EP1265828A1 - Verfahren zur reduktion organischer verbindungen mittels hydriden und/oder deren derivaten in einem mikroreaktor - Google Patents
Verfahren zur reduktion organischer verbindungen mittels hydriden und/oder deren derivaten in einem mikroreaktorInfo
- Publication number
- EP1265828A1 EP1265828A1 EP01919358A EP01919358A EP1265828A1 EP 1265828 A1 EP1265828 A1 EP 1265828A1 EP 01919358 A EP01919358 A EP 01919358A EP 01919358 A EP01919358 A EP 01919358A EP 1265828 A1 EP1265828 A1 EP 1265828A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- derivative
- microreactor
- hydride
- boranate
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 53
- 150000004678 hydrides Chemical class 0.000 title claims abstract description 26
- 150000002894 organic compounds Chemical class 0.000 title claims description 20
- 125000003118 aryl group Chemical group 0.000 claims abstract description 28
- -1 heterocyclic organic compounds Chemical class 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- 125000004423 acyloxy group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000004104 aryloxy group Chemical group 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 9
- 229910000085 borane Inorganic materials 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 239000003446 ligand Substances 0.000 claims description 8
- 239000011541 reaction mixture Substances 0.000 claims description 8
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical class [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 7
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 229910052782 aluminium Inorganic materials 0.000 claims description 6
- 230000003068 static effect Effects 0.000 claims description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 5
- 150000001540 azides Chemical class 0.000 claims description 5
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- 150000003342 selenium Chemical class 0.000 claims description 5
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 150000002170 ethers Chemical class 0.000 claims description 4
- 150000003003 phosphines Chemical class 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 150000003568 thioethers Chemical class 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 claims description 2
- 229910052796 boron Inorganic materials 0.000 claims description 2
- 238000004817 gas chromatography Methods 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 150000004756 silanes Chemical class 0.000 claims description 2
- 229910052718 tin Inorganic materials 0.000 claims description 2
- RMKXITVSCYOVMK-UHFFFAOYSA-N OBO.P.P Chemical compound OBO.P.P RMKXITVSCYOVMK-UHFFFAOYSA-N 0.000 claims 1
- JNFBEBLSKSTCJD-UHFFFAOYSA-N [Cu+2].[O-]B=O.[O-]B=O Chemical compound [Cu+2].[O-]B=O.[O-]B=O JNFBEBLSKSTCJD-UHFFFAOYSA-N 0.000 claims 1
- ILOKQJWLMPPMQU-UHFFFAOYSA-N calcium;oxido(oxo)borane Chemical compound [Ca+2].[O-]B=O.[O-]B=O ILOKQJWLMPPMQU-UHFFFAOYSA-N 0.000 claims 1
- 150000001728 carbonyl compounds Chemical class 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- ACPSIPROFDGOGE-UHFFFAOYSA-N cesium;oxido(oxo)borane Chemical compound [Cs+].[O-]B=O ACPSIPROFDGOGE-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- HZRMTWQRDMYLNW-UHFFFAOYSA-N lithium metaborate Chemical compound [Li+].[O-]B=O HZRMTWQRDMYLNW-UHFFFAOYSA-N 0.000 claims 1
- QXVQCIZYMCIUDZ-UHFFFAOYSA-N oxido(oxo)borane rubidium(1+) Chemical compound [Rb+].[O-]B=O QXVQCIZYMCIUDZ-UHFFFAOYSA-N 0.000 claims 1
- JVUYWILPYBCNNG-UHFFFAOYSA-N potassium;oxido(oxo)borane Chemical compound [K+].[O-]B=O JVUYWILPYBCNNG-UHFFFAOYSA-N 0.000 claims 1
- 229910000077 silane Inorganic materials 0.000 claims 1
- 229910052990 silicon hydride Inorganic materials 0.000 claims 1
- 229910000080 stannane Inorganic materials 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 claims 1
- 229910000083 tin tetrahydride Inorganic materials 0.000 claims 1
- PZRXQXJGIQEYOG-UHFFFAOYSA-N zinc;oxido(oxo)borane Chemical compound [Zn+2].[O-]B=O.[O-]B=O PZRXQXJGIQEYOG-UHFFFAOYSA-N 0.000 claims 1
- 238000006722 reduction reaction Methods 0.000 description 18
- 230000009467 reduction Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- MWDNZMWVENFVHT-UHFFFAOYSA-L (2-decoxy-2-oxoethyl)-[2-[2-[(2-decoxy-2-oxoethyl)-dimethylazaniumyl]ethylsulfanyl]ethyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCOC(=O)C[N+](C)(C)CCSCC[N+](C)(C)CC(=O)OCCCCCCCCCC MWDNZMWVENFVHT-UHFFFAOYSA-L 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000007824 aliphatic compounds Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001491 aromatic compounds Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- FKJVYIOTRBELHH-UHFFFAOYSA-N methyl 3-(3-methylimidazol-4-yl)prop-2-enoate Chemical compound COC(=O)C=CC1=CN=CN1C FKJVYIOTRBELHH-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OASSUDRXFIZFFD-UHFFFAOYSA-N 2-methyl-3-(3-methylimidazol-4-yl)prop-2-enoic acid Chemical compound OC(=O)C(C)=CC1=CN=CN1C OASSUDRXFIZFFD-UHFFFAOYSA-N 0.000 description 1
- YVUFMVOMUVLUSN-UHFFFAOYSA-N 3-(3-methylimidazol-4-yl)prop-2-en-1-ol Chemical compound CN1C=NC=C1C=CCO YVUFMVOMUVLUSN-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- QLFNUXTWJGXNLH-UHFFFAOYSA-N bis(2-methoxyethoxy)alumane Chemical compound COCCO[AlH]OCCOC QLFNUXTWJGXNLH-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000002944 cyanoaryl group Chemical group 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
- 239000004914 cyclooctane Substances 0.000 description 1
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B31/00—Reduction in general
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00873—Heat exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00984—Residence time
Definitions
- the present invention relates to a / experienced in the reduction of aliphatic, aromatic or heterocyclic organic compounds by means of hydrides and / or their derivatives.
- the object of the present invention is therefore to provide a process for reducing aliphatic, aromatic or heterocyclic organic compounds by means of hydrides and / or their derivatives, which avoids the disadvantages mentioned above.
- This process should in particular be able to be carried out in a simple, reproducible manner with increased safety for humans and the environment and with good yields, the reaction conditions should be very easy to control and those for It should be possible to implement the protective gas conditions necessary for the reaction without great technical outlay.
- This object is surprisingly achieved by the process according to the invention for reducing aliphatic, aromatic or heterocyclic organic compounds by means of hydrides and / or their derivatives, in which at least one organic compound in liquid or dissolved form with at least one hydride and / or its derivative in liquid or dissolved form is mixed in at least one microreactor, reacts during a residence time and the reduced organic compound is optionally isolated from the reaction mixture.
- an aliphatic, aromatic or heterocyclic organic compound or a mixture of at least two of these compounds is reduced by the claimed process.
- an aliphatic, aromatic or heterocyclic organic compound is used in the process according to the invention.
- a microreactor in the sense of the invention is a reactor with a volume ⁇ 1000 ⁇ l in which the liquids and / or solutions are intimately mixed at least once.
- the volume of the reactor is preferably ⁇ 100 ⁇ l, particularly preferably ⁇ 50 ⁇ l.
- the microreactor is preferably produced from thin, interconnected silicon structures.
- the microreactor is preferably a miniaturized flow reactor, particularly preferably a static micromixer.
- the microreactor is a static micromixer as described in the patent application with the international publication number WO 96/301 13, which is hereby introduced as a reference and is considered part of the disclosure.
- Such a microreactor has small channels in which liquids and / or chemical compounds present in solutions are mixed with one another by the kinetic energy of the flowing liquids and / or solutions.
- the channels of the microreactor preferably have a diameter of 10 to 1000 ⁇ m, particularly preferably 20 to 800 ⁇ m and very particularly preferably 30 to 400 ⁇ m.
- the liquids and / or solutions are preferably pumped into the microreactor in such a way that they flow through them at a flow rate of 0.01 ⁇ l / min to 100 ml / min, particularly preferably 1 ⁇ l / min to 1 ml / min.
- the microreactor can preferably be tempered.
- the microreactor is preferably connected via an outlet to at least one retention zone, preferably a capillary, particularly preferably a temperature-controlled capillary.
- the liquids and / or solutions are passed into this residence zone or capillary after they have been mixed in the microreactor in order to extend their residence time.
- the residence time in the sense of the invention is the time between the mixing of the starting materials and the working up of the resulting reaction solution for the analysis or isolation of the desired product (s).
- the required residence time in the process according to the invention depends on various parameters, such as, for example, the temperature or the reactivity of the starting materials. It is possible for the person skilled in the art to adapt the dwell time to these various parameters and thus to achieve an optimal course of the reaction.
- the residence time of the reaction solution in the system used can be set by selecting the flow rate of the liquids and / or solutions used.
- the reaction mixture is likewise preferably passed through two or more microreactors connected in series. This ensures that the residence time is extended even at an increased flow rate and the components used in the reduction reaction are reacted in such a way that an optimal product yield of the desired reduced organic compound (s) is achieved.
- reaction mixture is passed through two or more microreactors arranged in parallel in order to increase the throughput.
- the number and the arrangement of the channels in one or more microreactor (s) are varied in such a way that the residence time is increased, so that here, too, an optimal yield of the desired product is reduced at an increased flow rate organic compound (s) is achieved.
- the residence time of the reaction solution in the microreactor if appropriate in the microreactor and the residence zone, is preferably ⁇ 15 hours, particularly preferably ⁇ 3 hours, very particularly preferably ⁇ 1 hour.
- the process according to the invention can be carried out in a very wide temperature range, which is essentially due to the temperature resistance of the microreactor, optionally the residence zone, and other constituents, such as e.g. Connections and seals, materials used and limited by the physical properties of the solutions and / or liquids used.
- the process according to the invention is preferably carried out at a temperature of from -100 to +250 ° C., particularly preferably from -78 to +150 ° C. and very particularly preferably from 0 to +40 ° C.
- the process according to the invention can be carried out either continuously or batchwise. It is preferably carried out continuously.
- the course of the reduction reaction in the process according to the invention can be followed and optionally regulated using various analytical methods known to the person skilled in the art.
- the course of the reaction is preferably followed by chromatography, particularly preferably by gas chromatography and / or by high pressure liquid chromatography, and, if appropriate, regulated.
- the control of the reaction is included the method according to the invention significantly improved compared to known methods.
- the reduced organic compounds are optionally isolated.
- the reduced product (s) is (are) after working up the reaction mixture, e.g. isolated from the reaction mixture by acidification with hydrochloric acid, optionally neutralization and subsequent extraction with a suitable solvent. Extraction is particularly preferably carried out with an organic solvent.
- Aliphatic, aromatic or heterocyclic organic compounds which can be used in the process according to the invention are all aliphatic, aromatic or heterocyclic organic compounds known to the person skilled in the art as substrates for reductions by means of hydrides and / or their derivatives.
- Preferred aliphatic, aromatic or heterocyclic organic compounds are aliphatic, aromatic or heterocyclic carbonyl compounds, such as aldehydes and ketones, carboxylic acids, carboxylic acid halides, carboxylic acid esters, corresponding thio- or selenium analogues of the abovementioned compounds, nitriles, halides or azides.
- aliphatic carbonyl compounds carboxylic acids, carboxylic acid halides, carboxylic acid esters, corresponding thio- or selenium analogues of the above-mentioned compounds, nitriles, halides or azides, all aliphatic compounds of the above-mentioned substance classes known to the person skilled in the art can be used, which are suitable as substrates for reductions by means of hydrides and / or their derivatives are suitable.
- There are also straight-chain, branched, saturated and unsaturated Connections includes.
- Aromatic carbonyl compounds carboxylic acids, carboxylic acid halides, carboxylic acid esters, corresponding thio- or selenium analogues of the abovementioned compounds, nitriles, halides or azides, all aromatic compounds of the substance classes listed above which are known to the person skilled in the art can be used, which can be used as a substrate for reductions by means of hydrides and / or their derivatives are suitable.
- compounds and / or derivatives are therefore also included which have a monocyclic and / or polycyclic homoaromatic backbone or a corresponding partial structure, e.g. in the form of substituents.
- heterocyclic carbonyl compounds carboxylic acids, carboxylic acid halides, carboxylic acid esters, corresponding thio- or selenium analogues of the above-mentioned compounds, nitriles, halides or azides, all heterocyclic compounds of the above-mentioned substance classes known to the person skilled in the art can be used, which are suitable as substrates for reductions by means of hydrides and / or their derivatives are suitable and contain at least one heteroatom.
- Heterocyclic compounds within the meaning of the invention also include heterocyclic compounds and / or their derivatives which have at least one monocyclic and / or polycyclic heterocyclic backbone or a corresponding partial structure, e.g. in the form of substituents.
- the term "heterocyclic" also includes saturated, unsaturated and heteroaromatic compounds. Heterocyclic backbones or partial structures particularly preferably comprise at least one oxygen, nitrogen or sulfur atom.
- reducing agents known to those skilled in the art for reducing aliphatic, aromatic or heterocyclic organic compounds suitable hydrides and / or their derivatives are used. At least one compound selected from boron, aluminum, tin, silicon hydrides, their derivatives or a mixture of these reducing agents is preferably used as the hydride or its derivative. Only one hydride or derivative is preferably used as the reducing agent in the process according to the invention.
- a derivative of a hydride in the sense of the invention is a structurally analogous compound in which at least one hydrogen atom has been replaced by a radical other than hydrogen, but at least one hydrogen atom is still present.
- borohydride or its derivative is preferably lithium borohydride, sodium borohydride, potassium, Rubidiumboranat, Cäsiumboranat borohydride, zinc borohydride, Calciumboranat, Kupferboranat, tetra-alkylammoniumboranat, tri-or tri-alkylphosphoniumboranat arylphosphoniumboranat, or alkyl, aryl, alkoxy, aryloxy, acyloxy -, Cyano- or heteroaryl derivatives of boranates or a mixture of the above-mentioned compounds.
- borohydride or its derivative is a borane, in particular diborane, or alkyl, aryl, alkoxy, aryloxy, acyloxy or heteroaryl derivatives of boranes, complexes of boranes or the above derivatives with amines, phosphines, ethers or sulfides as ligands, the ligands each being the same or different or using a mixture of the above-mentioned compounds.
- Aluminum hydride or its derivative are preferably aluminum hydrogen (AIH 3 ), complex aluminum hydrides, in particular lithium alanate, sodium alanate, potassium alanate, or alkyl, aryl, alkoxy, aryloxy or acyloxy derivatives of hydrogen aluminum or alanates, for example Na bis (2 - Methoxyethoxy) aluminum hydride or di-isobutylaluminium hydride used. Also preferred are complexes of hydrogen aluminum, alanates or the above derivatives with amines, phosphines, ethers or Sulfides as ligands, where the ligands can each be the same or different, or a mixture of the compounds mentioned above.
- AIH 3 aluminum hydrogen
- complex aluminum hydrides in particular lithium alanate, sodium alanate, potassium alanate, or alkyl, aryl, alkoxy, aryloxy or acyloxy derivatives of hydrogen aluminum or alanates, for example Na bis (2 -
- Preferred silicon hydrides or their derivatives include silanes, in particular monosilane, or alkyl, aryl, alkoxy, aryloxy, acyloxy, cyano or heteroaryl derivatives of the stianes or a mixture of the compounds mentioned above.
- Examples of preferred tin hydrides or their derivatives include stannanes, in particular monostannan, or alkyl, aryl, alkoxy, aryloxy, acyloxy, cyano or heteroaryl derivatives of the stannanes or a mixture of the compounds mentioned above.
- Alkenes and alkynes can be inserted into the B -H bonds of boranes.
- the hydrolysis or peroxohydrolysis of the organylboranes formed in these hydroboration leads to hydrocarbons or alcohols. It must therefore be taken into account that these hydroboronations can also occur in the case of unsaturated compounds which are to be reduced according to the invention if boranes and / or derivatives of the boranes are used as reducing agents.
- the molar ratio of organic compound to hydride and / or its derivative in the process according to the invention depends on the reactivity of the organic compounds, hydrides and / or derivatives used.
- the hydride and / or its derivative is preferably used in an excess> 1, or equimolar, with respect to the organic compound.
- the selectivity of the reaction itself depends not only on the concentration of the reagents used but also on a number of other parameters, such as the temperature, the type of reducing agent used or the residence time. It is possible for the person skilled in the art to adapt the various parameters to the respective reduction reaction in such a way that the desired reduced product (s) is (are) obtained.
- Aromatic solvents are preferred as solvents, particularly preferably toluene, xylenes, ligroin or phenyl ether, straight-chain, branched or cyclic paraffins, particularly preferably pentane, hexane, heptane, octane, cyclopentane, cyclohexane, cycloheptane or cyclooctane or straight-chain, branched or cyclic ethers, particularly preferably diethyl ether, methyl tert-butyl ether, tetrahydrofuran or dioxane, or mixtures of these solvents.
- the risk to humans and the environment from escaping chemicals is considerably reduced and thus leads to increased safety when handling hazardous substances.
- the reduction of aliphatic, aromatic or heterocyclic organic compounds by the process according to the invention also enables better control of the reaction conditions, such as reaction time and reaction temperature, than is possible in the conventional processes.
- the temperature can be individually selected and kept constant in each volume element of the system.
- the course of the reduction reaction can be regulated very quickly and precisely in the process according to the invention. Shielding gas conditions are very easy to implement and maintained. The reduced organic products can thus be obtained in very good and reproducible yields.
- DIBAL-H diisobutyl aluminum hydride
- the static micromixer was connected via an outlet and an Omnifit medium pressure HPLC connection component (Omnifit, Great Britain) to a Teflon capillary with an inner diameter of 0.49 mm and a length of 1.0 m.
- the reaction was carried out at room temperature.
- the experimental set-up was calibrated for the dependence of the residence time on the pump flow rate before the reaction was carried out.
- the dwell time was set to 30, 15, 7.5 or 3.75 minutes.
- the reactions were followed using a Hewlett-Packard GC-MS or a Merck Hitachi LaChrom HPLC instrument.
- the resulting reaction mixture was acidified with 1N HCl and extracted with ethyl acetate. The organic extract was then dried over magnesium sulfate and the solvent was removed in vacuo.
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Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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DE10014298A DE10014298A1 (de) | 2000-03-23 | 2000-03-23 | Verfahren zur Reduktion aliphatischer, aromatischer oder heterocyclischer organischer Verbindungen mittels Hydriden und/oder deren Derivaten |
DE10014298 | 2000-03-23 | ||
PCT/EP2001/002302 WO2001070649A1 (de) | 2000-03-23 | 2001-03-01 | Verfahren zur reduktion organischer verbindungen mittels hydriden und/oder deren derivaten in einem mikroreaktor |
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EP1265828A1 true EP1265828A1 (de) | 2002-12-18 |
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EP01919358A Ceased EP1265828A1 (de) | 2000-03-23 | 2001-03-01 | Verfahren zur reduktion organischer verbindungen mittels hydriden und/oder deren derivaten in einem mikroreaktor |
Country Status (6)
Country | Link |
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US (1) | US7179925B2 (de) |
EP (1) | EP1265828A1 (de) |
JP (1) | JP2003528061A (de) |
AU (1) | AU2001246488A1 (de) |
DE (1) | DE10014298A1 (de) |
WO (1) | WO2001070649A1 (de) |
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DE102007023764A1 (de) * | 2006-08-10 | 2008-02-14 | Evonik Degussa Gmbh | Anlage und Vorrichtung zur kontinuierlichen industriellen Herstellung von 3-Chlorpropylchlorsilanen |
DE102007023763A1 (de) * | 2006-08-10 | 2008-02-14 | Evonik Degussa Gmbh | Anlage, Reaktor und Verfahren zur kontinuierlichen industriellen Herstellung von Polyetheralkylalkoxysilanen |
DE102007023762A1 (de) * | 2006-08-10 | 2008-02-14 | Evonik Degussa Gmbh | Anlage und Verfahren zur kontinuierlichen industriellen Herstellung von 3-Glycidyloxypropylalkoxysilanen |
DE102007023756A1 (de) * | 2006-08-10 | 2008-02-14 | Evonik Degussa Gmbh | Anlage und Verfahren zur kontinuierlichen industriellen Herstellung von Alkylalkoxysilanen |
DE102007023759A1 (de) * | 2006-08-10 | 2008-02-14 | Evonik Degussa Gmbh | Anlage und Verfahren zur kontinuierlichen industriellen Herstellung von Fluoralkylchlorsilan |
DE102007023760A1 (de) * | 2006-08-10 | 2008-02-14 | Evonik Degussa Gmbh | Anlage, Reaktor und Verfahren zur kontinuierlichen industriellen Herstellung von 3-Methacryloxypropylalkoxysilanen |
DE102007023757A1 (de) * | 2006-08-10 | 2008-02-14 | Evonik Degussa Gmbh | Anlage und Verfahen zur kontinuierlichen industriellen Herstellung von Organosilanen |
EA201000081A1 (ru) * | 2007-06-29 | 2010-10-29 | Лонца Лтд. | Способ получения альдегидов |
WO2012147900A1 (en) | 2011-04-28 | 2012-11-01 | Eisai R&D Management Co., Ltd. | Microreactor process for halichondrin b analog synthesis |
GB2494676A (en) * | 2011-09-15 | 2013-03-20 | Univ Warwick | Reduction of artemisinin to dihydroartemisinin and suitable apparatus |
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US5091595A (en) * | 1989-06-07 | 1992-02-25 | Choi Young M | Reduction of diethyl phenylmalonate to 2-phenyl-1,3-propanediol |
GB9723260D0 (en) * | 1997-11-05 | 1998-01-07 | British Nuclear Fuels Plc | A method of performing a chemical reaction |
-
2000
- 2000-03-23 DE DE10014298A patent/DE10014298A1/de not_active Withdrawn
-
2001
- 2001-03-01 WO PCT/EP2001/002302 patent/WO2001070649A1/de active Application Filing
- 2001-03-01 AU AU2001246488A patent/AU2001246488A1/en not_active Abandoned
- 2001-03-01 US US10/239,393 patent/US7179925B2/en not_active Expired - Fee Related
- 2001-03-01 EP EP01919358A patent/EP1265828A1/de not_active Ceased
- 2001-03-01 JP JP2001568863A patent/JP2003528061A/ja active Pending
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WO2001070649A1 (de) | 2001-09-27 |
DE10014298A1 (de) | 2001-09-27 |
US20040225157A1 (en) | 2004-11-11 |
JP2003528061A (ja) | 2003-09-24 |
AU2001246488A1 (en) | 2001-10-03 |
US7179925B2 (en) | 2007-02-20 |
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