EP2207783A1

EP2207783A1 - Method for hydroformylation

Info

Publication number: EP2207783A1
Application number: EP08847068A
Authority: EP
Inventors: Jens Rudolph; Joachim Schmidt-Leithoff; Rocco Paciello; Bernhard Breit; Tomas Smejkal
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 2007-11-05
Filing date: 2008-11-04
Publication date: 2010-07-21
Also published as: KR20100097672A; CN101848919A; DE102007052640A1; JP2011503028A; WO2009059963A1; US20100240896A1

Abstract

The invention relates to a method for the hydroformylation of compounds of formula (I), or the salts thereof. In formula (I), X is C, P(RX), P(O-RX) S or S(=O), wherein Rx is H, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl; A is a divalent bridging group comprising between 1 and 4 bridge atoms; and R1 is H, alkyl, alkenyl, alkinyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl. According to said method, the compound of formula (I) is reacted with carbon monoxide and hydrogen in the presence of a catalyst, the catalyst comprising a complex of a metal of the eighth subgroup with a compound of formula (II), wherein Pn is a pnicogen atom; W is a divalent bridging group comprising between 1 and 8 bridge atoms; R2 is a functional group that can form an intermolecular, non-covalent bond with the group -X(=O)OH; R3, R4 is alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl; a, b, c are 0 or 1; and Y1, Y2 and Y3 are O, S, NRa or SiRbRc. The method according to the invention is also for hydroformylation of compounds of formula (II.a), wherein W' is a bivalent bridging group comprising between 1 and 5 bridge atoms between the adjacent bonds, Z is O, S, S(=O), S(=O)2, N(RIX) or C(RIX)(RX); and R1 to Rx are independently H, halogen, nitro, cyano, amino, alkyl, etc.; or two radicals RI, RII, RIV, RVI, RVIII and RIX, for the bond part of a covalent bond.

Description

Process for hydroformylation

description

The present invention relates to a process for the hydroformylation of unsaturated compounds which have a functional group capable of forming an intermolecular, noncovalent bond, in which this compound is reacted with carbon monoxide and hydrogen in the presence of a catalyst, wherein the catalyst is a complex of a metal of VIII The subgroup comprises a pnicogen-containing compound as ligand, wherein the pnicogen-containing compound has a functional group which is complementary to the functional group of the compound to be hydroformylated capable of forming an intermolecular, noncovalent bond, such ligands, catalysts and their use.

Hydroformylation or oxo synthesis is an important industrial process and serves to prepare aldehydes from unsaturated compounds, carbon monoxide and hydrogen. These aldehydes may optionally be hydrogenated in the same operation with hydrogen to the corresponding oxo alcohols. The reaction itself is highly exothermic and generally proceeds under elevated pressure and at elevated temperatures in the presence of catalysts. The catalysts used are Co, Rh, Ir, Ru, Pd or Pt compounds or complexes which can be modified to influence the activity and / or selectivity with N- or P-containing ligands.

In the hydroformylation reaction of unsaturated compounds having more than two C atoms, it may be due to the possible CO addition to each of the two carbon atoms of a double bond to form mixtures of isomeric aldehydes. In addition, when using unsaturated compounds having at least four carbon atoms, double bond isomerization may also occur, i. H. to shift internal double bonds to a terminal position and vice versa. In addition, the use of mixtures of unsaturated compounds complex and difficult to separate product mixtures of the hydroformylation can be obtained.

It is known to use pnicogen-containing and in particular phosphorus-containing ligands for the stabilization and / or activation of the catalyst metal in the rhodium-low-pressure hydroformylation. Suitable phosphorus ligands are z. For example, phosphines, phosphinites, phosphonites, phosphites, phosphoramidites, phospholes and phosphabenzenes. The currently most widely used ligands are Triarylphosphi- ne, such as. As triphenylphosphine and sulfonated triphenylphosphine, since they have sufficient stability under the reaction conditions. A disadvantage of this Li However, it has been found that generally only very high excess ligands provide satisfactory yields.

In a publication by B. Breit and W. Seiche in J. Am. Chem. Soc. 2003, 125, 6608-6609 describes the dimerization of monodentate ligands via hydrogen bonds to form bidentate donor ligands and their use in hydroformylation catalysts with high regioselectivity.

EP 1 486 481 describes a process for the hydroformylation of olefins in the presence of a catalyst comprising at least one complex of a metal of subgroup VIII with monophosphorus compounds capable of dimerization via noncovalent bonds as ligands.

DE 10 2006 041 064 describes peptide group-containing phosphorus compounds,

wherein Y ^{1 is} a divalent bridging group having a bridging atom between the flanking bonds, R ^α and R ^{β are} alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl or together with the phosphorus atom and, if present, the groups X ¹ and X ² to which they are attached represent a 5- to 8-membered heterocycle, R ^{γ represents} a peptide group comprising at least two amino acid units, X ¹ and X ^{2 are} selected from O, S, SiR ^ε R ^ξ and NR ^η , Z is NR ^IX or CR ^IX R ^X , R ¹ to R ^{x are} hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, hetaryl, etc., wherein in each case two adjacent radicals R ¹ , R ", R ^ιv , R ^vι , RV ¹¹¹ and R ^ιx , also together may represent the bond ^{moiety of} a double bond between the ring atoms, and a, b and c are 0 or 1, catalysts containing such a compound as ligands and a process for hydroformylation in the presence of such Catalyst.

PCT / EP 2007/059722 (= WO 2008/031889) describes catalysts comprising at least one metal complex having at least two pnicogen atom-containing compounds capable of dimerization via ionic interactions as ligands, wherein the ligands have functional groups complementary to one another or two ligands having two complementary functional groups and additionally to the functional groups of the two ligands complementary polyvalent ionic and / or ionic compound is used, as well as methods in which such catalysts are used.

None of the aforementioned documents describes the ability of the ligands to aggregate with the compound (substrate) to be reacted.

It is an object of the present invention to provide a hydroformylation process which is suitable for the chemo- and regioselective hydroformylation of unsaturated compounds which comprise a functional group capable of forming intermolecular, noncovalent bonds. Preferably hydroformylation catalysts are to be used which, in addition to a high selectivity with respect to the substrate, have a high regioselectivity and / or a high selectivity in favor of the hydroformylation over the hydrogenation and / or allow a high RaurrW time yield.

Surprisingly, it has now been found that this object is achieved by the use of monopnicogen ligands which are capable of forming intermolecular, noncovalent bonds with the compound (substrate) to be reacted. As a result, a high regioselectivity of the hydroformylation reaction and a high selectivity with respect to the reacted substrate or the reacted functional group is achieved. As a result, the compounds according to the invention are particularly advantageously suitable for the selective hydroformylation of mixtures of unsaturated compounds or for the selective hydroformylation of unsaturated compounds which have more than one functional group capable of reacting.

The present invention therefore provides a process for the hydroformylation of compounds of the formula (I)

wherein

X is C, P (R ^x ), P (OR ^x ), S or S (= O), where R ^{x is} H, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where alkyl is optionally 1, 2 , 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy and where cycloalkyl, heterocycloalkyl, aryl and hetaryl optionally 1, Have 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents mentioned above for alkyl, A is a divalent bridging group of 1 to 4 bridge atoms between the flanking bonds and

R ^{1 is} H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where alkyl, alkenyl and alkynyl are optionally 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, Cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy and wherein cycloalkyl, heterocycloalkyl, aryl and hetaryl optionally have 1, 2, 3, 4 or 5 substituents which are selected from alkyl and those previously for the alkyl, alkenyl and Alkynyl substituents,

or their salts,

in which the compound of the formula (I) is reacted with carbon monoxide and hydrogen in the presence of a catalyst,

wherein the catalyst comprises at least one complex of a metal of transition group VIII of the Periodic Table of the Elements with at least one compound of formula (II),

wherein

Pn is a pnicogen atom;

W is a divalent bridging group of 1 to 8 bridging atoms between the flanking bonds,

R ^{2 has} a functional group capable of forming at least one intermolecular, noncovalent bond with the group -X (OO) OH of the compound of formula (I).

R ³ and R ⁴ independently of one another are alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where alkyl is optionally 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy , Aryl, aryloxy, hetaryl and hetaryloxy and wherein cycloalkyl, heterocycloalkyl, aryl and hetaryl optionally 1, 2, 3, 4 or 5 substituents selected from alkyl and the substituents previously mentioned for the alkyl; or together with the pnicogen atom and, if present together with the radicals Y ² and Y ^{3, represent} a 5- to 8-membered heterocycle, which may additionally be mono-, di-, tri- or tetravalent cycloalkyl, heterocycloalkyl,

Aryl or hetaryl is fused, wherein the heterocycle and, if present, the fused groups independently of each other 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkyl, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy , Aryl, aryloxy, hetaryl and hetaryloxy,

a, b and c are independently 0 or 1 and

Y ¹ , Y ² and Y ³ independently of one another represent O, S, NR ^a , or SiR ^b R ^c , in which R ^a , R ^b and R ^c independently of one another represent hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, wherein alkyl optionally has 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy and wherein cycloalkyl, heterocycloalkyl, aryl and hetaryl, if appropriate 1, 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents previously mentioned for the alkyl.

Furthermore, the present invention relates to the compounds of the formula (I I. a) used according to the invention as ligands

wherein

a, b, c, Pn, R ² , R ³ , R ⁴ , Y ¹ , Y ² and Y ^{3 have} one of the meanings given above,

W is a divalent bridging group with 1 to 5 bridging atoms between the flanking bonds,

Z is N (R ^IX ) or C (R ^IX ) (R ^X ) and R ¹ , R ", R ¹¹¹ , R ^IV , R ^v , R ^vι , R ^v ", R ^vm , R ^ιx and R ^{x are} independently H, halogen, nitro, cyano, amino, alkyl, alkoxy, alkylamino, dialkylamino , Cycloalkyl, heterocycloalkyl, aryl or hetaryl,

or in each case two radicals R ¹ , R ", R ^IV , R ^VI bound to adjacent ring atoms,

R ^vm and R ^ιx , together represent the bond ^{portion of} a double bond between the adjacent ring atoms, wherein the six-membered ring may have up to three non-cumulated double bonds,

Catalysts comprising at least one complex of a metal of VIII. Subgroup of the Periodic Table of the Elements with at least one compound of formula (II.a) and the use of such catalysts for hydroformylation.

According to the invention, ligands of the formula (II) or (I, Ia) which have a functional group R ² which is capable of forming intermolecular, noncovalent bonds with the substrate of the formula (I) are used. These bonds are preferably hydrogen bonds or ionic bonds, in particular hydrogen bonds. The functional groups capable of forming intermolecular noncovalent bonds enable the ligands to associate with the substrate, ie to form aggregates in the form of hetero-dimers.

A pair of functional groups of the ligands and the substrates capable of forming intermolecular noncovalent bonds are referred to in the present invention as "complementary functional groups". "Complementary compounds" are ligand / substrate pairs that have complementary functional groups. Such pairs are for association, i. H. capable of forming aggregates.

In the context of the present invention, "halogen" is fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine and bromine.

In the context of the present invention, "pnicogen" stands for phosphorus, arsenic, antimony and bismuth, in particular phosphorus.

In the context of the present invention, "alkyl" represents straight-chain and branched alkyl groups. These are preferably straight-chain or branched C 1 -C 20 -alkyl, preferably C 1 -C 12 -alkyl, more preferably C 1 -C 5 -alkyl and very particularly preferably C 1 -C 4 -alkyl groups. Examples of alkyl groups are in particular methyl, ethyl, propyl, isopropyl, n-butyl, 2-butyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methylbutyl, 3-methylbutyl, 1, 2 Dimethylpropyl, 1, 1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 2-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2,3-dimethylbutyl, 1, 1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1, 1, 2-trimethylpropyl, 1, 2, 2-trimethylpropyl, 1-ethylbutyl, 2-ethylbutyl, 1-ethyl-2-methylpropyl, n-heptyl, 2-heptyl, 3-heptyl, 2-ethylpentyl, 1-propylbutyl, n-octyl, 2-ethylhexyl, 2-propylheptyl , Nonyl, decyl.

The term "alkyl" also includes substituted alkyl groups, which generally have 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent. These are preferably selected from halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy.

In the context of the present invention, "cycloalkyl" is both unsubstituted and substituted cycloalkyl groups, preferably C3-C7-cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. In the case of a substitution, these may in general carry 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably 1 substituent. Preferably, these substituents are selected from alkyl, alkoxy and halogen.

In the context of the present invention, "alkenyl" stands for both unsubstituted and substituted straight-chain and branched alkenyl groups. These are preferably straight-chain or branched C 2 -C 20 -alkenyl, preferably C 2 -C 12 -alkenyl, particularly preferably C 1 -C 4 -alkenyl and very particularly preferably C 1 -C 4 -alkenyl groups.

In the context of the present invention, "alkynyl" represents both unsubstituted and substituted straight-chain and branched alkynyl groups. These are preferably straight-chain or branched C 2 -C 20 -alkynyl, preferably C 2 -C 12 -alkynyl, particularly preferably C 1 -C 4 -alkynyl and very particularly preferably C 1 -C 4 -alkynyl groups.

In the context of the present invention, "heterocycloalkyl" denotes saturated, cycloaliphatic groups having generally 4 to 7, preferably 5 or 6, ring atoms in which 1 or 2 of the ring carbon atoms are represented by heteroatoms selected from the elements O, N, S and P. , are replaced and which may optionally be substituted, wherein in the case of a substitution, these heterocycloaliphatic groups 1, 2 or 3, preferably 1 or 2, particularly preferably 1 substituent can carry. These substituents are preferably selected from alkyl, halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy, particularly preferred are alkyl radicals. Exemplary of such heterocycloaliphatic groups are pyrrolidinyl, piperidinyl, 2,2,6,6-tetramethylpiperidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, morpholidinyl, thiazolidinyl, isothiazolidinyl, Isoxazolidinyl, piperazinyl, tetrahydrothiophenyl, tetrahydrofuranyl, tetra hydropyranyl, called dioxanyl.

In the context of the present invention, "aryl" is both unsubstituted and substituted aryl groups, preferably phenyl, ToIyI, XyIyI, mesityl, naphthyl, fluoro, anthracenyl, phenanthrenyl or naphthacenyl and particularly preferably phenyl or naphthyl, these aryl groups in the case of a substitution in general 1, 2, 3, 4 or 5, preferably 1, 2 or 3 and particularly preferably a substituent selected from alkyl, halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, Aryl, aryloxy, hetaryl and hetaryloxy can carry.

In the context of the present invention, "hetaryl" denotes unsubstituted or substituted heterocycloaromatic groups, preferably selected from pyridyl, quinolinyl, acridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, indoisyl, purinyl, indazolyl, benzotriazolyl, 1, 2,3-triazolyl, 1, 3,4-triazolyl and carbazolyl. In the case of a substitution, these heterocycloaromatic groups can generally carry 1, 2 or 3 substituents selected from alkyl, halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, heteroaryl and hetaryloxy.

In the context of the present invention, "C 1 -C 4 -alkylene" is unsubstituted or substituted methylene, 1, 2-ethylene, 1, 3-propylene, 1, 4-butylene, this being, in the case of a substitution, 2, 3 or 4 substituents , selected from among alkyl, halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy.

The above explanations of the terms "alkyl", "cycloalkyl", "heterocycloalkyl", "aryl" and "hetaryl" apply mutatis mutandis to the terms "alkoxy", "cycloalkoxy", "heterocycloalkoxy", "aryloxy" and "hetaryloxy".

In the context of the present invention, "salts of the compounds of the formula (I)" denotes compounds of the formula M ⁺ OX (OO) -A-CH =CH-R ¹ , where M ^{+ is} a cation equivalent, ie a monovalent cation or is the proportion of a polyvalent cation corresponding to a positive single charge. The cation M ⁺ serves only as a counterion to the neutralization of negatively charged substituent groups, such as the OC (= 0), the OP (R ^X ) (= O) -, the OP (OR ^X ) (= O) - or the OS ( = O) ₂ group and can in principle be chosen arbitrarily. Preferably, therefore, alkali metal ions, in particular Na ⁺ , K ⁺ and Li ⁺ ions, alkaline earth metal ions, in particular Ca ²⁺ or Mg ²⁺ ions, or onium ions, such as ammonium, mono-, , Di-, tri-, tetraalkylammonium, phosphonium, tetraalkylphosphonium or tetraarylphosphonium ions. Without wishing to be bound by theory, it is believed that the catalyst comprising a metal of subgroup VIII of the Periodic Table of the Elements and a compound of formula (II), due to the group capable of forming an intermolecular, noncovalent bond R ² with the compound of formula (I), whose CC double bond is capable of interacting with the complex-bound metal of VIII. Subgroup forms an aggregate. Thus, a supramolecular, cyclic transition state could be run through.

The process according to the invention is particularly suitable for the hydroformylation of unsaturated compounds of the formula (I) which are capable of forming strong intermolecular, noncovalent binding. Compound classes which have this property are in particular carboxylic acids, phosphonic acids, sulfonic acids and salts thereof.

Compounds of the formula (I) in which X, A and R ^1, independently of one another or preferably in combination, have one of the meanings mentioned below, are particularly suitable for the process according to the invention.

X in the compounds of the formula (I) is preferably C, S (= O) or P (OR ^X ), where R ^{x is} H or in each case optionally substituted alkyl, cycloalkyl or aryl. X is particularly preferably C. In particular, X in the compounds of the formula (I) is C, P (OH) or S (= O). Most preferably, X is C.

A in the compounds of the formula (I) is preferably C 1 -C 4 -alkylene. A particularly preferably represents C 1 -C 2 -alkylene and very particularly preferably methylene.

R ¹ in the compounds of the formula (I) is preferably H, alkyl or alkenyl.

In a specific embodiment of the process according to the invention, the compound of the formula (I) is selected from compounds of the formula (I.a)

O _N

^X _/ XC (R ^a1 ) (R ^a2 ) -CH = CH-R ¹ (la)

HO ⁷

wherein

X is C, P (R ^X), P (OR ^X), S, S (= O), where R ^x is H or optionally substituted alkyl, cycloalkyl or aryl,

R ^a1 and R ^a2 independently represent H or CrC ₄ -AlkVl and R ^{1 is} H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl.

X preferably in the compounds of the formula (La) used according to the invention for C.

R ^a1 and R ^a2 are in the compounds of the formula (La) used ^according to the invention preferably for H.

In the compounds of the formula (Ia) used according to the invention, R ¹ is preferably H or alkyl, particularly preferably H or C 1 -C 6 -alkyl.

Compounds of the formula (II) in which Pn, R ² , R ³ , R ⁴ , W, a, b, c, Y ¹ , Y ² , Y ^{3 are,} independently of one another or preferably in combination, one of the compounds suitable for the process according to the invention are particularly suitable have the meanings mentioned below.

Pn in the compounds of the formula (II) is preferably phosphorus. Suitable examples of such compounds of formula (II) are phosphine, phosphinite, phosphonite, phosphoramidite or phosphite compounds.

R ² in the compounds of formula (II) is a functional group comprising at least one NH group. Suitable radicals R ² are -NHR ^W, = NH, -C (= O) NHR ^W, -C (= S) NHR ^W, -C (= NR ^y) NHR ^w, -OC (= O) NHR ^W, - OC (= S) NHR ^W, -OC (= NR ^y) NHR ^w, -N (R ^Z) -C (= O) NHR ^W, -N (R ^Z) -C (= S) NHR ^W or -N (R ^z ) -C (= NR ^y ) NHR ^w , wherein R ^w , R ^y and R ^{z are} each independently H, alkyl, cycloalkyl, aryl or hetaryl or in each case together with another substituent of the compound of formula (II ) Are part of a 4- to 8-membered ring system.

Particularly preferably, R ² in the compounds of the formula (II) is -NH-C (NHNH) NHR ^W , where R ^{w is} H, alkyl, cycloalkyl, aryl or hetaryl. Most preferably, R ^{2 is} -NH-C (= NH) NH ₂ .

R ³ and R ⁴ in the compounds of the formula (II) are preferably each optionally substituted phenyl, pyridyl or cyclohexyl. Particularly preferably, R ³ and R ^{4 are} optionally substituted phenyl.

The indices a, b and c are in the compounds of the formula (II), preferably 0.

In a specific embodiment, the compounds of the formula (II) used according to the invention are selected from compounds of the formula (IIa),

wherein

Z is O, S, S (= O), S (= O) ₂ , N (R ^IX ) or C (R ^IX ) (R ^X ) and

R ", R", R '", R ^ιv , R ^v , R ^vι , R ^v ", R ^vι ", and if present, R ^ιx and R ^{x are} independently H, halogen, nitro, cyano, amino, alkyl , Alkoxy, alkylamino, dialkylamino, cycloalkyl, heterocycloalkyl, aryl or hetaryl,

or in each case two radicals R ¹ , R ", R ^IV , R ^VI , R ^Vm and R ^Ix bound to adjacent ring atoms together represent the bond ^{portion of} a double bond between the adjacent ring atoms, the six-membered ring having up to three non-cumulated double bonds can.

With respect to preferred meanings of a, b, c, Pn, R ² , R ³ , R ⁴ , Y ¹ , Y ² and Y ³ , reference is made to the statements made above to the compounds of general formula (II).

Compounds of the formula (II.a) in which a, b, c, pn, R ² , R ³ , R ⁴ , R ¹ , R ¹¹ , R ¹¹¹ , R ^IV , R ^v , R are particularly suitable for the process according to the invention ^vι , R ^v ", R ^vι ", R ^ιx , R ^x , W, Y ¹ , Y ² , Y ³ and Z independently or preferably in combination have one of the previously mentioned as preferred or one of the meanings mentioned below.

In the compounds of the formula (II.a), W is preferably C 1 -C 8 -alkylene, (C 1 -C 4 -alkylene) carbonyl or C (OO). W in the compounds of the formula (II.a) is particularly preferably C (= O).

Z in the compounds of the formula (II.a) is preferably N (R ^IX ) or C (R ^IX ) (R ^X ). Z is particularly preferably N (R ^IX ). The radicals R ¹ ^vι with R ^11, R ^IV with R and R ^VIII "with R ^ιx are (II. A) in the compound of formula preferably in each case together for the binding portion of a double bond between adjacent ring atoms, ie, in the compound of formula (II. A) the six-membered ring is preferably substituted benzene or pyridine.

The radicals R ¹¹¹ , R ^v , R ^VM and, when present, R ^x in the compounds of the formula (II.a) are, independently of one another, preferably H, halogen, nitro, cyano, amino, C 1 -C ₄ -alkyl, C 1 -C ₄ -Alicoxy Ci-C4-alkylamino or di (Ci-C4-alkyl) amino. Particularly preferred are R ^m , R ^v , R ^VM and if present R ^x for H.

In a particularly preferred embodiment of the process according to the invention, the compounds of the formula (II) or (II.a) are chosen from the compounds of the formula (1) and (2)

(1) (2)

The compound of the formula (1) is very particularly preferably used in the process according to the invention for the hydroformylation.

The catalysts used according to the invention have at least one compound of the formula (II) or (II.a), as described above, as ligands. In addition to the ligands described above, the catalysts may also contain at least one other ligand, preferably selected from halides, amines, carboxylates, acetylacetonate, aryl or alkylsulfonates, hydride, CO, olefins, dienes, cycloolynes, nitriles, N containing heterocycles, aromatics and heteroaromatics, ethers, PF3, phospholes, phosphabenzenes and mono-, bi- and polydentate phosphine, phosphinite, phosphonite, phosphoramidite and phosphite.

The catalysts used in the invention have at least one metal of VIII. Subgroup of the Periodic Table of the Elements. The metal of the VIII subgroup is preferably Co, Ru, Rh, Ir, Pd or Pt, more preferably Co, Ru, Rh or Ir and most preferably Rh.

In general, catalytically active species of the general formula HχM _y (CO) _z Lq are formed under hydroformylation conditions from the particular catalysts or catalyst precursors used, where M is the metal of the VIII subgroup, L is a pnicogen-containing compound of the formula (II) and q, x, y, z for integers, depending on the valence and type of the metal and the ligand L, stand. Preferably z and q are independently of one another at least a value of 1, such. B. 1, 2 or 3. The sum of z and q is preferably from 1 to 5. In this case, the complexes may, if desired, additionally have at least one of the further ligands described above.

In a preferred embodiment, the hydroformylation catalysts are prepared in situ in the reactor used for the hydroformylation reaction. If desired, however, the catalysts according to the invention can also be prepared separately and isolated by customary processes. For in situ preparation of the catalysts of the invention can be z. B. at least one ligand used according to the invention of the formula (II), a compound or a complex of a metal of VIII. Subgroup, optionally at least one additional additional ligand and optionally implement an activating agent in an inert solvent under the hydroformylation.

Suitable rhodium compounds or complexes are, for. Rhodium (II) and rhodium (III) salts, such as rhodium (III) chloride, rhodium (III) nitrate, rhodium (III) sulfate, potassium rhodium sulfate, rhodium (II) or Rhodium (III) carboxylate, rhodium (II) and rhodium (III) acetate, rhodium (III) oxide, salts of rhodium (III) acid, trisammonium hexachlororhodate (III), etc. Furthermore, rhodium complexes are suitable such as rhodium bis-carbonyl acetylacetonate, acetylacetonato-bis-ethyl rhodium (I), etc. Preferably, rhodium bis-carbonyl acetylacetonate or rhodium acetate are used.

Also suitable are ruthenium salts or compounds. Suitable ruthenium salts are, for example, ruthenium (III) chloride, ruthenium (IV), ruthenium (VI) or ruthenium (VIII) oxide, alkali salts of ruthenium oxygen acids such as K 2 RUO ₄ or KRuO ₄ or complex compounds, such as. B. RuHCl (CO) (PPh3) 3. It is also possible to use the metal carbonyls of ruthenium, such as trisruthenium dodecacarbonyl or hexaruthenium octadecacarbonyl, or mixed forms in which CO has been partially replaced by ligands of the formula PR3, such as Ru (CO) 3 (PPh3) 2, in the process according to the invention.

Suitable cobalt compounds are, for example, cobalt (II) chloride, cobalt (II) sulfate, cobalt (II) carbonate, cobalt (II) nitrate, their amine or hydrate complexes, cobalt carboxylates, such as cobalt acetate, cobalt ethylhexanoate, cobalt naphthanoate, and cobalt caproate -Complex. Again, the carbonyl complexes of cobalt such as dicobaltoctacarbonyl, Tetracobaltdodecacarbonyl and Hexacobalthexadecacarbonyl can be used.

The above and other suitable compounds of cobalt, rhodium, ruthenium and iridium are known in principle and sufficiently described in the literature or they can be prepared by the skilled person analogously to the already known compounds.

Suitable activating agents are, for. B. Bronsted acids, Lewis acids, such as. BF3, AICb, ZnCb, and Lewis bases.

Suitable solvents are ethers, such as tert-butyl methyl ether, diphenyl ether and tetrahydrofuran. Further solvents are esters of aliphatic carboxylic acids with alkanols, for example ethyl acetate or oxo oils, such as Palatinol ™ or Texanol ™, aromatics, such as toluene and xylene, hydrocarbons or mixtures of hydrocarbons.

The molar ratio of Monopnicogenligand (II) to VIII metal subgroup is generally in a range of about 1: 1 to 1000: 1, preferably from 2: 1 to 500: 1, and more preferably from 5: 1 to 100: 1.

Preference is given to a process which is characterized in that the hydroformylation catalyst is prepared in situ, at least one ligand (II) which can be used according to the invention, a compound or a complex of a metal of subgroup VIII and, if appropriate, an activating agent in an inert solvent under the hydroformylation conditions to the reaction.

The hydroformylation reaction can be carried out continuously, semicontinuously or discontinuously.

Suitable reactors for the continuous reaction are known in the art and z. As described in Ullmann's Encyclopedia of Industrial Chemistry, Vol. 1, 3rd ed., 1951, p 743 ff.

Suitable pressure-resistant reactors are also known in the art and z. B. in Ullmann's Encyclopedia of Industrial Chemistry, Vol. 1, 3rd edition, 1951, p. 769 ff. Described. In general, an autoclave is used for the process according to the invention, which if desired can be provided with a stirring device and an inner lining.

The composition of the synthesis gas of carbon monoxide and hydrogen used in the process according to the invention can vary within wide ranges. The molar ratio of carbon monoxide and hydrogen is usually about 5:95 to 70:30, preferably about 40:60 to 60:40. Particularly preferred is a molar ratio of carbon monoxide and hydrogen in the range of about 1: 1 is used. The temperature in the hydroformylation reaction is generally in a range of about 20 to 180 C, preferably about 50 to 150 C. In general, the pressure is in a range of about 1 to 700 bar, preferably 1 to 600 bar, in particular 1 to 300 bar. The reaction pressure can be varied depending on the activity of the hydroformylation catalyst of the invention used. In general, the catalysts of the invention based on pnicogen-containing compounds of the formula (II) allow a reaction in a range of low pressures, such as in the range of 1 to 100 bar.

The hydroformylation catalysts according to the invention and the hydroformylation catalysts according to the invention can be separated off from the effluent of the hydroformylation reaction by customary methods known to the person skilled in the art and can generally be used again for the hydroformylation.

The catalysts described above can also be suitably, for. B. by attachment via suitable as anchor groups functional groups, adsorption, grafting, etc. to a suitable carrier, eg. Example of glass, silica gel, resins, polymers, etc., be immobilized. They are then also suitable for use as solid phase catalysts.

The hydroformylation activity of catalysts based on the above-described ligands of the formula (II) is generally higher than the isomerization activity with respect to the formation of internal double bonds. Advantageously, the catalysts used according to the invention in the hydroformylation of unsaturated compounds comprising a functional group capable of forming intermolecular, noncovalent bonds exhibit high chemo- and regioselectivities with respect to the hydroformylation of the reactive centers. Furthermore, the catalysts generally have a high stability under the hydroformylation conditions, so that they are usually achieved with longer catalyst life, as known from the prior art catalysts. Advantageously, the catalysts used according to the invention furthermore exhibit high activity, so that as a rule the corresponding aldehydes or alcohols are obtained in good yields.

Another object of the present invention relates to the compounds of the formula (I I. a) used in the invention

With regard to the preferred meanings of the variables a, b, c, Pn, R ² , R ³ , R ⁴ , Y ¹ , Y ² , Y ³ , W, Z, R ", R", R '", R ^IV , R ^v , R ^vι , R ^v ", R ^vι ", and if present, R ^ιx and R ^x is made to the statements made previously in the context of the inventive method.

Particular preference is given to compounds of the formula (I I. a) in which Pn is phosphorus.

Likewise particularly preferred compounds of the formula (I I. a), wherein R ^{2 is}

-NH-C (= NH) NHR ^W , where R ^{w is} H, alkyl, cycloalkyl, aryl or hetaryl, and in particular -NH-C (= NH) NH ₂ .

Equally particularly preferred are compounds of the formula (I I. a) in which R ³ and R ^{4 are} optionally substituted phenyl.

Likewise particularly preferred are compounds of the formula (I I. a) in which a, b and c are 0.

Likewise particularly preferred are compounds of the formula (I I. a), wherein W is a group C (= O).

Likewise particularly preferred compounds of the formula (I I. a), wherein Z is N (R ^IX ).

Likewise particularly preferred are compounds of formula (I I. a) wherein R ¹ with R ', R ^IV ^vι with R and R ^vm ^ιx with R in each case together for the binding portion of a double bond between adjacent ring atoms and R ¹ ", R ^v , R ^vll and, if present, R ^{x stands} for H.

The above for the compounds of formula (II. A) with respect to preferred meanings a, b, c, Pn, R ^2, R ^3, R ^4, R ^1, R ", R ^111, R ^IV, R ^V, R ^VI, R ^VI1 , R ^vι ", R ^ιx , R ^x , W, Y ¹ , Y ² , Y ³ and Z statements apply independently and in particular in any combination.

Very particular preference is given to the compounds of the formula (I I. a) chosen from the compounds of the formulas (1) and (2)

(1) (2)

Another object of the present invention relates to the invention preferably used catalysts comprising at least one complex of a metal of VIII. Subgroup of the Periodic Table of the Elements with at least one compound of formula (II.a), as defined above. With regard to preferred metals of the VIII. Subgroup and preferred inventive compounds of formula (II.a), reference is made to the statements made above.

Another object of the invention relates to the use of catalysts comprising at least one complex of a metal of VIII. Subgroup with at least one ligand of the formula (I), as described above, for the hydroformylation. With regard to preferred embodiments, reference is made to the statements made above on the catalysts according to the invention.

The invention is explained in more detail below with reference to non-limiting examples.

Examples

I. General

All reactions were carried out under argon atmosphere in dried glassware. Air and moisture sensitive liquids were transferred by syringes. All solvents were dried using standard methods and distilled. Solutions were freed of solvents using a rotary evaporator under reduced pressure. For the chromatographic purification of reaction products, Merck silica gel Si ^60® (200-400 mesh) was used. NMR spectra were determined using a Varian Mercury spectrometer (300 MHz, 121 MHz and 75 MHz for ¹ H, ³¹ P and ¹³ C), with a Bruker AMX 400 (400 MHz, 162 MHz and 101 MHz for ¹ H, ³¹ P and ¹³ C) or with a Bruker DRX 500 (500 MHz, 202 MHz and 125 MHz for ¹ H, ³¹ P and ¹³ C). As a reference TMS was used as internal standard ( ¹ H and ¹³ C NMR) or 85% H ₃ PO ₄ as standard ( ³¹ P NMR). ¹ H-NMR data are given as follows: chemical shift (δ in ppm), multiplicity (s = singlet, bs = broad singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constant (Hz) , Integration. ¹³ C NMR data are reported as follows: chemical shift (δ in ppm), multiplicity, coupling constant (Hz). High-resolution mass spectra were recorded on a Finnigan MAT 8200. Elemental analyzes were carried out with an elementar vario (from Elementar Analysensysteme GmbH).

II. Preparation of the compounds of the formula (II)

1. Preparation of N- (6-diphenylphosphanylpyridin-2-ylcarbonyl) guanidine (1)

1.1 2-Bromo-6-diphenylphosphanylpyridine

To a solution of 2,6-dibromopyridine (20 g, 0.084 mol, 1 eq.) In CH ₂ CI ₂ (750 ml) was added under argon at -78 mol ⁰ C n-butyllithium (48.2 ml, 0.093, 1 , 6 M in hexane, 1, 1 eq.) Was added slowly (15 min.). The reaction mixture was stirred for a further 30 min. touched. Subsequently, Ph ₂ PCI (17.6 ml (95%), 0.093 mol, 1.1 equiv) over a period of 10 min. added and the resulting reaction mixture for a further 30 min. at -78 ⁰ C stirred. The resulting solution was warmed to room temperature over a period of 1.5 h and stirred at this temperature for a further 2 hours. Then, the reaction mixture was added with water (400 ml). After separation of the phases obtained, the aqueous phase was extracted with CH ₂ Cl ₂ ( ₂ × 100 ml). The organic phases were combined, dried over Na ₂ SO ₄ and freed from the solvent under reduced pressure. The residue was dissolved in CH ₂ Cl ₂ (100 ml) and filtered through silica gel. Evaporation of the solvent followed by trituration of the residue with petroleum ether / Et ₂ O (3: 1) gave 2-bromo-6-diphenylphosphanylpyridine in an amount of 26 g (yield 90%) as a colorless solid.

M.p .: 81 ⁰ C. ¹ H-NMR (400.1 MHz, C ₆ D _6): δ = 6.43 to 6.48 (m, 1 H); 6.76-6.79 (m, 2H); 7.01-7.06 (m, 6H); 7.40-7.46 ppm (m, 4H). ¹³ C { ¹ H} NMR (100.6 MHz, C ₆ D ₆ ): δ = 126.5; 126.8 (d, J = 17.3 Hz); 128.9 (d, J = 7.2 Hz); 129.3; 134.6 (d, J = 20.3 Hz); 136.5 (d, J = 11, 6 Hz); 137.6 (d, J = 2.4 Hz); 143.1 (d, J = 10.6 Hz); 166.6 (d, J = 4.1 Hz). 3 ¹ P { ¹ H} NMR (161, 97 MHz, C ₆ D ₆ ): δ = -2.26. Elemental Analysis [%]: calc .: C, 59.67; H: 3.83; N: 4.09; Found: C: 59.47; H: 3.90; N: 4.26.

1.2 6-Diphenylphosphanylpyridin-2-ylcarboxylic acid

To a solution of 2-bromo-6-diphenylphosphinopyridine (mol 20 g, 0.059, 1 eq.) In CH ₂ CI ₂ (800 ml) under argon was added at -78 ⁰ C n-butyllithium (40.2 ml, 0.064 mol . 1, 6 M in hexane, 1, 1 eq.) Was added dropwise. The reaction mixture was stirred at this temperature for 75 min. touched. Subsequently, at -78 ⁰ C gaseous CO2 for 30 min. passed through the resulting solution. The reaction mixture was heated under CO 2 atmosphere over a period of 1, 5 h to a temperature of -30 ⁰ C. Subsequently, the reaction mixture was again cooled to -78 ⁰ C, with CO2 saturated (15 min) and over a period of 2 h at 0 ⁰ C heated. The reaction mixture was extracted with aqueous hydrochloric acid (2 M, 3x200 ml). The aqueous phase was then extracted with CH 2 Cl 2 (2 x 100 ml). The organic phases were combined, dried over Na 2 SO 4, filtered and freed from the solvent under reduced pressure. The yellowish, oily residue was taken up in ethyl acetate (50 ml) and filtered through a short silica gel column (rinsing with ethyl acetate). Removal of the solvent and trituration of the residue with petroleum ether / diethyl ether (2: 1) gave 6-diphenylphosphanylpyridin-2-ylcarboxylic acid in an amount of 18 g (80% yield) as a slightly yellowish solid. M.p .: 122 ⁰ C. ¹ H-NMR (400.1 MHz, C ₆ D _6): δ = 6.76 (ddd, J = 7.7; 7.7; 2.0 Hz, 1 H); 6.96 (ddd, J = 7.7, 1, 8, 1, 1 Hz, 1H); 7.02-7.08 (m, 6H); 7.26-7.33 (m, 4H); 7.71 (ddd, J = 7.7, 1, 0, 0.5 Hz, 1H); 10.66 ppm (bs, 1H). ¹³ C { ¹ H} NMR (100.6 MHz, C ₆ D ₆ ): δ = 121, 9 (s); 129.0 (d, J = 7.5 Hz); 129.8 (s); 131, 7 (d, J = 21, 7 Hz); 134.5 (d, J = 20.3 Hz); 135.6 (d, J = 10.4 Hz); 137.6 (d, J = 3.6 Hz); 147.0 (d, J = 7.0 Hz); 163, 1 (d, J = 7.2 Hz); 163.3 ppm (s). ³¹ P { ¹ H} NMR (161, 97 MHz, C ₆ D ₆ , H ₃ PO ₄ ): δ = -2.3 ppm. Elemental Analysis [%]: calc .: C: 70.36; H: 4.59; N: 4.56; Found: C: 70.20; H: 4.79; N: 4.70.

1.3 N'-tert-butoxycarbonyl-N- (6-diphenylphosphino-pyridin-2-ylcarbonyl) -guanidine

To a solution of 6-diphenylphosphinylpyridine-2-carboxylic acid (12.23 g,

39.79 mmol, 1 eq.), N'-tert-butyloxycarbonylguanidine (9.5 g, 59.68 mmol, 1.5 eq.) And

N-methylmorpholine (10.9 ml, 10.06 g, 99.5 mmol, 2.5 eq.) In DMF (250 ml) at 0 ⁰ C under argon atmosphere, 1-benzotriazolyloxy-tris- (dimethylamino) -phosphonium- hexafluorophosphate (BOP, 17.6 g, 39.79 mmol, 1 eq.). The reaction mixture was stirred for 2 h at 0 ^° C. and for a further 2 h at room temperature. The reaction was monitored by TLC control (petroleum ether / ethyl acetate / CH ₃ OH, 50: 25: 2). After addition of water (200 ml) at 0 ^° C., the reaction product precipitated. The resulting suspension was at 0 ⁰ C for 10 min. touched. The white solid was then isolated by filtration and washed with water (2 x 100 ml). The crude product was taken up in CH 2 Cl 2 and filtered. The filtrate was washed with water, dried over Na ₂ SO ₄ and freed from the solvent under reduced pressure. The residue was taken up in C ^ Cb / ethyl acetate (3: 1) and filtered through a short silica gel. Trituration with C 1 -Cb / petroleum ether and subsequent removal of the solvent gave N'-tert-butoxycarbonyl-N- (6-diphenylphosphanylpyridin-2-ylcarbonyl) -guanidine in an amount of 14.3 g (yield 80%) as a colorless solid. (Chromatographic purification (petroleum ether / ethyl acetate / CHsOH, 30: 10: 1) is also possible).

Rf (SiO ₂ , petroleum ether / ethyl acetate / CH ₂ OH, 30: 10: 1) = 0.4. M.p .: 150 ⁰ C (with decomposition). ¹ H-NMR (499.7 MHz, CDCl ₃ ): δ = 1.51 (s, 9H); 7.17 (bd, J = 7.8 Hz, 1H); 7.25-7.29 (m, 4H); 7.36-7.43 (m, 6H); 7.79 (td, J = 7.8, 7.8, 1, 3 Hz, 1H); 8.01 (d, J = 7.8 Hz, 1H); 9.14 (bs, 1H); 9.25 (bs, 1H); 10.08 ppm (bs, 1H). ¹³ C { ¹ H} NMR (125.7 MHz, CDCl ₃ ): δ = 28.2 (s); 79.5 (s); 121, 6 (s); 128.9 (d, J = 7.5 Hz); 129.5 (s); 131, 5 (d, J = 8.6 Hz); 134, 1 (d, J = 19.4 Hz); 134.9 (d, J = 10.7 Hz); 137.6 (s); 147.7 (d, J = 14.0 Hz); 158.5 (s); 163.4 (s); 164.5 (s); 165,9ppm (s). ³¹ P { ¹ H} NMR (202.3 MHz, CDCl ₃ ): δ = -4.13 ppm. IR (Film, CH ₂ Cl ₂ ): v = 3390, 2975, 1703, 1655, 1573, 1434, 1408, 1301 cm ^-1 MS (CI): [m / z] = 448.8 (100%, [ M + H] ⁺ ), 349 (45%, [M + H-Boc] ⁺ ) Elemental analysis [%]: calc .: 64.28, H: 5.62, N: 12.49; : C: 64.34; H: 5.58; N: 12.54.

1.4 N- (6-Diphenylphosphinylpyridin-2-ylcarbonyl) guanidine (1)

N'-tert-butoxycarbonyl-N- (6-diphenylphosphinylpyridine-2-carbonyl) -guanidine (10 g, 22.30 mmol, 1 eq.) And 1, 3-dimethoxybenzene (3.14 mL, 3.39 g, 24.53 mmol, 1, 1 eq.) Were dissolved in trifluoroacetic acid (80 ml) under an argon atmosphere and stirred at room temperature for 3 h (TLC control: CH ₂ Cl ₂ / CH ₃ OH / triethylamine, 30: 2: 1, Mo-Ce reagent). The excess of trifluoroacetic acid was removed under reduced pressure. The residue was dissolved in CH ₂ Cl ₂ (60 ml) and a Na ₂ CO ₃ solution (20% aq., 200 ml) was added at 0 ^° C. The biphasic mixture was stirred at 0 ^° C. for 15 min. stirred vigorously. This formed a white precipitate. The precipitate was filtered off and washed several times with water (alternatively, the precipitate can be suspended in about 200 ml of water, sonicated and filtered off). The precipitate was then washed again with ethyl acetate (2 × 25 ml), n-pentane (2 × 25 ml) and dried in vacuo over phosphorus pentoxide. N- (6-diphenylphosphinylpyridin-2-ylcarbonyl) guanidine was obtained as a dichloromethane adduct in an amount of 7.55 g (yield) as a colorless powder. This compound is insoluble in common solvents except DMSO.

Rf (SiO ₂ , CH ₂ Cl ₂ / CH ₃ OH / triethylamine - 30: 2: 1) = 0.4. M.p .:> 250 ⁰ C. ¹ H-NMR (499.7 MHz, d ⁶ -DMSO): δ = 6.96 (d, J = 7.6 Hz, 1 H); 7.25-7.34 (m, 4H); 7.38-7.44 (m, 6H); 7.76 (td, J = 7.6, 7.6, 1.6 Hz, 1H); 7.94 (d, J = 7.6 Hz, 1H); 6.79 and 8.05 ppm (bs, 4H). ¹³ C { ¹ H} NMR (125.7 MHz, d ⁶ -DMSO): δ = 122.2 (s); 127.8 (d, J = 1 1, 8 Hz); 128.7 (d, J = 6.4 Hz); 129, 1 (s); 133.6 (d, J = 19.3 Hz); 136.0 (d, J = 11, 8 Hz); 136.3 (s); 156.9 (d, J = 14.0 Hz); 161, 9 (d, J = 7.5 Hz); 163.2 (d, J = 8.6 Hz); 174.8 ppm (s). ³¹ P { ¹ H} NMR (161, 97 MHz, d ⁶ -DMSO, H ₃ PO ₄ ): δ = -5.63 ppm. MS (EI) [m / z] = 348.0 (100%, [M] ⁺ ). Elemental Analysis [%]: calcd. For M: C: 65.51; H: 4.92; N: 16.08; Calcd. for (M + 0.55 CH ₂ Cl ₂ ): C, 59.44; H: 4.62; N: 14,18; found: C: 59.37; H: 4.75; N: 14,49.

2. Preparation of N- (3-diphenylphosphanylbenzoyl) guanidine (2)

(2)

2.1 N'-tert-butoxycarbonyl-N- (3-diphenylphosphanylbenzoyl) guanidine

To a solution of 3- (diphenylphosphino) benzoic acid (1.2 g, 3.92 mmol, 1 eq.), Tert-butyloxycarbonylguanidine (936 mg, 5.88 mmol, 1.5 eq.) And N-methylmorpholine (862 uL, 793 mg, 7.84 mmol, 2 eq.) (in Dimethylformamic DMF, 25 ml) at 0 ⁰ C 1-benzotriazolyloxy-tris- (dimethylamino) phosphonium hexafluorophosphate (BOP, 1, 733 g, 3.92 mmol , 1 eq.). The reaction mixture was at 0 ⁰ C for 10 min. and stirred at room temperature under argon atmosphere for 4 hours. The reaction was monitored by TLC control (CH ₂ Cl ₂ / ethyl acetate, 10: 1). Water (40 ml) was added and a precipitate formed (stirred at 0 ^° C. for 10 minutes). The precipitate was filtered off and washed with water (20 ml). The precipitate was dissolved in CH 2 Cl 2 and filtered again. The filtrate was washed with water, dried over Na 2 SO 4 and freed from the solvent under reduced pressure. The residue was purified by column chromatography (CH ₂ Cl ₂ / ethyl acetate, 10: 1). N'-tert-butoxycarbonyl-N- (3-diphenylphosphanylbenzoyl) was obtained by guanidine Trituraturieren with n-pentane (20 ml) at -30 ⁰ C in an amount of 1, 195 g (yield 68%) as colorless white solid ,

Rf (SiO ₂ , CH ₂ Cl ₂ / ethyl acetate, 10: 1) = 0.65. M.p .: 79-82 ⁰ C. ¹ H-NMR (499.7 MHz, CDCl _3): δ = 1, 34 (s, 9H); 7.27-7.33 (m, 10H); 7.36-7.42 (m, 2H); 8.05 (d, J = 7.0 Hz, 1H); 8.13 (d, J = 7.9 Hz, 1H); 8.55 (bs, 1H); 8.56 ppm (bs, 2H). ¹³ C { ¹ H} NMR (125.7 MHz, CDCl ₃ ): δ = 27.9 (s); 82.9 (s); 128.3 (d, ³ J = 5.4 Hz); 128.6 (d, ³ J = 7.5 Hz); 128.7 (d); 128.8 (s); 129.5 (bs); 133.7 (d, J = 19.3 Hz); 134.3 (bd, J = 23.6 Hz); 136.8 (m); 137.5 (bd); 154.0 (s); 159.3 (s); 177.7ppm (s). ³¹ P { ¹ H} NMR (202.3 MHz, CDCl ₃ , H ₃ PO ₄ ): δ = -4.47 ppm. MS (EI): [m / z] = 305 (85%, [M- (NHCNBoc)] ⁺ ), 346 (100%, [MH-BoC] ⁺ ), 447.1 (30%, [M] ⁺ ). Elemental analysis [%]: calc .: C: 67.1; H: 5.86 N: 9.39; found: C: 67.1; H: 5.98; N: 9,19.

2.2 N- (3-diphenylphosphanylbenzoyl) guanidine (2)

N'-tert-butoxycarbonyl-N- (3-diphenylphosphanylbenzoyl) guanidine (800 mg, 1.789 mmol) was dissolved in trifluoroacetic acid (8 ml) under an argon atmosphere and stirred for 1.5 h at room temperature (TLC control: CH ₂ Cl ₂ / CH ₃ OH / triethylamine, 30: 2: 1; Mo-Ce reagent). The excess of trifluoroacetic acid was removed under reduced pressure. The residue was dissolved in CH ₂ Cl ₂ (10 ml) and washed with a Na2CO3 solution (20% aq., 10 ml) extracted. The aqueous phase was extracted with CH 2 Cl 2 (2x10 ml). The organic phases were combined, dried over MgSO ₄ , filtered and the solvent was removed under reduced pressure. The residue was triturated with n-pentane (2x10 ml) and dried in vacuo. N- (3-diphenylphosphinylbenzoyl) guanidine was obtained as a colorless solid in an amount of 590 mg (yield 95%).

Rf (SiO ₂ , acetone) = 0.5. M.p .: 75-77 ⁰ C. ¹ H-NMR (400.1 MHz, d ⁶ -DMSO): δ = 7.21-7.27 (m, 5H); 7.39-7.45 (m, 7H); 8.07 (d, J = 7.6 Hz, 1H); 8.10 (d, J = 9.1 Hz, 1H); 7.0 and 7.9 ppm (bs, 4H). ¹³ C { ¹ H} NMR (100.6 MHz, d ⁶ -DMSO, TMS): δ = 128.2 (d, J = 5.3 Hz); 128.7 (d, J = 6.8 Hz); 128.9 (s); 129.0 (s); 133.2 (d, J = 19.6 Hz); 133.6 (d, J = 26.1 Hz); 135.1 (d, J = 14.2 Hz); 136.2 (d, J = 1 1, 8 Hz); 136.4 (d, J = 11, 4 Hz); 138.5 (s); 162.1 (s); 174.3 ppm (s). ³¹ P { ¹ H} NMR (161, 98 MHz, d ⁶ -DMSO): δ = -5.83 ppm. MS (EI): [m / z] = 183 (25%), 330 (50%, [M-NHs] ⁺ ), 347 (100%, [M] ⁺ ). High resolution mass: calc .: 347.118750; F .: 347.1 19402.

II. Preparation of the Substrates

1. Preparation of (Z) -pent-3-enoic acid ((Z) -3)

1.1 (Z) -pent-3-en-1-ol

Lindyl catalyst (45 mg) was placed in a 250 ml Schlenk flask and degassed. Quinoline (780 mg, distilled under argon), diethyl ether (150 ml, abs.) And pent-3-yn-1-ol (2.74 ml, 2.5 g, 29.7 mmol) were added. The argon atmosphere was exchanged for an H2 atmosphere. The hydrogenation was carried out at a H 2 pressure of 1 bar at room temperature for 20 h. The resulting reaction mixture was filtered through Celite and washed with diethyl ether. The filtrate was freed from the solvent under reduced pressure. The residue was purified by distillation (140 ° C / normal pressure). (Z) -pent-3-en-1-ol was obtained as a colorless liquid in an amount of 2.4 g (yield 94%). The content of the product obtained in (Z) isomer was, according to GC analysis (GC: AGILENT TECHNOLOGIES 6890N; Column: SUPELCO 24079, Supelcowax 10, 30.0 x 0.25 mm x 0.25 micron; ⁰ 75 C isothermal, Flow He 0.7 ml / min; (E): 18.9 min., (Z): 19.3 min.) At> 96%. 1 H NMR (400.1 MHz, CDCl ₃ ): δ = 1.64 (d, J = 5.6 Hz, 3H); 2.33 (pseudo-q, J = 7.0 Hz, 2H); 3.63 (t, J = 6.6 Hz, 2H); 5.35-5.45 (m, 1H); 5.57-5.67 ppm (m, 1H). ¹³ C { ¹ H} NMR (100.6 MHz, CDCl ₃ ): δ = 12.5 (s); 30.3 (s); 62.0 (s); 126.0 (s); 126.5 ppm (s); By-product signals ((E) isomer): δ = 17.4; 35.7; 61, 9; 127.2; 127.5 ppm.

1.2 (Z) -pent-3-enoic acid ((Z) -3) To a solution of Na ₂ Cr ₂ Oz (69.2 mg, 0.23 mmol, 0.01 eq.), 65% nitric acid (450 mg, 4.64 mmol, 0.2 eq.) And NaIO ₄ ( 10.93 g, 51.1 mmol, 2.2 eq.) In H ₂ O (25 mL) were successively added to O ⁰ C CH ₃ CN (50 mL) and (Z) -pent-3-ene-1. added (2.36 mL, 2.0 g, 23.22 mmol, 1, 0 eq.). The reaction mixture was stirred at ⁰ C for 8 h and stirred overnight at 10 ⁰ C. The reaction by NMR was 98%. Inorganic salts were filtered off and washed with diethyl ether. After separation of the phases, the aqueous phase was extracted with ether (3 × 100 ml). The organic phases were combined, dried over Na ₂ SO ₄ and freed from the solvent under reduced pressure. The residue (2.04 g) was separated by distillation (100 ° C / 20 mbar). (Z) -pent-3-enoic acid was obtained as a colorless liquid in an amount of 1.83 g (yield 79%). According to ¹ H-NMR analysis, the content of (Z) isomer was 95%. 1 H-NMR (400.1 MHz, CDCl ₃ ): δ = 1.65 (ddt, J = 6.8, 1.8, 1.8 Hz, 3H); 3.13-3.16 (dm, J = 7.2 Hz, 2H); 5.53-5.74 (m, 2H); 10.8 ppm (bs, 1H). ¹³ C { ¹ H} NMR (100.6 MHz, CDCl ₃ ): δ = 13.0 (s); 32.5 (s); 121, 0 (s); 128.2 (s); 178.7 ppm (s); Signals of by-product ((E) isomer): δ = 18.0; 37.9; 122.0; 130.2; 179.0 ppm.

2. Preparation of 2-vinylhept-6-enoic acid (4)

2.1. p-Toluolsulfonsäurepent-4-enyl ester

To a solution of pent-4-en-1-ol (6.67 g, 77.5 mmol, 1 eq.) And pyridine (abs., 12.53 mL, 12.25 g, 154.9 mmol, 2 (eq.) in CH ₂ Cl ₂ 80 ml) was added (at 0 ⁰ C in small portions p-toluenesulfonyl chloride 22.15 g, 116 mmol, 1 5 eq. added). The reaction onslösung was stirred at 0 ⁰ C for 3 h. After adding water (60 ml), the mixture was extracted with diethyl ether (125 ml). The organic phase was washed successively with aqueous hydrochloric acid (2 M), an aqueous Na ₂ CO ₃ solution (5%) and water, dried over MgSO ₄ and freed from the solvent under reduced pressure. The residue was separated by column chromatography (petroleum ether / diethyl ether, 8: 1). P-toluenesulfonylpent-4-enyl ester was obtained in an amount of 17.7 g (yield 95%) as a colorless oil.

¹ H NMR (400.1 MHz, CDCl ₃ ): δ = 1, 71-1, 78 (m, 2H); 2.05-2.11 (m, 2H); 2.45 (s); 4.04 (t, J = 6.4 Hz, 2H); 4.93-4.98 (m, 2H); 5.64-5.74 (m, 1H); 7.35 (dm, J = 8.3 Hz, 2H); 7.79 ppm (dm, J = 8.3 Hz, 2H). ¹³ C { ¹ H} NMR (100.6 MHz, CDCl ₃ ): δ = 21, 6; 28.0; 29.4; 69.8; 115.8; 127.9; 129.8; 133.2; 136.6; 144.7 ppm.

2.2 2-vinylhept-6-enoic acid (4)

To a solution of diethylamine (7.3 g, 10.28 ml, 99.84 mmol, 2.4 eq.) In tetrahydro- furan (THF, 50 ml, abs.) Was added under argon at -78 ⁰ C n- Butyllithium (2.5 M in hexane, 39.9 mL, 99.84 mmol, 2.4 eq.) Was added slowly. The reaction mixture was added 0 ⁰ C stirred for 0.5 h and then cooled again to -78 ° C. To this reaction mixture at this temperature was added a solution of (E) -but-2-enoic acid (4.3 g, 49.92 mmol, 1.2 eq.) In THF (abs., 50 ml) over a period of 15 minute added. Subsequently, the reaction mixture was stirred for 1 h at 0 ⁰ C and again cooled to -78 ⁰ C. To this reaction mixture was added a solution of para

Toluene sulfonylpent-4-enylester (10 g, 41, 6 mmol, 1 eq.) In THF (50 ml, abs.) By means of syringe pump over a period of 1 h at -78 ⁰ C added. The reaction mixture was heated to -20 ⁰ C over 1 h and stirred at this temperature for a further 16 h. Then, H2O (300 ml) was added and washed with diethyl ether (3x200 ml). The aqueous phase was acidified with phosphoric acid (85%) under ice-cooling and then extracted with ethyl acetate (3x250 ml). The organic phases were combined and dried over MgSO ₄ and freed from the solvent under reduced pressure. The residue was separated by distillation (80 ⁰ C / 0.4 mbar). 2-Vinylhept-6-enoic acid was obtained in an amount of 5.2 g (yield, 81%) as a colorless oil.

¹ H-NMR (400.1 MHz, CDCl ₃ ): δ = 1, 31-1, 51 (m, 2H); 1, 51-1, 63 (m, 1H); 1, 75-1, 85 (m, 1H); 2.07 (dt, J = 7.0, 7.0 Hz, 2H); 3.02 (dt, J = 7.7, 7.7 Hz, 1H); 4.93-5.04 (m, 2H); 5.14-5.25 (m, 2H); 5.72-5.86 (m, 2H); 11.73 ppm (bs, 1H). ¹³ C { ¹ H} NMR (100.6 MHz, CDCl ₃ ): δ = 26.2 (s); 31, 4 (s); 33.4 (s); 50.0 (s); 114.9 (s); 117.8 (s); 135.4 (s); 138.2 (s); 181, 2 ppm (s). MS (CI (NH ₃ )): [m / z] = 109.1 (13%), 172.1 (100%, [M + NH ₃ + H] ⁺ ). Elemental Analysis [%]: calc .: C: 70.1; H: 9.15; found: C: 69.8; H: 9.04.

IV. General Rules for Hydroformylation

To a solution or suspension of [Rh (CO) 2acac], the corresponding ligand, 1, 3,5-trimethoxybenzene (as an internal standard) in a solvent, the compound to be reacted (substrate) is placed in a Schlenk flask. The reaction mixture is stirred for 5 minutes under argon. The reaction mixture is transferred with a syringe under an argon atmosphere into an autoclave. The autoclave is rinsed three times with the synthesis gas (CO / H2, 1: 1).

The hydroformylation reactions are carried out in

(A) an Argonaut Endeavor® reactor system consisting of eight parallel, mechanically stirred pressure reactors with independent temperature and pressure control. The progress of the reaction was determined by evaluating the synthesis gas consumption;

(B) a Premex stainless steel autoclave Medimex (100 ml) with magnetic stirrer. The autoclave is equipped with a glass insert and a device for sampling. equips. For kinetic investigations, the autoclave is thermostated and samples are taken and analyzed by NMR analysis.

The reactions are interrupted (if appropriate) by cooling the system, venting and purging the reactor with argon. Samples are analyzed by NMR analysis of the crude reaction mixtures in CDCb and / or by NMR analysis of the samples after removal of the solvent.

V. Hydroformylation Examples Regioselectivity

1. Hydroformylation of vinylacetic acid (5):

Experimental conditions: Reactor: autoclave (A); Molar ratio: [Rh (CO) ₂ acac]: ligand: (5): standard = 1: 10: 200: 100; Solvent: THF (2 ml); Initial concentration of the substrate (3): co (3) = 0.2 M; Synthesis gas: CO / H2 (1: 1); Reaction pressure: 10 bar; Reaction temperature: 40 ^° C; Reaction time: 4 h.

Main products of hydroformylation:

(6) (7)

The conversion frequency (TOF; mol (aldehyde) / mol (catalyst) hr ¹ ) was determined from the synthesis gas consumption. After removal of the solvent under reduced pressure (150 mbar) and addition of triethylamine (100 .mu.l), the degree of conversion (in%) and the regioselectivity of the reaction (molar ratio (6) / (7)) by integrating the characteristic signals of the resulting Reaction products in the ¹ H-NMR spectrum of the resulting reaction mixture determined. Each attempt was repeated at least twice. By-products were observed in this reaction in an amount of <5% in all reactions.

Used ligands not according to the invention:

XANTPHOS (8)

Table 1 :

(VB) = Comparative Example (not according to the invention)

[a] Due to the low conversion, the regioselectivity could not be determined with sufficient accuracy

[b] Reaction temperature deviating from basic instructions

[c] Reaction time deviating from basic rule

1.8 Preparation of 5-oxopentanoic acid (6) by hydroformylation of vinyl acetic acid (5)

Experimental conditions: Reactor: autoclave (B); Molar ratio: [Rh (CO) ₂ acac]: (1): (5) = 1: 20: 200; Solvent: THF (5 ml); Initial concentration of the substrate (5): co (5) = 0.39 M; Synthesis gas: CO / H2 (1: 1); Reaction pressure: 4 bar; Reaction temperature: room temperature; Reaction time: 20 h.

After removing the solvent under reduced pressure, the residue was taken up in CH 2 Cl 2, applied to a short silica gel column and eluted with diethyl ether. 5-Oxo-pentanoic acid (6) was obtained in an amount of 215.5 mg (yield 96%) as a colorless liquid. According to NMR analysis, the isolated product contains, as further component, 1.7 mol% of 3-methyl-4-oxobutyric acid (7). ¹ H-NMR (400.1 MHz, CDCl ₃ ): δ = 1.96 (pseudo-q, J = 7.2, 7.2 Hz, 2H); 2.44 (t, J = 7.2 Hz, 2H); 2.56 (dt, J = 1, 3, 7.2 Hz, 2H); 9.77 (bs, 1H); 9.85 ppm (bs, 1H). 1 ³ C { ¹ H} NMR (100.6 MHz, CDCl ₃ ): δ = 17.0 (s); 32.9 (s); 42.7 (s); 178.9 (s); 201, 3 (bs). MS (CI (NH ₃ ): [m / z] = 133.9 (100%) [M + NH ₃ + H] +). Elemental Analysis [%]: calc .: C: 51, 72; H: 6.94; Found: C: 51, 56; H: 6.71.

2. Hydroformylation of Pent-4-enoic Acid (9)

Reaction conditions: Reactor: autoclave (A); Molar ratio:

[Rh (CO) ₂ acac]: (1): (9): standard = 1: 10: 200: 100; Solvent: THF (2 ml); Initial concentration of the substrate (9): co (9) = 0.2 M; Synthesis gas: CO / H2 (1: 1); Reaction pressure: 10 bar; Reaction temperature: 40 ^° C; Reaction time: 4 h.

Possible products of hydroformylation:

The conversion frequency (TOF; mol (aldehyde) / mol (catalyst) hr ¹ ) was determined from the synthesis gas consumption. After removal of the solvent under reduced pressure (150 mbar), the degree of conversion (in%) and the regioselectivity of the reaction (molar ratio (10) / (1 1)) by integrating the characteristic signals of the resulting reaction products in the ¹ H-NMR spectrum of determined reaction mixture determined. Each attempt was repeated at least twice. By-products were observed in this reaction in an amount of <5% in all experiments.

Result: TOF = 49 hr ¹ ; Degree of conversion: 73%; Regioselectivity of the reaction: (10) / (11) = 3.6.

4. Hydroformylation of But-3-enoic Acid Methyl Ester (12) (Not According to the Invention)

Reaction conditions: Reactor: autoclave (A); Molar ratio: [Rh (CO) ₂ acac]: (1): (12): CH ₃ COOH: standard = 1: 10: 200: (according to Table 2): 100; Solvent: THF (2 ml); Initial concentration of the substrate (12): co (12) = 0.2 M; Synthesis gas: CO / H2 (1: 1); Reaction pressure: 10 bar; Reaction temperature: 40 ^° C; Reaction time: 4 h. Possible products of hydroformylation:

The conversion frequency (TOF; mol (aldehyde) / mol (catalyst) hr ¹ ) was determined from the synthesis gas consumption. The degree of conversion (in%) and the regioselectivity of the reaction (molar ratio (13) / (14)) was determined by integrating the characteristic signals of the resulting reaction products in the ¹ H-NMR spectrum of the resulting reaction mixture diluted with CDCb. Each attempt was repeated at least twice. By-products were observed in this reaction in an amount of <5% in all reactions.

Table 2

[a] moles of CH ₃ COOH per mole of (12)

[b] suspension (ligand 1 is insoluble in the reaction medium without carboxylic acid).

5. Hydroformylation of (Z) -pent-3-enoic acid ((Z) -3)

Reaction conditions: Reactor: autoclave (B); Molar ratio: [Rh (CO) 2acac]: ligand: ((Z) -3): standard = 1: 10: 50: 25; Initial concentration of the substrate ((Z) -3): Co ((Z) -3) = 0.2 M; Solvent: THF (4 ml); Synthesis gas: CO / H2 (1: 1); Reaction pressure: 6 bar; Reaction temperature: room temperature; Reaction time: 68 h.

After removal of the solvent under reduced pressure (150 mbar) and addition of triethylamine (100 .mu.l), the degree of conversion (in%) and the regioselectivity of the reaction (molar ratio (15) / (16)) by integrating the characteristic signals of the resulting Reaction products in the ¹ H-NMR spectrum of the resulting reaction mixture determined. The results are shown in Table 3.

Hydroformylation products:

Table 3

5.3 Preparation of 4-methyl-5-oxopentanoic acid (15) by hydroformylation of (Z) -pent-3-enoic acid ((Z) -3)

Experimental conditions: Reactor: autoclave (B); Molar ratio: [Rh (CO) ₂ acac]: (1): ((Z) -3) = 1: 10: 50; Initial concentration of the substrate ((Z) -3): c _o ((Z) -3) = 0.2 M; Solvent: THF (4 ml); Synthesis gas: CO / H ₂ (1: 1); Reaction pressure: 4 bar; Reaction temperature: room temperature; Reaction time: 68 h.

The resulting reaction mixture was treated with silica gel (1 g) and freed from the solvent under reduced pressure. The resulting solid was applied to a silica gel column and separated by chromatography (eluent: petroleum ether / diethyl ether / acetic acid, 100: 50: 1). A product mixture of (15) and (16) was obtained as a colorless solid in an amount of 70 mg (yield 67.2%). The product mixture contained 92% 4-methyl-5-oxopentanoic acid (15) and 8% 3-formylpentanoic acid (16). 7.4 mg (9.2%) of the starting compound and its (E) -isomer were recovered.

Rf (SiO ₂ , petroleum ether / diethyl ether / acetic acid = 100: 50: 1) = 0.12. ¹ H-NMR (400.1 MHz, CDCl ₃ ): δ = 1.15 (d, J = 7.1 Hz, 3H); 1, 66-1, 75 (m, 1H); 2.02-2.1 1 (m, 1H); 2.44 (t, J = 7.5 Hz, 2H); 2.40-2.50 (m, 1H); 9.62 (bs, 1H); 10.6 ppm (bs, 1H). 1 ³ C {1 H} NMR (100.6 MHz, CDCl ₃ ): δ = 13.2 (s); 24.9 (s); 31, 1 (s); 45.2 (s); 179.0 (s); 204.2 ppm (s). MS (CI (NH ₃ )): [m / z] = 113 (100% [MH ₂ CHH] ⁺ ), 131 (33% [M + H] ⁺ ), 148 (40% [M + NH ₃ + H ] ⁺ ). Elemental Analysis [%]: calc .: C: 55.37; H: 7.74; found: C: 55.29; H: 7.54.

6. Hydroformylation of vinylacetic acid (5) in the presence of an inhibitor Experimental conditions: Reactor: autoclave (A); Molar ratio: [Rh (CO) ₂ acac]: (1): Inhibitor: Standard = 1: 10: (according to Table 4): 200: 100; Initial concentration of the substrate (5): Co (5) = 0.2 M; Solvent: THF (2 ml); Synthesis gas: CO / H2 (1: 1); Reaction pressure: 10 bar; Reaction temperature: 40 ^° C; Reaction time: 4 h.

With regard to the further experimental conditions, reference is made to the statements made in paragraph V.1 for the evaluation of the reaction of vinylacetic acid (5). The results are summarized in Table 4.

Table 4

[a] mol CH3CO2H based on 1 mol of vinylacetic acid (5).

VI. Hydroformylation Examples of Chemoselectivity

1. Hydroformylation of Vinyl Acetic Acid (5) in Addition to Vinyl Acetic Acid Methyl Ester (17)

Reaction conditions: Reactor: autoclave (B); Molar ratio [Rh (CO) ₂ acac]: ligand: (5): (17): standard = 1: 20: 200: 200: 25; Initial concentration of substrates (5) and (17): co (5) = Co (17) = 0.13 M; Solvent: THF (6 ml); Synthesis gas: CO / H2 (1: 1); Reaction pressure: 4 bar; Reaction temperature: room temperature.

Hydroformylation products of (17):

(18) (19)

The degree of conversion of (5) and (17) (in%) and the regioselectivity of the reaction of (17) ((18) / (19)) were determined by NMR analysis of the crude reaction mixture. thin with CDCb. The regioselectivity of the reaction of (5) ((6) / (7)) was determined after removal of the solvent from the reaction mixture. The results are summarized in Table 5.

2. Hydroformylation of vinylacetic acid (5) in addition to 1-octene (20)

Reaction conditions: Reactor: autoclave (B); molar ratio: [Rh (CO) ₂ acac]: (1): (5): (20): standard = 1: 20: 200: 200: 100; Initial concentration of substrates (5) and (20): co (5) = c _o (2O) = 0.13 M; Solvent; THF (6 ml); Synthesis gas: CO / H2 (1: 1); Reaction pressure: 4 bar; Reaction temperature: room temperature.

Hydroformylation products of (20):

(21) (22)

The degree of conversion of (5) and (20) (in%) and the regioselectivity of the reaction of (20) ((21) / (22)) was determined by NMR analysis of the crude reaction mixture diluted with CDCb. The regioselectivity of the reaction of (5) ((6) / (7)) was determined after removal of the solvent from the reaction mixture. The results are summarized in Table 6.

Table 6

3. Hydroformylation of 2-vinylhept-6-enoic acid (23) (internal selectivity)

Experimental conditions: Reactor: autoclave (B); Molar ratio: [Rh (CO) 2acac]: ligand: (23): standard = 1: 10: 150: 50; Initial concentration of the substrate (23): c _o (23) = 0.2 M; Solvent: THF (8 ml); Synthesis gas: CO / H ₂ (1: 1); Reaction pressure: 4 bar; Reaction temperature: 25 ^° C.

Reaction Centers for the Hydroformylation of (23):

Double bond (B)

(a.1) (a.2)

Double bond (A)

The hydroformylation reaction was sampled (0.5 ml) at the times given in Tables 7 and 8. On the basis of these samples, the selectivity of the hydroformylation reaction with respect to the double bonds ((A) / (B)) and the regioselectivity of the hydroformylation reaction at the respective double bonds ((a.1) / (a.2) or (b. 1) / (b.2)) determined by NMR analysis. The results of hydroformylation of (23) in the presence of ligand (1) are summarized in Table 7. For comparison purposes, the results of hydroformylation of (23) in the presence of triphenylphosphine as a ligand are summarized in Table 8

Table 7. Reaction of (23) in the presence of the ligand (1)

From these results, using ligand (1) as reaction frequencies with respect to the two double bonds of (23), TOF (A) = 46.5 h- ¹ and TOF (B) = 5.3 h- ¹ .

Table 8. Reaction of (23) in the presence of PPh ₃ as ligand (not according to the invention)

From these results, the use of triphenylphosphine as ligand as reaction frequencies with respect to the two double bonds of (23) TOF (B) = 4.6 h- ¹ and TOF (A) = 3.7 Ir ¹ .

3.12 Preparation of 2- (3-oxopropyl) hept-6-enoic acid (24) by hydroformylation of 2-vinylhept-6-enoic acid (23)

Experimental conditions: Reactor: autoclave (B); Molar ratio: [Rh (CO) ₂ acac]: (1): (23) = 1: 10: 150; Initial concentration of the substrate (23): c _o (23) = 0.2 M; Solvent: THF (8 ml); Synthesis gas: CO / H ₂ (1: 1); Reaction pressure: 4 bar; Reaction temperature: 25 ^° C .; Reaction time: 6.25 h.

The reaction mixture obtained after the reaction was added with silica gel (1 g) and freed from the solvent under reduced pressure. The resulting solid was applied to a silica gel column and separated by chromatography (eluent: petroleum ether / diethyl ether / acetic acid, 100: 50: 1). 2- (3-Oxopropyl) hept-6-enoic acid (24) was obtained as a colorless liquid (220 mg, yield 74.6%). In addition, 17.6 mg (7.1%) of the starting compound (23) were recovered.

Rf (SiO ₂ , petroleum ether / diethyl ether / acetic acid = 100: 50: 2) = 0.27. ¹ H-NMR (400.1 MHz, CDCl ₃ ): δ = 1, 39-1, 57 (m, 3H); 1, 64-1, 74 (m, 1H); 1, 83-1, 97 (m, 2H); 2.44 (ddt, 2H, J = 7.0, 7.0, 1.3 Hz); 2.38-2.45 (m, 1H); 2.47-2.61 (m, 2H); 4.95-5.04 (m, 2H); 5.73-5.83 (m, 1H); 9.77 (bs, 1H), 11, 14 ppm (bs, 1H). ¹³ C { ¹ H} NMR (100.6 MHz, CDCl ₃ ): δ = 23.8 (s); 26.2 (s); 31, 4 (s); 33.4 (s); 41, 4 (s); 44.3 (s); 114.9 (s); 138.0 (s); 181, 8 (s); 201, 4 ppm (s). MS (CI (NH ₃ )): [m / z] = 110.0 (55%), 167.0 (67% [MH ₂ O + H] ⁺ ), 185.1 (100% [M + H] ⁺ ), 202.1 (95% [M + NH ₃ + H] ⁺ ). Elemental Analysis [%]: calc .: C: 65.19 H: 8.75; Found: C: 65.0 H: 8.69.

VII. Molecular Modeling

Catalyst and substrate mutual recognition capability was verified for the catalyst / substrate pair of Example V.1.1 (Rh (CO) 2acac / (1) / vinylacetic acid) by Molecular Modeling (MMFF, Spartan Pro). The obtained data support the experimental findings regarding the mutual recognition of catalyst and substrate.

Claims

claims

1. Process for the hydroformylation of compounds of the formula (I),

wherein

X is C, P (R ^x ), P (OR ^x ), S or S (= O), where R ^{x is} H, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where alkyl is optionally 1, 2,

3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy and wherein cycloalkyl, heterocycloalkyl, aryl and hetaryl optionally 1, 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents mentioned above for alkyl,

A is a divalent bridging group of 1 to 4 bridge atoms between the flanking bonds and

R ^{1 is} H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where alkyl, alkenyl and alkynyl are optionally 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, Cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy and wherein cycloalkyl, heterocycloalkyl, aryl and

Hetaryl optionally have 1, 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents mentioned above for the alkyl, alkenyl and alkynyl,

or their salts,

wherein

Pn is a pnicogen atom;

R ^{2 is} one for forming at least one intermolecular, noncovalent

Bond with the group -X (OO) OH of the compound of formula (I) capable functional group,

R ³ and R ⁴ independently of one another are alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl, where alkyl is optionally 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy , Heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy and where cycloalkyl, heterocycloalkyl, aryl and hetaryl optionally have 1, 2, 3, 4 or 5 substituents which are selected from alkyl and the substituents mentioned above for the alkyl ; or together with the pnicogen atom and, if present together with the radicals Y ² and Y ^{3, represent} a 5- to 8-membered heterocycle which may optionally additionally fused once, twice, three or four times with cycloalkyl, heterocycloalkyl, aryl or hetaryl wherein the heterocycle and, if present, the fused groups are each independently 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkyl, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy , Hetaryl and hetaryloxy,

a, b and c are independently 0 or 1 and

Y ¹ , Y ² and Y ³ are each independently O, S, NR ^a , or SiR ^b R ^c , wherein R ^a , R ^b and R ^c independently of one another are hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl where alkyl is optionally 1, 2, 3, 4 or 5 substituents selected from halogen, cyano, nitro, alkoxy, cycloalkyl, cycloalkoxy, heterocycloalkyl, heterocycloalkoxy, aryl, aryloxy, hetaryl and hetaryloxy and wherein cycloalkyl, heterocycloalkyl, aryl and Hetaryl optionally have 1, 2, 3, 4 or 5 substituents, which are selected from alkyl and the substituents previously mentioned for the alkyl.

2. The method of claim 1, wherein the catalyst due to the group R ^{2 is} capable of forming an aggregate with the compound of formula (I), wherein the CC double bond of the compound of formula (I) for interaction with the complexed metal of VIII Subgroup is capable.

3. The method according to any one of the preceding claims, wherein X in the compounds of the formula (I) is C, S (= O) or P (OR ^X ), wherein R ^{x is} H or in each case optionally substituted alkyl, cycloalkyl or Aryl stands.

4. The method of claim 3, wherein X is C.

5. The method according to any one of the preceding claims, wherein the compound of formula (I) is selected from compounds of formula (I.a)

O _N

^X _/ XC (R ^a1 ) (R ^a2 ) -CH = CH-R ¹ (la)

Hθ '

wherein

R ^a1 and R ^{a2 are} independently H or Ci-C ₄ -AlkVl and

R ^{1 is} H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or hetaryl.

6. The method according to any one of the preceding claims, wherein the metal of

VIII. Subgroup of the Periodic Table of the Elements is selected from Co, Ru, Rh, Ir, Pd and Pt.

7. The method according to claim 6, wherein the metal of VIII. Subgroup of Rh periodical Rh system.

8. The method according to any one of the preceding claims, wherein Pn in the compounds of formula (II) is phosphorus.

9. The method according to any one of the preceding claims, wherein the radical R ² in the compound of formula (II) comprises at least one NH group.

10. The method of claim 9, wherein R ² is selected from -NHR ^W, = NH, -C (= O) NHR ^W, -C (= S) NHR ^W, -C (= NR ^y) NHR ^w, -OC (= O) NHR ^W , -OC (= S) NHR ^W ,

-OC (= NR ^y) NHR ^w, -N (R ^Z) -C (= O) NHR ^W, -N (R ^Z) -C (= S) NHR ^W and -N (R ^z) -C (= NR ^y ) NHR ^w , in which R ^w , R ^y and R ^{z are} each independently of one another H, alkyl, cycloalkyl, aryl or hetaryl or in each case together with another substituent of the compound of the formula (II) are part of a 4- to 8- are membered ring system.

1 1. The method of claim 10, wherein R ^{2 is} -NH-C (= NH) NHR ^W , wherein R ^{w is} H, alkyl, cycloalkyl, aryl or hetaryl.

12. The method according to any one of the preceding claims, wherein R ³ and R ⁴ are each selected from optionally substituted phenyl, pyridyl or cyclohexyl.

13. The method according to any one of the preceding claims, wherein a, b and c are 0.

14. The method according to any one of the preceding claims, wherein the compound of formula (II) is selected from compounds of formula (II.a),

wherein

a, b, c, Pn, R ² , R ³ , R ⁴ , Y ¹ , Y ² and Y ^{3 have} one of the meanings given in any one of claims 1 to 13,

Z is O, S, S (= O), S (= O ₂ ), N (R ^IX ) or C (R ^IX ) (R ^X ) and R ^1, R ", R ^1" ^vι, R ^IV, R ^V, R, R ^v ", R ^VI11, R ^ιx and R ^x are independently H, halogen, nitro, cyano, amino, alkyl, alkoxy, alkylamino, Dialkylamino, cycloalkyl, heterocycloalkyl, aryl or hetaryl,

or in each case two radicals R ¹ , R ", R ^IV , R ^VI , R ^VI " and R ^IX bound to adjacent ring atoms, together represent the bond ^{portion of} a double bond between the adjacent ring atoms, wherein the six-membered ring may have up to three non-cumulated double bonds ,

15. The method of claim 14, wherein W in the compound of formula (II.a) is C (= O).

16. The method according to any one of claims 14 or 15, wherein R ^{2 is} for

-NH-C (= NH) NHR ^W , where R ^{w is} H, alkyl, cycloalkyl, aryl or hetaryl.

17. The method according to any one of claims 14 to 16, wherein the radicals R ¹ with R ", R ^ιv with R ^vι and R ^vm with R ^ιx in the compound of formula ( ^II.a ) in each case together for the binding ^{portion of} a double bond between the standing adjacent ring atoms.

18. A compound of formula (II.a) as defined in any one of claims 14 to 17.

19. A compound according to claim 18, selected from the compounds of the formula (1) and (2)

(1) (2)

20. Catalyst comprising at least one complex of a metal of subgroup VIII of the Periodic Table of the Elements with at least one compound of formula (II.a) as defined in one of claims 18 or 19.

21. Catalyst according to claim 20, wherein the metal of the VIII. Subgroup of the Periodic Table of the Elements is selected from Co, Ru, Rh, Ir, Pd and Pt.

22. Use of a catalyst as defined in any one of claims 20 or 21, for the hydroformylation.