PHOSPHORAMIDITE DERIVATIVES IN THE HYDROFORMYLATION OF OLEFIN-CONTAINING MIXTURES

Abstract

The invention relates to: a) phosphoramidites of formula (I); b) transition-metal-containing compounds of the formula Me(acac)(CO)L, wherein L is selected from formula (I); c) catalytically active compositions in hydroformylation that have the compounds mentioned under a) and b); d) a method for the hydroformylation of unsaturated compounds by using the catalytically active composition mentioned under c); and e) a multi-phase reaction mixture, containing unsaturated compounds, a gas mixture, which comprises carbon monoxide and hydrogen, aldehydes, and the catalytically active composition described under c).

Claims

1. Phosphoramidites, of the formulae (I) ##STR00031## where Q is a divalent substituted or unsubstituted aromatic radical; where R.sup.1 is selected from alkyl, substituted or unsubstituted cycloalkyl and aryl radicals; where R.sup.2 is selected from alkyl, substituted or unsubstituted cycloalkyl and aryl radicals, but R.sup.1 and R.sup.2 are not i-propyl radicals, or R.sup.1 and R.sup.2 together with N form a heterocyclic structure.

2. Phosphoramidites according to claim 1, where Q is selected from substituted or unsubstituted 1,1-biphenyl, 1,1-binaphthyl and ortho-phenyl radicals.

3. Phosphoramidites according to claim 2, where Q is selected from substituted or unsubstituted 1,1-biphenyl radicals.

4. Phosphoramidites according to claim 3, where R.sup.1 is selected from C.sub.1-C.sub.5-alkyl, substituted or unsubstituted cycloalkyl and aryl radicals; R.sup.2 is selected from C.sub.1-C.sub.5-alkyl, substituted or unsubstituted cycloalkyl and aryl radicals, but R.sup.1 and R.sup.2 are not i-propyl radicals, or R.sup.1 and R.sup.2 together with N form a heterocyclic structure via alkylene groups.

5. Phosphoramidites according to claim 4, where R.sup.1 is selected from C.sub.1-C.sub.5-alkyl, C.sub.4-C.sub.6-cycloalkyl and phenyl radicals; R.sup.2 is selected from C.sub.1-C.sub.5-alkyl, C.sub.4-C.sub.6-cycloalkyl and phenyl radicals, but R.sup.1 and R.sup.2 are not i-propyl radicals, or R.sup.1 and R.sup.2 together with N form a heterocyclic structure via alkylene groups.

6. Phosphoramidites according to claim 5, where the compounds of the formula (I) are selected from: ##STR00032##

7. Transition metal compounds of the formula Me(acac)(CO)L with Me=transition metal, where L is selected from: ##STR00033## where Q is a divalent substituted or unsubstituted aromatic radical; where R.sup.1 is selected from alkyl, substituted or unsubstituted cycloalkyl and aryl radicals; R.sup.2 is selected from alkyl, substituted or unsubstituted cycloalkyl and aryl radicals, but R.sup.1 and R.sup.2 are not i-propyl radicals, or R.sup.1 and R.sup.2 together with N form a heterocyclic structure.

8. Transition metal compounds according to claim 7, where Q is selected from substituted or unsubstituted 1,1-biphenyl, 1,1-binaphthyl and ortho-phenyl radicals.

9. Transition metal compounds according to claim 8, where Q is selected from substituted or unsubstituted 1,1-biphenyl radicals.

10. Transition metal compounds according to claim 9, where R.sup.1 is selected from C.sub.1-C.sub.5-alkyl, substituted or unsubstituted cycloalkyl and aryl radicals; R.sup.2 is selected from C.sub.1-C.sub.5-alkyl, substituted or unsubstituted cycloalkyl and aryl radicals, but R.sup.1 and R.sup.2 are not i-propyl radicals, or R.sup.1 and R.sup.2 together with N form a heterocyclic structure via alkylene groups.

11. Transition metal compounds according to claim 10, where R.sup.1 is selected from C.sub.1-C.sub.5-alkyl, C.sub.4-C.sub.6-cycloalkyl and phenyl radicals; R.sup.2 is selected from C.sub.1-C.sub.5-alkyl, C.sub.4-C.sub.6-cycloalkyl and phenyl radicals, but R.sup.1 and R.sup.2 are not i-propyl radicals, or R.sup.1 and R.sup.2 together with N form a heterocyclic structure via alkylene groups.

12. Transition metal compounds of the formula Me(acac)(CO)L with Me=transition metal according to claim 11, where L is selected from: ##STR00034##

13. Transition metal compounds of the formula Me(acac)(CO)L with Me=transition metal according to claim 12, where Me is selected from rhodium, iridium, ruthenium, cobalt.

14. Transition metal compounds according to claim 13, where the transition metal is rhodium.

15. Catalytically active compositions in the hydroformylation comprising: a) transition metal compounds according to claims 7-14; b) free ligands according to claims 1-6; c) solvents.

16. Use of a catalytically active composition according to claim 15 in a process for hydroformylating unsaturated compounds.

17. Process for hydroformylating unsaturated compounds using a catalytically active composition according to claim 15, where the unsaturated compounds are selected from: hydrocarbon mixtures from steamcracking plants; hydrocarbon mixtures from catalytically operated cracking plants; hydrocarbon mixtures from oligomerization processes; hydrocarbon mixtures comprising polyunsaturated compounds; olefin-containing mixtures including olefins having up to 30 carbon atoms.

18. Process according to claim 17, wherein, in a first process step, phosphoramidites according to claims 1-6 are initially charged as ligands in at least one reaction zone, and reacted with a precursor of the transition metal to give a transition metal compound according to claims 7-14 and finally, after adding free ligands according to claims 1-6, and also solvents and a carbon monoxide- and hydrogen-containing gas mixture, to give a catalytically active composition according to claim 15; in a subsequent step, the unsaturated compounds are added under the reaction conditions to form a polyphasic reaction mixture; after the end of the reaction, the reaction mixture is separated into aldehydes, alcohols, high boilers, ligands, degradation products of the catalytically active composition.

19. Polyphasic reaction mixture comprising: unsaturated compounds, a gas mixture including carbon monoxide, hydrogen; aldehydes, catalytically active compositions according to claim 15.

Description

EXAMPLES

[0111] General Working Methods

[0112] All the preparations which follow were conducted with standard Schlenk technology under protective gas. The solvents were dried over suitable desiccants before use (Purification of Laboratory Chemicals, W. L. F. Armarego (Author), Christina Chai (Author), Butterworth Heinemann (Elsevier). 6th edition, Oxford 2009).

[0113] Phosphorus trichloride (Aldrich) was distilled under argon before use. All preparative operations were effected in baked-out vessels. The products were characterized by means of NMR spectroscopy. Chemical shifts are reported in ppm. The .sup.31P NMR signals were referenced according to: SR.sub.31PSR.sub.1H*(BF.sub.31P/BF.sub.1H)SR.sub.1H*0.4048. (Robin K. Harris, Edwin D. Becker, Sonia M. Cabral de Menezes, Robin Goodfellow, and Pierre Granger, Pure Appl. Chem., 2001, 73, 1795-1818; Robin K. Harris, Edwin D. Becker, Sonia M. Cabral de Menezes, Pierre Granger, Roy E. Hoffman and Kurt W. Zilm, Pure Appl. Chem., 2008, 80, 59-84).

[0114] The recording of nuclear resonance spectra was effected on Bruker Avance 300 or Bruker Avance 400, gas chromatography analysis on Agilent GC 7890A, elemental analysis on Leco TruSpec CHNS and Varian ICP-OES 715, and ESI-TOF mass spectrometry on Thermo Electron Finnigan MAT 95-XP and Agilent 6890 N/5973 instruments,

Example 1

[0115] General Synthesis Method.

##STR00019##

[0116] To a stirred solution of the chlorophosphite A (4 mmol) (preparation according to US 20080188686 A1) in toluene (15 ml) were added Et.sub.3N (8 mmol) and the appropriate amine (4.8 mmol). The solution was stirred at room temperature. The progress of the reaction was monitored by means of .sup.31P NMR spectroscopy. Once the chlorophosphite had been fully converted (2-10 h), the readily evaporable liquids were distilled off under reduced pressure. Subsequently, dried toluene (15 ml) was again added. The resultant suspension was filtered through a layer of neutral alumina (about 3 cm, =2 cm; Schlenk filter, porosity 4) and then washed through with toluene (10 ml). After the solution had been concentrated, the residue was dried under reduced pressure at 45-50 C. for 3 h. If necessary, the product can be purified by recrystallization.

Example 2

N-(2,4,8,10-Tetra-tert-butyldibenz[d,f]{1,3,2}dioxaphosphepin-6-yl)-N-methylpropylamine

[0117] ##STR00020##

[0118] (1a)

[0119] The compound was prepared analogously to the method of Example 1. Yield: 89%; white solid. .sup.1H NMR (300 MHz, CDCl.sub.3): 0.76 (br. s, 3H), 1.27 (s, 18H), 1.39-1.41 (2 overlapping signals, 18H+2H), 2.28 (br, s, 3H), 2.91 (br, s, 2H), 7.09 (d, 2H, J=2.5 Hz), 7.32 (d, 2H, J=2.5 Hz). .sup.31P NMR (121 MHz, CDCl.sub.3): 147.8 (br. s). .sup.13C NMR (75 MHz, CDCl.sub.3): 11.1 (s, CH.sub.3CH.sub.2), 21.0 (d, .sup.3J=3.7 Hz, CH.sub.3CH.sub.2), 30.9 (d, J=2.8 Hz, (CH.sub.3).sub.3C), 31.6 (s, (CH.sub.3).sub.3C), 34.6 (s, (CH.sub.3).sub.3C), 35.4 (s, (CH.sub.3).sub.3C), 51.2 (br, s, NCH.sub.2), 123.9 (s, CH.sub.Ar), 126.2 (s, CH.sub.Ar), 132.7 (d, J=3.6 Hz, C.sub.Ar), 139.7 (s, C.sub.Ar), 145.6 (s, C.sub.Ar), 147.8 (d, J=5.4 Hz, C.sub.Ar).MS (EI, 70 eV): m/z (I, %): 511 (10), 439 (39), 72 (9), 57 (100). HRMS (ESI-TOF/MS): calculated: m/z (C.sub.32H.sub.51N.sub.1O.sub.2P.sub.1, (M+H).sup.+) 512.36519; found 512.36557; calculated m/z (C.sub.32H.sub.50N.sub.1Na.sub.1O.sub.2P.sub.1, (M+Na).sup.+) 534.34714; found 534.34778. Anal. calculated for C.sub.32H.sub.50N.sub.1O.sub.2P.sub.1: C, 75.11; H, 9.85; N, 2.74; P, 6.05. Found: C, 74.64; H, 10.19; N, 2.40; P, 5.95.

[0120] The compound was prepared analogously to the method of Example 1. Yield: 98%; white solid; .sup.1H NMR (300 MHz, CDCl.sub.3): 0.72 (t, 3H, J=7.4 Hz), 1.26 (s, 18H), 1.36-1.38 (2 overlapping singlets, 20H), 2.67 (pentet, 2H, J=7.4 Hz), 2.84-3.00 (m, 1H), 7.07 (d, 2H, J=2.4 Hz), 7.32 (d, 2H, J=2.4 Hz). .sup.31P NMR (121 MHz, CDCl.sub.3): 148.0 (s). .sup.13C NMR (62 MHz, CDCl.sub.3): 11.1 (s, CH.sub.3), 26.0 (d, J=3.4 Hz, CH.sub.2), 31.2 (d, J=2.8 Hz, (CH.sub.3).sub.3C), 31.6 (s, (CH.sub.3).sub.3C), 34.6 (s, (CH.sub.3).sub.3C), 35.6 (s, (CH.sub.3).sub.3C), 42.4 (d, J=14.0 Hz, CH.sub.2), 124.0 (s, CH.sub.Ar), 126.2 (s, CH.sub.Ar), 133.1 (d, J=3.5 Hz, C.sub.Ar), 140.0 (d, J=1.8 Hz, C.sub.Ar), 145.7 (s, C.sub.Ar), 147.0 (d, J=5.2 Hz, C.sub.Ar). HRMS (EI): calculated m/z (C.sub.31H.sub.48N.sub.1O.sub.2P.sub.1) 497.34172; found 497.34214.MS (EI, 70 eV): m/z (I, %): 497 (69), 482 (100), 439 (40), 57 (46). Anal. calculated for C.sub.31H.sub.48N.sub.1O.sub.2P.sub.1: C, 74.81; H, 9.72; N, 2.81; P, 6.22. Found: C. 73.67; H, 9.65; N, 2,65; P, 6.56.

Example 3

N-(2,4,8,10-Tetra-tert-butyldibenz[d,f]{1,3,2}dioxaphosphepin-6-yl)diethylamine

[0121] ##STR00021##

[0122] (1b)

[0123] The compound was prepared analogously to the method of Example 1. Yield: 51%; white solid (recrystallized from CH.sub.3CN/toluene (10/1); .sup.1H NMR (300 MHz, CDCl.sub.3): 0.94 (br, s, 6H), 1.27 (s, 18H), 1.40 (s, 18H), 2.90 (br, s, 4H), 7.08 (d, 2H, J=2.4 Hz), 7.32 (d, 2H, J=2.5 Hz). .sup.31P NMR (121 MHz, CDCl.sub.3): 148.4 (s). .sup.13C NMR (75 MHz, CDCl.sub.3): 15.6 (br, s, CH.sub.2CH.sub.3), 31.0 (d, J=2.8 Hz, (CH.sub.3).sub.3C), 31.6 (s, (CH.sub.3).sub.3C), 34.6 (s, (CH.sub.3).sub.3C), 35.4 (s, (CH.sub.3).sub.3C), 40.7 (br, s, CH.sub.3CH.sub.2), 123.9 (s, CH.sub.Ar), 126.3 (s, CH.sub.Ar), 132.5 (d, J=3.6 Hz, C.sub.Ar), 139.7 (d, J=1.3 Hz, C.sub.Ar), 145.4 (s, C.sub.Ar), 147.8 (d, J=5.4 Hz, C.sub.Ar). HRMS (ESI-TOF/MS): calculated m/z (C.sub.32H.sub.51N.sub.1O.sub.2P.sub.1, (M+H).sup.+) 512.36519; found 512.36531; calculated m/z (C.sub.32H.sub.50N.sub.1Na.sub.1O.sub.2P.sub.1, (M+Na).sup.+) 534.34714; found 534.34781.MS (EI, 70 eV): m/z (I, %): 511 (62), 496 (35), 439 (100), 72 (28), 57 (39).

Example 4

N-(2,4,8,10-Tetra-tert-butyldibenz[d,f]{1,3,2}dioxaphosphepin-6-yl)-N-methylaniline

[0124] ##STR00022##

[0125] (1c)

[0126] The compound was prepared analogously to the method of Example 1. Yield: 34%; white solid (after recrystallizing twice from CH.sub.3CN/toluene (3/2)); .sup.1H NMR (300 MHz, CDCl.sub.3): 1.29 (s, 18H), 1.36 (s, 18H), 2.71 (s, 3H), 6.90 (t, 1H, J=7.2 Hz), 7.12 (d, 2H, J=2.4 Hz), 7.14-7.28 (m, 4H), 7.33 (d, 2H, J=2.4 Hz). .sup.31P NMR (121 MHz, CDCl.sub.3): 147.8 (br, s). .sup.13C NMR (62 MHz, CDCl.sub.3): 30.9 (d, J=2.9 Hz, (CH.sub.3).sub.3C), 31.6 (s, (CH.sub.3).sub.3C), 33.1 (br, s, NCH.sub.3), 34.6 (s, (CH.sub.3).sub.3C), 35.5 (s, (CH.sub.3).sub.3C), 119.6 (d, J=16.5 Hz, CH.sub.Ar), 122.0 (s, CH.sub.Ar), 124.2 (s, CH.sub.Ar), 126.5 (s, CH.sub.Ar), 128.9 (s, CH.sub.Ar), 132.4 (d, J=3.7 Hz, C.sub.Ar), 139.9 (d, J=1.5 Hz, C.sub.Ar), 146.1 (s, C.sub.Ar), 146.7 (s, C.sub.Ar), 147.5 (d, J=5.5 Hz, C.sub.Ar).MS (EI, 70 eV): m/z (I, %): 545 (30), 439 (100), 57 (30). Anal. calculated for C.sub.35H.sub.48N.sub.1O.sub.2P.sub.1: C, 77.03; H, 8.87; N, 2.57; P, 5.68. Found: C, 76.74; H, 9.05; N, 2.26; P, 5.76.

Example 5

N-(2,4,8,10-Tetra-tert-butyldibenz[d,f]{1,3,2}dioxaphosphepin-6-yl)piperidine

[0127] ##STR00023##

[0128] (1d)

[0129] The compound was prepared analogously to the method of Example 1. Yield: 92%; white solid. .sup.1H NMR (300 MHz, CDCl.sub.3): 1.27 (s, 18H), 1.40 (s, 18H), 1.20-1.53 (m, 6H), 2.86 (br, s, 4H), 7.08 (d, 2H, J=2.5 Hz), 7.32 (d, 2H, J=2.5 Hz). .sup.31P NMR (121 MHz, CDCl.sub.3): 144.4 (s). .sup.13C NMR (75 MHz, CDCl.sub.3): 25.0 (s, CH.sub.2), 27.4 (br, s, CH.sub.2), 31.0 (d, J=2.7 Hz, (CH.sub.3).sub.3C), 31.6 (s, (CH.sub.3).sub.3C), 34.6 (s, (CH.sub.3).sub.3C), 35.4 (s, (CH.sub.3).sub.3C), 45.8 (br, s, CH.sub.2), 124.0 (s, CH.sub.Ar), 126.2 (s, CH.sub.Ar), 132.7 (d, J=3.4 Hz, C.sub.Ar), 139.8 (d, J=1.5 Hz, C.sub.Ar), 145.5 (s, C.sub.Ar), 147.5 (d, J=5.4 Hz, C.sub.Ar). HRMS (ESI-TOF/MS): calculated m/z (C.sub.33H.sub.51N.sub.1O.sub.2P.sub.1, (M+H).sup.+) 524.36519; found 524.36557. MS (EI, 70 eV): m/z (I, %): 523 (28), 439 (12), 84 (6), 57 (12), 45 (100). Anal. calculated for C.sub.33H.sub.50N.sub.1O.sub.2P.sub.1, C, 75.68; H, 9.62; N, 2.67; P, 5.91. Found: C, 75.85; H, 9.58; N, 2.78; P, 6.12.

Example 6

[0130] General method for the synthesis of Rh(acac)(CO)L from the transition metal precursor. To a stirred solution of Rh(acac)(CO).sub.2 (1 mmol) in dried CH.sub.2Cl.sub.2 (8 ml) was added dropwise, within 40 min, a solution of the phosphoramidite (1 mmol) in dried CH.sub.2Cl.sub.2 (8 ml). The solution was stirred at room temperature for 2 h. Subsequently, the solvent was distilled off under reduced pressure and the residue was dried in vacuo for 1 h.

Example 7

Rh-Containing Complex with Ligand (1d)

[0131] The compound was synthesized analogously to the method detailed in Example 6. Yield: 96%; light grey powder. .sup.1H NMR (300 MHz, CDCl.sub.3): 1.26-1.36 (m, overlapping signals, 3H), 1.27 (s, 18H), 1.36-1.44 (m, overlapping signals, 3H), 1.48 (s, 18H), 1.89 (s, 3H), 1.98 (s, 3H), 3.16 (br, s, 4H), 5.40 (s, 1H), 7.08 (d, 2H, J=2.4 Hz), 7.37 (d, 2H, J=2.4 Hz). .sup.31P NMR (121 MHz, CDCl.sub.3): 142.39 (d, .sup.1J.sub.RhP=276.7 Hz). .sup.13C NMR (75 MHz, CDCl.sub.3): 24.8 (s, CH.sub.2), 26.4 (d, J=3.2 Hz, CH.sub.2), 27.1 (s, CH.sub.3acac), 27.5 (d, J=7.9 Hz, CH.sub.3acac), 31.4-31.5 (2 overlapping singlets, 2 (CH.sub.3).sub.3C), 34.6 (s, (CH.sub.3).sub.3C), 35.6 (s, (CH.sub.3).sub.3C), 47.7 (s, CH.sub.2), 100.6 (d, J=2.1 Hz, CH.sub.acac), 124.6 (s, CH.sub.Ar), 126.7 (s, CH.sub.Ar), 131.6 (d, J=2.4 Hz, C.sub.Ar), 140.2 (d, J=3.8 Hz, C.sub.Ar), 146.6 (s, C.sub.Ar), 146.7 (s, C.sub.Ar), 185.3 (s, CH.sub.3CO.sub.acac), 187.4 (s, CH.sub.3CO.sub.acac). HRMS (ESI-TOF/MS): calculated m/z (C.sub.39H.sub.57N.sub.1Na.sub.1O.sub.5P.sub.1Rh.sub.1, (M+Na).sup.+) 776.29216; found 776,29243. MS (EI, 70 eV): m/z (I, %): 753 (19), 725 (100), 439 (13), 84 (23), 57 (33). IR (CaF.sub.2 cuvette 0.1 mm, 0.1 M solution in toluene): 2005 cm.sup.1 (CO band).

Example 8

[0132] In one embodiment of the invention, the hydroformylation was conducted in a 200 ml autoclave equipped with pressure-retaining valve, gas flow meter, sparging stirrer and pressure pipette as reaction zone. To minimize the influence of moisture and oxygen, the toluene used as solvent was treated with sodium ketyl and distilled under argon. The mixture of the n-octenes used as substrate was heated at reflux over sodium and distilled under argon for several hours. The transition metal was added as a precursor in the form of [(acac)Rh(COD)] (acac=acetylacetonate anion; COD=1,5-cyclooctadiene), dissolved in toluene. The latter was mixed with a solution of the respective ligand in the autoclave under an argon atmosphere. The reactor was heated up under synthesis gas pressure and the unsaturated compounds, especially the olefin, the mixture of olefins, were introduced by means of a pressure-resistant pipette once the reaction temperature had been attained. In further embodiments of the process according to the invention, the unsaturated compounds to be hydroformylated were introduced into the reaction zone prior to the addition of the hydrogen- and carbon monoxide-containing gas mixture. This applies especially to unsaturated compounds present in a liquid state at room temperature and standard pressure. In these cases, there is no need to add an external solvent, the solvents being the secondary products formed internally, for example those formed in situ during the reaction from the aldol condensation of the primary aldehyde product.

[0133] The reaction was conducted at constant pressure. After the reaction time had elapsed, the autoclave was cooled to room temperature, decompressed while stirring and purged with argon. 1 ml of each reaction mixture was removed immediately after the stirrer had been switched off, diluted with 5 ml of pentane and analyzed by gas chromatography. Inventive working examples are compiled in Tables 1 and 2, in which one entry also relates to the use of the phosphite ligands known by the CAS Registry Numbers [93347-72-9], [31570-04-4]trade name Alkanox240.

Example 9

[0134]

TABLE-US-00002 TABLE 1 Hydroformylation of 1-octene.sup.a Yield Of Ligand aldehydes [%] n-Nonanal [%] TOF.sub.40 min [h.sup.1] [00024] 98 55.5 8020 [00025] 97 55.0 7940 .sup.aconditions: [Rh] = 0.01728 mmol; 40 ppm Rh; P/Rh = 5:1, 50 bar CO/H.sub.2, [1-octene] = about 94 mmol; tolune, 100 C.; 40 min.

TABLE-US-00003 TABLE 2 Hydroformylation of a mixture of n-octenes.sup.a,b Yield Selectivity Ligand Structure k.sub.obs. [min.sup.1] [%] [%] (1a) [00026] 0.199 99 17.5 (1b) [00027] 0.347 97 18.0 (1d) [00028] 0.198 98 16.0 (1c) [00029] 0.099 96 23.8 Comparative Alkanox 240 as per CAS 0.194 95 20.0 ligand Reg. No. [93347-72-9], [31570-04-4] .sup.afor conditions see Table 1; .sup.bconsisting of: 1-octene, 3%; cis + trans-2-octene, 49%; cis + trans-3-octene, 29%; cis + trans-4-octene, 16%; structurally isomeric octenes, ~3%.

[0135] The relative activities are determined by the ratio of 1st order k to k0, i.e. the k value at time 0 in the reaction (start of reaction), and describe the relative decrease in activity during the experiment duration.

[0136] The 1st order k values are obtained from a plot of (-In(1-conversion)) against time.

[0137] The hydroformylation results in Tables 1 and 2 reveal that the inventive phosphoramidites (1a) to (1d) have at least comparable results in terms of catalytic efficacymeasured as k.sub.obs. [min.sup.1]and in terms of yield and the n-selectivity with the comparative Alkanox240 ligand as per CAS Reg. No. [93347-72-9], [31570-04-4], and are even superior to the comparative ligand in some of these individual features.

Example 10

[0138] Hydrolysis Experiments.

[0139] To a 0.0175 M solution of the phosphoramidite in dried 1,4-dioxane were added 20 equivalents of distilled water. This sample was divided between two NMR tubes which had been dried under reduced pressure beforehand in a flame and which contained tri-n-octylphosphine oxide in o-xylene-D10 as external standard. For comparison, one sample was stored at room temperature, the other heated to 80-85 C. If the compound was stable over a prolonged period at this temperature, the temperature was increased to 100 C. The samples were analyzed quantitatively by means of .sup.31P NMR (manually adjusted lock signal based on CDCl.sub.3, NS=256, D1=5 sec).

[0140] As is apparent from FIG. 1, the two phosphoramidites of the formulae (1a) and (1d), which derive from a secondary amine with low steric hindrance, are many times more stable than those phosphoramidites which derive from a primary amine (VGL 1 and VGL 2 each=comparative ligand).

[0141] The inventive ligands (1a) and (1d) thus achieve the stated object because of their exceptional hydrolysis stability, as already detailed above.

##STR00030##