US007847 126B2

(12) United States Patent (10) Patent No.: US 7,847,126 B2 Rampf et al. (45) Date of Patent: Dec. 7, 2010

(54) PROCESS FOR PREPARING TERTIARY (56) References Cited U.S. PATENT DOCUMENTS 3,499,039 A 3/1970 Lorenz et al...... 260/606.5 (75) Inventors: Florian Rampf, Köln (DE), 4,668,823. A 5/1987 Murray ...... 567/424 Hans-Christian Militzer, Odenthal 6,335,471 B1 1/2002 Eastham et al...... 568, 17 (DE) OTHER PUBLICATIONS Tomori, H. etal: "An Improved Synthesis 11-19.21, of Functionalized (73) Assignee: LANXESS Deutschland GmbH, Biphenyl-Based 23 Ligands' Journal of Organic Chem Leverkusen (DE) istry (2000), 65(17), 5334-5341, 2000, XPO02248873 Tabelle 1. Kaye, S. et al: “The use of catalytic amounts of CuCl and other (*) Notice: Subject to any disclaimer, the term of this improvements in the benzyne route to biphenyl-based phosphine patent is extended or adjusted under 35 ligands' Advanced Synthesis & Catalysis (2001), 343(8), 789-794, U.S.C. 154(b) by 854 days. 2001, XPOOI161250 das gauze Dokument. Schmidbauer H. et al.: “Extreme sterische Hinderung: Synthese and (21) Appl. No.: 11/810,374 Strunktur des Tetra (tert-butyl) phosphonium Kations—ein Fall von T-Symmetrie” Chemische Berichte. Bod. 113, Nr. 4, 1980, Seiten (22) Filed: Jun. 5, 2007 1612-1622, XPO02248874 Verlag Chemie GMBH. Weinheim., DE ISSN: 0009-2940 Seite 1613, unten; Seite 1614, Verbindung 5. Dumont W.W. et al.: IIZinn(II)-halogenidKomplexe mit Tri-tert (65) Prior Publication Data butylphosphin und Tris(dimethylamino)phosphin Zeitschrift fur US 2007/0299273 A1 Dec. 27, 2007 Anorganischeund Allgemeine Chemie. Bd. 441, 1978, Seiten 86-92. XPOO1 160738 Verlag Johann Ambrosius Barth. Leipzig., DDISSN: Related U.S. Application Data 0044-2313 Verbindung der Formel VII. Adv. Synth. Catal., (month unavailable) 2001, 343 (8), 789-794, (62) Division of application No. 10/417.989, filed on Apr. Kaye et all “The Use of Catalytic Amounts of CuCl and Other Improvements in the Benzyne Route to Biphenyl-Based Phosphine 17, 2003, now Pat. No. 7,230,136. Ligands'. J. Am. Chem. Soc., (month unavailable) 2001, 123 (11), 2677-2678, (30) Foreign Application Priority Data Stambuli et al., “Screening of Homogeneous Catalysts by Fluores Apr. 19, 2002 (DE) ...... 102 17 517 cence Resonance Energy Transfer. Identification of Catalysts for May 17, 2002 (DE) ...... 102 22 O33 Room-Temperature Heck Reations”. Primary Examiner Elvis O Price (51) Int. Cl. (74) Attorney, Agent, or Firm Michael A. Miller C07F 9/54 (2006.01) C07F 5/02 (2006.01) (57) ABSTRACT C07F 7/28 (2006.01) The invention relates to a process for synthesizing tertiary (52) U.S. Cl...... 568/2:568/9:556/7:556/23; phosphines by reacting halophosphines with organomagne 556/51 sium compounds in the presence of copper compounds and (58) Field of Classification Search ...... 568/2, optionally of salts. 568/9: 556/7, 23,51 See application file for complete search history. 1 Claim, No Drawings US 7,847,126 B2 1. 2 PROCESS FOR PREPARING TERTARY SUMMARY OF THE INVENTION PHOSPHINES A process has now been found for preparing compounds of This application is a divisional of U.S. patent application the formulae (Ia) and (Ib) Ser. No. 10/417,989 filed Apr. 17, 2003 now U.S. Pat. No. PR'Ars. (Ia) 7,230,136, entitled “Process for Preparing Tertiary Phos phines, the contents of which are hereby incorporated by RP B PR, (Ib) reference in their entirety. where 10 BACKGROUND OF THE INVENTION R" is in each case C-C2-alkyl, SiRs, (C-Cs-alkylene)- SiRs, C-C2-fluoroalkyl, Ca-Ca-aryl or Cs-Cls-aryla 1. Field of the Invention lkyl where the radicals The invention relates to a process for synthesizing tertiary Rare in each case independently C-C2-alkyl phosphines by reacting halophosphines with organomagne 15 and where, in formula (Ia). sium compounds in the presence of copper compounds and n is one, two or three and optionally of salts. Ar is a substituted or unsubstituted aryl radical 2. Brief Description of the Prior Art Tertiary phosphines, and methods of using and preparing and where, in formula (Ib), the same are generally known in the art. Many tertiary phos B is an unsubstituted or substituted radical from the group of phines have a high industrial significance, for example as C-C2-alkylene, C-C2-alkenylene, Ca-Co-arylene, ligands for metal atoms for forming metal complexes, as Cs-Cao-bisarylene, Co-Cao-ferrocenylene, reducing agents or, in the form of their oxides, as flame characterized in that halophosphines of the formula (IIa) or retardants or extractants. Metal complexes with tertiary phos 25 (IIb) phines are frequently used as catalysts in chemical reactions. PX, Arg, (IIa) Tertiary phosphines may also be used for absorbing metals, for example from liquid media. XP-B-PX (IIb) Tertiary phosphines may typically be synthesized by react ing organometallic compounds with halophosphines. The 30 where organometallic compounds used are predominantly organo n is one, two or three magnesium and organolithium compounds. However, with X is in each case independently chlorine, bromine or iodine increasing steric demands of the organic radicals to be intro and duced or already present in the molecule, it becomes very 35 Ar informula (IIa) has the same definition as specified under difficult to obtain tertiary phosphines. the formula (Ia) and B in formula (IIb) has the same defi For example, trichloride reacts with an excess nition as specified under the formula (Ib) of tert-butylmagnesium chloride to only give di(tert-butyl) are reacted with organomagnesium compounds of the formu chlorophosphine (see Hoffmann, Schellenbeck, Chemische Berichte, 1967, 100 (2), 692-693), or dichlorophenylphos 40 lae (IIIa) phine reacts with an excess of tert-butylmagnesium chloride (R'),Mg(Y)(2) (IIIa) to only give tert-butylchlorophenylphosphine (see Hoff mann, Schellenbeck, Chemische Berichte, 1966, 99, 1134 where 1142). R" have the definitions specified under the formula (Ia) and In the synthesis of tricyclohexylphosphine from phospho 45 m is one or two and rus trichloride and cyclo-hexylmagnesium compounds, the Y is chlorine, bromine or iodine desired product is obtained only at high temperature and in low yields (see Issleib, Brack; Zeitschr, allg. anorg. Chem. or halophosphines of the formula (Ic) 1954, 277,258-270). 50 RPX (IIc) Stambuliet al. were able to demonstrate that when copper (I) iodide is added in the presence of lithium bromide, it is also where possible to use organomagnesium compounds to obtain Sub R" has the definition given under the formulae (Ia) and (Ib) stitutions on bulky arylalkylchlorophosphines and tert-butyl chlorophosphine (J. Am. Chem. Soc., 2001, 123 (11), 2677 55 are reacted with organomagnesium compounds of the for 2678). The high copper and salt requirements, and likewise mula (IIIb) the required reaction temperatures of -78°C., make the pro B—(MgY) (IIIb) cess industrially impracticable. where Kaye et al. (Adv. Synth. Catal., 2001, 343 (8), 789-794) 60 describes the reaction of bis(aryl Grignard) compounds with Y is chlorine, bromine or iodine chlorophosphines in the presence of copper(I) chloride, requiring large amounts of copper compounds, which com and plicates the industrial realization. where the reaction is in each case carried out There was therefore the need to provide a process which 65 in the presence of one or more copper compounds and makes it possible to synthesize tertiary phosphines in an optionally in the presence of Salt and efficient and industrially acceptable manner. optionally in the presence of Solvent. US 7,847,126 B2 3 4 It is pointed out at this juncture that the scope of the inven C-C2-alkenylene is, for example, 1.2-ethenylene, 1,4- tion also encompasses any desired combinations of areas of but-2-enylene, 1.2-cyclopentenylene and 1.2-cyclohex preference. enylene. C-C-alkoxy is, for example, methoxy, ethoxy, isopro DETAILED DESCRIPTION OF THE INVENTION 5 poxy, n-propoxy, n-butoxy and tert-butoxy. The general term aryl as a further substituent encompasses In the scope of the invention, Aris, for example and with carbocyclic radicals and heteroaromatic radicals in which no, preference, a carbocyclic aromatic radical having 6 to 24 one, two or three framework atoms per cycle, but at least one framework carbonatoms or a heteroaromatic radical having 4 framework atom in the entire radical, are heteroatoms to 24 framework atoms where no, one, two or three frame 10 selected from the group of , Sulphur or oxygen. work atoms per cycle, but at least one framework atom in the Ca-Ca-Aryl is, for example and with preference, phenyl, entire molecule, are heteroatoms which are selected from the pyridyl, o-, m-, or p-tolyl, naphthyl or anthracenyl. group of nitrogen, Sulphur or oxygen. The carbocyclic aro The same applies to the aryl moiety of an arylalkyl radical. matic radical or heteroaromatic radical may also be substi Cs-Cs-Arylalkyl is, for example and with preference, ben tuted by up to five identical or different substituents per cycle 15 Zyl. which are selected from the group of fluorine, chlorine, bro For the purposes of the invention, fluoroalkyl is in each mine, nitro, cyano, protected formyl, C-C2-alkyl, C-C2 case independently a straight-chain, cyclic, branched or fluoroalkyl, Ca-Ca-aryl, Cs-C-arylalkyl, -PO—(C- unbranched alkyl radical which may be singly, multiply or Cs)-alkyl, —PO (C-C)-aryl —PO—(C-Cs)- fully substituted by fluorine atoms. alkyl)(C-C)-aryl), tri(C-C-alkyl)siloxyl or radicals of For example and with preference, C-C-fluoroalkyl is tri the general formula (IV) fluoromethyl, 2.2.2-trifluoroethyl, pentafluoroethyl and non A-D-R (IV) afluorobutyl, C-C-fluoroalkyl is additionally perfluorocy clohexyl, perfluorohexyl and perfluorooctyl, and C-C2 where, independently, fluoroalkyl is further additionally perfluorodecyl and A is absent or is a C-Cs-alkylene radical and 25 perfluorododecyl. D is oxygen, sulphur or NR Protected formyl denotes a formyl radical which is pro where tected by conversion to an aminal, acetal or mixed aminalac R" is hydrogen, C-Cs-alkyl, Cs-Cis-arylalkylor Ca-Ca-aryl etal where the aminals, acetals and mixed aminalacetals may and be acyclic or cyclic. R is C-Cs-alkyl, Cs-Cis-arylalkyl, C-Cs-haloalkyl or 30 For example and with preference, protected formyl is a Ca-Ca-aryl or 1,1-(2,5-dioxy)-cyclopentylene radical. NR'R' together is a cyclic amino radical For the purposes of the invention, Ar is with particular preference a radical selected from the group of phenyl, naph or radicals of the general formulae (Va.-d) 35 thyl, phenanthrenyl, anthracenyl, fluorenyl, pyridinyl, A-SOR (Va) oxazolyl, thiophenyl, benzofuranyl, benzothiophenyl, diben Zofuranyl, dibenzothiophenyl, furanyl, indolyl pyridazinyl, A-SO-R (Vb) pyrazinyl, pyrimidinyl, triazolyl and quinolinyl, each of which may also be substituted by no, one, two or three radi A-CN (Vc) cals per cycle, each of which is independently selected from 40 the group of A-COM (Vd) fluorine, chlorine, bromine, nitro, cyano, di(C-C-alkyl) where amino, C-C-alkyl, Ca-Ca-aryl, C-C-fluoroalkyl, A and Rare each as defined above and M may be an alkali O—(C-C-fluoroalkyl). O—(C-C-alkyl). —COO— metalion, half an equivalent of an alkaline earth metalion 45 (C-C)alkyl and —CONCC-C-alkyl). or a quaternary ammonium ion. For the purposes of the invention, Aris with very particular For the purposes of the invention, alkyl, alkylene, alkoxy, preference a radical selected from the group of phenyl, naph alkenyl and alkenylene are each independently a straight tyl, phenanthrenyl, anthracenyl and fluorenyl, each of which chain, cyclic, branched or unbranched alkyl, alkylene, alkoxy may also be substituted by no, one, two or three radicals per radical, alkenyl and alkenylene radical respectively, each of 50 cycle, each of which is independently selected from the group which may optionally be further substituted by C-C-alkoxy of fluorine, chlorine, bromine, nitro, cyano, dimethylamino, radicals. The same applies to the alkylene moiety of an ary diethylamino, phenyl, C-C-alkyl, C-C-fluoroalkyl, lalkyl radical. O—(C-C-fluoroalkyl) and O—(C-C-alkyl). C-C-alkyl is, for example, methyl, ethyl, n-propyl, iso For the purposes of the invention, B is, for example and propyl. n-butyl and tert-butyl, C-Cs-alkyl is additionally 55 with preference, a radical selected from the group of C-Cs n-pentyl, cyclohexyl, n-hexyl, n-heptyl, n-octyl or iso-octyl, alkylene, C-C2-alkenylene, 1.2-phenylene, 1.3-phenylene, C-C2-alkyl is further additionally for example n-decyl and 1,4-phenylene, 1.2-cyclohexylene, 1,1'-ferrocenylene and n-dodecyl. 1.2-ferrocenylene, each of which may also be mono- or C-C-alkylene is, for example, methylene, 1,1-ethylene, polysubstituted by radicals which are selected from the group 1.2-ethylene, 1,1-propylene, 1,2-propylene, 1,3-propylene, 60 of dimethylamino, diethylamino, phenyl, C-C-alkyl, bro 1,1-butylene, 1,2-butylene, 2,3-butylene and 1,4-butylene, mine, chlorine, fluorine, O—(C-C-alkyl), S -(C-C- C-Cs-alkylene is additionally 1.5-pentylene, 1.6-hexylene, alkyl). O—(C-C-fluoroalkyl), CO-O-(C-C-alkyl). 1,1-cyclohexylene, 1,4-cyclohexylene, 1.2-cyclohexylene vinyl and allyl. and 1.8-octylene, and C-C2-alkylene is further additionally When B is chiral C-C-alkylene or C-C2-alkenylene 1.2-(1,2-dicyclopentyl)ethylene. 65 substituted by the radicals specified, the definition encom C-C2-alkenyl is, for example, ethenyl, allyl, but-3-enyl, passes both pure Stereoisomers, enantiomers or diastere hex-5-enyl and dec-10-enyl. omers, and any desired mixtures thereof. US 7,847,126 B2 5 6 Also for the purposes of the invention, B is, for example The halophosphines used for the process according to the and with preference, 1,1'-binaphthyl-2,2'-diyl which is invention are also with particular preference those of the optionally, in each case independently, Substituted at the3.3'-. formulae (IIa) and (IIb) where 4,4'-, 5,5'-, 6,6'-, 7.7"- or 8.8'-positions by radicals which are X is chlorine. selected from the group of C-C-alkyl, bromine, chlorine, The halophosphines used for the process according to the fluorine, O—(C-C-alkyl). S-(C-C-alkyl). O—(C-C- invention are with very particular preference the following fluoroalkyl). CO O—(C-C-alkyl), vinyl and allyl. B is compounds: also, for example and with preference, 1,1'-biphenyl-2,2'-diyl trichlorophosphine, , dichloro-2- which is optionally, in each case independently, Substituted at methoxyphenylphosphine, dichloro-4-methoxyphenylphos the 3.3-, 4,4'-, 5,5'- or 6,6'-positions with radicals which are 10 phine, dichloro-2,4-dimethoxyphenylphosphine, dichloro-2, selected from the group of dimethylamino, diethylamino, 4,6-trimethoxyphenylphosphine, dichloro-2-tolylphosphine, phenyl, C-C-alkyl, bromine, chlorine, fluorine, O—(C- dichloro-4-tolylphosphine, dichloro-2,4-xylylphosphine, C-alkyl). S-(C-C-alkyl), O (C-C-fluoroalkyl). dichloro-3,5-xylylphosphine, dichloro-2,4,6-trimethylphe CO-O-(C-C-alkyl), vinyl, allyl, or where in each case nylphosphine, dichloropentafluorophenylphosphine, 15 dichloro-3,5-difluorophenylphosphine, dichloro-2,4-difluo two adjacent ring positions (i.e. 3.4; 4.5; 5.6; and/or 3',4'; rophenylphosphine, dichloro-4-fluorophenylphosphine, 4',5': 5'6") are linked by substituents selected from the group dichloro-4-chlorophenylphosphine, dichloro-4-bromophe of C-C-alkylene, C-C-alkylenedioxy, 2-oxyphenyl, nylphosphine, dichloro-4-(tert-butyl)phenylphosphine, 2-thiophenyl, or where the two 6,6'-positions are linked by dichloro-2,4,6-tri(tert-butyl)phenylphosphine, dichloro-4- Substituents selected from the group of C-C-alkylene, (trifluoromethyl)phenylphosphine, dichloro-3,5-bis(trifluo C-C-alkylenedioxy, (R)- or (S)-1-alkylethylenedioxy, (R)- romethyl)phenylphosphine, dichloro-2-biphenylphosphine, or (S)-1-arylethylenedioxy, (R,R)-, (R.S)- or (S,S)-1,2-di dichloro-3-biphenylphosphine, dichloro-1-naphthylphos alkylethylenedioxy, (R,R)-, (R.S)- or (S,S)-1,2-diarylethyl phine, dichloro-2-naphthylphosphine, dichloro-5-acenaph enedioxy, (R,R)-, (R.S)- or (S,S)-1-alkyl-2-arylethylene thenylphosphine, dichloro-9-fluorenyl-phosphine, dichloro dioxy. 25 9-anthracenylphosphine, dichloro-9-phenanthrylphosphine, When racemization-stable atropisomers are observed by dichloro-1-pyrenylphosphine. the substitution of the biary1 framework, the definition For the purposes of the invention, R' is preferably C-C2 encompasses both the racemates and the pure stereoisomers alkyl, SiR CH-SiR or Ca-Ca-aryl where the R radicals and also any desired mixtures thereof. are in each case independently C-C2-alkyl, although in each 30 case the condition applies that either For the purposes of the invention, B is with particular the R' radicals are bonded via a secondary, tertiary or preference 6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl, 5,5'- quaternary sp-carbonatom or a quaternary silicon atom dichloro-6,6'-dimethoxy-1,1'-biphenyl-2,2'-diyl. 6,6'-dim and, in the case of bonding via a secondary sp-carbon ethyl-1,1'-biphenyl-2,2'-diyl. 5,5'-dichloro-6,6'-dimethyl-1, atom, this secondary sp-carbon atom also bears a qua 1'-biphenyl-2,2'-diyl. 3,3'-di(tert-butyl)-5.5',6,6'- 35 ternary sp-carbon or silicon atom which is likewise a tetramethyl-1,1'-biphenyl-2,2'-diyl, 6,6'-methylenedioxy-1, component of the R radical or 1'-biphenyl-2,2'-diyl. 6,6'-ethylenedioxy-1, 1'-biphenyl-2,2'- the R' radicals are C-C-aryl radicals which are mono- or diyl. 6,6'-propylene -dioxy-1, 1'-biphenyl-2,2'-diyl. 6,6'- disubstituted in the ortho-positions. ethylene-1,1'-biphenyl-2,2'-diyl. 6,6'-propylene-1,1'- Such radicals are, for example and with preference, isopro biphenyl-2,2'-diyl. 6,6'-butylene-1,1'-biphenyl-2,2'-diyl. 40 pyl, sec-butyl, tert-butyl, trimethylsilyl, 1-methylbutyl, 6,6'-(S)-1-methylethylenedioxy)-1,1'-biphenyl-2,2'-diyl. 1-ethylpropyl, 1,1-dimethylpropyl. 1,2-dimethylpropyl. 6,6'-((R)-1-methylethylenedioxy-1, 1'-biphenyl-2,2'-diyl. 1-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3- 6,6'-(S)-1-phenylethylenedioxy-1,1'-biphenyl-2,2'-diyl. dimethylbutyl, 1-ethylbutyl, 1,1,2-trimethylpropyl, 1.2.2-tri 6,6'-((R)-1-phenylethylenedioxy-11'-biphenyl-2,2'-diyl. methylpropyl, 1-ethyl-1-methylpropyl. 2.2-dimethylpropyl. 3,3'-dimethyl-1,1'-binaphthyl-2,2'diyl. 3,3'-dimethoxy-11'- 45 (trimethylsilyl)methyl, cyclopentyl, cyclohexyl and cyclo binaphthyl-2,2'diyl. 3,3'-dictert-butyl)-1,1'-binaphthyl-2, heptyl and also 2'diyl. 6,6'-dibromo-1,1'-binaphthyl-2.2"diyl. 6,6'-divinyl-1, o-tolyl. 2,6-dimethylphenyl, 2,4,6-trimethylphenyl, 2-iso 1'-binaphthyl-2.2"diyl. 6,6'-diallyl-1,1'-binaphthyl-2.2"diyl. propylphenyl, 2,4- or 2,6-diisopropylphenyl, 2-(tert-butyl) bis-4,4'-dibenzofuran-3,3'-diyl (R)-1-methylethylene-1,2- 50 phenyl, 2,4- or 2,6-di(tert-butyl)phenyl oro-anisyland 2,4- or diyl, (S)-1-methylethylene-1,2-diyl. (R,R)-1,2-dimethyleth 2,6-dimethoxyphenyl. ylene-1,2-diyl. (S,S)-1,2-dimethylethylene-1,2-diyl. (R,R)- R" is with particular preference isopropyl, tert-butyl, 1,2-dimethylpropylene-1,3-diyl. (S,S)-1,2- cyclohexyl, ortho-tolyl and ortho-anisyl, and even greater dimethylpropylene-1,3-diyl. (R,R)-1,2-dimethylbutylene-1, preference is given to tert-butyl. 4-diyl. (S,S)-1,2-dimethylbutylene-1,4-diyl. (R,R)-1- 55 Organomagnesium compounds are used for the process methyl-2-ethylethylene-1,2-diyl. (S,R)-1-methyl-2- according to the invention. Organomagnesium compounds in ethylethylene-1,2-diyl. (R.S)-1-methyl-2-ethylethylene-1,2- solution are frequently in equilibrium with their more or less diyl. (R,R)-1-methyl-2-propylethylene-1,2-diyl. (S,R)-1- halogen-rich analogues or with solvent- or halogen-bridged methyl-2-propylethylene-1,2-diyl. (RS)-1-methyl-2- di-, oligo- or polymeric structures (known as a Schlenk equi propylethylene-1,2-diyl. (R,R)-1-methyl-2-butylethylene-1, 60 librium). 2-diyl. (S,R)-1-methyl-2-butylethylene-1,2-diyl and (R.S)-1- The representation of organomagnesium compounds in the methyl-2-butylethylene-1,2-diyl. form of the formulae (IIIa) and (IIIb), with regard to these equilibria, is not intended to constitute any restriction, but The halophosphines used for the process according to the rather merely illustrates organomagnesium compounds in invention are with particular preference of the formulae (IIa) 65 their most frequently reproduced notation. and (IIb) where For the purposes of the invention, organomagnesium com n is equal to two or three. pounds, known as Grignard reagents in particular, may, for US 7,847,126 B2 7 8 example, be those which have been prepared in situ from the Examples of preferred copper salts of the formula (VI) analogous halogen compounds and magnesium, and the include copper(I) acetate, copper(I) chloride, copper(I) bro preparation may be effected with the optional use of stoichio mide, copper(I) iodide, copper(I) cyanide, copper(I) thiocy metric or catalytic amounts of assistants and additives. anate, copper(II) acetate, copper(II) acetylacetonate, copper These assistants and additives include further Grignard 5 (II) chloride, copper(II) bromide, copper(II) ethylhexanoate, reagents and alkyl halides Such as 1,2-dibromethane, coordi copper(II) fluoride, copper(II) formate, copper(II) methox nating additives to the solvent such as triethylamine or N.N. ide, copper(II) nitrate, copper(II) sulphate, copper(II) tartrate, N',N'-tetramethyl-1,2-ethylenediamine or metal salts such as copper(II) trifluoroacetylacetonate and copper(II) trifluo iron(II) chloride. romethanesulphonate, and greater preference is given to cop The organomagnesium compounds used may advanta 10 per(I) chloride, copper(I) bromide and copper(I) iodide, and geously be used in the form of Solutions, some of which are even greater preference is given to copper(I) iodide. commercially available. Preferred copper complexes are those which bear ligands Solvents may also be added to the reaction mixture. which are selected from the group of organic amines and The solvents used are aprotic solvents. diamines, nitriles, Sulphides, phosphines and phosphites. Preferred aprotic solvents are ethers, for example diethyl 15 Examples include 1.2-ethylenediamine, 2.2-bipyridine, ether, tert-butyl methyl ether, dioxane, tetrahydrofuran, tet 1,10-phenanthroline for amines, acetonitrile and benzonitrile rahydropyran, 1,1-dimethoxymethane, 1,2-dimethoxy for nitriles, dimethyl sulphide for sulphides, triphenylphos ethane, diethylene glycol dimethyl ether, tetraethylene glycol phine for phosphines and trimethyl phosphite for phosphites. dimethyl ether, aliphatic hydrocarbons, for example pentane, Particularly preferred copper complexes are copper(I) bro hexane, heptane, octane and relatively long-chain mide-dimethyl sulphide complex, copper(II) nitrate-1,10 unbranched or branched aliphatic hydrocarbons, cyclohex phenanthroline complex, copper(II) (1,10-phenanthroline) ane, methylcyclohexane, petroleum ether having different bromide, copper(II) (1,10-phenanthroline)chloride, copper boiling ranges and paraffin oils, aromatic hydrocarbons, for (II) phthalo-cyanine, copper(I) tetrakis(acetonitrile) example , toluene, o-, m- or p-Xylene and mesitylene, hexafluorophosphate, copper(I) (triphenylphosphine) and aromatic chlorohydrocarbons such as chlorobenzene or 25 chloride, and even greater preference is given to copper(I) the isomeric chlorotoluenes and also mixtures of Such sol bromide-dimethyl sulphide complex. VentS. For the process according to the invention, very particular Particularly preferred solvents are diethyl ether, tetrahy preference is given to using copper(I) iodide and copper(I) drofuran, toluene, hexane, heptane or mixtures thereof. 30 bromide-dimethyl sulphide complex. In a preferred embodiment of the process according to the For the process according to the invention, the molar ratio invention, the proportion by volume of aromatic or aliphatic of X to be exchanged in compounds of the formulae (Ia), (Ib) hydrocarbons is selected in Such a way that, based on the or (Ic) to copper may be, for example, 5 to 2000, although entire reaction mixture, it is 10% or more, preferably 25% or preference is given to a ratio of 10 to 500, very particular O. 35 preference to one of 50 to 200. In view of the hydrolysis sensitivity of organomagnesium The process according to the invention in a preferred compounds, the use of dried solvents is advantageous. embodiment is carried out in the presence of at least one, In the case of solvents which form a relatively low-boiling preferably one, salt. azeotrope with water, it has proven Sufficient in practice to The salts used for the process according to the invention carry out an azeotropic distillation for drying. 40 are, for example and with preference, salts of the general Further drying possibilities are sufficiently well known to formula (VII) those skilled in the art. The amount of any solvent used may be, for example, 50 ml (cation)(anion) (VII) to 5000 ml, preferably 300 to 1000 ml, per mole of com where pounds of the general formulae (IIa), (IIb) or (IIc). 45 The amount of organomagnesium compound used may be, (cation") is a substituted ammonium, phosphonium or arso for example, 0.2 to 10 times the molar amount of the halogen nium cation or an alkali metal ion and atoms to be substituted in the halophosphines of the formulae (anion) is the anion of an organic or inorganic acid. (IIa), (IIb) or (IIc), and particular preference is given to 0.5 to 5 times, very particular preference to 1 to 2 times. Even 50 (Cation") is preferably an alkali metal cation or a cation of the greater preference is given to 1.05 to 1.5 times. formula (VIII) The copper compounds used are, for example and with preference, copper salts of the formula (VI) Co-aryl), (VIII)

CuAn g (VI) 55 where where Pnic is nitrogen orphosphorus and An is an organic or inorganic monoanion or half an equivalent (m+q+r)=4. of an organic or inorganic dianion or 60 (Cation") is with particular preference lithium, tetraphe copper complexes containing one or more organic ligands nylphosphonium, tetra-butylammonium, tetrabutylphospho which are bonded to the copper atom via one or more atoms nium and tributyldodecylphosphonium. from the group of oxygen, nitrogen, Sulphur and phosphorus. (Anion) is with preference fluoride, chloride, bromide, Preference is given to using copper salts in anhydrous iodide, cyanate, thiocyanate, acetate, hydroxide, nitrate, form. Hydrous copper salts may in principle likewise be used, 65 hydrogensulphate, tetrafluoroborate, hexafluorophosphate, but it is then advantageous to add an excess of organomag tosylate, and triflate, with particular preference chloride, bro nesium compound, in order to eliminate the water. mide, iodide. US 7,847,126 B2 9 10 Very particularly preferred salts are tetrabutylphospho Owing to the oxidation sensitivity of phosphines, it is nium chloride, tetrabutylphosphonium bromide, tetraphe advantageous for all of the liquid media used to be substan nylphosphonium chloride, tributyldodecylphosphonium tially freed of oxygen by degassing. chloride, lithium chloride, lithium bromide and lithium In the manner according to the invention, phosphines of the iodide or mixtures thereof. 5 formulae (Ia) and (Ib) Even greater preference is given to lithium bromide. The molar ratio of salt to copper in the reaction mixture PR'Ars (Ia) may be, for example, 0.05:1 to 10:1, and preference is given RP B P R (Ib) to 0.5:1 to 10:1, particular preference to 1:1 to 4:1. The reaction temperature may be, for example, -60° C. to 10 are obtained, or the analogous phosphonium tetrafluorobo 70° C., preferably -20°C. to 70° C. and particularly prefer rates, hexafluorophosphates, hydrogen hexafluorozirconates, ably -10° C. to 50° C. hydrogen hexafluorotitanates or Sulphonates The reaction pressure is uncritical and may be, for example, 0.2 to 100 bar, preferably ambient pressure. where The reaction time may be, for example, 5 minutes to 24, 15 R", Ar, n and Beach have the definitions and areas of prefer hours, preferably 30 minutes to 240 minutes. ence described above. The reaction and workup are preferably carried out under The process according to the invention is suitable in par protective gas with Substantial exclusion of oxygen and mois ticular for the preparation of aryidialkylphosphines of the ture. Substantial exclusion of oxygen means, for example, a general formula (IX) content of oxygen in the protective gas of 1% or less, prefer- 20 ably 0.5% or less. Useful protective gases include, for Ar PR', (DX) example, nitrogen and noble gases, for example argon, or mixtures of Such gases. where In a preferred embodiment of the process according to the Ar has the definition and areas of preference stated under the invention, the copper compound and the salt together with the 25 general formulae (Ia) and (Ib) and Solvent and the halophosphine are initially charged in a reac tion vessel under protective gas and the mixture is brought to R" has the definition and areas of preference stated under the the reaction temperature with stirring. The organomagnesium formulae (Ia) and (Ib), and also for their above-cited phos compound is then slowly metered in while controlling the phonium salts. reaction temperature. Cooling may optionally be effected. On 30 The process according to the invention is also Suitable in completion of addition, the reaction mixture is allowed to particular for the preparation of trialkylphosphines of the adjust to room temperature and is stirred until the end of the general formula (X) reaction time. Hydrolysis may then be effected using ammo PR's (X) nium chloride solution. After phase separation, the organic phase is washed repeatedly with aqueous ammonia Solution 35 where and then with water. The organic phase is then dried (for R" has the definition and areas of preference stated under the example over MgSO) and subsequently freed of solvents. formulae (Ia) and (Ib), and also for their above-cited phos If necessary, sufficiently volatile products are then dis phonium salts. tilled, while solid products may optionally be further purified, The process according to the invention is suitable with for example by recrystallization or reprecipitation. 40 particular preference for preparing: An alternative form of workup comprises extraction of the resulting phosphine into the aqueous phase with the aid of di-(tert-butyl)phenylphosphine, di(1-methylbutyl)phe inorganic acid and Subsequent reextraction into an organic nylphosphine, di (1,1-dimethylpropyl)phenylphosphine, phase after neutralization of the acid with base. The further di(1,1-dimethylbutyl)phenylphosphine, di-(tert-butyl)-2- workup may optionally be effected by distillation or crystal- 45 methoxyphenylphosphine, di(1-methylbutyl)-2-methox lization. yphenylphosphine, di(1,1-dimethylpropyl)-2-methoxyphe Yet another alternative form of workup comprises the pre nylphosphine, di(1,1-dimethylbutyl)-2- cipitation of the phosphine formed using a strong acid to give methoxyphenylphosphine, bis(trimethylsilyl)-2- a phosphonium salt, in particular those which have negligible methoxyphenylphosphine, di-(tert-butyl)-4- solubility in the organic phase. Examples of acids suitable for 50 methoxyphenylphosphine, di(1-methylbutyl)-4- this purpose include tetrafluoroboric acid, hexafluorophos methoxyphenylphosphine, di(1,1-dimethylpropyl)-4- phoric acid, hexafluorotitanic acid, hexafluorozirconic acid, methoxyphenylphosphine, di(1,1-dimethylbutyl)-4- Sulphonic acids, for example tri-fluoromethanesulphonic methoxyphenylphosphine di-(tert-butyl)-2,4- acid, methaneSulphonic acid, toluenesulphonic acid and ben dimethoxyphenylphosphine, di(1-methylbutyl)-2,4- Zenesulphonic acid, preference is given to tetrafluoroboric 55 dimethoxyphenylphosphine, di(1,1-dimethylpropyl)-2,4- acid, hexafluorophosphoric acid, hexafluorotitanic acid and dimethoxyphenylphosphine, di(1,1-dimethylbutyl)-2,4- hexafluorozirconic acid, and even greater preference is given dimethoxyphenylphosphine, di-(tert-butyl)-2,4,6- to tetrafluoroboric acid and hexafluorophosphoric acid. trimethoxyphenylphosphine, di(1-methylbutyl)-2,4,6- The acids specified can also each be used in the form of trimethoxyphenylphosphine, di(1,1-dimethylpropyl)-2,4,6- aqueous solutions. 60 trimethoxyphenylphosphine, di(1,1-dimethylbutyl)-2,4,6- An aqueous solution of tetrafluoroboric acid is especially tri-methoxyphenylphosphine, di-(tert-butyl)-2- suitable. The solid may be isolated and purified. Subse methylphenylphosphine, di(1-methyl-butyl)-2- quently, the free phosphine may be obtained by reextraction methylphenylphosphine, di(1,1-dimethylpropyl)-2- into an organic phase after neutralization of the acid with base methylphenylphosphine, di(1,1-dimethylbutyl)-2- and optionally further purified by distillation or crystalliza- 65 methylphenylphosphine, di(tert-butyl)-4- tion or the phosphonium salt may be stored or used for further methylphenylphosphine, di(1-methylbutyl)-4- reactions. methylphenylphosphine, di(1,1-dimethylpropyl)-4- US 7,847,126 B2 11 12 methylphenylphosphine, di(1,1-dimethylbutyl)-4-meth ylpropyl)-5-acenaphthylphosphine, di(1,1-dimethylbutyl)-5- ylphenyl-phosphine, di-(tert-butyl)-2,4-dimethylphe acenaphthylphosphine, di-(tert-butyl)-9-fluorenylphosphine, nylphosphine, di(1-methylbutyl)-2,4-dimethylphenylphos di(1-methylbutyl)-9-fluorenylphosphine, di(1,1-dimethyl phine, di(1,1-dimethylpropyl)-2,4- propyl)-9-fluorenylphosphine, di(1,1-dimethylbutyl)-9-fluo , di(1,1-dimethylbutyl)-2,4- renylphosphine, di-(tert-butyl)-9-anthracenylphosphine, dimethylphenylphosphine, di-(tert-butyl)-2,4,6-trimethyl di(1-methylbutyl)-9-anthracenylphosphine, di(1,1-dimethyl phenylphosphine, di(1-methylbutyl)-2,4,6- propyl)-9-anthracenylphosphine, di(1,1-dimethylbutyl)-9- trimethylphenylphosphine, di(1,1-dimethylpropyl)-2,4,6- anthracenylphosphine, di-(tert-butyl)-9-phenanthrylphos trimethylphenylphosphine, di(1,1-dimethylbutyl)-2,4,6-tri phine, di(1-methylbutyl)-9-phenanthrylphosphine, di(1,1- methyl-phenylphosphine, di-(tert-butyl) 10 dimethylpropyl)-9-phenanthrylphosphine, di(1,1- pentafluorophenylphosphine, di(1-methylbutyl) dimethylbutyl)-9-phenanthrylphosphine, di-(tert-butyl)-1- pentafluorophenylphosphine, di(1,1-dimethylpropyl) pyrenylphosphine, di(1-methylbutyl)-1-pyrenylphosphine, pentafluorophenylphosphine, di(1,1-dimethylbutyl) di (1,1-dimethylpropyl)-1-pyrenylphosphine, di(1,1-dimeth pentafluorophenylphosphine, di-(tert-butyl)-2,4- ylbutyl)-1-pyrenylphosphine, 1,2-bis(di-tert-butylphos difluorophenylphosphine, di(1-methylbutyl)-2,4- 15 phino)benzene, 1.2-, 1.2-bis(di-1-methylbutyl-phosphino) difluorophenylphosphine, di(1,1-dimethylpropyl)-2,4- benzene, 1.2-bisdic1,1-dimethylpropyl)phosphinobenzene, difluorophenylphosphine, di(1,1-dimethylbutyl)-2,4- 1.2-bis(bis(1,1-dimethylbutyl)phosphinobenzene, 1,2-bis difluorophenylphosphine, di-(tert-butyl)-3,5- bis(trimethylsilyl)methylphosphino)benzene, 1,3-bis(di difluorophenylphosphine, di(1-methylbutyl)-3,5- tert-butylphosphino)benzene, 1,3-bis(bis-(trimethylsi difluorophenylphosphine, di(1,1-dimethylpropyl)-3,5- lylphosphino)benzene, 1,3-bis(di-1-methylbutylphosphino) difluorophenylphosphine, di(1,1-dimethylbutyl)-3,5- benzene, 1,3-bis-di(1,1-dimethylpropyl)phosphino difluorophenylphosphine, di(tert-butyl)-4- benzene, 1,3-bis(bis(1,1-dimethylbutyl)phosphinobenzene, fluorophenylphosphine, di(1-methylbutyl)-4- 1,3-bis-bis(trimethylsilyl)methylphosphino)benzene, 1,4- fluorophenylphosphine, di(1,1-dimethylpropyl)-4- bis(di-tert-butyl-phosphino)benzene, 1,4-bis(di-1-methylbu fluorophenylphosphine, di(1,1-dimethylbutyl)-4- 25 tylphosphino)benzene, 1,4-bisdic1,1-dimethylpropyl)phos fluorophenylphosphine, di(1,2-dimethylbutyl)-4- phinobenzene, 1,4-bis bis(1,1-dimethylbutyl)phosphino fluorophenylphosphine, di(tert-butyl)-4- benzene, 1,4-bis bis(trimethylsilyl)methylphosphino) chlorophenylphosphine, di(1-methylbutyl)-4- benzene, 1,4-bis(di-tert-butyl-phosphino)cyclohexane, 1,4- chlorophenylphosphine, di(1,1-dimethylpropyl)-4- bis(di-1-methylbutylphosphino)cyclohexane, 1,4-bisdic1,1- chlorophenylphosphine, di(1,1-dimethylbutyl)-4- 30 di-methylpropyl)phosphinocyclohexane, 1,4-bis bis(1,1- chlorophenylphosphine, di(tert-butyl)-4- dimethylbutyl)phosphino-cyclohexane, 1,4-bisbis bromophenylphosphine, di (1-methylbutyl)-4- (trimethylsilyl)methylphosphino)cyclohexane, 1,1'-bis(di bromophenylphosphine, di(1,1-dimethylpropyl)-4- tert-butylphosphino) , 1,1'-bis(di-1- bromophenylphosphine, di(1,1-dimethylbutyl)-4- methylbutylphosphino) ferrocene, 1,1'-bisdic1,1- bromophenylphosphine, di(tert-butyl)-4-(tert-butyl) 35 dimethylpropyl)phosphinoferrocene, 1,1'-bisbis phenylphosphine, di(1-methylbutyl)-4-(tert-butyl) (trimethylsilyl)methylphosphino) ferrocene, 1,2-bis(di-tert phenylphosphine, di(1,1-dimethylpropyl)-4-(tert-butyl) butylphosphino) ferrocene, 1.2-bis(di-1- phenylphosphine, di(1,1-dimethylbutyl)-4-(tert-butyl) methylbutylphosphino) ferrocene, 1.2-bisdic1,1- phenylphosphine, bis(trimethylsilyl)-4-(tert-butyl) dimethylpropyl)phosphinoferrocene, 1.2-bis bis(1,1- phenylphosphine, di(tert-butyl)-2,4,6-trictert-butyl) 40 dimethylbutyl)phosphinoferrocene, 1.2-bisbis phenylphosphine, di(1-methylbutyl)-2,4,6-trictert-butyl) (trimethylsilyl)methylphosphino) ferrocene, tri-tert phenylphosphine, di(1,1-dimethylpropyl)-2,4,6-tri(tert butylphosphine, trineopentylphosphine, tris(trimethylsilyl) butyl)phenylphosphine, di(1,1-dimethylbutyl)-2,4,6-trictert phosphine, tri(1-methylbutyl)phosphine, tri(1-ethylpropyl) butyl)phenylphosphine, di-(tert-butyl)-4- phosphine, tri(1,1-dimethylpropyl)phosphine, tris(1.2- trifluoromethylphenylphosphine, di(1-methylbutyl)-4- 45 dimethylpropyl)phosphine, tri(1-methylpentyl)phosphine, trifluoro-methylphenylphosphine di(1,1-dimethylpropyl)-4- tris(1,1-dimethylbutyl)phosphine, tris(1,2-dimethylbutyl) trifluoromethylphenylphosphine, di(1,1-dimethylbutyl)-4- phosphine, tris(1,3-dimethylbutyl)phosphine, tri(1-ethylbu trifluoromethylphenylphosphine, di-(tert-butyl)-3,5-bis tyl)phosphine, tris(1,1,2-trimethylpropyl)phosphine, tris(1, (trifluoromethyl)phenylphosphine, di(1-methylbutyl)-3,5- 2.2-trimethylpropyl)phosphine, tri(1-ethyl-1-methylpropyl) bis(trifluoromethyl)phenylphosphine, di(1,1- 50 phosphine and tris(trimethylsilyl)methylphosphine, and dimethylpropyl)-3,5-bis(trifluoromethyl)phenylphosphine, even greater preference is given to tri(tert-butyl)phosphine, di(1,1-dimethylbutyl)-3,5-bis(trifluoromethyl)phenylphos di-tert-butylphosphine and trineopentylphosphine. The pro phine, di-(tert-butyl)-2-biphenylphosphine, di(1-methylbu cess according to the invention is also suitable in particular for tyl)-2-biphenylphosphine, di(1,1-dimethylpropyl)-2-biphe preparing di(tert-butyl)phenylphosphonium tetrafluorobo nylphosphine, di(1,1-dimethylbutyl)-2-biphenylphosphine, 55 rate, di(tert-butyl)phenylphosphonium hexafluorophosphate, di(1,2-dimethylbutyl)-2-biphenylphosphine, bis(trimethylsi di(tert-butyl)phenylphosphonium hydrogenhexafluorozir lyl)-2-biphenylphosphine, di-(tert-butyl)-3-biphenylphos conate and di(tert-butyl)phenylphosphonium hydrogen phine, di(1-methylbutyl)-3-biphenylphosphine, di(1,1-dim hexafluorotitanate. The phosphonium salts mentioned are ethylpropyl)-3-biphenylphosphine, di(1,1-dimethyl-butyl)- hitherto unknown and, owing to their outstanding storage 3-biphenylphosphine, di-(tert-butyl)-1-naphthylphosphine, 60 stability and the low oxidation sensitivity, they are particu di(1-methylbutyl)-1-naphthylphosphine, di(1,1-dimethyl larly Suitable for use in catalytic processes, in which case the propyl)-1-naphthylphosphine, di(1,1-dimethylbutyl)-1- free phosphines are released by adding a base. The phospho naphthylphosphine, di-(tert-butyl)-2-naphthylphosphine, nium salts mentioned are therefore likewise encompassed by di(1-methylbutyl)-2-naphthylphosphine, di(1,1-dimethyl the invention. propyl)-2-naphthylphosphine, di(1,1-dimethylbutyl)-2- 65 The phosphines which can be prepared according to the naphthylphosphine, di-(tert-butyl)-5-acenaphthylphosphine, invention are suitable for use as ligands in catalytic reactions, di(1-methylbutyl)-5-acenaphthylphosphine, di(1,1-dimeth in particular in homogeneously transition metal-catalyzed US 7,847,126 B2 13 14 reactions, for example C-C coupling reactions, C-N cou tion, while the reactant reacts predominantly to form the pling reactions, C-O coupling reactions, C S coupling undesired 1,2-di(tert-butyl)-1,2-diphenylphosphine. reactions, olefin hydrogenations, olefin hydroformylations, C. C double bond isomerizations, hydrosilylations or ally Example 2 lalkylations. They can also be used for metal-free catalytic reactions, for example the oligomerization of isocyanates. Non Inventive The phosphines which can be prepared according to the Attempt to Prepare di(tert-butyl)phenylphosphine without invention are very particularly suitable for catalytic C C Catalyst in Ether: coupling reactions such as the coupling of halogen com 10 In a reaction vessel, 0.4 ml of dichlorophenylphosphine pounds with organomagnesium, organotin, organozinc or and 3 ml of diethyl ether are initially charged. tert-Butylmag organoboron compounds, olefins or alkines, and also for nesium chloride in diethyl ether is then slowly added drop C N linkages such as the arylamination, C-Slinkages and wise with gentle cooling and then stirred at room temperature. C-O linkages. After removing the precipitated solid, the course of the reac 15 tion is followed by recording a 'P NMR spectrum. The The corresponding phosphonium salts may also advanta course of the reaction is illustrated in Table 1. geously be used in a similar manner to the phosphines when operation is effected with the addition of a base. TABLE 2 This is especially true for di(tert-butyl)phenylphospho Reaction Mol% of Mol% of Mol% of nium tetrafluoroborate, di(tert-butyl)phenylphosphonium timeh CIPPh(tert-butyl) PPh(t-butyl)), PPh(tert-butyl), hexafluorophosphate, di(tert-butyl)phenyl-phosphonium 1 76 18 hydrogen hexafluorozirconate and di(tert-butyl)phenylphos 5 48 41 1.5 phonium hydrogen hexafluorotitanate. 25 12 70 2.2 The advantage of the process according to the invention 25 lies in the simple operation thereof (performability), the high From Table 2, it can be seen that the desired product di(tert yields and excellent selectivity for tertiary phosphines. The butyl)phenylphosphine is only formed in a very Small propor process may also be carried out in aliphatic and aromatic tion, while the reactant reacts predominantly to form the Solvents, which is advantageous for an industrial application. undesired 1,2-di(tert-butyl)-1,2-diphenylphosphine. 30 In addition, the reaction Succeeds at temperatures which can Example 3 be attained without considerable cost and inconvenience within the scope of an industrial reaction. The process accord Inventive Synthesis of di(tert-butyl)phenylphosphine: ing to the invention is also notable in that it permits excellent 5.1 g of copper(I) iodide and 4.6 g of lithium bromide are yields and selectivity with Small amounts of catalyst. 35 weighed into a round-bottomed flask equipped with a reflux These and other aspects of the invention are further illus condenser, thermometer, stirrer and dropping funnel and put trated by the following non-limiting examples. under a protective gas atmosphere. 75 ml of hexane are then added, then 36.2 ml of dichlorophenylphosphine are added EXAMPLES dropwise. Another 110 ml of hexane are then added and 40 stirred at room temperature for half an hour. The mixture is then cooled to -20° C. and 400 ml of a 2 M tert-butyl Example 1 magnesium chloride Solution in diethyl ether are then added dropwise at Such a rate that no noticeable temperature rise Non Inventive occurs. Stirring is then continued at this temperature for one 45 hour, then the mixture is slowly brought to room temperature Attempt to Prepare di(tert-butyl)phenylphosphine without and stirred for a further two hours. Hydrolysis is then effected using 110 ml of ammonium chloride solution, then the phases Catalyst in Hexane: are separated and the organic phase is washed three times In a reaction vessel, 0.4 ml of dichlorophenylphosphine with conc. ammonia Solution, then once with water. The and 3 ml of hexane are initially charged. tert-Butylmagne 50 organic phase is then dried over MgSO and freed of solvent. sium chloride in diethyl ether is then slowly added dropwise The liquid residue is distilled and delivers 41.8 g (71% of with gentle cooling and then stirred at room temperature. theory) of the desired product in a purity of >99.4%. After removing the precipitated solid, the course of the reac tion is followed by recording a 'P NMR spectrum. The Examples 4 to 10 course of the reaction is illustrated in Table 1. 55 Dependence of the Reaction. Upon the Catalyst Concentra TABLE 1. tion: In a round-bottomed flask equipped with a stirrer, copper Reaction Mol% of Mol% of Mol% of (I) iodide and lithium bromide are weighed in, then put under timeh CIPPh(tert-butyl) (PPh(t-butyl), PPh(tert-butyl), 60 protective gas, and admixed with hexane solvent and dichlo 1 83 14 1.3 rophenylphosphine. The 2M tert-butylmagnesium chloride 49 41 1.3 solution (in diethyl ether) is then slowly added dropwise at 25 15 71 2.1 room temperature. Stirring is then continued for 30 minutes and the yield of the tertiary phosphine is determined by 65 recording a 'P NMR spectrum. From Table 1, it can be seen that the desired product di(tert The results with variation of the catalyst concentration are butyl)phenylphosphine is only formed in a very Small propor presented in Table 3. US 7,847,126 B2 15

TABLE 3 Grignard Cl2PPh solution Hexane Cu(I)I LiBr Cu content Reaction Yield Example ml ml ml mg mg mol % time min (%) 4 O.3 3.31 4.5 42.1 38.4 10 30 94.6 5 O6 6.63 9 42.1 38.4 5 30 94.5 6 1.2 13.3 18 33.7 30.7 2 30 91 7 3.0 33.2 44 42.1 38.4 1 30 92.3 8 4.5 49.7 67 31.6 28.8 O.S 210 61 9 2.71 3O.O 26 41.12 34.7 1 60 88 10 4.07 45 59 31.02 26.0 O.S 120 90 'based on the phosphorus content 'using copper(I) bromide-dimethylsulphide complex 15 Examples 11 to 17 TABLE 5 Dependence of the Reaction. Upon the Temperature: CIPPh Grignard Solvent Cu(I) I LiBir Yield In a reaction vessel equipped with a stirrer, copper(I) iodide Example ml solution ml) (3 ml) mg mg 9/o and lithium bromide are weighed in, then put under protective 18 O.204 2.25 hexane 29 26 98.7 gas, and admixed with hexane solvent and dichlorophe 19 O.204 2.25 toluene 29 26 93.1 nylphosphine. The 2 M tert-butylmagnesium chloride solu 2O O.204 2.25 dioxane 29 26 91.7 tion (in diethyl ether) is then added dropwise with stirring at Examples 21 to 24 the selected temperature at such a rate that there is no distinct 25 Dependence of the Reaction. Upon the Temperature: increase in the reaction temperature (generally over the course of 20 min). The heating bath is then removed and In a round-bottomed flask equipped with a stirrer, copper stirring is continued until the mixtures have attained room (I) iodide and lithium bromide are weighed in, then put under temperature once more. Stirring is then continued for a fur protective gas, and admixed with hexane solvent (26 ml) and ther 1.5 hours and the yield of the tertiary phosphine is deter dichlorophenylphosphine. 30 ml of 2 Mtert-butylmagnesium mined by recording a 'P NMR spectrum. 30 chloride solution (in diethyl ether) are then added dropwise The results with variation of the reaction temperature are with stirring at the selected temperature at such a rate that presented in Table 4. there is no noticeable temperature rise. Stirring is then con

TABLE 4 Grignard Cl2PPh solution Hexane Cu(I)I LiBr Cu content Temperature Yield Example ml ml ml mg mg mol % C. %

11 0.275 3.0 4 38.6 35.2 10 -40 95.6 12 0.275 3.0 4 38.6 35.2 10 -20 95.8 13 0.275 3.0 4 38.6 35.2 10 -10 94.8 14 0.275 3.0 4 38.6 35.2 10 O 94.9 15 1.35 14.9 2O 189.S 172.8 10 50 94.3 16 2.71 30 26 O 34.7 1 40 6.0 17 2.71 30 26 38.1 34.7 1 40 85.9

based on the phosphorus content 50 Examples 18 to 20 tinued for 30 minutes and the yield of the tertiary phosphine is determined by recording a 'P NMR spectrum. Use of Different Solvents: The results with variation of the temperature are presented in Table 6. 55 In a reaction vessel equipped with a stirrer, copper(I) iodide and lithium bromide are weighed in, then put under protective TABLE 6 gas, and admixed with solvent and dichlorophenylphosphine. The 2M tert-butylmagnesium chloride solution (in diethyl Cu Temper 60 Exam- ClPPh Cu(I)BrMeS content LiBr ature Yield ether) is then added dropwise with stirring at room tempera ple ml ng mol % mg C. 9%) ture at Such a rate that there remains no possibility of exces 21 2.71 29 1 34.7 -40 93.2 sive heating. Stirring is then continued for 30 minutes and the 22 2.71 29 1 34.7 -20 94.3 yield of the tertiary phosphine is determined by recording a 23 2.71 29 1 34.7 O 95.0 24 2.71 29 1 34.7 40 90.4 'P NMR spectrum. 65 The results with variation of the solvent are presented in based on the phosphorus content Table 5. US 7,847,126 B2 17 18 Example 25 Example 28 Synthesis of tri(tert-butyl)phosphine: Synthesis of di(tert-butyl)phosphonium hexafluorophos 1.09 g of copper(I) iodide and 1.00g of lithium bromide are phate: weighed into a flask equipped with a thermometer, reflux Similar to Example 27, except that, for workup, the mix condenser and dropping funnel and put under protective gas. ture was admixed with 19 ml of degassed 65% hexafluoro 55 ml of hexane, and then 5 ml of are phosphoric acid which had been diluted to a concentration of subsequently added and flushing is effected using a further 55 2 M. The mixture is then stirred vigorously for approx. 15 ml of hexane. The mixture is then cooled to -20° C. and 115 min. Filtration with suction is then effected and the filter cake ml of 2 M tert-butylmagnesium chloride solution (in diethyl 10 is washed with a little cold water. The residue is dried under ether) are slowly added dropwise. Stirring is then continued at reduced pressure to constant weight. Yield: 8.6 g (79% of -20°C. for 1 hour and room temperature for 3 hours. theory) purity >99%. For workup, hydrolysis is effected using 70 ml of sat. H NMR (CDC1, ppm): 7.9 (m, broad); 7.81 (t): 7.69 (2H, NHCl solution and the organic phase is then removed. This td); 6.807 (d. 483 Hz); 1.53 (d. 17 Hz); is washed twice with 30 ml each time of conc. ammonia 15 'P NMR (CDC1, ppm): 45.35 (s): -143.63 (hept., 714 Solution and once with water. The organic phase is dried over Hz) magnesium Sulphate and Subsequently concentrated and dis Example 29 tilled. 10.23 g yield (88.3% of theory) of colourless liquid which solidifies in the vessel. Synthesis of di(tert-butyl)phosphonium hydrogen hexafluorotitanate: Example 26 Similar to Example 27, except that, for workup, the mix ture was admixed with 24 ml of degassed 60% hexafluoroti Synthesis of trineopentylphosphine: tanic acid. The mixture is then stirred vigorously for approx. 0.70 g of copper(1) iodide and 0.64 g of lithium bromide 25 15 min, the phases are separated and the aqueous phase is are weighed into a flask equipped with a thermometer, reflux extracted using methylene chloride. The methylene chloride condenser and dropping funnel and put under protective gas. phase is Subsequently dried over magnesium Sulphate. After 50 ml of hexane, and then 3.2 ml of phosphorus trichloride are distilling off the solvent, the product remains as a colourless subsequently added and flushing is effected using a further 25 residue which is dried under reduced pressure. Yield: 2.4 g. ml of hexane. The mixture is then cooled to -20°C. and 90 ml 30 corresponds to 21% of theory. of 1.27 M neopentylmagnesium chloride solution (in diethyl H NMR (CDC1, ppm): 7.84(m, broad); 7.73 (t, broad); ether) are slowly added dropwise. Stirring is then continued at 7.61 (m, broad); 6.85 (d. J=483.5 Hz); 1.46 (d. 17.2 Hz) -20°C. for 1 hour and room temperature for 3 hours. The 'P 'P NMR (CDC1, ppm): 45,11 (s) NMR shows a yield of 75.4% of tri(neopentyl)phosphine. For workup, hydrolysis is effected using 30 ml of sat. 35 Example 30 NHCl solution and the organic phase is then removed. This is washed twice with 20 ml each time of conc. ammonia Preparation of di(tert-butyl)phosphonium hydrogen Solution and once with water. The organic phase is dried over hexafluorozirconate: magnesium Sulphate and Subsequently concentrated. The Similar to Example 27, except that, for workup, the mix remaining oily residue is recrystallized twice from methanol 40 ture was admixed with 25 ml of degassed 45% hexafluorozir and yields 3.1 g (34.6% of theory) of colourless needles. conic acid. The mixture is then stirred vigorously for approx. 15 min, the phases are separated and the aqueous phase is Example 27 extracted using methylene chloride. The methylene chloride phase is Subsequently dried over magnesium Sulphate. After Synthesis of di(tert-butyl)phenylphosphonium tetrafluo 45 distilling off the solvent, the product remains as a colourless residue which is dried under reduced pressure. Yield: 3.67 g. roborate: corresponds to 29% of theory. In a round-bottomed flask, 60.6 mg of copper(I) bromide dimethyl sulphide complex and 51.2 mg of lithium bromide H NMR (CDC1, ppm): 7.82 (m, broad); 7.73 (t, broad); are initially charged under protective gas. 20 ml of hexane, 4 7.61 (dt), 6.741 (d. J=387 Hz); 1.46 ppm (d. 17.2 Hz) 50 'P NMR (CDC1, ppm): 44.979 (s) ml of dichlorophenylphosphine and another 19 ml of hexane Although the invention has been described in detail in the are subsequently added. The reaction solution is cooled to 0° foregoing for the purpose of illustration, it is to be understood C. 32.4 ml of a 2 M solution of tert-butylmagnesium chloride that such detail is solely for that purpose and that variations in ether are then slowly added dropwise. The mixture is Subsequently allowed to slowly adjust to room temperature can be made therein by those skilled in the art without depart 55 ing from the spirit and scope of the invention except as it may and is then stirred at room temperature for a further two hours. be limited by the claims. For workup, the mixture is cautiously admixed with 75 ml of What is claimed is: degassed 2 M HBF. Another 5 ml of 8 M HBF are then 1. A phosphonium salt selected from the group consisting additionally added and stirred for 15 min. Filtration with of di(tert-butyl)phenylphosphonium tetrafluoroborate, suction is then effected and the filter cake is washed with a 60 di(tert-butyl)phenylphosphonium hexafluorophosphate, little cold water. The residue is dried under reduced pressure di(tert-butyl)phenylphosphonium hydrogen hexafluorozir to constant weight. Yield: 7.9 g (86% of theory) purity >99%. conate and di(tert-butyl)phenylphosphonium hydrogen H NMR (CDC1, ppm): 7.9 (m, broad); 7.80(t); 7.69 (2H, hexafluorotitanate. td); 6.92 (d. 485 Hz); 1.53 (d. 17 Hz.); 'P NMR (CDC1, ppm); 44.93 (s)