Process for producing hydroxymethyl-alcohols

Abstract

A process can be used for producing an organic compound A, which contains at least one primary alcoholic hydroxy group and at least one secondary alcoholic hydroxy group. The process involves reacting a compound B, which contains at least one nitrile group and at least one ketone group, with hydrogen and water in the presence of at least one homogeneous transition metal catalyst TMC 1.

Claims

1. A process for producing an organic compound A, the process comprising: reacting a compound B with hydrogen and water in the presence of at least one homogeneous transition metal catalyst TMC 1 in a single process step, wherein the organic compound A is a compound of the formula (I) ##STR00024## wherein R.sup.1 is an organic radical having from 1 to 40 carbon atoms, R.sup.2 is hydrogen or an organic radical having from 1 to 40 carbon atoms, and R.sup.3 is hydrogen or an organic radical hvying from 1 to 40 carbon atoms, or wherein R.sup.1 together with R.sup.3 or R.sup.2 together with R.sup.3, together with the atoms connecting them, form a divalent organic group having from 1 to 40 carbon atoms, and wherein x is an integer from 1 to 10; wherein the compound B is a compound of the formula (II) ##STR00025## wherein R.sup.2 is hydrogen or an organic radical having from 1 to 40 carbon atoms, R.sup.3 is hydrogen or an organic radical having from 1 to 40 carbon atoms, and R.sup.4 is an organic radical having from 1 to 40 carbon atoms, or wherein R.sup.4 together with R.sup.3 or R.sup.2 together with R.sup.3, together with the atoms connecting them, form a divalent organic group having from 1 to 40 carbon atoms, and wherein x is an integer from 1 to 10.

2. The process according to claim 1, wherein the homogeneous transition metal catalyst TMC 1 comprises a transition metal selected from the group consisting of metals of groups 8, 9 and 10 of the periodic table of the elements according to IUPAC.

3. The process according to claim 1, wherein the homogeneous transition metal catalyst TMC 1 is selected from the group consisting of [Ru(PPh.sub.3).sub.3(CO)(H)Cl], [Ru(PPh.sub.3).sub.3(CO)Cl.sub.2], [Ru(PPh.sub.3).sub.3(CO)(H).sub.2], [Ru(binap)(Cl).sub.2], [Ru(PMe.sub.3).sub.4(H).sub.2], [Ru(PEt.sub.3).sub.4(H).sub.2], [Ru(Pn-Pr.sub.3).sub.4(H).sub.2], [Ru(Pn-Bu.sub.3).sub.4(H).sub.2], [Ru(Pn-Octyl.sub.3).sub.4(H).sub.2], [Ru(Pn-Bu.sub.3).sub.4(H).sub.2], [Ru(PnOctyl.sub.3).sub.4(H).sub.2], [Ru(PPh.sub.3).sub.3(CO)(H)Cl], and [Ru(PPh.sub.3).sub.3(CO)(H).sub.2].

4. The process according to claim 1, wherein the homogenous transition metal catalyst TMC_1 is used in an amount of 0.001 mol % to 20 mol %, calculated as transition metal and based on the amount of compound B used in the process.

5. The process according to claim 1, wherein the reaction between compound B, water and hydrogen is performed at a pressure in the range from 20 to 180 bar.

6. The process according to claim 1, wherein the reaction between compound B, water and hydrogen is performed at a temperature in the range from 50° C. to 180° C.

7. The process according to claim 1, wherein the reaction between compound B, water and hydrogen is performed in the presence of at least one solvent selected from the group consisting of dioxane, tetrahydrofuran, glymes, methanol, and ethanol.

8. The process according to claim 1, wherein the homoueneous transition metal catalyst TMC 1 is recycled by removing the compound A and other volatile compounds of the reaction mixture via distillation.

Description

GENERAL

[0196] All chemicals and solvents were purchased from Sigma-Aldrich or ABCR and used without further purification. Analytical thin layer chromatography (TLC) was performed on pre-coated Macherey-Nagel POLYGRAM° SIL G/UV.sub.254 polyester sheets. Visualization was achieved using potassium permanganate stain [KMnO.sub.4 (10 g), K.sub.2CO.sub.3 (65 g), and aqueous NaOH solution (1 N, 15 mL) in water (1000 mL)] followed by heating. Column chromatography was carried out on Aldrich silica gel (60 Å, 70-230 mesh, 63-200 μm). .sup.1H and .sup.13C NMR spectra were recorded on either a Bruker Avance III 300, Bruker Avance III 400, or a Bruker Avance III 500 spectrometer at ambient temperature. Chemical shifts δ are reported in ppm relative to either the residual solvent or tetramethylsilane (TMS). The multiplicities are reported as: s=singlet, bs=broad singlet, d=doublet, t=triplet, q=quartet, m=multiplet, td=triplet of doublets, tt=triplet of triplets.

Example 1

[0197] ##STR00021##

TABLE-US-00001 Reagents MW [g/mol] equiv mmol grams (mg) 1 165.24 1 1 165.2 2 952.41 0.05 0.05 47.6

[0198] Procedure: A ca. 80 mL Parr autoclave was charged with RuHCl(CO)(PPh.sub.3).sub.3 (47.6 mg, 0.05 mmol), the nitrile (165.2 mg, 1 mmol), 1,4-dioxane (12.0 mL) and water (12.0 mL) under air. The mixture was degassed gently with argon. After closing the reaction vessel, the system was purged first with nitrogen (3×) and then with hydrogen (3×). Finally, the autoclave was pressurized with hydrogen (45 bar) and heated at 140° C. Stirred under these conditions for 22 h. Note: At this temperature the internal pressure rises up to 55 bar. Then, the reaction was allowed to cool down to rt and was depressurized carefully. To the crude was added brine (10 mL) and the organic phase was extracted with EtOAc (3×30 mL), washed with brine and dried over Na.sub.2SO.sub.4. Filtered through a short cotton pad and concentrated under vacuum. The crude was purified by flash column chromatography over SiO.sub.2 using Hexane/EtOAc/Acetone (1:1:0.1) as eluent. The product was isolated as a 3:1 mixture of diastereomers. Yellow oil (136.8 mg, 80% yield). Major isomer: .sup.1H NMR (300 MHz, CDCl.sub.3) δ3.98 (tt, J=11.4, 4.1 Hz, 1 H), 3.23 (s, 2 H), 1.81-1.72 (m, 2 H), 1.71-1.62 (m, 2 H), 1.15 (s, 2 H), 1.04 (s, 3 H), 1.03 (s, 3 H), 0.96 (s, 3 H). .sup.13C NMR (75 MHz, CDCl.sub.3) δ75.1, 65.9, 49.0, 45.9, 43.2, 37.6, 35.2, 32.5, 28.4, 23.2. Minor isomer: .sup.1H NMR (300 MHz, CDCl.sub.3) δ3.87 (tt, J=11.4, 4.1 Hz, 1 H), 3.51 (s, 2 H), 1.96-1.84 (m, 2 H), 1.52-1.44 (m, 2 H), 1.11 (s, 2 H), 1.07 (s, 3 H), 0.99 (s, 3H+3H). Note: Some of the .sup.1H NMR signals are partially overlapped with the signals of the major isomer. .sup.13C NMR (75 MHz, CDCl.sub.3) δ69.1, 65.7, 48.7, 46.2, 44.0, 37.8, 35.2, 32.3, 29.3, 28.0.

Example 2

[0199] ##STR00022##

TABLE-US-00002 Reagents MW [g/mol] equiv mmol grams (mg) 1 111.14 1 1 111.1 2 952.41 0.05 0.05 47.6

[0200] Procedure: A ca. 40 mL Premex autoclave was charged with RuHCl(CO)(PPh.sub.3).sub.3, the nitrile, 1,4-dioxane (6.0 mL) and water (6.0 mL) under air. The mixture was degassed gently with argon. After closing the reaction vessel, the system was purged first with nitrogen (3×) and then with hydrogen (3×). Finally, the autoclave was pressurized with hydrogen (45 bar) and heated at 140° C. Stirred under these conditions for 22 h. Note: At this temperature the internal pressure rises up to 55 bar. Then, the reaction was allowed to cool down to rt and was depressurized carefully. To the crude was added brine (10 mL) and the organic phase was extracted with EtOAc (3×30 mL), washed with brine and dried over Na.sub.2SO.sub.4. Filtered through a short cotton pad and concentrated under vacuum. The crude was purified by flash column chromatography over SiO.sub.2 using Hexane/EtOAc (gradient from 40% to 70%) as eluent. The product was isolated as a brown oil (47.7 mg, 40% yield).

[0201] .sup.1H NMR (400 MHz, CDCl.sub.3) δ3.85-3.77 (m, 1 H), 3.66 (t, J=6.4 Hz, 2 H), 1.66 (bs, 2 H), 1.63-1.38 (m, 6 H), 1.19 (d, J=6.2 Hz, 3 H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ68.2, 62.9, 39.0, 32.7, 23.7, 22.1.

Example 3

[0202] ##STR00023##

TABLE-US-00003 Reagents MW [g/mol] equiv mmol grams (mg) 1 151.21 1 1 151.2 2 952.41 0.05 0.05 47.6

[0203] Procedure: A ca. 40 mL Premex autoclave was charged with RuHCl(CO)(PPh.sub.3).sub.3, the nitrile, 1,4-dioxane (6.0 mL) and water (6.0 mL) under air. The mixture was degassed gently with argon. After closing the reaction vessel, the system was purged first with nitrogen (3×) and then with hydrogen (3×). Finally, the autoclave was pressurized with hydrogen (45 bar) and heated at 140° C. Stirred under these conditions for 22 h. Note: At this temperature the internal pressure rises up to 55 bar. Then, the reaction was allowed to cool down to rt and was depressurized carefully. To the crude was added brine (10 mL) and the organic phase was extracted with EtOAc (3×30 mL), washed with brine and dried over Na.sub.2SO.sub.4. Filtered through a short cotton pad and concentrated under vacuum. The crude was purified by flash column chromatography over SiO.sub.2 using Hexane/EtOAc (gradient from 70% to 100%) as eluent. The product was isolated as a 3:1 mixture of diastereomers. Yellow oil (130.0 mg, 82% yield, [95% purity based on NMR]. Major isomer: .sup.1H NMR (500 MHz, CDCl.sub.3) δ3.87 (s, J=1.7 Hz, 1 H), 3.68-3.55 (m, 2 H), 2.50 (s, 2 H), 1.80-1.71 (m, 1 H), 1.66-1.50 (m, 4 H), 1.50-1.30 (m, 6 H), 1.29-1.18 (m, 2 H). .sup.13C NMR (126 MHz, CDCl.sub.3) δ69.1, 63.0, 41.2, 33.0, 30.0, 27.9, 27.2, 25.1, 20.8. Minor isomer: The .sup.1H NMR signals are all overlaped with the exception of .sup.1H NMR (400 MHz, CDCl.sub.3) δ3.23 (td, J=9.5, 4.5 Hz, 1 H), 1.98-1.91 (m, 1 H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ74.8, 63.3, 44.8, 36.0, 30.6, 29.7, 28.4, 25.7, 25.1.