WO2014006433A2 - Process for the activation of the c-h bond of organic compounds and a reactions system serving the process - Google Patents
Process for the activation of the c-h bond of organic compounds and a reactions system serving the process Download PDFInfo
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- WO2014006433A2 WO2014006433A2 PCT/HU2013/000064 HU2013000064W WO2014006433A2 WO 2014006433 A2 WO2014006433 A2 WO 2014006433A2 HU 2013000064 W HU2013000064 W HU 2013000064W WO 2014006433 A2 WO2014006433 A2 WO 2014006433A2
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- Prior art keywords
- substituted
- bond
- reaction
- unsubstituted
- cyclic
- Prior art date
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 104
- 238000000034 method Methods 0.000 title claims abstract description 65
- 230000008569 process Effects 0.000 title claims abstract description 65
- 230000004913 activation Effects 0.000 title claims abstract description 14
- 150000002894 organic compounds Chemical class 0.000 title description 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 44
- 239000003054 catalyst Substances 0.000 claims abstract description 31
- 239000000758 substrate Substances 0.000 claims abstract description 31
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 15
- 238000011065 in-situ storage Methods 0.000 claims abstract description 12
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 claims description 85
- 229940040102 levulinic acid Drugs 0.000 claims description 39
- 125000004122 cyclic group Chemical group 0.000 claims description 28
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 claims description 13
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 13
- 229910052805 deuterium Inorganic materials 0.000 claims description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 claims description 11
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 10
- 150000001298 alcohols Chemical class 0.000 claims description 10
- 150000001336 alkenes Chemical class 0.000 claims description 10
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 9
- 150000001299 aldehydes Chemical class 0.000 claims description 8
- 150000001345 alkine derivatives Chemical class 0.000 claims description 8
- 150000001735 carboxylic acids Chemical class 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 8
- 150000002825 nitriles Chemical class 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000007789 gas Substances 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 claims description 5
- CGHIBGNXEGJPQZ-UHFFFAOYSA-N 1-hexyne Chemical compound CCCCC#C CGHIBGNXEGJPQZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 239000011903 deuterated solvents Substances 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
- 150000003003 phosphines Chemical class 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- CSCPPACGZOOCGX-WFGJKAKNSA-N deuterated acetone Substances [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 claims description 4
- 125000003010 ionic group Chemical group 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- 229960004592 isopropanol Drugs 0.000 claims 2
- 230000003213 activating effect Effects 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 4
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 239000003446 ligand Substances 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 238000010499 C–H functionalization reaction Methods 0.000 description 5
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical class OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000004696 coordination complex Chemical class 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 3
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical class OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 3
- 206010001488 Aggression Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- PNHHVOISKCAJLC-UHFFFAOYSA-N benzaldehyde;methanol Chemical class OC.O=CC1=CC=CC=C1 PNHHVOISKCAJLC-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- RAPAKVICBRKHJV-UHFFFAOYSA-N hex-1-ene;methanol Chemical class OC.CCCCC=C RAPAKVICBRKHJV-UHFFFAOYSA-N 0.000 description 2
- OVMROSRHMZSBIR-UHFFFAOYSA-N hex-1-yne;methanol Chemical class OC.CCCCC#C OVMROSRHMZSBIR-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- PYKTXHYUFLYSEC-UHFFFAOYSA-N methanol;4-oxopentanoic acid Chemical class OC.CC(=O)CCC(O)=O PYKTXHYUFLYSEC-UHFFFAOYSA-N 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- HHAVHBDPWSUKHZ-UHFFFAOYSA-N propan-2-ol;propan-2-one Chemical class CC(C)O.CC(C)=O HHAVHBDPWSUKHZ-UHFFFAOYSA-N 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 229910052594 sapphire Inorganic materials 0.000 description 2
- 239000010980 sapphire Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- JIZZISDLUZICJY-UHFFFAOYSA-N Cc(cc1)ccc1P(CCCCP(c1ccccc1)C1=CCCC=C1)c1ccccc1 Chemical compound Cc(cc1)ccc1P(CCCCP(c1ccccc1)C1=CCCC=C1)c1ccccc1 JIZZISDLUZICJY-UHFFFAOYSA-N 0.000 description 1
- 238000005361 D2 NMR spectroscopy Methods 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 238000004639 Schlenk technique Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- -1 carboxymethylene Chemical group 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- YOCUPQPZWBBYIX-UHFFFAOYSA-N copper nickel Chemical compound [Ni].[Cu] YOCUPQPZWBBYIX-UHFFFAOYSA-N 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000003345 natural gas Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
Definitions
- the invention relates to a process for the activation of the single carbon-hydrogen bond covalent (in the following: C-H bond) of organic substrate compounds, and a reaction system serving said process.
- the aim of the processes for the activation of the C-H bonds is quite often, though not always the exchange of the H atom in the C-H bond of organic compounds for deuterium (in the following: D), the so called H-D exchange.
- a catalyst is used, which enables reacting of the C-H bond within mild reaction conditions, in particular the H-D exchange.
- the process according to the invention has made possible to achieve the H-D exchange of a number of organic compounds.
- JP63198638 A Japanese publication document discloses a process for the preparation of deuterated acrylic acid or methacrylic acid by the direct exchange of the hydrogen by deuterium deriving from D 2 0 in the presence of a catalyst. The process needs less time and smaller excess of D 2 0 as compared to the state of the art, and ensures a better yield of the deuterated compounds.
- catalyst palladium-, nickel- and copper-based compounds are used for the process.
- deuterium source D 2 0 deuterated water
- the reaction is different from our invention in each substantive reactant and reaction step.
- EP0203588 A2 European publication document also discloses a process for the preparation of deuterated acrylic acid or methacrylic acid. According to the process, the hydrogen of the acrylic acid and methacrylic acid is replaced by deuterium in the presence of a catalyst.
- the catalysts used in the process include palladium-, rhutenium-, iridium-, and/or platinum-based catalysts. In one embodiment the process is carried out at a temperature between 60 and 200 °C, in dimethyl formamide or dimethyl acetamide solvent; this process also shows significant differences from the solution offered by our invention.
- WO 2004/060831 Al international publication document also discloses a process for deuteration.
- a compound according to the general formula R1-X-R2 (wherein Rl stands for - among others - an alkyl moiety; R2 stands for an alkyl, OH moiety etc.; and X stands for a carbonyl or carboxymethylene moiety) is reacted with a deuterium source in the presence of a catalyst, wherein the catalyst is selected from the group consisting of activated palladium, platinum, rhodium, nickel and cobalt.
- WO 2009/005069 Al international publication document discloses a process for the efficient deuteration of a substrate using a rhutenium (Ru) catalyst. According to the process, compounds, which possess an OH moiety, optionally an amino group, an etheric bond and/or an NH bond, are reacted with a deuterium source in the presence of a Ru-catalyst and hydrogen gas.
- Ru rhutenium
- the problem to be solved by the present invention is that the C-H activation of the organic compounds, as well as the H-D exchange reactions, which are closely related to said C-H activation, quite often require the application of aggressive reaction conditions. So far, the state of the art failed to give a process, which at the same time: a) is mild, b) may universally used for a wide circle of substrate compounds, c) is selective, d) may be proceeded in a homogenous catalytic system. In the publications or patent documents first of all heterogenic systems or the use of other transition metal catalysts have so far been reported.
- the invention relates in its first aspect to a process for the activation of the single carbon- hydrogen bond covalent (C-H bond) of organic substrate compounds, and reacting thereof, wherein the aforementioned organic substrate compound is contacted with a rhutenium complex and a hydrogen-substituting source, thus the hydrogen (H) of one or more C-H bond is replaced by a hydrogen-substituting agent through the activation of one or more C-H bond(s) by an in situ prepared metal-phosphine catalyst.
- the organic substrate used in the process is not in particular limited: as a substrate unsubstituted or substituted alcohols, preferably C 1-10 straight, branched or cyclic, optionally unsaturated alcohols, more preferably methanol, ethanol, 2-propanol, unsubstituted or substituted ketones, preferably C O straight, branched or cyclic, optionally unsaturated ketones, more preferably acetone, unsubstituted or substituted aldehydes, preferably C MO straight, branched or cyclic, optionally unsaturated aldehydes, more preferably benzaldehyde, unsubstituted or substituted carboxylic acids es carboxylic acid esthers, preferably C 1-10 straight, branched or cyclic, optionally unsaturated carboxylic acids, more preferably levulinic acid, butyric acid, unsubstituted or substituted alkenes, preferably C 1-10 straight, branched or cyclic, optionally
- the phosphin used according to the process is not in particular limited; as metal complex (M) rhutenium (Ru), preferably a complex containing +2 oxidation number Ru, preferably [Ru(H 2 0) 6 ](tos)2 complex; as a phosphine (L) unsubstituted or substituted phosphine, preferably a monodental phosphine or bidental phosphine substituted in the rings by an alkyl-, aryl- or ionic group, or the water soluble, preferably sulphonated analogues thereof, preferably dppm, dpp, dppp, dppb, more preferably dppp is used, thus in situ a catalyst according to the formula M(L) n is prepared, wherein M and L is as defined above, and n is 1- 4; preferably a catalyst according to the formula [Ru(H 2 0)2(P-P)2](tos) 2 is prepared, where
- the hydrogen-substituting agent used in the present process is not in particular limited.
- the reaction is accomplished within mild reaction conditions, preferably in the temperature range of 30 to 250 °C, more preferably 50 to 150 °C, most preferably at 60 to 80 °C, and in the pressure range of 0.5-1200 bar, preferably in the pressure range of 0.5 to 600, more preferably under 1 to 100 bar, most preferably under 1 to 10 bar pressure, in the time range of 1 to 30, preferably 6 to 16 hours, and activation and reaction of the C-H bond is performed selectively.
- the position of the hydrogen of C-H as compared to the functional group of the subtrate is not in particular limited, preferably the exchange of the C-H-hydrogen of the -CH 2 - groups positioned in a-position from the functional groups of the substrates by a hydrogen- substituting agent is achieved.
- the invention relates to a process for the deuteration of the carbon- hydrogen single, covalent bond (C-H bond) of organic substrate compounds, said process comprising contacting an aforementioned organic substrate compound with a metal complex, a phosphine and a deuterium source, thus the deuteration of one or more C-H bond(s) by an in situ prepared metal-phosphine catalyst is effected.
- the organic substrate used in the process is not in particular limited: as a substrate unsubstituted or substituted alcohols, preferably C 1-10 straight, branched or cyclic, optionally unsaturated alcohols, more preferably methanol, ethanol, 2-propanol, unsubstituted or substituted ketones, preferably Ci.
- the phosphin used according to the deuteration process is not in particular limited; as metal complex (M) rhutenium (Ru), preferably a complex containing +2 oxidation number Ru, preferably [Ru(H 2 0)6](tos) 2 complex; as a phosphine (L) unsubstituted or substituted phosphine, preferably a monodental phosphine or bidental phosphine substituted in the rings by an alkyl-, aryl- or ionic group, or the water soluble, preferably sulphonated analogues thereof, preferably dppm, dpp, dppp, dppb, more preferably dppp is used, thus in situ a catalyst according to the formula M(L) n is prepared, wherein M and L is as defined above, and n is 1-4; preferably a catalyst according to the formula [Ru(H20)2(P-P)2](tos)2 is prepared, where
- R,; R 3 H, alkil, aril
- the deuterium source used in the process according to the invention is not in particular limited: preferably a deuterated solvent, more preferably deuterated methyl-alcohol (MeOD) or deuterated acetone, or D 2 gas, preferably D 2 gas pressurized to 100 bar is used.
- a deuterated solvent more preferably deuterated methyl-alcohol (MeOD) or deuterated acetone, or D 2 gas, preferably D 2 gas pressurized to 100 bar is used.
- the reaction is accomplished within mild reaction conditions, preferably in the temperature range of 30 to 250 °C, more preferably 50 to 150 °C, most preferably at 60 to 80 °C, and in the pressure range of 0.5-1200 bar, preferably in the pressure range of 0.5 to 600, more preferably under 1 to 100 bar, most preferably under 1 to 10 bar pressure, in the time range of 1 to 30, preferably 6 to 16 hours, and activation and reaction of the C-H bond is performed selectively.
- the position of the hydrogen of C-H as compared to the functional group of the subtrate is not in particular limited, preferably the deuteration of the -CH 2 - groups positioned in a-position from the functional groups of the substrates by a hydrogen- substituting agent is achieved.
- Example 12 The acetone-methanol H-D exchange is shown in Fig. 9 to 16.
- Example 13 The acetone H-D exchange is illustrated by Scheme 14.
- Example 14 Process for the H-D exchange of levulinic acid.
- the invention discloses the optimization of the reaction as well, said optimization includes not only the selection of the appropriate reaction conditions, but also the selection of the suitable phosphine ligand. It was therefore investigated that amongst the diphosphine ligands including 1 to 4 carbon atoms (dppm, dppe, dppp, dppb), the application of which results in the most effective transformation. It was found that the equilibrium is achieved most rapidly when dppp is selected as a phosphine.
- the invention is of excellent use in the field of hydrocarbon chemistry, where C-H activation of hydrocarbons (alkanes, alkenes), and the preparation of catalysts active in such processes gained significant interest, as these reactions open the possibility to transform synthetically the compounds found in natural gas and petrol, or the preparation of alternative energy sources.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
A process is disclosed for the activation of the single covalent carbon-hydrogen bond of organic substrate compounds, and for the reaction, in particular deuteratrion thereof within mild reaction conditions, wherein said organic substrate compound is contacted with a Rutenium-complex, a phosphine, and a source of a hydrogen-substituent, thus the hydrogen of the C-H-bond is substituted by a hydrogen-substituent through the activation of the C-H bond by an in situ prepared Ru-phosphine catalyst. A reaction system for reacting of the C-H-bond is also disclosed. The process makes possible the selective reaction of the C-H-bond.
Description
PROCESS FOR THE ACTIVATION OF THE C-H BOND OF ORGANIC COMPOUNDS AND A
REACTIONS SYSTEM SERVING THE PROCESS
The invention relates to a process for the activation of the single carbon-hydrogen bond covalent (in the following: C-H bond) of organic substrate compounds, and a reaction system serving said process. The aim of the processes for the activation of the C-H bonds is quite often, though not always the exchange of the H atom in the C-H bond of organic compounds for deuterium (in the following: D), the so called H-D exchange. For the process according to the invention a catalyst is used, which enables reacting of the C-H bond within mild reaction conditions, in particular the H-D exchange. The process according to the invention has made possible to achieve the H-D exchange of a number of organic compounds.
Description of the state of the art
A number of attempts have been made to effect to C-H activation and the corresponding H-D exchange. JP63198638 A Japanese publication document discloses a process for the preparation of deuterated acrylic acid or methacrylic acid by the direct exchange of the hydrogen by deuterium deriving from D20 in the presence of a catalyst. The process needs less time and smaller excess of D20 as compared to the state of the art, and ensures a better yield of the deuterated compounds. As catalyst palladium-, nickel- and copper-based compounds are used for the process. As deuterium source D20 (deuterated water) is used for the process, and otherwise, the reaction is different from our invention in each substantive reactant and reaction step.
EP0203588 A2 European publication document also discloses a process for the preparation of deuterated acrylic acid or methacrylic acid. According to the process, the hydrogen of the acrylic acid and methacrylic acid is replaced by deuterium in the presence of a catalyst. The catalysts used in the process include palladium-, rhutenium-, iridium-, and/or platinum-based catalysts. In one embodiment the process is carried out at a temperature between 60 and 200 °C, in dimethyl formamide or dimethyl acetamide solvent; this process also shows significant differences from the solution offered by our invention.
WO 2004/060831 Al international publication document also discloses a process for deuteration. According to the process, a compound according to the general formula R1-X-R2 (wherein Rl stands for - among others - an alkyl moiety; R2 stands for an alkyl, OH moiety etc.; and X stands for a carbonyl or carboxymethylene moiety) is reacted with a deuterium source in the presence of a catalyst, wherein the catalyst is selected from the group consisting of activated palladium, platinum, rhodium, nickel and cobalt. With the help of the above- mentioned process, the deuteration, which had to be done among agressive reaction conditions before, can be effected within neutral reaction conditions: even the compounds containing double bonds may be deuterated without the requirement of reducing the double bond.
WO 2009/005069 Al international publication document discloses a process for the efficient deuteration of a substrate using a rhutenium (Ru) catalyst. According to the process, compounds, which possess an OH moiety, optionally an amino group, an etheric bond and/or an NH bond, are reacted with a deuterium source in the presence of a Ru-catalyst and hydrogen gas.
A M. Lersch, M. Tilset, Chem. Rev., 2005, 106(6), pp 2471-2526. disclose a summarizing review of the topic of C-H activation, however, they do not anticipate the process and reaction system according to the present invention.
A G. Bhalla, L. Y. Xiang, J. Oxgaard, W. A. Goddard III, R. A. Periana, J. Am. Chem. Soc, 2005, 127 (32), 1 1372-11389. disclose the role of (acac-0,0)2Ir(R)(L) type complexes in the activation of the C-H bond. The catalytic activity of differently formed Ir-complexes is investigated in this type of reaction with a number of O-chelating ligands. Reaction kinetics measurements were made and elaborating the corresponding reaction rate equations, a number of suggestions have been given to support the mechanism of the proceeding reaction. The suggested mechanisms, key reaction steps are supported also by theoretical calculations. Both the catalysts and the ligands in the complexes, and the substrates and D-sources mentioned in the review are different from those disclosed in our invention.
A J. H. Y. Kenneth, O. A. Mironov, R. J. Nielsen, M-J. Cheng, T. Stewart, W. A. Goddard III, R. A. Periana, Organometallics, 2011, 30(19), 5088-5094. discover the catalytic features of Os-complexes formed with O-chelating ligands in relation with the CH-activation. They also suggest the possible mechanisms of the processes. In the article only the H-D exchange is disclosed as CH-activation. The mechanism is also supported by theoretical calculations. Both the catalysts and the ligands in the complexes, and the substrates and D-sources mentioned in the review are different from those disclosed in our invention.
A T. Maegawa, Y. Fujiwara, Y. Inagaki, Y. Monguchi, H. Sajiki, Adv. Synth. Catal., 2008, 350, 2215 - 2218. use Ru/C es Ir/C heterogenous catalysts in the deuteration of a number of different alcohols. Besides the used reactants being different from those disclosed in our invention, the reference does not disclose a homogenous catalytic system and the deuteration is proceeding at the carbon coupled to the functional group. A Y. Fujiwara, H. Iwata, Y. Sawama, Y. Monguchi, H. Sajiki, Chem. Commun., 2010, 46, 4977-4979. achieve the labeling of a number of sugars with deuterium through heterogenous catalysis, following the article wherein alcohols are deuterated. In the article besides Ru/C and Ir/C, the Rh C and Pd/C also appear as active catalysts in this reaction type. The mechanisms of the processes are also suggested. Besides the fact that the reactants used in the article are different from those disclosed in our invention, considering the location of the deuteration, the authors failed to achieve selective reaction: in the reaction perdeuterated derivatives are formed.
A V. M. Due, A. Fedorov, R. H. Grubbs, Organometallics, 2012, 31 (1), 39-41. use Ir-pincer type complexes for the deuteration of first of all aromatic CH bond. The authors give suggestions also for the mechanism of the process. The structure of the catalytically active intermediate product was also determined by NMR spectroscopy. The reactants used in the article are different from those disclosed in our invention.
The problem to be solved by the present invention is that the C-H activation of the organic compounds, as well as the H-D exchange reactions, which are closely related to said C-H activation, quite often require the application of aggressive reaction conditions. So far, the state of the art failed to give a process, which at the same time: a) is mild, b) may universally used for a wide circle of substrate compounds, c) is selective, d) may be proceeded in a homogenous catalytic system. In the publications or patent documents first of all heterogenic systems or the use of other transition metal catalysts have so far been reported. In all cases more aggressive reaction conditions (elevated temperature, longer reaction time, eventually higher pressure) were applied, or other substrates were used to study the C-H activation, therefore it can be concluded that objectives of the above-mentioned a) to d) points cannot be reached by them at the same time.
As a result of our research, it was surprisingly experienced that such catalysts, namely Ru(II) phosphine complexes have been "in situ" prepared, which catalyse within relatively mild reaction conditions and selectively - among others - the H/D exchange of C¾ groups, which are positioned in a different, among others alpha (a) position as compared to the functional groups of - among others - alcohols, alhedydes, ketones, alkenes, nitiles, estheres. Thus, we have resolved the above-mentioned technical problem, and completed our invention, which is disclosed in details as follows.
Detailed description of the invention
The invention relates in its first aspect to a process for the activation of the single carbon- hydrogen bond covalent (C-H bond) of organic substrate compounds, and reacting thereof, wherein the aforementioned organic substrate compound is contacted with a rhutenium complex and a hydrogen-substituting source, thus the hydrogen (H) of one or more C-H bond is replaced by a hydrogen-substituting agent through the activation of one or more C-H bond(s) by an in situ prepared metal-phosphine catalyst. The organic substrate used in the process is not in particular limited: as a substrate unsubstituted or substituted alcohols, preferably C1-10 straight, branched or cyclic, optionally unsaturated alcohols, more preferably methanol, ethanol, 2-propanol, unsubstituted or substituted ketones, preferably C O straight, branched or cyclic, optionally unsaturated ketones, more preferably acetone, unsubstituted or substituted aldehydes, preferably CMO straight, branched or cyclic, optionally unsaturated aldehydes, more preferably benzaldehyde, unsubstituted or substituted carboxylic acids es carboxylic acid esthers, preferably C1-10 straight, branched or cyclic, optionally unsaturated carboxylic acids, more preferably levulinic acid, butyric acid, unsubstituted or substituted alkenes, preferably C1-10 straight, branched or
cyclic, optionally unsaturated alkenes, more preferably hexene, unsubstituted or substituted alkynes, preferably CMO straight, branched or cyclic, optionally unsaturated alkynes, more preferably hexyne, unsubstituted or substituted nitriles, preferably Ci.10 straight, branched or cyclic, optionally unsaturated nitriles may be used.
The phosphin used according to the process is not in particular limited; as metal complex (M) rhutenium (Ru), preferably a complex containing +2 oxidation number Ru, preferably [Ru(H20)6](tos)2 complex; as a phosphine (L) unsubstituted or substituted phosphine, preferably a monodental phosphine or bidental phosphine substituted in the rings by an alkyl-, aryl- or ionic group, or the water soluble, preferably sulphonated analogues thereof, preferably dppm, dpp, dppp, dppb, more preferably dppp is used, thus in situ a catalyst according to the formula M(L)n is prepared, wherein M and L is as defined above, and n is 1- 4; preferably a catalyst according to the formula [Ru(H20)2(P-P)2](tos)2 is prepared, wherein P-P stands for dppm, dppe, dppp, dppb, preferably dppp. The preferred examples of the chelating phospines are as follows:
dppm dppe dppp dppb Although it is not our intention to restrict the in situ chelate formation to one or more theories, it is quite likely that the reaction takes place according to the following reaction scheme:
[Ru(H20)6](tos)2 + 2 P-P ► [Ru(H20)2(P-P)2](tos)2. The hydrogen-substituting agent used in the present process is not in particular limited. The reaction is accomplished within mild reaction conditions, preferably in the temperature range of 30 to 250 °C, more preferably 50 to 150 °C, most preferably at 60 to 80 °C, and in the pressure range of 0.5-1200 bar, preferably in the pressure range of 0.5 to 600, more preferably under 1 to 100 bar, most preferably under 1 to 10 bar pressure, in the time range of 1 to 30, preferably 6 to 16 hours, and activation and reaction of the C-H bond is performed selectively. Although the position of the hydrogen of C-H as compared to the functional group of the subtrate is not in particular limited, preferably the exchange of the C-H-hydrogen of the -CH2- groups positioned in a-position from the functional groups of the substrates by a hydrogen- substituting agent is achieved.
In the second aspect the invention relates to a process for the deuteration of the carbon- hydrogen single, covalent bond (C-H bond) of organic substrate compounds, said process comprising contacting an aforementioned organic substrate compound with a metal complex,
a phosphine and a deuterium source, thus the deuteration of one or more C-H bond(s) by an in situ prepared metal-phosphine catalyst is effected.
The organic substrate used in the process is not in particular limited: as a substrate unsubstituted or substituted alcohols, preferably C1-10 straight, branched or cyclic, optionally unsaturated alcohols, more preferably methanol, ethanol, 2-propanol, unsubstituted or substituted ketones, preferably Ci.10 straight, branched or cyclic, optionally unsaturated ketones, more preferably acetone, unsubstituted or substituted aldehydes, preferably C1-10 straight, branched or cyclic, optionally unsaturated aldehydes, more preferably benzaldehyde, unsubstituted or substituted carboxylic acids and carboxylic acid esthers, preferably C1-10 straight, branched or cyclic, optionally unsaturated carboxylic acids, more preferably levulinic acid, butyric acid, unsubstituted or substituted alkenes, preferably C1-10 straight, branched or cyclic, optionally unsaturated alkenes, more preferably hexene, unsubstituted or substituted alkynes, preferably Ci-10 straight, branched or cyclic, optionally unsaturated alkynes, more preferably hexyne, unsubstituted or substituted nitriles, preferably Ci-10 straight, branched or cyclic, optionally unsaturated nitriles may be used.
The phosphin used according to the deuteration process is not in particular limited; as metal complex (M) rhutenium (Ru), preferably a complex containing +2 oxidation number Ru, preferably [Ru(H20)6](tos)2 complex; as a phosphine (L) unsubstituted or substituted phosphine, preferably a monodental phosphine or bidental phosphine substituted in the rings by an alkyl-, aryl- or ionic group, or the water soluble, preferably sulphonated analogues thereof, preferably dppm, dpp, dppp, dppb, more preferably dppp is used, thus in situ a catalyst according to the formula M(L)n is prepared, wherein M and L is as defined above, and n is 1-4; preferably a catalyst according to the formula [Ru(H20)2(P-P)2](tos)2 is prepared, wherein P-P stands for dppm, dppe, dppp, dppb, preferably dppp.
The general scheme of the deuteration is illustrated below: Scheme 1: The general reaction scheme of deuteration
HC≡ C-R2
I
D
R,; R3 = H, alkil, aril
R2; R4 = alkil
The deuterium source used in the process according to the invention is not in particular limited: preferably a deuterated solvent, more preferably deuterated methyl-alcohol (MeOD) or deuterated acetone, or D2 gas, preferably D2 gas pressurized to 100 bar is used.
The reaction is accomplished within mild reaction conditions, preferably in the temperature range of 30 to 250 °C, more preferably 50 to 150 °C, most preferably at 60 to 80 °C, and in the pressure range of 0.5-1200 bar, preferably in the pressure range of 0.5 to 600, more preferably under 1 to 100 bar, most preferably under 1 to 10 bar pressure, in the time range of 1 to 30, preferably 6 to 16 hours, and activation and reaction of the C-H bond is performed selectively. Although the position of the hydrogen of C-H as compared to the functional group of the subtrate is not in particular limited, preferably the deuteration of the -CH2- groups positioned in a-position from the functional groups of the substrates by a hydrogen- substituting agent is achieved.
In the following the invention is illustrated with preparation examples, which, however, in no ways are to be construed as limitations of the present invention. The H-D exchange has been followed by NMR spectroscopy (13C NMR and 2H NMR). In the majority of the experiments a deuterated solvent (deuterated methanol, deuterated acetone) was used as deuterium source, but deuterium gas with 100 bar pressure was also used to investigate the reaction. To this high pressure sapphire NMR tube was used. The schematic figure of the sapphire NMR tube is shown in Fig. 1. The catalytic system did not contain any additives except for the catalyst and the solvents. In all systems investigated it was found that within the given, relatively mild reaction conditions the H-D exchange leads to an equilibrium in the homogenous catalytic reaction.
Typical reaction mixtures used in the studied reactions were as follows:
1. 4X10"4 mol [Ru(H20)6](tos)2, δχΐθ"4 mol diphosphine (dppm, dppe, dppp, dppb), 2xl0"3 mol substrate (benzaldehyde, levulinic acid, butyric acid, hexene, hexyne), 0,5 ml deuterated methanol;
2. 4X 10"4 mol [Ru(H20)6](tos)2, 8x10^ mol diphosphine (dppm, dppe, dppp, dppb), 0,5 ml solvent mixture (substrate:deuterated solvent=l :1)
3. δχΐθ"4 mol [Ru(H20)6](tos)2, l,6xl0"3 mol diphosphine (dppm, dppe, dppp, dppb), 2 ml solvent or solvent mixture, p(D2)=100 bar.
In all examples solid [Ru(H20)6](tos)2 was measured in the NMR tube, then two equivalents diphosphine based on the amount of Ru also in solid state was added. Within inert conditions normal and deuterated solvents were added using the Schlenk-technique, and the 60 to 80 °C temperature was ensured using a thermostate. At the testing of the temperature-dependence the measuring head of the NMR device was set to the appropriate temperature, and the measurings were immediately started.
Example 1: Deuterated methanol-acetone reaction
The reaction according to Scheme 2. was made in line with the general example.
Scheme 2: Deuterated methanol-acetone reaction
O O
D3C'0D + H r A H ► rA - w + H D c^OD(H)
3 H3C CH3 H(3.X)DXC CDXH(3.X) HXD(3.X)U
The NMR-spectrum of the reaction is shown in Fig. 2. Example 2: Deuterated acetone-2-propanol reaction
The reaction according to Scheme 3 was made in line with the general example. Scheme 3: Deuterated acetone-2-propanol reaction
The NMR-spectrum of the reaction is shown in Fig. 3. Example 3: Deuterated methanol-hexene reaction
The reaction according to Scheme 4 was made in line with the general example. Scheme 4: Deuterated methanol-hexene reaction
The NMR-spectrum of the reaction is shown in Fig. 4. Example 4: Deuterated methanol-hexyne reaction
The reaction according to Scheme 5 was made in line with the general example. Scheme 5: Deuterated methanol-hexyne reaction
The NMR-spectrum of the reaction is shown in Fig. 5.
Example 5: Deuterated methanol-benzaldehyde reaction
The reaction according to Scheme 6 was made in line with the general example.
The NMR-spectrum of the reaction is shown in Fig. 6.
Example: Deuterated methanol-levulinic acid reaction
The reaction according to Scheme 7 was made in line with the general example.
The NMR-spectrum of the reaction is shown in Fig. 7.
Example 7: Deuterated methanol-acetofenone reaction
The reaction according to Scheme 8 was made in line with the general example.
The NMR-spectrum of the reaction is shown in Fig. 8.
Example 8: Methanol reaction using 100 bar pressure of D2
The reaction according to Scheme 9 was made in line with the general example.
Scheme 9: Methanol reaction using 100 bar pressure of D2
OH 100 bar D2 .OD
HxD(3-x)C
kat.
Example 9: Ethanol reaction using 100 bar pressure of D2
The reaction according to Scheme 10 was made in line with the general example.
Scheme 10: Ethanol reaction using 100 bar pressure of D2
H2 100 bar D2 DxH(2-x)
H3C' C vOH kat H3CC¾OD
Example 10: Acetone reaction using 100 bar pressure of D2
The reaction according to Scheme 11 was made in line with the general example.
Scheme 11: Acetone reaction using 100 bar pressure of D2
° 100 bar D2 ^ °
H3C CH3 k t * H(3.X)DXC CDXH(3.X)
Example 11: Levulinic acid reaction using 100 bar pressure of D2
The reaction according to Scheme 12 was made in line with the general example.
Scheme 12: Levulinic acid reaction using 100 bar pressure of D2
Example 12: The acetone-methanol H-D exchange is shown in Fig. 9 to 16.
The levulinic acid-methylesther formation and H-D exchange is illustrated by Scheme 13.
Scheme 13: Levulinic acid-methylesther formation and H-D exchange
2 DPPP
MeOO, N R-csSben, 70"C
The reaction is shown in Fig.17-20.
Example 13: The acetone H-D exchange is illustrated by Scheme 14.
In the course of the reaction [Ru(H20)6](tos)2 + 2 dppp complex was used The reaction is illustrated in Fig. 21-22.
Example 14: Process for the H-D exchange of levulinic acid.
Scheme 15: Levulinic acid H-D exchange
The reaction is illustrated in Fig. 23-24.
Example 15: Alternative process for the H-D exchange of levulinic acid (ii).
Scheme 16: Levulinic acid H-D-exchange
The reaction is illustrated in Fig.25-26.
Example 16: Alternative process for the H-D exchange of levulinic acid (iii). Scheme 17: Levulinic acid H-D-exchange
The reaction is illustrated in Fig 27-28.
Example 17: Alternative process for the H-D exchange of levulinic acid (iv)
Scheme 18: Levulinic acid H-D-exchange
{[Ru(H
The reaction is illustrated in Fig. 29-30.
Example 18: Alternative process for the H-D exchange of levulinic acid (v) Scheme 19: Levulinic acid H-D-exchange
The reaction is illustrated in Fig. 31-32.
Example 19: Alternative process for the H-D exchange of levulinic acid (vi) Scheme 20: Levulinic acid H-D-exchange
The reaction is illustrated in Fig. 33-34.
Example 20: Alternative process for the H-D exchange of levulinic acid (vii) Scheme 21: Levulinic acid H-D-exchange
The reaction is illustrated in Fig. 35-36.
Example 21: Alternative process for the H-D exchange of levulinic acid (viii) Scheme 22: Levulinic acid H-D-exchange
The reaction is illustrated in Fig. 37.
Example 22: Alternative process for the H-D exchange of levulinic acid (ix) Scheme 23: Levulinic acid H-D-exchange
0D
The reaction is illustrated in Fig. 38.
Example 23: Alternative process for the H-D exchange of levulinic acid (x)
The reaction is illustrated in Fig. 39-40.
Example 24: Alternative process for the H-D exchange of levulinic acid (xi)
Scheme 25: Levulinic acid H-D-exchange
DPPE
oc y in NMR tube ¾ ?
^ + H3C^ O¾D5 2h nmr - ΒίΥ γ\
The reaction is illustrated in Fig. 41.
Example 25: Alternative process for the H-D exchange of levulinic acid (xii)
Scheme 26: Levulinic acid H-D-exchange
The reaction is illustrated in Fig. 42.
Example 26: Alternative process for the H-D exchange of levulinic acid (xiii)
Scheme 27: Levulinic acid H-D-exchange
The reaction is illustrated in Fig. 43-44.
Example 27: Alternative process for the H-D exchange of levulinic acid (xiv)
Scheme 28: Levulinic acid H-D-exchange
ΌΡΡΡ
Example 28: Alternative process for the H-D exchange of levulinic acid (xv) Scheme 29: Levulinic acid H-D-exchan e
The reaction is illustrated in Fig. 46.
Example 29: Alternative process for the H-D exchange of levulinic acid (xvi) Scheme 30: Levulinic acid H-D-exchange
The reaction is illustrated in Fig. 47-48.
The invention discloses the optimization of the reaction as well, said optimization includes not only the selection of the appropriate reaction conditions, but also the selection of the suitable phosphine ligand. It was therefore investigated that amongst the diphosphine ligands including 1 to 4 carbon atoms (dppm, dppe, dppp, dppb), the application of which results in the most effective transformation. It was found that the equilibrium is achieved most rapidly when dppp is selected as a phosphine.
Industrial applicability
The invention is of excellent use in the field of hydrocarbon chemistry, where C-H activation of hydrocarbons (alkanes, alkenes), and the preparation of catalysts active in such processes gained significant interest, as these reactions open the possibility to transform synthetically the compounds found in natural gas and petrol, or the preparation of alternative energy sources.
Claims
1. A process for the activation of the single covalent carbon-hydrogen bond (C-H bond) of organic substrate compounds and for the reaction of said bond characterized in that the aforementioned organic substrate compound is contacted with a rhutenium (Ru) containing complex, preferably +2 oxidation number Ru containing complex, preferably [Ru(H20)6](tos)2-complex, a phosphine and a hydrogen-substituting source, thus the hydrogen (H) of one or more C-H bond is replaced by a hydrogen-substituting agent through the activation of one or more C-H bond(s) by an in situ prepared metal -phosphine catalyst.
2. The process according to Claim 1 characterized in that
a) as organic substrate unsubstituted or substituted alcohols, preferably CMO straight, branched or cyclic, optionally unsaturated alcohols, more preferably methanol, ethanol, 2- propanol, unsubstituted or substituted ketones, preferably C1-10 straight, branched or cyclic, optionally unsaturated ketones, more preferably acetone, unsubstituted or substituted aldehydes, preferably C1-10 straight, branched or cyclic, optionally unsaturated aldehydes, more preferably benzaldehyde, unsubstituted or substituted carboxylic acids es carboxylic acid esthers, preferably C O straight, branched or cyclic, optionally unsaturated carboxylic acids, more preferably levulinic acid, butyric acid, unsubstituted or substituted alkenes, preferably CMO straight, branched or cyclic, optionally unsaturated alkenes, more preferably hexene, unsubstituted or substituted alkynes, preferably CMO straight, branched or cyclic, optionally unsaturated alkynes, more preferably hexyne, unsubstituted or substituted nitriles, preferably CMO straight, branched or cyclic, optionally unsaturated nitriles;
b) as phosphine (L) unsubstituted or substituted phosphine, preferably a monodental phosphine or bidental phosphine substituted in the rings by an alkyl-, aryl- or ionic group, or the water soluble, preferably sulphonated analogues thereof, preferably dppm, dpp, dppp, dppb, more preferably dppp is used;
thus, in situ a catalyst according to the general formula of Ru(L)n is prepared, wherein Ru and L is as defined above, and n is 1-4; preferably a catalyst according to the formula [Ru(H20)2(P-P)2](tos)2 is prepared, wherein P-P stands for dppm, dppe, dppp, dppb, preferably dppp;
c) furthermore, as hydrogen-substituting source a deuterium source, preferably a deuterated solvent, more preferably deuterated methyl-alcohol (MeOD), deuterated formic acid (DCOOD) or deuterated acetone, or D2 gas, preferably D2 gas pressurized to 100 bar is used.
3. The process according to Claim 1 or 2, characterized in that the reaction is accomplished within mild reaction conditions, preferably in the temperature range of 30 to 250 °C, more preferably 50 to 150 °C, most preferably at 60 to 80 °C, and in the pressure range of 0.5-1200 bar, preferably in the pressure range of 0.5 to 600, more preferably under 1 to 100 bar, most preferably under 1 to 10 bar pressure, in the time range of 1 to 30, preferably 6 to 16 hours.
4. The process according to Claims 1 to 3, characterized in that the activation of the C-H bond and the reaction thereof is accomplished selectively.
5. The process according to Claims 1 to 4, characterized in that the deuteration of the -CH2- groups positioned in -position from the functional groups of the substrates by a hydrogen- substituting agent is achieved.
6. A process for the deuteration of the single covalent carbon-hydrogen bond (C-H bond) of organic substrate compounds characterized in that the aforementioned organic substrate compound is contacted with a rhutenium (Ru) containing complex, preferably +2 oxidation number Ru containing complex, preferably [Ru(H20)6](tos)2-complex, a phosphine and a hydrogen-substituting source, deuteration of one or more C-H bond is made by an in situ prepared metal-phosphine catalyst.
7. The process according to Claim 6. characterized in that
a) as organic substrate unsubstituted or substituted alcohols, preferably C1-10 straight, branched or cyclic, optionally unsaturated alcohols, more preferably methanol, ethanol, 2- propanol, unsubstituted or substituted ketones, preferably CMO straight, branched or cyclic, optionally unsaturated ketones, more preferably acetone, unsubstituted or substituted aldehydes, preferably CMO straight, branched or cyclic, optionally unsaturated aldehydes, more preferably benzaldehyde, unsubstituted or substituted carboxylic acids es carboxylic acid esthers, preferably CMO straight, branched or cyclic, optionally unsaturated carboxylic acids, more preferably levulinic acid, butyric acid, unsubstituted or substituted alkenes, preferably CMO straight, branched or cyclic, optionally unsaturated alkenes, more preferably hexene, unsubstituted or substituted alkynes, preferably C1-10 straight, branched or cyclic, optionally unsaturated alkynes, more preferably hexyne, unsubstituted or substituted nitriles, preferably CMO straight, branched or cyclic, optionally unsaturated nitriles;
b) as phosphine (L) unsubstituted or substituted phosphine, preferably a monodental phosphine or bidental phosphine substituted in the rings by an alkyl-, aryl- or ionic group, or the water soluble, preferably sulphonated analogues thereof, preferably dppm, dpp, dppp, dppb, more preferably dppp is used;
thus, in situ a catalyst according to the general formula of Ru(L)„ is prepared, wherein Ru and L is as defined above, and n is 1-4; preferably a catalyst according to the formula [Ru(H20)2(P-P)2](tos)2 is prepared, wherein P-P stands for dppm, dppe, dppp, dppb, preferably dppp;
c) furthermore, as deuterium source, preferably a deuterated solvent, more preferably deuterated methyl-alcohol (MeOD), deuterated formic acid (DCOOD) or deuterated acetone, or D2 gas, preferably D2 gas pressurized to 100 bar is used.
8. The process according to Claim 6 or 7, characterized in that the reaction is accomplished within mild reaction conditions, preferably in the temperature range of 30 to 250 °C, more preferably 50 to 150 °C, most preferably at 60 to 80 °C, and in the pressure range of 0.5-1200
bar, preferably in the pressure range of 0.5 to 600, more preferably under 1 to 100 bar, most preferably under 1 to 10 bar pressure, in the time range of 1 to 30, preferably 6 to 16 hours.
9. The process according to Claims 6 to 9, characterized in that the deuteration of the C-H bond and the reaction thereof is accomplished selectively.
10. The process according to Claims 6 to 4, characterized in that the deuteration of the - CH2- groups positioned in oc-position from the functional groups of the substrates by a hydrogen-substituting agent is achieved.
11. A reaction system capable of activating of the single covalent carbon-hydrogen bond (C-H bond) of organic substrate compounds and of reacting, preferably deuterating said bond, which comprises an organic substrate compound as defined in Claims 1 to 2, a rhutenium (Ru) containing complex, preferably +2 oxidation number Ru containing complex, preferably [Ru(H20)6](tos)2-complex, a phosphine and a hydrogen-susbstituting source.
12. The reaction system according to Claim 11, which comprises an organic substrate compound as defined in Claim 1 to 2, an in situ forming [Ru(H20)2(P-P)2](tos)2 complex and a hydrogen-susbstituting source.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN112851469A (en) * | 2021-01-19 | 2021-05-28 | 温州大学 | Method for synthesizing chiral deuterated primary alcohol |
CN112851469B (en) * | 2021-01-19 | 2022-05-20 | 温州大学 | Method for synthesizing chiral deuterated primary alcohol |
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