.Solution transferred to the mechanical stirring autoclave and at 250psi 1: 1H
2/ CO stirs 1h down.P-[Me
2(CO
2Me) C] C
6H
4[C (H) is (CH=CH (OH)
2)] (639mg, 2.73mmol) and α, (730mg, solution 2.73mmol) prepares in 10mL THF for α-phenylbenzene-4-piperidines and methyl alcohol.With pressure exhaust to autoclave with contrary 1: 1 H of substrate solution
2The mobile injecting reactor of/CO.With reactor under 75 ℃ at 1 of 400psi (2760kPa): 1H
2/ CO is heating down.After 18h, reactor cooling is arrived envrionment temperature and exhaust.Evaporation reaction mixture is the required product of orange spumescence solid to obtain 1.49g.
Claims (16)
1. a method is included under the hydrogen aminomethylation condition and makes a) alkene; B) primary amine or secondary amine or ammonia; C) step that contacts of synthetic gas neutral rhodium-monodentate phosphite ligands title complex and d).
2. the process of claim 1 wherein and prepare title complex by the neutral rhodium procatalyst is contacted with monodentate phosphite ligands.
3. the method for claim 2, wherein the neutral rhodium procatalyst is selected from [Rh (CO)
2(acac)], [Rh
4(CO)
12], [Rh
2(OAc)
4], [Rh (C
2H
4)
2(acac)], [Rh (cyclooctadiene) (acac)] or [Rh (acac)
3].
4. the method for claim 1, wherein alkene is selected from tetrahydrobenzene, oleic acid diethyl amide, the different polypropylene of terminal unsaturation, ethylidene norbornene, polyhutadiene, vinylbenzene, α-phenylcyclohexane ethene or tetrahydrochysene phenyl aldehyde, amine or ammonia are selected from dimethylamine, N, N '-dimethyl trimethylene diamine, morpholine, piperidines, diethanolamine, dibenzylamine or ammonia.
5. the method for claim 1, wherein monodentate phosphite ligands is selected from the triphenyl phosphorous acid ester, three (2, the 4-di-tert-butyl-phenyl) phosphorous acid ester, the tri-o-tolyl phosphorous acid ester, three p-methylphenyl phosphorous acid esters, trimethyl phosphite, triethyl phosphorite, three n-propyl phosphorous acid esters, three normal-butyl phosphorous acid esters, the tri-tert phosphorous acid ester, three-1-naphthyl phosphorous acid ester, three-2-naphthyl phosphorous acid ester, 2,2 '-the bis-phenol phenyl phosphites, 2,2 ', 4,4 '-tetra-tert-2,2 '-bis-phenol 2,4-di-tert-butyl-phenyl phosphorous acid ester, or tribenzyl phosphorous acid ester.
6. the process of claim 1 wherein, primary amine or secondary amine or ammonia are added when the reaction beginning or after conversion of olefines becomes the hydroformylation intermediate product, be sequentially added into.
7. the method for claim 6, wherein alkene be 1,1 '-dibasic, after conversion of olefines becomes the hydroformylation intermediate product, be sequentially added into primary amine or secondary amine or ammonia.
8. method is included in the step that makes following material contact under the hydrogen aminomethylation condition:
A) classification ArXCR=CR
2Alkene; B) secondary amine; C) rhodium-nickel/phosphorous ligand title complex; And d) synthetic gas; Wherein Ar is aryl or substituted aryl, and each R is hydrogen, alkyl, cycloalkyl, aryl, aralkyl, substituted alkyl, substituted cycloalkyl, substituted aryl or contains heteroatomic group and X is a linking group that condition is to be-CH as X independently
2-or-OCH
2In-time, nickel/phosphorous ligand is a phosphite ester ligand.
9. the method for claim 8, wherein Ar is that substituted-phenyl and X are the hydroxyl methylene radical.
10. the method for claim 9, wherein Ar is p-Y-phenyl or methanesulfonamido phenyl, wherein Y is C (CH
3)
2R ", wherein R " is methyl, cyano group, hydroxyl methylene radical, alkoxyl group methylene radical, carbonyl hydroxyl, carbo methoxy group, carbonyl oxyethyl group, carbonyl benzyloxy, amido, ortho-formiate, formyl radical, 2-oxazoline or 2-benzoxazole.
11. the method for claim 9, wherein Ar is to tert-butyl-phenyl, to the methanesulfonamido phenyl or to (α-carbo methoxy group-α '-methyl) ethylphenyl.
12. the method for claim 11, wherein amine is α, α-phenylbenzene-4-piperidines and methyl alcohol.
13. the method for claim 12, wherein nickel/phosphorous ligand is a phosphorous acid ester.
14. the method for claim 12, wherein nickel/phosphorous ligand is represented by following structure:
Part 2
15. classification ArXCR=CR
2Alkene, be selected from the alkene of representing by following structural formula, wherein R is H or trialkylsilkl:
16. the alkene of claim 15, wherein R is H.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54316804P | 2004-02-10 | 2004-02-10 | |
| US60/543,168 | 2004-02-10 | ||
| US60/565,781 | 2004-04-27 |
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| Publication Number | Publication Date |
|---|---|
| CN1918110A true CN1918110A (en) | 2007-02-21 |
Family
ID=37738641
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|---|---|---|---|
| CN 200580004602 Pending CN1918110A (en) | 2004-02-10 | 2005-01-21 | Hydroaminomethylation of olefins |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109622006A (en) * | 2018-11-30 | 2019-04-16 | 中国科学院山西煤炭化学研究所 | One kind lower fatty amine catalyst containing ammonia synthesis gas and preparation method thereof |
| CN109777377A (en) * | 2019-02-12 | 2019-05-21 | 西南石油大学 | Shale intercalation inhibitor made of a kind of Ultra-low molecular weight branching tertiary amine-type polyamine |
| CN113563200A (en) * | 2021-07-03 | 2021-10-29 | 复旦大学 | Method for preparing linear amine by olefin selective hydroaminomethylation |
| WO2023115292A1 (en) * | 2021-12-21 | 2023-06-29 | Rhodia Operations | Process for preparing tertiary amines |
-
2005
- 2005-01-21 CN CN 200580004602 patent/CN1918110A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109622006A (en) * | 2018-11-30 | 2019-04-16 | 中国科学院山西煤炭化学研究所 | One kind lower fatty amine catalyst containing ammonia synthesis gas and preparation method thereof |
| CN109622006B (en) * | 2018-11-30 | 2021-11-12 | 中国科学院山西煤炭化学研究所 | Catalyst for preparing low-grade aliphatic amine from ammonia-containing synthesis gas and preparation method thereof |
| CN109777377A (en) * | 2019-02-12 | 2019-05-21 | 西南石油大学 | Shale intercalation inhibitor made of a kind of Ultra-low molecular weight branching tertiary amine-type polyamine |
| CN113563200A (en) * | 2021-07-03 | 2021-10-29 | 复旦大学 | Method for preparing linear amine by olefin selective hydroaminomethylation |
| WO2023115292A1 (en) * | 2021-12-21 | 2023-06-29 | Rhodia Operations | Process for preparing tertiary amines |
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