Patent Application
20250019334
The present disclosure generally relates to fluorophosphite ligands, catalyst solutions comprising the same, and hydroformylation processes for preparing linear and branched aldehydes employing the catalyst solutions.
Hydroformylation, also known as the oxo reaction, is one of the most widely practiced homogeneous catalyzed reactions in industry. Aldehydes produced by hydroformylation are routinely used in commodity chemicals, fragrances, and pharmaceuticals. The hydroformylation reaction is used extensively in commercial processes for the preparation of aldehydes by the reaction of an olefin with hydrogen (H2) and carbon monoxide (CO).
In one aspect, the present disclosure provides fluorophosphite ligands of formula (I):
wherein:
In other aspects, the present disclosure provides processes for preparing linear and branched aldehydes, the processes comprising contacting an olefin with hydrogen (H2) and carbon monoxide (CO) in the presence of a catalyst solution.
The contacting of the olefin with the H2 and the CO in the presence of the catalyst solution at a temperature ranging from 95° C. to 130° C., a carbon monoxide partial pressure (PCO) ranging from 110 pounds per square inch absolute (psia) to 350 psia, and a hydrogen partial pressure (H2) ranging from 20 psia to 150 psia, may produce a ratio of linear aldehydes to branched aldehydes (l/b) of less than 1.0.
The contacting of the olefin with the H2 and the CO in the presence of the catalyst solution at a temperature ranging from 60° C. to 100° C., a PCO ranging from 5 psia to 150 psia, and a PH2 ranging from 100 psia to 350 psia, may produce l/b of greater than 1.0.
Before any embodiments of the disclosure are explained in detail, it is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The disclosure is capable of other embodiments and of being practiced or of being carried out in various ways.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict, the present document, including definitions, will control. Methods and materials are described below, although methods and materials similar or equivalent to those described herein may be used in practice or testing of the present disclosure. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting.
The terms “comprise(s),” “include(s),” “having,” “has,” “can,”, “may,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not.
As used herein, the term “about” is used to indicate that exact values are not necessarily attainable. Therefore, the term “about” is used to indicate this uncertainty limit. The term “about” may refer to plus or minus 10% of the indicated number. For example, “about 10%” may indicate a range of 9% to 11%, and “about 1” may mean from 0.9-1.1. Other meanings of “about” may be apparent from the context, such as rounding off, so, for example “about 1” may also mean from 0.5-1.4. The modifier “about” should also be considered as disclosing the range defined by the absolute values of the two endpoints. For example, the expression “from about 2 to about 4” also discloses the range “from 2 to 4.”
Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987; the entire contents of each of which are incorporated herein by reference.
The term “alkoxy,” as used herein, refers to a group —O-alkyl. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy and tert-butoxy.
The term “alkyl,” as used herein, means a straight or branched, saturated hydrocarbon chain. The term “lower alkyl” or “C1-6alkyl” means a straight or branched chain hydrocarbon containing from 1 to 6 carbon atoms. The term “C1-4alkyl” means a straight or branched chain hydrocarbon containing from 1 to 4 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.
The term “alkenyl,” as used herein, means a straight or branched, hydrocarbon chain containing at least one carbon-carbon double bond.
The term “alkoxyalkyl,” as used herein, refers to an alkoxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein.
The term “alkylamino,” as used herein, means at least one alkyl group, as defined herein, is appended to the parent molecular moiety through an amino group, as defined herein.
The term “amide,” as used herein, means —C(O)NR— or —NRC(O)—, wherein R may be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl.
The term “aminoalkyl,” as used herein, means at least one amino group, as defined herein, is appended to the parent molecular moiety through an alkylene group, as defined herein.
The term “amino,” as used herein, means —NRxRy, wherein Rx and Ry may be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl. In the case of an aminoalkyl group or any other moiety where amino appends together two other moieties, amino may be —NRx—, wherein Rx may be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl.
The term “aryl,” as used herein, refers to a phenyl or a phenyl appended to the parent molecular moiety and fused to a cycloalkane group (e.g., the aryl may be indan-4-yl), fused to a 6-membered arene group (i.e., the aryl is naphthyl), or fused to a non-aromatic heterocycle (e.g., the aryl may be benzo[d][1,3]dioxol-5-yl). The term “phenyl” is used when referring to a substituent and the term 6-membered arene is used when referring to a fused ring. The 6-membered arene is monocyclic (e.g., benzene or benzo). The aryl may be monocyclic (phenyl) or bicyclic (e.g., a 9- to 12-membered fused bicyclic system).
The term “cyanoalkyl,” as used herein, means at least one —CN group, is appended to the parent molecular moiety through an alkylene group, as defined herein.
The term “cycloalkoxy,” as used herein, refers to a cycloalkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom.
The term “cycloalkyl” or “cycloalkane,” as used herein, refers to a saturated ring system containing all carbon atoms as ring members and zero double bonds. The term “cycloalkyl” is used herein to refer to a cycloalkane when present as a substituent. A cycloalkyl may be a monocyclic cycloalkyl (e.g., cyclopropyl), a fused bicyclic cycloalkyl (e.g., decahydronaphthalenyl), or a bridged cycloalkyl in which two non-adjacent atoms of a ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms (e.g., bicyclo[2.2.1]heptanyl). Representative examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, adamantyl, and bicyclo[1.1.1]pentanyl.
The term “cycloalkenyl” or “cycloalkene,” as used herein, means a non-aromatic monocyclic or multicyclic ring system containing all carbon atoms as ring members and at least one carbon-carbon double bond and preferably having from 5-10 carbon atoms per ring. The term “cycloalkenyl” is used herein to refer to a cycloalkene when present as a substituent. A cycloalkenyl may be a monocyclic cycloalkenyl (e.g., cyclopentenyl), a fused bicyclic cycloalkenyl (e.g., octahydronaphthalenyl), or a bridged cycloalkenyl in which two non-adjacent atoms of a ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms (e.g., bicyclo[2.2.1]heptenyl). Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl. Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl.
The term “carbocyclyl” means a “cycloalkyl” or a “cycloalkenyl.” The term “carbocycle” means a “cycloalkane” or a “cycloalkene.” The term “carbocyclyl” refers to a “carbocycle” when present as a substituent.
The terms cycloalkylene and heterocyclylene refer to divalent groups derived from the base ring, i.e., cycloalkane, heterocycle. For purposes of illustration, examples of cycloalkylene and heterocyclylene include, respectively,
and
Cycloalkylene and heterocyclylene include a geminal divalent groups such as 1,1-C3-6cycloalkylene
A further example is 1,1-cyclopropylene
The term “halogen” or “halo,” as used herein, means Cl, Br, I, or F.
The term “haloalkyl,” as used herein, means an alkyl group, as defined herein, in which one, two, three, four, five, six, seven or eight hydrogen atoms are replaced by a halogen.
The term “haloalkoxy,” as used herein, means at least one haloalkyl group, as defined herein, is appended to the parent molecular moiety through an oxygen atom.
The term “halocycloalkyl,” as used herein, means a cycloalkyl group, as defined herein, in which one or more hydrogen atoms are replaced by a halogen.
The term “heteroalkyl,” as used herein, means an alkyl group, as defined herein, in which one or more of the carbon atoms has been replaced by a heteroatom selected from S, O, P and N. Representative examples of heteroalkyls include, but are not limited to, alkyl ethers, secondary and tertiary alkyl amines, amides, and alkyl sulfides.
The term “heteroaryl,” as used herein, refers to an aromatic monocyclic heteroatom-containing ring (monocyclic heteroaryl) or a bicyclic ring system containing at least one monocyclic heteroaromatic ring (bicyclic heteroaryl). The term “heteroaryl” is used herein to refer to a heteroarene when present as a substituent. The monocyclic heteroaryl are five or six membered rings containing at least one heteroatom independently selected from the group consisting of N, O and S (e.g. 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N). The five membered aromatic monocyclic rings have two double bonds and the six membered aromatic monocyclic rings have three double bonds. The bicyclic heteroaryl is an 8- to 12-membered ring system and includes a fused bicyclic heteroaromatic ring system (i.e., 10π electron system) such as a monocyclic heteroaryl ring fused to a 6-membered arene (e.g., quinolin-4-yl, indol-1-yl), a monocyclic heteroaryl ring fused to a monocyclic heteroarene (e.g., naphthyridinyl), and a phenyl fused to a monocyclic heteroarene (e.g., quinolin-5-yl, indol-4-yl). A bicyclic heteroaryl/heteroarene group includes a 9-membered fused bicyclic heteroaromatic ring system having four double bonds and at least one heteroatom contributing a lone electron pair to a fully aromatic 10π electron system, such as ring systems with a nitrogen atom at the ring junction (e.g., imidazopyridine) or a benzoxadiazolyl. A bicyclic heteroaryl also includes a fused bicyclic ring system composed of one heteroaromatic ring and one non-aromatic ring such as a monocyclic heteroaryl ring fused to a monocyclic carbocyclic ring (e.g., 6,7-dihydro-5H-cyclopenta[b]pyridinyl), or a monocyclic heteroaryl ring fused to a monocyclic heterocycle (e.g., 2,3-dihydrofuro[3,2-b]pyridinyl). The bicyclic heteroaryl is attached to the parent molecular moiety at an aromatic ring atom. Other representative examples of heteroaryl include, but are not limited to, indolyl (e.g., indol-1-yl, indol-2-yl, indol-4-yl), pyridinyl (including pyridin-2-yl, pyridin-3-yl, pyridin-4-yl), pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl (e.g., pyrazol-4-yl), pyrrolyl, benzopyrazolyl, 1,2,3-triazolyl (e.g., triazol-4-yl), 1,3,4-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, imidazolyl, thiazolyl (e.g., thiazol-4-yl), isothiazolyl, thienyl, benzimidazolyl (e.g., benzimidazol-5-yl), benzothiazolyl, benzoxazolyl, benzoxadiazolyl, benzothienyl, benzofuranyl, isobenzofuranyl, furanyl, oxazolyl, isoxazolyl, purinyl, isoindolyl, quinoxalinyl, indazolyl (e.g., indazol-4-yl, indazol-5-yl), quinazolinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, isoquinolinyl, quinolinyl, imidazo[1,2-a]pyridinyl (e.g., imidazo[1,2-a]pyridin-6-yl), naphthyridinyl, pyridoimidazolyl, thiazolo[5,4-b]pyridin-2-yl, and thiazolo[5,4-d]pyrimidin-2-yl.
The term “heterocycle” or “heterocyclic,” as used herein, means a monocyclic heterocycle, a bicyclic heterocycle, or a tricyclic heterocycle. The term “heterocyclyl” is used herein to refer to a heterocycle when present as a substituent. The monocyclic heterocycle is a three-, four-, five-, six-, seven-, or eight-membered ring containing at least one heteroatom independently selected from the group consisting of O, N, and S. The three- or four-membered ring contains zero or one double bond, and one heteroatom selected from the group consisting of O, N, and S. The five-membered ring contains zero or one double bond and one, two or three heteroatoms selected from the group consisting of O, N and S. The six-membered ring contains zero, one or two double bonds and one, two, or three heteroatoms selected from the group consisting of O, N, and S. The seven-and eight-membered rings contains zero, one, two, or three double bonds and one, two, or three heteroatoms selected from the group consisting of O, N, and S. Representative examples of monocyclic heterocyclyls include, but are not limited to, azetidinyl, azepanyl, aziridinyl, diazepanyl, 1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl, isoxazolinyl, isoxazolidinyl, morpholinyl, 2-oxo-3-piperidinyl, 2-oxoazepan-3-yl, oxadiazolinyl, oxadiazolidinyl, oxazolinyl, oxazolidinyl, oxetanyl, oxepanyl, oxocanyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl, pyrazolidinyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothienyl, thiadiazolinyl, thiadiazolidinyl, 1,2-thiazinanyl, 1,3-thiazinanyl, thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1-dioxidothiomorpholinyl (thiomorpholine sulfone), thiopyranyl, and trithianyl. The bicyclic heterocycle is a monocyclic heterocycle fused to a 6-membered arene, or a monocyclic heterocycle fused to a monocyclic cycloalkane, or a monocyclic heterocycle fused to a monocyclic cycloalkene, or a monocyclic heterocycle fused to a monocyclic heterocycle, or a monocyclic heterocycle fused to a monocyclic heteroarene, or a spiro heterocycle group, or a bridged monocyclic heterocycle ring system in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, or an alkenylene bridge of two, three, or four carbon atoms. The bicyclic heterocyclyl is attached to the parent molecular moiety at a non-aromatic ring atom (e.g., indolin-1-yl). Representative examples of bicyclic heterocyclyls include, but are not limited to, chroman-4-yl, 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzothien-2-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl, 2-azaspiro[3.3]heptan-2-yl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, azabicyclo[2.2.1]heptyl (including 2-azabicyclo[2.2.1]hept-2-yl), azabicyclo[3.1.0]hexanyl (including 3-azabicyclo[3.1.0]hexan-3-yl), 2,3-dihydro-1H-indol-1-yl, isoindolin-2-yl, octahydrocyclopenta[c]pyrrolyl, octahydropyrrolopyridinyl, tetrahydroisoquinolinyl, 7-oxabicyclo[2.2.1]heptanyl, hexahydro-2H-cyclopenta[b]furanyl, 2-oxaspiro[3.3]heptanyl, 3-oxaspiro[5.5]undecanyl, 6-oxaspiro[2.5]octan-1-yl, and 3-oxabicyclo[3.1.0]hexan-6-yl. Tricyclic heterocycles are exemplified by a bicyclic heterocycle fused to a 6-membered arene, or a bicyclic heterocycle fused to a monocyclic cycloalkane, or a bicyclic heterocycle fused to a monocyclic cycloalkene, or a bicyclic heterocycle fused to a monocyclic heterocycle, or a bicyclic heterocycle in which two non-adjacent atoms of the bicyclic ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, or an alkenylene bridge of two, three, or four carbon atoms. Examples of tricyclic heterocycles include, but are not limited to, octahydro-2,5-epoxypentalene, hexahydro-2H-2,5-methanocyclopenta[b]furan, hexahydro-1H-1,4-methanocyclopenta[c]furan, aza-adamantane (1-azatricyclo[3.3.1.13,7]decane), and oxa-adamantane (2-oxatricyclo[3.3.1.13, 7]decane). The monocyclic, bicyclic, and tricyclic heterocyclyls are connected to the parent molecular moiety at a non-aromatic ring atom.
The term “hydroxyl” or “hydroxy,” as used herein, means an —OH group.
The term “hydroxyalkyl,” as used herein, means at least one —OH group, is appended to the parent molecular moiety through an alkylene group, as defined herein.
Terms such as “alkyl,” “cycloalkyl,” “alkylene,” etc. may be preceded by a designation indicating the number of atoms present in the group in a particular instance (e.g., “C1-4alkyl,” “C3-6cycloalkyl,” “C1-4alkylene”). These designations are used as generally understood by those skilled in the art. For example, the representation “C” followed by a subscripted number indicates the number of carbon atoms present in the group that follows. Thus, “C3alkyl” is an alkyl group with three carbon atoms (i.e., n-propyl, isopropyl). Where a range is given, as in “C1-4,” the members of the group that follows may have any number of carbon atoms falling within the recited range. A “C1-4alkyl,” for example, is an alkyl group having from 1 to 4 carbon atoms, however arranged (i.e., straight chain or branched).
The term “substituted” refers to a group that may be further substituted with one or more non-hydrogen substituent groups. Substituent groups include, but are not limited to, halogen, ═O (oxo), ═S (thioxo), cyano, nitro, fluoroalkyl, alkoxyfluoroalkyl, fluoroalkoxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, heteroalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, heteroarylalkyl, arylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkylene, aryloxy, phenoxy, benzyloxy, amino, alkylamino, acylamino, aminoalkyl, arylamino, sulfonylamino, sulfinylamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, sulfinyl, —COOH, ketone, amide, carbamate, and acyl.
For compounds described herein, groups and substituents thereof may be selected in accordance with permitted valence of the atoms and the substituents, such that the selections and substitutions result in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc.
The term “hydroformylation,” as used herein is contemplated to include, but is not limited to, all hydroformylation processes that involve converting one or more substituted or unsubstituted olefinic compounds or a reaction mixture comprising one or more substituted or unsubstituted olefinic compounds to one or more substituted or unsubstituted aldehydes or a reaction mixture comprising one or more substituted or unsubstituted aldehydes. The aldehydes may be asymmetric or non-asymmetric.
The term “fractional conversion,” as used herein means the number of moles of a compound that reacted divided by the amount of the moles that were fed.
The term “free ligand,” as used herein means ligand that is not complexed with, tied to or bound to, the metal, e.g., metal atom, of the complex catalyst.
The term “Syngas,” (from synthesis gas) as used herein is the name given to a gas mixture that contains varying amounts of carbon monoxide (CO) and hydrogen (H2). Production methods are well known and include, for example: (1) steam reforming and partial oxidation of natural gas or liquid hydrocarbons and (2) the gasification of coal and/or biomass. Hydrogen and CO typically are the main components of syngas, but syngas may contain carbon dioxide and inert gases such as nitrogen (N) and argon (Ar). The molar ratio of H2 to CO varies greatly but generally ranges from 1:100 to 100:1 and may be between 1:10 and 10:1. Syngas is commercially available and is often used as a fuel source or as an intermediate for the production of other chemicals. The H2:CO molar ratio for chemical production may be between 3:1 and 1:3 and usually is targeted to be between about 1:2 and 2:1 for most hydroformylation applications.
The term “catalyst solution” as used herein, may include, but is not limited to, a mixture comprising: (a) a metal-organophosphorous ligand complex catalyst, (b) free metal, (c) free organophosphorous ligand, and (d) a solvent for said metal-organophosphorous ligand complex catalyst, said free metal, and said free organophosphorous ligand.
The term “complex” as used herein and in the claims means a coordination compound formed by the union of one or more electronically rich molecules or atoms capable of independent existence with one or more electronically poor molecules or atoms, each of which is also capable of independent existence. The phosphite ligands employed herein, which possesses one phosphorus donor atom, have one available or unshared pair of electrons which may form a coordinate covalent bond independently or with another phosphite ligand in concert (e.g., via chelation) with rhodium (Rh). Carbon monoxide (which is also properly classified as a ligand) is also present and complexed with Rh.
Generally, in hydroformylation processes, a transition metal-organophosphorus ligand complex catalyst produces an isomeric mixture comprising a linear (l, normal, or n-) aldehyde and one or more branched (b, iso-, or i-) aldehydes. A ratio of the linear aldehyde to the sum of the branched aldehydes, calculated by molar or by weight, is often described as l/b selectivity or l/b ratio. Since all isomeric aldehydes produced from a given olefinically-unsaturated compound have an identical molecular weight, the molar l/b ratio is identical to the weight l/b ratio. For the purposes of this disclosure, an l/b selectivity of a catalyst refers to the l/b ratio obtained from hydroformylation of an olefin unless otherwise stated.
In industry settings it is a labor-intensive process to shift from linear-selective reactions to branched-selective reactions. Typically, in industry, the aldehyde products are separated from the catalyst solution via distillation or extraction and said catalyst solution is recycled. However, when transitioning from branch-selective processes to linear-selective processes, the rhodium catalyst system may need to be altered, because a different organophosphorus ligand may be required to generate the opposite selectivity. This ligand-Rh disengagement is a costly process that poses a need for modular phosphine ligands that enable formation of both linear and branched aldehydes depending on simple and adjustable reaction parameters.
The present disclosure provides hydroformylation processes that enable selective formation of linear and branched aldehyde products.
Broadly, exemplary processes comprise a fluorophosphite ligand, a catalyst solution comprising the same, and a regioselective hydroformylation process employing the catalyst solution. Aldehydes produced by hydroformylation processes may be referred to as “oxo aldehydes,” which have a wide range of utility, for example, as intermediates for hydrogenation to aliphatic alcohols, for amination to aliphatic amines, for oxidation to aliphatic acids, and for aldol condensation to plasticizers. Various aspects of exemplary processes, including descriptions of a fluorophosphite ligand, a catalyst solution comprising the same, and a regioselective hydroformylation process employing the catalyst solution, are discussed in the following sections.
The present disclosure provides processes for preparing linear and branched aldehydes, comprising contacting an olefin with hydrogen and carbon monoxide in the presence of a catalyst solution, under hydroformylation conditions, as herein described.
The disclosure further provides a highly active catalyst solution for use in regioselective hydroformylation reactions. A hydroformylation process comprises contacting under reaction conditions an olefin with carbon monoxide and hydrogen in the presence of a catalyst to produce one or more aldehydes.
Hydroformylation processes typically employ transition metal-organophosphorus ligand complex catalysts. The present disclosure employs transition metal-fluorophosphite ligand complex catalysts.
Transition metals may include, but are not limited to, iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium and platinum. Rhodium may be a preferred transition metal for some reactions.
Rhodium compounds that may be used as a source of rhodium for the active catalyst may include rhodium (II) or rhodium (III) salts of carboxylic acids, examples of which include di-rhodium tetraacetate dihydrate, rhodium (II) acetate, rhodium (II) isobutyrate, rhodium (II)2-ethylhexanoate, rhodium (II) benzoate, and rhodium (II) octanoate. Also, rhodium carbonyl species such as Rh4(CO)12, Rh6(CO)16, and rhodium (I) acetylacetonate dicarbonyl may be suitable rhodium feeds. Other rhodium sources may include rhodium salts of strong mineral acids such as chlorides, bromides, nitrates, sulfates, phosphates, and the like.
In some aspects, the present disclosure provides compounds of formula (I), wherein X, R, R1, R2, R3, R4, R5, R6, R7, and R8 are as defined herein.
Unsubstituted or substituted rings (i.e., optionally substituted) such as aryl, heteroaryl, etc. are composed of both a ring system and the ring system's optional substituents. Accordingly, the ring system may be defined independently of its substituents, such that redefining only the ring system leaves any previous optional substituents present. For example, a 5- to 12-membered heteroaryl with optional substituents may be further defined by specifying the ring system of the 5- to 12-membered heteroaryl is a 5- to 6-membered heteroaryl (i.e., 5- to 6-membered heteroaryl ring system), in which case the optional substituents of the 5- to 12-membered heteroaryl are still present on the 5- to 6-membered heteroaryl, unless otherwise expressly indicated.
Fluorophosphite ligands that may be useful in the present disclosure are set forth in the following numbered embodiments. The first embodiment is denoted E1, the second embodiment is denoted E2 and so forth.
E1. A fluorophosphite ligand of formula (I):
wherein:
E2. The fluorophosphite ligand of E1, wherein R is C1-4alkyl or a 3- to 6-membered carbocycle.
E3. The fluorophosphite ligand of E1 or E2, wherein X is
E4. The fluorophosphite ligand of E1-E3, wherein R1, R2, R3, and R4 are each C1-4alkyl.
E5. The fluorophosphite ligand of E1-E4, wherein R1, R2, R3, and R4 are each —CH3.
E6. The fluorophosphite ligand of any one of E1-E5, wherein R5 and R6 are each independently
E7. The fluorophosphite ligand of any one of E1-E6, wherein R7 and R8 are each C1-4alkyl or the unsubstituted or substituted phenyl.
E8. The fluorophosphite ligand of any one of E1-E7, wherein R7 and R8 are each —CH3 or unsubstituted phenyl.
E9. The fluorophosphite ligand of any one of E1-E8, wherein the fluorophosphite ligand of formula (I) is a ligand of formula (Ia):
E10. The fluorophosphite ligand of any one of E1-E9, wherein the fluorophosphite ligand of formula (I) is a ligand of formula (Ib):
E11. The fluorophosphite ligand of any one of E1-E10, wherein the fluorophosphite ligand of formula (I) is
The fluorophosphite ligands of this disclosure may be prepared by any effective method. Various methods for preparing fluorophosphites are reported in the literature. For example, it has been found that fluorophosphites may be prepared by using a (benzyl)phenol starting material such as 2,2′-methylene bis(4,6-di(α,α-dimethylbenzyl)phenol) and following the procedures described in U.S. Pat. No. 4,912,155; Tullock et al., J. Org. Chem., 25, 2016 (1960); White et al., J. Am. Chem. Soc., 92, 7125 (1970); Meyer et al., Z. Naturforsch, Bi. Chem. Sci., 48, 659 (1993); or Puckette, in “Catalysis of Organic Reactions,” Edited by S. R. Schmidt, CRC Press (2006), pp. 31-38.
The ratio of gram moles fluorophosphite ligand of formula (I) to gram atoms transition metal may vary over a wide range, e.g., gram mole fluorophosphite:gram atom transition metal ratio of 1:1 to 400:1. For rhodium-containing catalyst systems, the gram mole fluorophosphite:gram atom rhodium ratio in some aspects of the present disclosure is in the range of 1:1 to 200:1 with ratios in the range of 1:1 to 120:1.
In some aspects of the present disclosure, the ratio of Rh to the ligand of formula (I) ranges from 10:1 to 400:1.
In some aspects of the present disclosure, the ratio of Rh to the ligand of formula (I) ranges from 10:1 to 100:1.
In some aspects of the present disclosure, the ratio of Rh to the ligand of formula (I) ranges from 10:1 to 50:1.
The absolute concentration of rhodium in the reaction mixture or solution may vary from 1 mg/liter up to 5000 mg/liter or more. In some aspects of the present disclosure, the normal concentration of rhodium in the reaction solution may be in the range of 20 mg/liter (mg/L) to 300 mg/L. Concentrations of rhodium lower than this range may yield lower reaction rates with most olefin reactants and/or require reactor operating temperatures that are so high as to be detrimental to catalyst stability.
A catalyst of high activity may be obtained if all manipulations of the rhodium and fluorophosphite ligand components are carried out under an inert atmosphere, e.g., nitrogen, argon, and the like or if the catalyst is pre-activated (see IV. Experimental Examples, “Materials and Methods” for pre-activation conditions).
A wide variety of olefins may be used as the starting material for the methods disclosed herein. Specifically, olefins may include, but are not limited to, ethylene, propylene, butene, pentene, hexene, octene, styrene, non-conjugated dienes such as 1,5-hexadiene, and blends of these olefins. Furthermore, the olefin may be substituted with functional groups so long as they do not interfere with the hydroformylation reaction. Suitable substituents on the olefin may include any functional group that does not interfere with the hydroformylation reaction, such as, but not limited to, carboxylic acids and derivatives thereof such as esters and amides, alcohols, nitriles, and ethers. Examples of substituted olefins may include, but are not limited to, esters such as methyl acrylate or methyl oleate, alcohols such as allyl alcohol and 1-hydroxy-2,7-octadiene, and nitriles such as acrylonitrile.
In some aspects, the olefin may be a C3-20alkene or a C3-8cycloalkene. The olefin may be a C3-10alkene. The olefin may be propylene, 1-octene, or 2-octene.
The amount of olefin present in the reaction mixture may vary. For example, relatively high-boiling olefins such as 1-octene may function both as the olefin reactant and the process solvent. In the hydroformylation of a gaseous olefin feedstock such as propylene, the partial pressures in the vapor space in the reactor are in the range of 1 psia to 500 psia. The rate of reaction may be favored by high concentrations of olefin in the reactor. In the hydroformylation of propylene, the partial pressure of propylene in some aspects of the present disclosure is greater than 20 psia, e.g., from 20 psia to 145 psia. In the case of ethylene hydroformylation, the partial pressure of ethylene in the reactor in some aspects of the present disclosure is greater than 2 psia.
The hydroformylation solvent may be selected from a wide variety of compounds, mixture of compounds, or materials that are liquid at the pressure at which the process is being operated. Such compounds and materials include various alkanes, cycloalkanes, alkenes, cycloalkenes, carbocyclic aromatic compounds, alcohols, esters, ketones, acetals, ethers, and water. Examples of such solvents may include, but are not limited to, alkanes and cycloalkanes such as dodecane, decalin, octane, iso-octane mixtures, cyclohexane, cyclooctane, cyclododecane, methylcyclohexane; aromatic hydrocarbons such as benzene, toluene, xylene isomers, tetralin, cumene, alkyl-substituted aromatic compounds such as the isomers of diisopropylbenzene, triisopropylbenzene and tert-butylbenzene; alkenes and cycloalkenes such as 1,7-octadiene, dicyclopentadiene, 1,5-cyclooctadiene, 1-octene, 2-octene, 4-vinylcyclohexene, cyclohexene, 1,5,9-cyclododecatriene, 1-pentene; crude hydrocarbon mixtures such as naphtha, mineral oils and kerosene; and high-boiling esters such as 2,2,4-trimethyl-1,3-pentanediol diisobutyrate. The aldehyde product of the hydroformylation process also may be used.
The solvent may include the higher boiling by-products that are naturally formed during the process of the hydroformylation reaction and the subsequent steps, e.g., distillations, that may be required for aldehyde product isolation. The main criterion for the solvent is that it dissolves the catalyst and olefin substrate and does not act as a poison to the catalyst. Some examples of solvents for the production of volatile aldehydes, e.g., butyraldehydes, may be those that are sufficiently high boiling to remain, for the most part, in a gas sparged reactor. Some examples of solvents and solvent combinations that are useful in the production of less volatile and nonvolatile aldehyde products include 1-methyl-2-pyrrolidinone, dimethyl formamide, perfluorinated solvents such as perfluoro-kerosene, sulfolane, water, and high boiling hydrocarbon liquids as well as combinations of these solvents. Non-hydroxylic compounds, in general, and hydrocarbons, in particular, may be used advantageously as the hydroformylation solvent since their use may minimize decomposition of the fluorophosphite ligands. In some aspects of the present disclosure, the hydroformylation solvent is toluene.
The reaction conditions for the process of the present disclosure may include conventional hydroformylation conditions. The process may be carried out at temperatures in the range of 50° C. to 135° C. In some aspects of the present disclosure, reaction temperatures may range from 60° C. to 130° C. The temperature in the feed may be selected according to the desired linear:branched aldehyde ratio (l/b). In some aspects of the present disclosure, the reaction temperature ranges from 95° C. to 130° C. In other aspects, the reaction temperature ranges from 60° C. to 100° C. In some aspects of the present disclosure, the temperature ranges from 100° C. to 120° C. In other aspects, the temperature ranges from 75° C. to 85° C.
The total reaction pressure may range from ambient or atmospheric pressure up to 1000 psia. The hydrogen:carbon monoxide mole ratio in the reactor likewise may vary considerably ranging from 10:1 to 1:10, and the sum of the absolute partial pressures of hydrogen and carbon monoxide may range from 5 psia to 500 psia. The partial pressures of the ratio of the hydrogen to carbon monoxide in the feed may be selected according to the linear:branched aldehyde ratio (l/b) desired. Generally, the partial pressure of hydrogen (PH2) and carbon monoxide (PCO) in the reactor may be maintained within the range of 5 psia to 350 psia for each gas. The partial pressure of carbon monoxide (PCO) in the reactor may be maintained within the range of 5 psia to 350 psia and may be varied independently of the hydrogen partial pressure (PH2). The partial pressure of hydrogen (PH2) in the reactor may be maintained within the range of 5 psia to 350 psia and may be varied independently of the carbon monoxide partial pressure (PCO). The molar ratio of hydrogen to carbon monoxide may be varied widely within these partial pressure ranges for the hydrogen and carbon monoxide. The ratios of hydrogen-to-carbon monoxide and the partial pressure of each in the synthesis gas (syngas-carbon monoxide and hydrogen) may be readily adjusted by the addition of either hydrogen or carbon monoxide to the syngas stream. With the fluorophosphite ligands described herein, the ratio of linear to branched (l/b) products may be adjusted by changing the partial pressures of the carbon monoxide in the reactor.
For example, in some aspects of the present disclosure, the PCO may range from 110 psia to 350 psia and the PH2 may range from 20 psia to 150 psia. In other aspects, the PCO may range from 5 psia to 150 psia and the PH2 may range from 100 psia to 350 psia.
Any of the known hydroformylation reactor designs or configurations such as overflow reactors and vapor take-off reactors may be used in carrying out the process provided by the present disclosure. Thus, a gas-sparged, vapor take-off reactor design may be used. In this mode of operation, the catalyst, which is dissolved in a high boiling organic solvent under pressure, does not leave the reaction zone while the aldehyde product is taken overhead by the unreacted gases. The overhead gases then are chilled in a vapor/liquid separator to liquefy the aldehyde product and the gases may be recycled to the reactor. The liquid product may be let down to atmospheric pressure for separation and purification by conventional techniques. The process also may be performed in a batchwise manner by contacting the olefin, hydrogen and carbon monoxide with the present catalyst in an autoclave.
A reactor design where catalyst and feedstock are pumped into a reactor and allowed to overflow with product aldehyde, i.e., liquid overflow reactor design, may be used. For example, high boiling aldehyde products such as nonyl aldehydes may be prepared in a continuous manner with the aldehyde product being removed from the reactor zone as a liquid in combination with the catalyst. The aldehyde product may be separated from the catalyst by conventional means such as by distillation or extraction, and the catalyst then recycled back to the reactor. Water soluble aldehyde products, such as hydroxy butyraldehyde products obtained by the hydroformylation of allyl alcohol, may be separated from the catalyst by extraction techniques. A trickle-bed reactor design is also suitable for this process. It will be apparent to those skilled in the art that other reactor schemes may be used with the processes of this disclosure.
The temperature, partial pressure of hydrogen (PH2), and partial carbon monoxide (PCO) in the feed may be selected according to the desired linear:branched aldehyde ratio (l/b).
In some aspects, contacting the olefin with H2 and CO in the presence of the catalyst solution at a temperature ranging from 95° C. to 130° C., a PCO ranging from 110 psia to 350 psia, and a PH2 ranging from 20 psia to 150 psia, produces l/b of less than 1.0. In some aspects, contacting the olefin with H2 and CO in the presence of the catalyst solution at a temperature ranging from 100° C. to 120° C., a PCO ranging from 130 psia to 230 psia, and a PH2 ranging from 30 psia to 130 psia, produces l/b of less than 0.90. In other aspects, contacting the olefin with H2 and CO in the presence of the catalyst solution at a temperature ranging from 100° C. to 120° C., a PCOranging from 200 psia to 300 psia, and a PH2 ranging from 20 psia to 50 psia, produces l/b of less than 0.60.
In some aspects, contacting the olefin with H2 and CO in the presence of the catalyst solution at a temperature ranging from 60° C. to 100° C., a PCO ranging from 5 psia to 150 psia, and a PH2 ranging from 100 psia to 350 psia, produces l/b of greater than 1.0. In some aspects, contacting the olefin with H2 and CO in the presence of the catalyst solution at a temperature ranging from 75° C. to 85° C., a PCO ranging from 5 psia to 10 psia, and a PH2 ranging from 200 psia to 300 psia, produces l/b of greater than 1.6. In some aspects, contacting the olefin with H2 and CO in the presence of the catalyst solution at a temperature ranging from 75° C. to 85° C., a PCO ranging from 50 psia to 150 psia, and a PH2 ranging from 110 psia to 210 psia, produces a l/b of greater than 1.6.
The foregoing may be better understood by reference to the following examples, which are presented for purposes of illustration and are not intended to limit the scope of the technology.
Toluene (99.8% Anhydrous), 1-octene, nonanal (95%), butyraldehyde (99.5%), isobutraldehyde (+99%), and 1,3,5-trimethoxybenzene, 2,4-bis(α,α-dimethylbenzyl)phenol, trioctylphosphine, and ethylmagnesium bromide in ether (3.0 M) were purchased from Sigma Aldrich. 2-Methyl octanal was purchased from BOC chemicals. Dicarbonyl 2,4-pentanedionato rhodium (I) 97% and 75% trimethylacetaldehyde in t-BuOH were purchased from Alfa Aesar. 2-Octene (mixture of cis+trans isomer) (+98%) was purchased from TCI. Deuterated DCM was purchased from Fisher Scientific. Carbon monoxide, hydrogen, and nitrogen were purchased from Airgas at 99.9% purity. Propylene was purchased from Airgas at 99.95% purity. 1-octene and 2-octene were purified over silica gel columns before use. Octene isomers were degassed with argon before use.
The preparation of cyclic monofluorophosphite ligand L was accomplished via previously described methods as shown in Scheme A below.
Ligands analogous to L may be prepared similarly using the appropriate starting materials.
2,4-Bis(α,α-dimethylbenzyl)phenol (850 g, 2.6 moles) and 1.8 L of toluene were combined under nitrogen in a 5-L, 3-neck round bottom flask equipped with boiling stones, a Dean-Stark trap, and a glycol-cooled condenser. The reaction mixture was heated to reflux for a period of time sufficient to collect 200 mL of liquid in the Dean-Stark trap, after which the flask was allowed to cool naturally to ambient temperature. The Dean-Stark trap was replaced with an addition funnel containing 800 mL of 3 Methylmagnesium bromide (2.4 moles) in ether followed by dropwise addition of the Grignard reagent. Once complete, the mixture was allowed to cool to ambient temperature for 1 h, after which a clean addition funnel containing 165 g of 75% trimethylacetaldehyde/t-BuOH (1.4 moles) was attached to the flask and added. After the removal each addition funnel, a clean reflux condenser was attached, and the reaction mixture was heated to reflux for 2 days (color is initially a bright green that slowly transitions to brown). After cooling to ambient temperature, a magnetic stir bar was added, and the reaction was quenched with slow addition of 1.25 L of 2 M HCl followed by rapid stirring overnight. The organic phase was then washed with 2× 500 mL of deionized water followed by slow evaporation of solvent with nitrogen gas flow. The crude solid was transferred to a 4 L beaker containing MeOH (1 L) and stirred mechanically until a white powder precipitates, after which the slurry was heated to a boil for 5 min, then allowed to cool naturally to ambient temperature. The white precipitate was the filtered and washed with 2×500 mL of MeOH, after which the final product was dried in vacuo to give 699 grams (80% isolated yield) of white powder.
Under a nitrogen atmosphere, 6,6′-(2,2-dimethylpropane-1,1-diyl)bis(2,4-bis(2-phenylpropan-2-yl)phenol) was dissolved in a triethylamine in toluene solution at a ratio of 1.4 g phenol:1 mL triethylamine:4.3 mL toluene and added to a cooled (5° C.) solution of PCl3 in toluene (0.09 mL PCl3:1 mL toluene) over a time period of 1.25 h. At the end of the addition, the slurry was stirred for additional 15 min then warmed to room temperature. After stirring overnight at room temperature, SbF3 was added to the mixture, and the temperature was raised to 85° C. and kept at 85° C. stirring for 6.5 h. After cooling, the toluene layer was separated and purified by column chromatography. 1H NMR (600 MHZ, CD2Cl2): δ 8.14-6.64 (m, 24H, ArH), 4.21 (s, 1H, bridge C—H), 2.09-1.28 (m, 24H, 4×C(CH3)2), 0.74 (s, 9H, bridge C(CH3)3). 13C NMR (151 MHz, CD2Cl2): 150.61-150.40 C(1), 149.07-148.94 C(2), 146.40-145.80 C(3), 138.84-122.80 C(4), 46.27-45.41 C(5), 42.80-41.93 C(6), 35.96-35.82 C(7), 33.26-27.88 C(8). 31P NMR (243 MHZ, CD2Cl2): δ 130.18 (d, J=1305.7 Hz), 127.47 (d, J=1296.3 Hz), 98.01 (d, J=1269.1 Hz). 19F NMR (564 MHz, CD2Cl2): δ −67.25-−70.30 (m), −69.55 (d, J=1269.9 Hz), −70.40 (d, J=1305.8 Hz). Three Isomers of L are observed by NMR:
HRMS: (EI) m/z: [M]+ Calcd for C53H58FO2P: 776.42; Found: 776.42
The desired amount of ligand L was weighed in a glass container and the corresponding amount of dicarbonyl 2,4-pentanedionato rhodium (I) was added from a 1 mg/mL stock solution in toluene. The solution was diluted with toluene to [Rh]=0.25 mM. The olefin (1- or 2-octene) was added to the solution at a concentration of 0.5 M and 2 mL of the final solution was transferred to a glass vial. No octene was added in the propylene hydroformylation experiment. The glass vial containing the liquid mixture and a magnetic stir bar was placed in a Buchiglas Tinyclave (35 mL)—except for experiments with PCO=6 psia which were conducted in a Buchiglas Miniclave (280 mL)—under inert atmosphere. The autoclave was connected to the gas supply manifold and the lines were purged three times with nitrogen prior to each experiment. The autoclave was then opened and purged an additional three times with nitrogen and two times with hydrogen. Carbon monoxide and hydrogen pressures were then sequentially introduced into the autoclave. The autoclave was sealed under pressure. The manifold was then purged with nitrogen and the autoclave was disconnected and placed in an oil bath on a hot plate. Upon reaction completion, the autoclave was removed from the oil bath and cooled in a water bath until it reached room temperature. After the autoclave was cooled down to the room temperature it was reconnected to the gas manifold. The autoclave was vented through the manifold and purged three times with nitrogen before opening. Aliquots were taken from the liquid mixture inside the vial and diluted with toluene for analysis.
Stainless steel syringes (8 mL) containing 0.5 M 1-octene in toluene, 0.25 mM Rh in toluene, and 10:1 L:Rh were prepared under inert atmosphere and then connected to the stainless steel flow reactor coil (⅛″ outer diameter, OD,× 1/16″ inner diameter, ID) with a 40-cm long fluorinated ethylene propylene tubing (Microsolv, 1/16″ OD×0.02″ ID), and 1/16″ OD nuts and ferrules (IDEX H&S). Liquid flowrates were controlled by Harvard PHD ULTRA syringe pumps and gas flowrates were controlled by individual Bronkhorst mass flow controllers (EL-Flow® Select MFCs). The flow reactor temperature was controlled through a hotplate and oil bath with a temperature probe. The flow reactor pressure was controlled with a nitrogen pressure connected to the control port of an Equilibar backpressure regulator integrated at the outlet of the flow reactor coil. The flow reactor effluent was passed through a 10-way selector valve (VICI, EUHB) and directed to a custom-designed waste collection chamber equipped with an exhaust line for CO and H2. After changing reaction conditions, the flow reactor was allowed to stabilize for twice the length of the residence time for a given reaction condition, before a sample was taken by directing the selector valve towards a collection vial for 30 min. Following the sample collection, the flow reactor effluent was directed to the waste vial during the transient period of the next hydroformylation reaction condition.
The desired amount of ligand L was weighed in a glass vial and the corresponding amount of dicarbonyl 2,4-pentanedionato rhodium (I) was added from a 1 mg/mL stock solution in toluene. The solution was diluted with toluene to the target Rh concentration. The glass vial equipped with a magnetic stir bar was then placed in a Buchiglas Miniclave (280 mL) under inert atmosphere. The autoclave was connected to the gas supply manifold and the lines were purged three times with nitrogen. The autoclave was then opened and purged an additional three times with nitrogen and two times with hydrogen. Carbon monoxide and hydrogen pressures were then introduced sequentially each at 75 psia (total pressure of 150 psia). The autoclave was sealed under pressure. The gas manifold was then purged with nitrogen and the autoclave was disconnected and placed in an oil bath at 85° C. After 1 h, the autoclave was taken out of the oil bath and cooled in a water bath until it reached room temperature. After the autoclave was cooled down to the room temperature, it was then reconnected to the gas manifold. The autoclave was vented through the gas manifold and purged three times with nitrogen before opening.
Aliquots of the reaction samples (100 μL for each sample) were collected from either batch or flow reactor and diluted with 1 mL of toluene and 100 L of 0.05 M 1,3,5-trimethoxybenzene in toluene as an internal calibration standard. 1 μL of GC mixture was injected into Shimadzu GCMS-2010 with a Zebron ZB-5MSi column 30 m×0.25 mm×0.25 μm.
7 min at 40° C. then 20° C./min to 5 min at 85° C. and 20° C./min to 210° C. Product calibrations were performed on 1-octene, cis-2-octene, trans-2-octene, trans-3-octene, trans-4-octene, cis-4-octene, nonanal, 2-methyl octanal, isobutyraldehyde, and n-butyraldehyde. The ratio of 2-propylhexanal/2-ethylheptanal/2-methyl octanal/nonanal in the hydroformylation product was calculated from peak area ratio and verified by NMR.
30 mg of L was dissolved in 1 mL of deuterated DCM and the 1H, 19F, and 31P spectra were collected with a Bruker Avance NEO 600 MHz NMR.
The hydroformylation of 1-octene in toluene was performed in a continuous flow and a batch reactor at four different temperatures (65° C., 75° C., 95° C., and 110° C.). The developed flow chemistry platform, utilizing a continuous segmented flow reactor, for accelerated fundamental studies of hydroformylation of olefins is illustrated
In the first set of experiments, the difference in activity and selectivity between reactions performed under batch versus flow conditions was investigated. The total aldehyde yield, internal isomer yield, and aldehyde regioselectivity (i.e., l/b=l/(b1+b2+b3)) were monitored. Data was collected at different reaction (i.e., residence) times, tR, in the flow reactor and at a 2 h reaction time in the batch reactor. These data are presented in
For these experiments, the maximum aldehyde yield was observed at 95° C. for both the batch and flow reactor systems (
S-shaped yield vs. time curves were observed at 75° C. and 65° C. with a decrease in reactivity between 5 min and 7 min (
The reaction temperature appeared to have a greater effect on accelerating the olefin isomerization than hydroformylation (
Despite achieving similar total aldehyde yields at 30 min for reaction temperatures of 75° C., 95° C., and 110° C., the l/b ratio decreased from 1.5 to 0.75 in flow, and from 1.7 to 0.76 in batch, as the reaction temperature increased (
To understand the effect of the different reaction parameters on the aldehyde regioselectivity and the differences between batch and flow, the effects of reaction parameters were systematically investigated. The reaction parameters explored were the CO pressure (PCO), the ligand concentration [L], and the temperature for 1-octene hydroformylation at fractional conversion. Under the experimental conditions shown in
Hydroformylation with a pre-activated Rh catalyst in the presence of L at variable [L] and at PCO=7 psia demonstrated a monotonic increase in the l/b selectivity with [L], shown in
The graph depicted in
Next, the dependence of TOF and l/b on the catalyst loading at a constant [L], PCO=7 psia, and T=75° C. was investigated using a pre-activated catalyst (
The results shown in
Next, the effect of H2 pressure, PH2, on the yield of each produced aldehyde was studied at the maximum observed 1-octene isomerization PCO (85 psia) in flow. Under these conditions, simultaneous hydroformylation of octene isomers occur, and the yield of all aldehydes increased in an apparent first order trend with PH2 up to 115 psia. At pressures higher than 115 psia, a slight increase in the yield of l was observed. However, an increase in yield was not observed for b2 and b3 (
A varying PCO experiment was also conducted for the hydroformylation of a cis and trans 2-octene mixture at 75° C. to investigate the effect of PCO on the hydroformylation of the internal olefins with L (
With the linear aldehyde-favoring, and branched aldehyde-favoring conditions in hand, on-line alternating aldehyde regioselectivity from a predominantly linear (l/b=13) to a predominantly branched (l/b=0.28) aldehyde was performed in the continuous flow reactor. For a total time on stream (TOS) of 12 h in 1-octene hydroformylation, the aldehyde throughput remained constant with a pre-activated Rh catalyst in the presence of L (
Following the alternating in-flow aldehyde regioselectivity enabled by L, the alternating regioselectivity capabilities of L was tested in a batch reactor with 1-octene and a pre-activated Rh/L catalyst at the L:Rh ratio of 40:1. For the linear-favoring experiments, based on the results shown in
Next, the effect of ligand loading in the batch reactor with 0.05 mol % Rh was investigated. For these experiments, all catalysts, including the non-ligated control experiment, were pre-activated before use in the hydroformylation reaction. The total aldehyde yields ranged from 35% to 50% for all reactions, except for the reaction with the non-ligated Rh catalyst. For the reaction with a non-ligated Rh catalyst less than 5% aldehyde yield was afforded, further confirming the accelerating effect of L in the batch reactor (Table 2A).
When [L] is less than 10 mM, a decrease in the l/b was observed, with a minimum of l/b=2 at [L]=1 mM. A relatively high n-octane formation and complete 1-octene conversion was observed for all experiments, except for the non-ligated catalyst reaction. To demonstrate the ability of ligand L to promote 1-octene hydroformylation at low l/b in the batch reactor, the reaction was performed at 110° C. to promote 1-octene isomerization to internal octenes that results in the formation of b1, b2, and b3. The hydrogen partial pressure (PH2) was kept at 35 psia to retard the hydroformylation reaction to l relative to the isomerization. This approach resulted in an l/b ratio of 0.51 at 69% total aldehyde yield after 5 h (Scheme 2, entry (2)).
An alternative, two-step, one-pot reaction to obtain lower l/b was devised based on the observation that rapid olefin isomerization occurs under CO with ligand L (
Additional experiments further demonstrated that the hydroformylation of 1-octene could be switched from linear-selective to branched-selected (and vice versa) by manipulating temperature (T), carbon monoxide pressure (PCO), and hydrogen pressure (PH2) are manipulated, with all other variables remaining constant (Table 2B).
In the next set of experiments, the flexibility of L was tested against representative mono and bidentate phosphine and phosphite ligands. The ligands tested are shown in Table 3.
The ligands triphenylphosphine (L′-2), tris(2,4-di-t-butylphenyl)phosphite (L′-3), trioctylphosphine (L′-4), 2,2′-bis((diphenylphosphaneyl)methyl)-1,1′-biphenyl(BISBI) (L′-5), and 6,6′-[(3,3′-di-tert-butyl-5,5′-dimethoxy-[1,1′-biphenyl]-2,2′-diyl)bis(oxy)]bis(6H-dibenzo[d,f][1,3,2]dioxaphosphepine) (BiPhePhos) (L′-6) were tested under the identified linear- and branched-selective hydroformylation reaction conditions in
For 1-octene, the total aldehyde yield was 53.8% and 46.2% for L′-2 and L′-3, respectively, under the linear aldehyde-favoring conditions, while L′-4 resulted in an only 6.8% total aldehyde yield under these conditions. For 1-octene, the difference in the performance of L when compared to L′-2, L′-3, and L′-4 under the branched aldehyde-favoring conditions may be attributed to the accelerating effect of L on the hydroformylation of the internal olefins as indicated by the higher content of aldehydes b2 and b3 with L (Table 4). Despite the high reaction temperature, the l/b remained high at 28.66 and 84.77 for the bidentate L′-5 and L′-6, respectively (Table 4).
The Ligand:Rh ratio was lowered to 1.1:1 (2.2:1 phosphorus (P):Rh) for the L′-5 and L′-6 ligands. At this Ligand:Rh, the l/b spanned from 1.01-2.73 for L′-5 and from 1.23-4.29 for L′-6, indicating that bidentate ligands may not be made branched aldehyde-selective under the developed branched aldehyde-favoring condition.
The selective formation of the commercially valuable isobutyraldehyde from propylene hydroformylation remains a challenge. The flexible hydroformylation of propylene in a batch reactor was explored with a pre-activated Rh catalyst with L. The branched-selective propylene hydroformylation was performed under a PCO of 255 psia, a PH2 of 30 psia, and a reaction temperature of 120° C. These conditions resulted in a high selectivity towards isobutyraldehyde (l/b=0.74, 57.5% selectivity), as presented in Table 5A. The linear aldehyde-favoring hydroformylation of propylene to n-butyraldehyde was performed under a PCO of 6 psia, a PH2 of 264 psia, and a temperature of 75° C. These conditions resulted in high selectivity towards n-butyraldehyde (l/b=5.01 and 6.60 at L:Rh=10:1 and 100:1, respectively). Increasing the propylene pressure, PC3H6, to 60 psia resulted in a further increase in the aldehyde regioselectivity towards n-butyraldehyde (l/b=7.79). Alternating aldehyde regioselectivity comparisons of l/b for propylene hydroformylation using the cyclic monofluorophosphite ligand L versus other ligands shown in
Additionally, experiments assessing the selectivity of propylenehydroformylation were conducted a constant CO pressure (PCO), H2 pressure (PH2), and temperature (T) at different L:Rh values ranging from 0 to 100:1 for T=75° C. and T=110° C. The results are summarized in Tables 5B-5D.
1ratio of gas chromatography (GC) peak areas
1ratio of gas chromatography (GC) peak areas
1ratio of gas chromatography (GC) peak areas
Due to the high activity of the pre-activated Rh/L catalyst for the hydroformylation of internal olefins, the efficacy of L in the regioselective hydroformylation of a cis-and trans-2-octene (70:30) mixture was investigated. To allow for a high rate of 2-octene hydroformylation to b1 and b2 relative to isomerization to 1-, 3-, and 4-octenes, the reaction temperature was set at 50° C., the PCO was set at 75 psia, and the PH2 was set at 200 psia, where L:Rh=10:1. These conditions resulted in the regioselective hydroformylation of 2-octene to b1 and b2 without noticeable isomerization. The total aldehyde yield after 4 h was 61.5% (entry 1, Table 6). Extending the reaction time to 12 h increased the total aldehyde yield to 91.4% with a 93% selectivity of b1+b2 (entry 2, Table 6). The l/b ratio in this case was as low as 0.02 (i.e., 98% of the produced aldehydes were branched). The unique effect of ligand L on the regioselective hydroformylation of internal olefins is presented in entry 3, Table 6, where, in the absence of L, the l/b ratio increased to 0.11 at a total aldehyde yield of 28.3%. Increased olefin isomerization to the 3- and 4-octenes also occurred in the absence of L, which resulted in an increase in b3.
Ligand L may become linear-selective for the hydroformylation of 2-octene by altering the temperature, PCO, PH2, and L:Rh ratio (100° C., PCO=6 psia, PH2=200 psia, and L:Rh=40:1). Hydroformylation at the aforementioned reaction conditions resulted in a l/b of 1.62 (1.62=62% selectivity to l) at 39.1% total aldehyde yield (Table 6, entry 4). The results in Table 6, entries 1 and 3, illustrate the flexibility of ligand L in tuning of regioselective aldehyde formation from internal olefins.
Traditionally, hydroformylation reactions are studied in pressurized autoclaves that have relatively large volumes in the order of 10-100 mL for bench scale units. Autoclaves are often pressurized before heating to minimize evaporation, and the time needed to reach the target temperature is relatively long (˜10 min). This limitation hampers the ability of batch reactors to elucidate the effect of reaction temperature on the catalyst/ligand activity and aldehyde selectivity. Furthermore, accurate pressure control in autoclaves may be challenging due to the gas thermal expansion upon heating, and pressure changes as the reaction consumes or produces gaseous species.
The developed flow chemistry platform described herein is equipped with a continuous gas-liquid segmented flow reactor that allows for rapid reaction parameter space mapping for the catalyst activity and aldehyde regioselectivity. The utilized flow reactor allows for gas-liquid segmentation at the target reaction conditions with high surface area to volume ratios, thereby accelerating both heat and mass transfer rates. These intensified heat and mass transport rates, in combination with the precise control over reaction conditions, allow for accurate investigation of reactivity and selectivity at early reaction times (5-10 min), which is challenging in batch reactors. Such early-time monitoring and analysis of the hydroformylation reactions in the flow reactor may facilitate understanding of the change in reactivity attributed to the catalyst activation. These advantages make the developed flow chemistry platform a suitable tool for accurate mechanistic investigations of high pressure/temperature gas-liquid reactions, particularly hydroformylation of olefins.
Cyclic fluorophosphites are strong x-acceptor ligands and 8-membered cycles exhibit reasonable stability. However, their performance as a hydroformylation ligand is not well explored. The hydroformylation mechanism and the active catalyst species depend heavily on the ligand structure and the reaction conditions. A higher catalytic activity was observed in the flow reactor relative to the batch reactor (
With a H2:CO ratio of 1, the maximum total aldehyde yield was achieved at 95° C. (
The catalyst pre-activation with L appears to be more sensitive to temperature than the hydroformylation reaction. At 75° C., the effect of catalyst pre-activation may be observed up to tR=30 min. However, it the effect of catalyst pre-activation is not noticeable at 110° C. even at residence times as low as 5 min (
Aside from olefin isomerization, higher reaction temperature appears to favor the branched aldehyde formation from terminal olefin in the presence of L by destabilizing the bis-ligated L-Rh-L species and convert them to the mono-ligated L-Rh carbonyl species. This effect is likely the reason for the decrease in the l/b and TOF observed in
An increase in the l/b ratio in the presence of L occurs in the low PCO range (7 psia to 60 psia) where an l/b ratio as high as 14 may be obtained in both flow and batch reactors (
Carbon monoxide inhibits the formation of the linear aldehyde at PCO>12 psia. Similar inhibition was observed in the olefin isomerization experiment with no H2 at PCO>100 psia (
The rate of formation of all aldehydes appeared to be first order with respect to H2 up to PH2=115 psia where PCO remains constant at 85 psia. The reaction rate dependence on PH2 suggests that the reaction is limited by either the oxidative addition of molecular H2 to the Rh acyl or the reductive elimination of the aldehyde. At higher PH2, the formation of l and b1 appears to increase, while the formation of b2 and b3 appears to remain constant. As olefin isomerization occurs at PH2=0, higher PH2 promotes the hydroformylation of the olefin over olefin isomerization, thus increasing l/b ratios at a constant total aldehyde yield (
Furthermore, high PCO (75 psia) was observed to promote the selective hydroformylation of 2-octene to b1 and b2 with minimum formation of the l and b3 isomers. The reaction temperature was maintained at 50° C. to minimize olefin isomerization. However, this PCO was efficient in preventing the formation of linear aldehydes even at L:Rh ratios as high as 10:1 (Table 6).
Ligands L2-L5 and their corresponding NMR assignments are shown in Table 7. The ligands were prepared using the methods described in the general methods section above with the appropriate starting materials. After the synthesis and characterization of ligands L2-L5, l/b modulation conditions were investigated, and the results are shown below in Tables 8-11.
1H NMR (600 MHz, C6D6-d6 Benzene): δ 7.83 (d, 2H, ArH), δ 7.38 (d, 2H, ArH), δ 4.99 (s, 1H, bridge C—H), δ 1.46-1.19 (m, 45H, 5 × C(CH3)3). 31P NMR (243 MHz): δ 136.43 (d, J = 1261.2 Hz), 105.78 (d, J = 1241.7 Hz). 19F NMR (564 MHz): δ −62.71 (d, J = 1240.8 Hz), −71.53 (d, J = 1257.7 Hz).
1H NMR (600 MHz, C7D8-d8 Toluene): δ 7.53 (d, 2H, ArH), δ 7.37 (d, 2H, ArH), δ 4.58 (d, 1H, bridge C—H), δ 1.52-1.32 (m, 36H, 4 × C(CH3)3), δ 2.16-1.62 (m, 11H, Cyclohexyl 5 × CH2, 1 × C—H). 31P NMR (243 MHz) δ 104.84 (d, J = 1232.0 Hz). 19F NMR (564 MHz): δ −63.90 (d, J = 1235.2 Hz), −69.91 (d, J = 1246.4 Hz), −71.58 (d, J = 1257.7 Hz).
1H NMR (600 MHz, C7D8-d8 Toluene): δ 7.36- 7.01 (m, 24H, ArH), δ 4.42 (q, 1H, bridge C—H), δ 1.64 (s, 24H, 4 × C(CH3)2), δ 1.54 (d, 3H, bridge CH3).
1H NMR (600 MHz, C7D8-d8 Toluene): δ 7.24 7.01 (m, 24H, ArH), δ 4.14 (d, 1H, bridge C—H), δ 2.15 (m, 1H, Cyclohexyl C—H), δ 1.71-1.55 (m, 34H, Cyclohexyl5 × CH2, 4 × C(CH3)2). 31P NMR (243 MHz): δ 101.48 (d, J = 1268.5 Hz). 19F NMR (564 MHz): δ −66.88 (d, J = 1263.4 Hz), −67.27 (d, J = 1302.8 Hz), −68.35 (d, J = 1308.5 Hz).
The foregoing description of the specific aspects will so fully reveal the general nature of the technology that others can, by applying knowledge within the skill of the art, readily modify and/or adapt for various applications such specific aspects, without undue experimentation, without departing from the general concept of the present disclosure. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed aspects, based on the teaching and guidance presented herein. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance.
The breadth and scope of the present disclosure should not be limited by any of the above-described exemplary aspects but should be defined only in accordance with the following claims and their equivalents.
All publications, patents, patent applications, and/or other documents cited in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent, patent application, and/or other document were individually indicated to be incorporated by reference for all purposes.
For reasons of completeness, various aspects of the hydroformylation process are set out in the following numbered embodiments. The first embodiment is denoted E1, the second embodiment is denoted E2 and so forth.
E1. A process for preparing linear and branched aldehydes, the process comprising:
E15. The process of any one of E1-E14, wherein R1, R2, R3, and R4 are each C1-4alkyl.
E16. The process of any one of E1-E15, wherein R1, R2, R3, and R4 are each —CH3.
E17. The process of any one of E1-E16, wherein R5 and R6 are each independently
E18. The process of any one of E1-E17, wherein R7 and R8 are each C1-4alkyl or the unsubstituted or substituted phenyl.
E19. The process of any one of E1-E18, wherein R7 and R8 are each —CH3 or unsubstituted phenyl.
E20. The process of any one of E1-E19, wherein the fluorophosphite ligand of formula (I) is a ligand of formula (Ia):
E21. The process of any one of E1-E20, wherein the fluorophosphite ligand of formula (I) is a ligand of formula (Ib):
E22. The process of any one of E1-E21, wherein the fluorophosphite ligand of formula (I) is
This application claims priority to U.S. Provisional Patent Application No. 63/219,213 filed on Jul. 7, 2021, and U.S. Provisional Patent Application No. 63/248,290 filed Sep. 24, 2021, the entire contents of which are incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2022/036380 | 7/7/2022 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63219213 | Jul 2021 | US | |
| 63248290 | Sep 2021 | US |
