WO2006122683A2 - Verfahren zur herstellung von 2-formylfuran-4-boronsäure - Google Patents
Verfahren zur herstellung von 2-formylfuran-4-boronsäure Download PDFInfo
- Publication number
- WO2006122683A2 WO2006122683A2 PCT/EP2006/004369 EP2006004369W WO2006122683A2 WO 2006122683 A2 WO2006122683 A2 WO 2006122683A2 EP 2006004369 W EP2006004369 W EP 2006004369W WO 2006122683 A2 WO2006122683 A2 WO 2006122683A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- boronic acid
- optionally substituted
- furfural
- metallation
- groups
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- RIBSTTPRQPAXRS-UHFFFAOYSA-N (5-formylfuran-3-yl)boronic acid Chemical compound OB(O)C1=COC(C=O)=C1 RIBSTTPRQPAXRS-UHFFFAOYSA-N 0.000 title description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- -1 furfural acetals Chemical class 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 238000006263 metalation reaction Methods 0.000 claims abstract description 12
- 150000001642 boronic acid derivatives Chemical class 0.000 claims abstract description 9
- 150000008064 anhydrides Chemical class 0.000 claims abstract description 8
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 6
- 239000000460 chlorine Substances 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 5
- HYBBIBNJHNGZAN-UHFFFAOYSA-N Furaldehyde Natural products O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims abstract description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 4
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims abstract description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 claims abstract description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 10
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 9
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 150000001639 boron compounds Chemical class 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 239000011777 magnesium Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- CDKCEZNPAYWORX-UHFFFAOYSA-N 1-tert-butyl-4-(4-tert-butylphenyl)benzene Chemical group C1=CC(C(C)(C)C)=CC=C1C1=CC=C(C(C)(C)C)C=C1 CDKCEZNPAYWORX-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000011877 solvent mixture Substances 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 claims 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims 2
- 150000002901 organomagnesium compounds Chemical class 0.000 claims 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 1
- RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 claims 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims 1
- 150000002505 iron Chemical class 0.000 claims 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 claims 1
- 125000001979 organolithium group Chemical group 0.000 claims 1
- 239000003208 petroleum Substances 0.000 claims 1
- 230000027756 respiratory electron transport chain Effects 0.000 claims 1
- 150000001241 acetals Chemical group 0.000 abstract description 7
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 150000002367 halogens Chemical group 0.000 abstract description 2
- 229910052740 iodine Chemical group 0.000 abstract description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 abstract 1
- 239000011630 iodine Chemical group 0.000 abstract 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 13
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 9
- ISTFZLMKXMGKTN-UHFFFAOYSA-N 4-bromo-2-(diethoxymethyl)furan Chemical compound CCOC(OCC)C1=CC(Br)=CO1 ISTFZLMKXMGKTN-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000007717 exclusion Effects 0.000 description 4
- 150000002900 organolithium compounds Chemical class 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- MYMKNEUWNLCERL-UHFFFAOYSA-N 1-(diethoxymethyl)cyclopenta-1,3-diene Chemical compound CCOC(OCC)C1=CC=CC1 MYMKNEUWNLCERL-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- CETVQRFGPOGIQJ-UHFFFAOYSA-N lithium;hexane Chemical compound [Li+].CCCCC[CH2-] CETVQRFGPOGIQJ-UHFFFAOYSA-N 0.000 description 2
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 2
- 150000002902 organometallic compounds Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- JUWYQISLQJRRNT-UHFFFAOYSA-N (5-formylfuran-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)O1 JUWYQISLQJRRNT-UHFFFAOYSA-N 0.000 description 1
- YCMUCDYHDNYGOS-UHFFFAOYSA-N 2-(4-bromofuran-2-yl)-1,3-dioxolane Chemical compound BrC1=COC(C2OCCO2)=C1 YCMUCDYHDNYGOS-UHFFFAOYSA-N 0.000 description 1
- LIOSIVCDJIZIQP-UHFFFAOYSA-N 2-(diethoxymethyl)-4-iodofuran Chemical compound CCOC(OCC)C1=CC(I)=CO1 LIOSIVCDJIZIQP-UHFFFAOYSA-N 0.000 description 1
- RYMLQMSMBGGEQW-UHFFFAOYSA-N 4-chloro-2-(diethoxymethyl)furan Chemical compound CCOC(OCC)C1=CC(Cl)=CO1 RYMLQMSMBGGEQW-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- UQRKYTFOFYASRJ-UHFFFAOYSA-N [Mg].BrBr Chemical group [Mg].BrBr UQRKYTFOFYASRJ-UHFFFAOYSA-N 0.000 description 1
- 238000006359 acetalization reaction Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- GRJWDJVTZAUGDZ-UHFFFAOYSA-N anthracene;magnesium Chemical class [Mg].C1=CC=CC2=CC3=CC=CC=C3C=C21 GRJWDJVTZAUGDZ-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000005621 boronate group Chemical group 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000012707 chemical precursor Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 150000001983 dialkylethers Chemical class 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 150000004252 dithioacetals Chemical class 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical class OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- LWLPYZUDBNFNAH-UHFFFAOYSA-M magnesium;butane;bromide Chemical compound [Mg+2].[Br-].CCC[CH2-] LWLPYZUDBNFNAH-UHFFFAOYSA-M 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 150000002917 oxazolidines Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Definitions
- the present method solves this problem and relates to a process for the preparation of furfural-4-boronic acid (III) by reacting furfural acetals (I), which are halogen-substituted in the 4-position, with boronic acid esters or
- anhydrides (II) by metallation of the compound (I) and simultaneous or subsequent reaction with a boronic acid ester or anhydride (II) to an acetal-protected furfural-4-boronic acid ester and subsequent acid hydrolysis, with elimination of the acetal protecting group to furfural-4 boronic acid (III).
- X is chlorine, bromine or iodine
- R is a branched, unbranched and / or cyclic, optionally substituted CiC ⁇ o, in particular C 1 -C 8 -alkyl radical, an optionally substituted or an optionally substituted C 3 -C 8 - Cycloalkyl radical, wherein the two radicals R may together form a ring;
- R ', R ", R” independently represent acylic or cyclic, branched or unbranched, optionally substituted C1-C20 alkyl groups, or optionally substituted aryl groups, where appropriate two of the radicals R', R “and R '” together form a ring, or represent further radicals B (OR) 3 .
- X is preferably chlorine, bromine or iodine, particularly preferably bromine in the case of metalation by halogen-metal exchange, particularly preferably chlorine in the case of lithiation with metallic lithium.
- R ', R "and R'” are preferably alkyl radicals, in particular linear or branched lower alkanes and cycloalkanes, preferably methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tert-butyl, pentyl, isopentyl, neo-pentyl, cyclopentyl, hexyl, isohexyl , Cyclohexyl, cycloheptyl, cyclooctyl, etc.
- Protection and deprotection steps are carried out either in bulk or a suitable solvent appropriate to the reaction.
- Suitable protecting groups are, for example, Imines, open-chain or cyclic thio and dithioacetals, oxazolidines and acetals. Particularly preferred are acetals.
- the alcohol used for the acetalization is a solvent appropriate to the reaction.
- a solvent suitable for the deprotection reaction is usually an aqueous solvent or solvent mixture.
- Suitable metalating reagents are, for example, Grignard compounds, diorganomagnesium compounds, organolithium compounds, thorganomagnesium-at complexes or alkali metal diorganoamides. It is also possible to use combinations of organolithium compound and complexing agents, or combinations of organolithium compound and alkali metal alcoholate, and the reactive metal itself, such as, for example, sodium, lithium, magnesium or zinc in suitable form, if appropriate in the presence of a catalyst.
- metallating reagents are secondary Grignard compounds such as isopropyl, cyclohexyl or cyclopentylmagnesium halides, and primary or secondary alkyllithium compounds such as butyllithium, hexyllithium or cyclohexyllithium, or metallic lithium or magnesium, if appropriate in the presence of a catalyst.
- secondary Grignard compounds such as isopropyl, cyclohexyl or cyclopentylmagnesium halides
- primary or secondary alkyllithium compounds such as butyllithium, hexyllithium or cyclohexyllithium, or metallic lithium or magnesium, if appropriate in the presence of a catalyst.
- Suitable catalysts are in principle all compounds which have the capability of transferring individual electrons (one-electron transfer reagent), for example salts of many transition metals, such as e.g. Iron, or condensed polynuclear aromatics such as e.g. Anthracene or naphthalene or optionally substituted bi- or oligophenyls such.
- concentration of such a catalyst can be between 0.0001 and 200 mol%, more preferably concentrations of 0.01 to 1 mol% are used.
- the metallated furfural acetal obtained is reacted with 0.8 to 10 substance equivalents, in particular 1.0 to 1.4 equivalents of a triorganoborate (II), which may already be present in the reaction mixture during the metallation.
- II triorganoborate
- the metallation step of the process according to the invention is carried out in one or more suitable organic solvents (n), preferably in an aliphatic, aromatic or ethereal solvent or mixtures of these solvents, more preferably in tetrahydrofuran, lower dialkyl ethers, glyme, diglyme, toluene, cyclohexane, pentane , Hexane or heptane.
- suitable organic solvents n
- suitable organic solvents preferably in an aliphatic, aromatic or ethereal solvent or mixtures of these solvents, more preferably in tetrahydrofuran, lower dialkyl ethers, glyme, diglyme, toluene, cyclohexane, pentane , Hexane or heptane.
- the furfural acetal (I) is borylated either in situ by the boron compound present in the reaction mixture or after metalation by addition of the corresponding boron compound, resulting in a borate complex.
- the triorganoboric acid ester (II) which in this case should carry sterically demanding substituents, may also be initially charged with the 4-halofurfural acetal (I) and the organometallic compound added slowly at low temperatures.
- the intermediate furyl metal compound reacts immediately with the triorganoboric acid ester (II) present in the solution. It is stirred until complete reaction, where appropriate, is heated.
- the workup is generally carried out under the usual aqueous conditions, wherein (III) is obtained either as a boronic acid ester, boronic acid or boronic anhydride.
- the temperature for the metallation step is usually in the range of -120 0 C to +120 0 C 1 is preferably carried out between O 0 C and 50 0 C when using Grignard compounds, between -80 C and -4O 0 C. the use of organolithium compounds. Due to the moisture and oxygen sensitivity of the organometallic reagents and intermediates, the reaction is preferably carried out under dry inert gas, such as nitrogen or argon.
- furfural-4-boronic acid (III) in high yields and purities.
- water or aqueous solutions of salts, acids or bases or buffer solutions may be used for the hydrolysis in a suitable concentration known to the person skilled in the art.
- the deprotection if not already done during the work-up of the boronic acid derivative, is carried out under precisely controlled conditions in a manner compatible with the boronate group, i. as little as possible leads to protodeboration.
- the product (II) can be further purified by recrystallization.
- An advantage of this method is the good accessibility of 2-formylfuran-4-boronic acid, which is accessible only in poor yields by the known methods.
- Another advantage of the method according to the invention is that the purity of the product is very high (> 99%, HPLC) and no products are formed by rearrangement.
- the proportion of such as e.g. 2-formylfuran-5-boronic acid in the process according to the invention is, for example, ⁇ 0.1% (HPLC).
- the furfural-4-boronic acid is obtained in yields of> 60%.
- Example 1 Synthesis of 2-formylfuran-4-boronic acid starting from 4-bromo-2-diethoxymethylfuran in the presence of triisopropyl borate with n-butyllithium
- the mixture is warmed to -4O 0 C and treated with 119 g of MIBK (methyl isobutyl ketone). Subsequently, the low boilers are distilled off at 100 mbar and a maximum temperature in the bottom of 55 0 C. After cooling to room temperature, the black, liquid residue is introduced into 193 g of ice water (0-5 ° C.) (pH ⁇ 12). Thereafter, the pH of the mixture with ⁇ 16 g of HCl (15%) is adjusted to 0.8 to 1.5. In a 90-minute After stirring at 0 to 5 0 C, the 2-formylfuran-4-boronic acid precipitates from the solution and is obtained by suction through needle felt. After washing the precipitate with 24 g of cold MIBK, 2-formylfuran-4-boronic acid as a colorless powder after drying in vacuo at 4O 0 C under N 2 15.1 g supplies (91%).
- MIBK methyl isobutyl ketone
- the low boilers are distilled off at 100 mbar and a maximum temperature in the bottom of 55 ° C.
- the black, liquid residue is after cooling to room temperature in 61 g of ice water (0 - 5 0 C) registered (pH ⁇ 12).
- the pH of the mixture with - 16 g of HCl (15%) is adjusted to 0.8 to 1.5.
- the 2-formylfuran-4-boronic acid precipitates out of the solution and is obtained by suction through needle felt.
- 2-formylfuran-4-boronic acid as a colorless powder after drying in vacuo at 40 0 C under N 2 5:06 g supplies (80%).
- Example 3 As in Example 1, but the reaction was carried out with n-butyllithium at -100 0 C. The yield was 82%.
- Example 4 As Example 1, but n-butyllithium was added dropwise at -65 ° C within 3 h. The yield was 73%.
- Example 5 same as Example 1 except that n-hexyllithium was used instead of n-butyl lithium. The yield was 71%.
- Example 6 As in Example 1, 4-bromofurfuraldimethylacetal was used instead of 4-bromofurfuraldiethylacetal. The yield was 69%.
- Example 7 As in Example 1, 2- (4-bromo-furan-2-yl) - [1,3] -dioxolane was used in place of 4-bromofurfuraldiethyl acetal. The yield was 76%.
- Example 8 same as Example 1 except that the reaction with tributyl borate was used in place of triisopropyl borate. The yield was 65%.
- Example 9 same as Example 1 except that the reaction was carried out with xylene instead of toluene. The yield was 60%.
- Example 10 same as Example 1 except that 260 g of toluene and 162 g of THF were used. The yield was 63%.
- the low boilers are distilled off at 100 mbar and a maximum temperature in the bottom of 55 0 C.
- the black, liquid residue is introduced into 96 g of ice water (0-5 ° C.) (pH ⁇ 12).
- the pH of the mixture with ⁇ 10 g of HCl (15%) to 0.8 to 1.5 set.
- the 2-formylfuran-4-boronic acid precipitates out of the solution and is obtained by suction through needle felt.
- 2-formylfuran-4-boronic acid as a colorless powder after drying in vacuo at 4O 0 C under N2 7.4 g provides (73%).
- the black, liquid residue is after cooling to room temperature in 50 g of ice water (0 - 5 ° C) added (pH ⁇ 12). Thereafter, the pH of the mixture with ⁇ 6 g of HCl (15%) is adjusted to 0.8 to 1.5.
- the 2-formylfuran-4-boronic acid precipitates out of the solution and is obtained by suction through needle felt. After washing the precipitate with 10 g of cold MIBK, 2-formylfuran-4-boronic acid as a colorless powder after drying in vacuo at 4O 0 C under N 2 3:35 g supplies (66%).
- Example 13 Synthesis of 2-formylfuran-4-boronic acid starting from 4-bromo-2-diethoxymethylfuran by bromine-metal exchange by means of lithium tributylmagnesate
- the low boilers are distilled off at 100 mbar and a maximum temperature in the bottom of 55 0 C.
- the black, liquid residue is after cooling to room temperature in 96 g of ice water (0 - 5 0 C) registered (pH ⁇ 12). Thereafter, the pH of the mixture is adjusted to 0.8-1.5 with ⁇ 10 g HCl (15%). In a 90-minute
- the black, liquid residue is after cooling to room temperature in 50 g of ice water (0 - 5 ° C) added (pH ⁇ 12). Thereafter, the pH of the mixture with - 6 g of HCl (15%) is adjusted to 0.8 to 1.5.
- the 2-formylfuran-4-boronic acid precipitates out of the solution and is obtained by suction through needle felt. After washing the precipitate with 10 g of cold MIBK, 2-formylfuran-4-boronic acid is obtained as a colorless powder which after drying in vacuo at 40 ° C. under N 2 gives 3.09 g (61%).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06742855A EP1885729A2 (de) | 2005-05-20 | 2006-05-10 | Verfahren zur herstellung von 2-formylfuran-4-boronsäure durch metallierung von 4-halogenfurfuralacetalen in gegenwart geeigneter boronsäureester oder -anhydride |
US11/912,157 US20080188671A1 (en) | 2005-05-20 | 2006-05-10 | Method for Producing 2-Formylfuran-4-Boronic Acid by the Metalation of 4-Halofurfural Acetals in the Presence of Suitable Boronic Acid Esters or Anhydrides |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102005023989.7 | 2005-05-20 | ||
DE102005023989A DE102005023989A1 (de) | 2005-05-20 | 2005-05-20 | Verfahren zur Herstellung von 2-Formylfuran-4-boronsäure durch Metallierung von 4-Halogenfurfuralacetalen in Gegenwart geeigneter Boronsäureester oder -anhydride |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2006122683A2 true WO2006122683A2 (de) | 2006-11-23 |
WO2006122683A3 WO2006122683A3 (de) | 2007-05-03 |
Family
ID=37116107
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2006/004369 WO2006122683A2 (de) | 2005-05-20 | 2006-05-10 | Verfahren zur herstellung von 2-formylfuran-4-boronsäure |
Country Status (5)
Country | Link |
---|---|
US (1) | US20080188671A1 (de) |
EP (1) | EP1885729A2 (de) |
CN (1) | CN101175761A (de) |
DE (1) | DE102005023989A1 (de) |
WO (1) | WO2006122683A2 (de) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2938538B1 (fr) * | 2008-11-17 | 2011-08-05 | Univ Nice Sophia Antipolis | Procede de preparation d'acides et d'esters boroniques en presence de magnesium metallique |
CN107987096B (zh) * | 2017-12-17 | 2020-06-05 | 沧州普瑞东方科技有限公司 | 一种合成2-醛基呋喃-4-硼酸频那醇酯的方法 |
CN110229177A (zh) * | 2019-06-14 | 2019-09-13 | 南京博源医药科技有限公司 | 一种5-醛基呋喃-3-硼酸的制备工艺 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60302309T2 (de) * | 2002-09-25 | 2006-07-20 | Degussa Ag | Herstellung von 5-Formyl-2-furylborsäure |
-
2005
- 2005-05-20 DE DE102005023989A patent/DE102005023989A1/de not_active Withdrawn
-
2006
- 2006-05-10 EP EP06742855A patent/EP1885729A2/de not_active Withdrawn
- 2006-05-10 WO PCT/EP2006/004369 patent/WO2006122683A2/de not_active Application Discontinuation
- 2006-05-10 US US11/912,157 patent/US20080188671A1/en not_active Abandoned
- 2006-05-10 CN CNA200680017155XA patent/CN101175761A/zh active Pending
Non-Patent Citations (2)
Title |
---|
FLORENTIN, D. ET AL: "Étude des pKa et la protodéboronation des acides furanneboroniques" BULLETIN DE LA SOCIETE CHIMIQUE DE FRANCE , (11-12, PT. 2), 1999-2005 CODEN: BSCFAS; ISSN: 0037-8968, 1976, XP002404888 in der Anmeldung erwähnt * |
FLORENTIN, D. ET AL: "Synthèse et étude RMN des acides furanneboroniques et formylfuranneboroniques" JOURNAL OF HETEROCYCLIC CHEMISTRY , 13(6), 1265-72 CODEN: JHTCAD; ISSN: 0022-152X, 1976, XP002404889 * |
Also Published As
Publication number | Publication date |
---|---|
WO2006122683A3 (de) | 2007-05-03 |
DE102005023989A1 (de) | 2006-11-23 |
US20080188671A1 (en) | 2008-08-07 |
CN101175761A (zh) | 2008-05-07 |
EP1885729A2 (de) | 2008-02-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1291347B1 (de) | Verfahren zur Herstellung von Bisallylboranen und nicht-aromatischen Boronsäuren | |
EP1988095B1 (de) | Verfarhen zur Herstellung von Aminoaryl- bzw. heteroarylboronsaeuren und ihren Derivaten | |
DE69401813T2 (de) | Enantioselektive oxazaborolidin-katalysatoren | |
US5358546A (en) | Highly reactive forms of zinc and reagents thereof | |
EP1537126A1 (de) | Verfahren zur metallorganischen herstellung organischer zwischenprodukte ber aryllithium-basen | |
WO2006122683A2 (de) | Verfahren zur herstellung von 2-formylfuran-4-boronsäure | |
EP1479686B1 (de) | Verfahren zur Herstellung von Anilinboronsäuren und ihren Derivaten | |
EP1994037A1 (de) | Magnesiumorganisches synthesemittel | |
WO2003033503A2 (de) | Verfahren zur metallierung von aromaten durch lithiumorganische verbindungen | |
EP1046640A2 (de) | Verfahren zur Herstellung von substituierten Phenyl-boronsäuren | |
EP0934246B1 (de) | Verfahren zur herstellung von alpha-alkoxy-alpha-trifluormethyl-arylessigsäureestern und -arylessigsäuren | |
EP1070718B1 (de) | Verfahren zur Herstellung von Grignard-Reagenzien und neue Grignard-Reagenzien | |
EP2297101B1 (de) | Verfahren zur herstellung von magnesiumamiden | |
DE69914847T2 (de) | Verfahren zur Herstellung von Fluoraryl-Magnesium-Halogeniden | |
DE10322844A1 (de) | Verfahren zur Herstellung von Pyridin-2-boronsäureestern | |
DE102006050717A1 (de) | Verfahren zur Herstellung funktionalisierter Fünfringheterocyclen und deren Verwendung | |
EP1943258B1 (de) | Verfahren zur herstellung funktionalisierter fünfringheterocyclen und deren verwendung | |
WO2011113925A2 (de) | Carbonylierung von organischen zinkverbindungen | |
DE102007020401A1 (de) | Verfahren zur Herstellung von Aminoaryl- bzw. heteroarylboronsäuren und ihren Derivaten | |
DE69810924T2 (de) | Verfahren zur herstellung von arylmalonaten | |
EP1295887B1 (de) | Verfahren zur Herstellung von reinen Aryllithiumverbindungen | |
WO2007121805A1 (de) | Verfahren zur herstellung von cyanoalkyl-, carboxyl- und aminocarbonylgruppen tragenden boronsäuren und ihren derivaten | |
DE102007025449A1 (de) | Verfahren zur Herstellung von Aminoaryl- bzw. heteroarylboronsäuren und ihren Derivaten | |
DE2651775A1 (de) | Verfahren zur herstellung von triarylboranen | |
DE102007010956A1 (de) | Magnesiumorganisches Synthesemittel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DPE1 | Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2006742855 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 4359/KOLNP/2007 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200680017155.X Country of ref document: CN |
|
NENP | Non-entry into the national phase |
Ref country code: RU |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: RU |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2006742855 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2006742855 Country of ref document: EP |