EP1077911A1 - Method for orthometalation of a carbocyclic aromatic derivative bearing at least an electron donor group - Google Patents
Method for orthometalation of a carbocyclic aromatic derivative bearing at least an electron donor groupInfo
- Publication number
- EP1077911A1 EP1077911A1 EP99919335A EP99919335A EP1077911A1 EP 1077911 A1 EP1077911 A1 EP 1077911A1 EP 99919335 A EP99919335 A EP 99919335A EP 99919335 A EP99919335 A EP 99919335A EP 1077911 A1 EP1077911 A1 EP 1077911A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- radical
- carbon atoms
- aromatic
- linear
- branched
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 42
- 238000007122 ortho-metalation reaction Methods 0.000 title abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 43
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 24
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 6
- 229910052801 chlorine Chemical group 0.000 claims abstract description 6
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
- 125000003367 polycyclic group Chemical group 0.000 claims abstract description 5
- 229910052751 metal Inorganic materials 0.000 claims abstract description 3
- 239000002184 metal Substances 0.000 claims abstract description 3
- -1 hydrocarbon radical Chemical group 0.000 claims description 74
- 238000006243 chemical reaction Methods 0.000 claims description 29
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 150000003254 radicals Chemical class 0.000 claims description 19
- 229910052783 alkali metal Inorganic materials 0.000 claims description 18
- 150000001340 alkali metals Chemical class 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 15
- MBIZFBDREVRUHY-UHFFFAOYSA-N 2,6-Dimethoxybenzoic acid Chemical compound COC1=CC=CC(OC)=C1C(O)=O MBIZFBDREVRUHY-UHFFFAOYSA-N 0.000 claims description 14
- 238000006263 metalation reaction Methods 0.000 claims description 13
- 239000011734 sodium Substances 0.000 claims description 11
- 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 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 claims description 10
- CNDHHGUSRIZDSL-UHFFFAOYSA-N 1-chlorooctane Chemical compound CCCCCCCCCl CNDHHGUSRIZDSL-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- OHBQPCCCRFSCAX-UHFFFAOYSA-N 1,4-Dimethoxybenzene Chemical compound COC1=CC=C(OC)C=C1 OHBQPCCCRFSCAX-UHFFFAOYSA-N 0.000 claims description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- LKUDPHPHKOZXCD-UHFFFAOYSA-N 1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1 LKUDPHPHKOZXCD-UHFFFAOYSA-N 0.000 claims description 4
- NQMUGNMMFTYOHK-UHFFFAOYSA-N 1-methoxynaphthalene Chemical compound C1=CC=C2C(OC)=CC=CC2=C1 NQMUGNMMFTYOHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- DLRJIFUOBPOJNS-UHFFFAOYSA-N phenetole Chemical compound CCOC1=CC=CC=C1 DLRJIFUOBPOJNS-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- RESHZVQZWMQUMB-UHFFFAOYSA-N 1,3-bis(phenylmethoxy)benzene Chemical compound C=1C=CC=CC=1COC(C=1)=CC=CC=1OCC1=CC=CC=C1 RESHZVQZWMQUMB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 3
- 150000002894 organic compounds Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 150000003738 xylenes Chemical class 0.000 claims description 3
- VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 claims description 2
- QZYDOKBVZJLQCK-UHFFFAOYSA-N 1,2-diethoxybenzene Chemical compound CCOC1=CC=CC=C1OCC QZYDOKBVZJLQCK-UHFFFAOYSA-N 0.000 claims description 2
- CPEDYIVPGWUOGI-UHFFFAOYSA-N 1,3,5-triethoxybenzene Chemical compound CCOC1=CC(OCC)=CC(OCC)=C1 CPEDYIVPGWUOGI-UHFFFAOYSA-N 0.000 claims description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- MKGFYMKFBCWNCP-UHFFFAOYSA-N 1,3-diethoxybenzene Chemical compound CCOC1=CC=CC(OCC)=C1 MKGFYMKFBCWNCP-UHFFFAOYSA-N 0.000 claims description 2
- UTFRNSPYRPYKDV-UHFFFAOYSA-N 1,3-dipropoxybenzene Chemical compound CCCOC1=CC=CC(OCCC)=C1 UTFRNSPYRPYKDV-UHFFFAOYSA-N 0.000 claims description 2
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 claims description 2
- GUMOJENFFHZAFP-UHFFFAOYSA-N 2-Ethoxynaphthalene Chemical compound C1=CC=CC2=CC(OCC)=CC=C21 GUMOJENFFHZAFP-UHFFFAOYSA-N 0.000 claims description 2
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 claims description 2
- ONNUYWHIJSKABC-UHFFFAOYSA-N 2-methylpropoxybenzene Chemical compound CC(C)COC1=CC=CC=C1 ONNUYWHIJSKABC-UHFFFAOYSA-N 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001348 alkyl chlorides Chemical class 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 2
- YFNONBGXNFCTMM-UHFFFAOYSA-N butoxybenzene Chemical compound CCCCOC1=CC=CC=C1 YFNONBGXNFCTMM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 238000007336 electrophilic substitution reaction Methods 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- BOTNYLSAWDQNEX-UHFFFAOYSA-N phenoxymethylbenzene Chemical compound C=1C=CC=CC=1COC1=CC=CC=C1 BOTNYLSAWDQNEX-UHFFFAOYSA-N 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- ZYNMJJNWXVKJJV-UHFFFAOYSA-N propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=CC=C1 ZYNMJJNWXVKJJV-UHFFFAOYSA-N 0.000 claims description 2
- DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical compound CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 claims description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- OJAJJFGMKAZGRZ-UHFFFAOYSA-N trimethyl(phenoxy)silane Chemical compound C[Si](C)(C)OC1=CC=CC=C1 OJAJJFGMKAZGRZ-UHFFFAOYSA-N 0.000 claims description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- GNWXVOQHLPBSSR-UHFFFAOYSA-N oxolane;toluene Chemical compound C1CCOC1.CC1=CC=CC=C1 GNWXVOQHLPBSSR-UHFFFAOYSA-N 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000008378 aryl ethers Chemical class 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-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
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 description 2
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 2
- FPEUDBGJAVKAEE-UHFFFAOYSA-N 1,3-dimethoxy-2-methylbenzene Chemical compound COC1=CC=CC(OC)=C1C FPEUDBGJAVKAEE-UHFFFAOYSA-N 0.000 description 1
- CKZBRKLFMRHHMA-UHFFFAOYSA-N 1,3-dimethoxy-2-phenylbenzene Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1 CKZBRKLFMRHHMA-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- AOPDRZXCEAKHHW-UHFFFAOYSA-N 1-pentoxypentane Chemical compound CCCCCOCCCCC AOPDRZXCEAKHHW-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- AQZGPSLYZOOYQP-UHFFFAOYSA-N Diisoamyl ether Chemical compound CC(C)CCOCCC(C)C AQZGPSLYZOOYQP-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000004996 alkyl benzenes Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000004320 controlled atmosphere Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000006471 dimerization reaction Methods 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
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical group CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000012800 visualization Methods 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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/04—Sodium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/15—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis
Definitions
- the present invention relates to a process for metallation of a carbocyclic aromatic derivative.
- the invention preferably relates to the orthometallation of 1, 3-dimethoxybenzene and more particularly to the preparation of 2,6-dimethoxybenzoic acid.
- an o-metallation designates a reaction leading to the generation of an anion in the ortho position with respect to an electron donor group present on an aromatic system.
- the present invention relates to an addition of an electrophile at the level of aromatic systems carrying an anion.
- This mechanism requires, in a first step, the departure of a leaving group, commonly a proton, prior to the addition of the electrophilic group carried out in a consecutive step.
- One of the approaches conventionally used to carry out the first step consists in bringing together the aromatic derivative which it is sought to functionalize with an organometallic compound in order to achieve its metallation.
- the usual reagent proposed for this reaction is butyllithium.
- the major drawback of this metallation is precisely to use butyllithium which is an expensive reagent.
- Li has also been described the reaction of sodium with 1,3-dimethoxy-benzene in the presence of chlorobenzene followed by carboxylation (G. Erhardt; Chem. Ber. 2042 (1963)).
- the reaction yield of the expected product remains very low due to the formation of side products.
- the objective of the present invention is therefore to propose a new metallation pathway for aromatic derivatives which is more advantageous in terms of cost and yield than those mentioned above.
- the present invention firstly relates to a process for orthometallation of a carbocyclic aromatic derivative carrying at least one electron donor group, characterized in that said carbocyclic aromatic derivative is reacted with an effective amount of at least one alkali metal in the presence of a compound of formula (I):
- R represents a hydrocarbon radical having from 1 to 20 carbon atoms which can be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical carrying a cyclic substituent; and
- - X represents a bromine or chlorine atom.
- aromatic the classic notion of aromaticity as defined in the literature, in particular by Jerry MARCH, Advanced Organic Chemistry, 4th edition, John Wiley and Sons, 1992, pp. 40 and following.
- the subject of the present invention is a process for orthometallation of a carbocyclic aromatic derivative of general formula (II):
- - A symbolizes the remainder of a cycle forming all or part of an aromatic, monocyclic or polycyclic carbocyclic system, system comprising at least one group R ', said cyclic residue being able to carry one or more substituents, - R "represents one or more substituents, identical or different, of electron donor nature possibly linked to each other, and
- a linear or branched al yl radical having from 1 to 12 carbon atoms, the hydrocarbon chain possibly being interrupted by a heteroatom (for example oxygen), by a functional group (for example -CO-) and / or carrier a substituent such as for example a cyclic substituent, aromatic or not.
- alkyl radical linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, dry - butyl, tert-butyl or of a linear or branched alkenyl radical having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl or from a C arylalkyl radical, to C 12 like benzyl,
- a carbocyclic radical saturated or comprising 1 or 2 unsaturations in the ring generally having 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring, said ring being able to be substituted with substituents such as R '. It may especially be a cycloalkyl group having 3 to 8 carbon atoms such as a cyclohexyl group and
- an aromatic carbocyclic radical preferably a monocyclic radical, generally having at least 4 carbon atoms, preferably 6 carbon atoms in the ring, said ring possibly being substituted. It can in particular be phenyl;
- a hydrogen atom • an alkyl radical, linear or branched at C 1 to C 6 and preferably at C, to C 4 such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl;
- R 2 representing a valential bond or a divalent linear or branched, saturated or unsaturated hydrocarbon radical having from 1 to 6 carbon atoms such as, for example, methylene, ethylene, propylene, isopropylene or isopropylidene and the radicals R 3 , which are identical or different, representing a hydrogen atom or a linear or branched alkyl radical having from 1 to 6 carbon atoms or else
- R ′ groups can be linked and form alkylenedioxy or alkylenedithio groups, preferably a methylenedioxy, ethylenedioxy, methylenedithio or ethylenedithio group.
- the residue A can represent the remainder of an aromatic, monocyclic carbocyclic compound having at least 4 carbon atoms and preferably 6 carbon atoms or the remainder of a polycyclic carbocyclic compound which can be constituted by at least 2 aromatic carbocycles and forming between them ortho- or ortho- and pericondensed systems or by at least 2 carbocycles of which at least one of them is aromatic and forming between them ortho- or ortho systems - and pericondensed. Mention may more particularly be made of a naphthalene residue.
- the remainder A can carry one or more radicals R 'on the aromatic nucleus.
- alkoxy groups denote, in a simplified manner, groups of the type -0-R ⁇ in which R, has the meaning given above.
- R ⁇ therefore represents both an acyclic or cycloaliphatic, saturated, unsaturated or aromatic aliphatic radical as a saturated or unsaturated aliphatic radical carrying a cyclic substituent, aromatic or not, or a trialkylsilyl radical.
- the carbocyclic aromatic ether which is involved in the process of the invention preferably corresponds to formula (II) in which R 1 in OR represents an acyclic aliphatic radical, saturated or unsaturated, linear or branched.
- R 1 of the aromatic ether represents a linear or branched alkyl radical having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms, the hydrocarbon chain possibly being interrupted by a hetero atom (for example l 'oxygen), by a functional group (for example -CO-) and / or carrying a substituent.
- acyclic aliphatic radical saturated or unsaturated, linear or branched, may optionally carry a cyclic substituent.
- ring is preferably understood to mean a saturated, unsaturated or aromatic carbocyclic ring, preferably cycloaliphatic or aromatic, in particular cycloaliphatic ring comprising 6 carbon atoms in the ring or benzene.
- the acyclic aliphatic radical can be linked to the cycle by a valential bond, a heteroatom or a functional group as illustrated in the case of the definition of R '.
- the ring can be optionally substituted and, by way of examples of cyclic substituents, it is possible, among others, to consider substituents such as R ′, the meaning of which is specified for the formula (IIa).
- R can also represent a saturated carbocyclic radical or comprising 1 or 2 unsaturations in the ring, generally having 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring, said ring being able to be substituted with substituents such as those proposed for
- R T can also represent an aromatic carbocyclic radical, preferably a monocyclic radical generally having at least 4 carbon atoms, of preferably 6 carbon atoms in the ring, said ring being able to be substituted with substituents such as those proposed for R '.
- the process of the invention is particularly applicable to aromatic ethers of formula (II) in which R represents a linear or branched alkyl radical having from 1 to 4 carbon atoms, an arylalkyl radical or a trialkylsilyl radical.
- R 1 radicals As examples of preferred R 1 radicals according to the invention, mention may be made of methyl or ethyl, benzyl and trimethysilyl radicals.
- R preferably represents an alkyl radical, linear or branched, having from 1 to 4 carbon atoms, preferably a methyl or ethyl radical or an arylalkyl radical or a trialkylsilyl radical and R 'and n are as defined above.
- aromatic ethers of formula (II) or (IIa) are preferably used in the process of the invention in which:
- R represents an alkyl radical, linear or branched, having from 1 to 4 carbon atoms, or an arylalkyl and preferably benzyl radical or a trialkylsilyl radical,
- R - R ' represents an alkoxy radical, linear or branched, having from 1 to 4 carbon atoms, preferably a methoxy or ethoxy radical or an OR 1 radical with R, as defined above.
- - monoethers such as anisole, ethoxybenzene (phenetole), propoxybenzene, isopropoxybenzene, butoxybenzene, isobutoxybenzene, benzyloxybenzene, 1-methoxynaphthalene, 2-methoxynaphthalene, 2-ethoxynaphthalene; substituted monoethers such as 1-methoxy-2-allyloxybenzene, phenoxytrimethylsilane;
- - diethers such as veratrole, 1,3-dimethoxybenzene, 1,4-dimethoxybenzene, 1,2-diethoxybenzene, 1,3-diethoxybenzene, 1,2-dimethoxybenzene, 1,3-dipropoxybenzene, 1, 2-methylenedioxybenzene, 1, 2-ethylenedioxybenzene; 1,3-dibenzyloxybenzene; 1,3-diphenol-bis-trimethylsilyl;
- the compounds to which the process according to the invention applies more particularly advantageously are 1,3-dimethoxybenzene, anisole, 1,4-dimethoxybenzene, 1,2-dimethoxybenzene and 1,3-dibenzyloxybenzene, 1,3-diphenol-bis-terbutyldimethylsilylated.
- R represents a linear or branched C 10 -C 10 alkyl group, C 3 -C 10 cycloalkyl, C 6 aryl
- R represents a linear or branched C 10 -C 10 alkyl group, C 3 -C 10 cycloalkyl, C 6 aryl
- C 12 or C 7 to C 15 alkylaryl such as for example a benzyl radical.
- it is a C 10 to 10 alkyl group and more preferably a C 3 to C 10 alkyl group with the alkyl chain possibly being interrupted by one or more oxygen atoms. It is more preferably a chloroalkane and preferably chlorobutane or chlorooctane.
- alkali metal used according to the invention may be sodium, lithium or potassium.
- the claimed process is more particularly advantageous when sodium is used as an alkali metal.
- the carbanion R " is generated which, by reaction with the aromatic carbocyclic derivative of general formula (II) or (IIa), leads to the metallation thereof.
- the carbanion R ′′ is advantageously generated in the presence of a carbocyclic aromatic derivative and therefore reacts immediately with it. Consequently, the claimed process makes it possible to significantly reduce the risks of parasitic reactions of dimerization, more particularly observed in the presence of sodium, and consisting of a reaction of carbanion R " on a compound of general formula
- This alkali metal can be introduced for the metallation reaction either in the form of a dispersion or in the molten state.
- the dispersed form is preferred, which is more advantageous in terms of reactivity.
- This dispersed form available commercially, can also be obtained in situ by vigorous stirring of the previously molten metal.
- the compound of general formula (I) is generally introduced in an amount of at least one equivalent of the aromatic carbocyclic derivative and preferably between approximately 1 to 2 equivalents.
- the alkali metal is for its part present between approximately 2 to 4 equivalents of the aromatic carbocyclic derivative and preferably between approximately 2 to 2.5 equivalents.
- reaction of the aromatic carbocyclic derivative with the compound of formula (I) and the alkali metal is carried out in an inert organic aprotic liquid under the appropriate reaction conditions.
- solvents suitable for the present invention there may be mentioned in particular aliphatic or aromatic hydrocarbons, aliphatic, cycloaliphatic or aromatic ether-oxides.
- paraffins such as, in particular, hexane, heptane, octane, nonane, decane, undecane, dodecane, tetradecane or cyclohexane
- aromatic hydrocarbons such as benzene, toluene, xylenes, cumene, cuts petroleum based on a mixture of alkylbenzenes, in particular the Solvesso® type cuts.
- organic solvents aliphatic, cycloaliphatic or aromatic ether-oxides and, more particularly, diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, methyltertiobutyl ether , dipentyl oxide, diisopentyl oxide, dimethyl ether of ethylene glycol (or 1,2-dimethoxyethane), dimethyl ether of diethylene glycol (or 1,5-dimethoxy 3-oxapentane); phenyl oxide, benzyl oxide; dioxane, tetrahydrofuran (THF).
- Preferred solvents are anhydrous aromatic hydrocarbons such as toluene, THF, xylenes and the like.
- the concentration of the aromatic carbocyclic derivative in the medium can vary within wide limits. Thus, it can be between 5 and 40% by weight of the medium and, preferably, is of the order of 20% by weight.
- the orthometallation reaction is carried out by first loading the alkali metal into the organic solvent. The whole is then kept under stirring.
- the consecutive addition of the aromatic carbocyclic derivative can be carried out according to two variants.
- the other preferably preferred variant consists in successively adding the aromatic carbocyclic derivative then the compound of general formula (I).
- the introduction of the various compounds is carried out at a temperature between -20 ° C and 50 ° C and, preferably, at room temperature. Subsequent heating of the reaction medium to a temperature between 20 ° C and 100 ° C and more preferably between 40 ° C and 60 ° C may if necessary be advantageous.
- the reaction is carried out at atmospheric pressure. It is preferred to carry out the reaction under a controlled atmosphere of inert gases such as nitrogen or rare gases such as argon.
- the progress of the metallation reaction can if necessary be monitored by visualization of the disappearance of the alkali metal.
- the metallic form of the aromatic carbocyclic derivative is present in the reaction medium in a solubilized form. If necessary, the excess of alkali metal is neutralized.
- an organic compound capable of interacting by electrophilic substitution with said metallation product is introduced into the reaction medium.
- R 5 representing a C 1 to C 12 alkyl radical, linear or branched, or C 3 to C 12 cycloalkyl, or a trifluoromethyl radical
- X' representing an atom of halogen such as chlorine or bromine.
- the electrophilic derivative is conventionally introduced in an amount of approximately 1.0 to 2 equivalents relative to the aromatic carbocyclic metallized derivative and preferably of approximately 1 to 1.5.
- the reaction can be carried out at a temperature between 20 ° C and 80 ° C and preferably between 20 ° C and 50 ° C. It is generally carried out at atmospheric pressure and under an intimate atmosphere.
- the reaction product can be isolated at the end of the substitution reaction by any conventional extraction type technique for example.
- a particular embodiment of the invention relates in particular to the preparation of 2,6-dimethoxybenzoic acid from 1,3-dimethoxybenzene.
- the subject of the present invention is a process for the preparation of 2,6-dimethoxybenzoic acid from 1,3-dimethoxybenzene via the orthometallation of the latter, characterized in that said metallation is carried out by reacting the 1, 3-dimethoxybenzene with an alkali metal in the presence of a compound of general formula (I):
- R represents a hydrocarbon radical having from 1 to 20 carbon atoms which can be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical carrying a cyclic substituent; and
- - X represents a bromine or chlorine atom.
- the alkali metal is as defined above. Preferably, it is sodium.
- the medium After acidification using a concentrated hydrochloric acid solution, the medium is concentrated under partial pressure.
- the residue is dissolved in acetone.
- the inorganic salts are removed by filtration.
- Example 4 is reproduced by substituting chlorobenzene for chlorooctarfe.
- the orthometallation reaction is carried out as in Example 1, using different substrates and C0 2 as electrophilic.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention concerns a method for orthometalation of a carbocyclic aromatic derivative bearing at least an electron donor group, characterised in that it consists in reacting said carbocyclic aromatic derivative with an efficient amount of at least one alkaline metal in the presence of a compound of formula (I): RX, wherein: R represents a hydrocarbon radical having 1 to 20 carbon atoms which can be a saturated or unsaturated, linear or branched, acyclic aliphatic radical; a saturated or unsaturated, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical bearing a cyclic substituent; and X represents a bromine or chlorine atom.
Description
Procédé d'orthométallation d'un dérivé aromatique carbocyclique portant au moins un groupement électrodonneur. Method for orthometallation of a carbocyclic aromatic derivative carrying at least one electron donor group.
La présente invention a pour objet un procédé de métallation d'un dérivé aromatique carbocyclique.The present invention relates to a process for metallation of a carbocyclic aromatic derivative.
L'invention vise préférentiellement l'orthométallation du 1 ,3- diméthoxybenzène et plus particulièrement la préparation de l'acide 2,6- diméthoxybenzoïque.The invention preferably relates to the orthometallation of 1, 3-dimethoxybenzene and more particularly to the preparation of 2,6-dimethoxybenzoic acid.
De manière conventionnelle, une o-métallation désigne une réaction conduisant à la génération d'un anion en position ortho par rapport à un groupe électrodonneur présent sur un système aromatique.Conventionally, an o-metallation designates a reaction leading to the generation of an anion in the ortho position with respect to an electron donor group present on an aromatic system.
Plus précisément, la présente invention a trait à une addition d'un électrophile au niveau de systèmes aromatiques porteurs d'un anion. Ce mécanisme requiert, dans une première étape, le départ d'un groupe partant, communément un proton, préalablement à l'addition du groupement électrophile réalisée dans une étape consécutive.More specifically, the present invention relates to an addition of an electrophile at the level of aromatic systems carrying an anion. This mechanism requires, in a first step, the departure of a leaving group, commonly a proton, prior to the addition of the electrophilic group carried out in a consecutive step.
Une des approches classiquement retenues pour réaliser la première étape consiste à mettre en présence le dérivé aromatique que l'on cherche à fonctionnaliser avec un composé organométallique en vue de réaliser sa métallation.One of the approaches conventionally used to carry out the first step consists in bringing together the aromatic derivative which it is sought to functionalize with an organometallic compound in order to achieve its metallation.
Le réactif usuel proposé pour cette réaction est le butyllithium. L'inconvénient majeur de cette métallation est précisément de faire appel à du butyllithium qui est un réactif coûteux. li a également été décrit la réaction du sodium sur du diméthoxy-1 ,3 benzène en présence du chlorobenzène suivie d'une carboxylation (G. Erhardt; Chem. Ber. 2042 (1963)). Toutefois, le rendement de la réaction en produit attendu demeure très faible en raison de la formation de produits secondaires. L'objectif de la présente invention est donc de proposer une nouvelle voie de métallation de dérivés aromatiques plus intéressante en terme de coût et de rendement que celles évoquées ci-dessus.
En conséquence, la présente invention a pour premier objet un procédé d'orthométallation d'un dérivé aromatique carbocyclique portant au moins un groupement électrodonneur, caractérisé en ce que l'on fait réagir ledit dérivé aromatique carbocyclique avec une quantité efficace d'au moins un métal alcalin en présence d'un composé de formule (I) :The usual reagent proposed for this reaction is butyllithium. The major drawback of this metallation is precisely to use butyllithium which is an expensive reagent. Li has also been described the reaction of sodium with 1,3-dimethoxy-benzene in the presence of chlorobenzene followed by carboxylation (G. Erhardt; Chem. Ber. 2042 (1963)). However, the reaction yield of the expected product remains very low due to the formation of side products. The objective of the present invention is therefore to propose a new metallation pathway for aromatic derivatives which is more advantageous in terms of cost and yield than those mentioned above. Consequently, the present invention firstly relates to a process for orthometallation of a carbocyclic aromatic derivative carrying at least one electron donor group, characterized in that said carbocyclic aromatic derivative is reacted with an effective amount of at least one alkali metal in the presence of a compound of formula (I):
RX (I) dans laquelleRX (I) in which
- R représente un radical hydrocarboné ayant de 1 à 20 atomes de carbone qui peut être un radical aliphatique acyclique saturé ou insaturé, linéaire ou ramifié ; un radical cycloaliphatique saturé, insaturé, monocyclique ou polycyclique ; un radical aliphatique saturé ou insaturé, linéaire ou ramifié porteur d'un substituant cyclique ; et- R represents a hydrocarbon radical having from 1 to 20 carbon atoms which can be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical carrying a cyclic substituent; and
- X représente un atome de brome ou de chlore.- X represents a bromine or chlorine atom.
Dans l'exposé qui suit de la présente invention, on entend parIn the following description of the present invention, the term “
"aromatique", la notion classique d'aromaticité telle que définie dans la littérature, notamment par Jerry MARCH, Advanced Organic Chemistry, 4ème édition, John Wiley and Sons, 1992, pp. 40 et suivantes."aromatic", the classic notion of aromaticity as defined in the literature, in particular by Jerry MARCH, Advanced Organic Chemistry, 4th edition, John Wiley and Sons, 1992, pp. 40 and following.
Plus précisément, la présente invention a pour objet un procédé d'orthométallation d'un dérivé aromatique carbocyclique de formule générale (II):More specifically, the subject of the present invention is a process for orthometallation of a carbocyclic aromatic derivative of general formula (II):
dans laquelle : in which :
- A symbolise le reste d'un cycle formant tout ou partie d'un système carbocyclique aromatique, monocyclique ou polycyclique, système comprenant au moins un groupement R', ledit reste cyclique pouvant porter un ou plusieurs substituants, - R" représente un ou plusieurs substituants, identiques ou différents, à caractère électrodonneur éventuellement liés entre eux, et- A symbolizes the remainder of a cycle forming all or part of an aromatic, monocyclic or polycyclic carbocyclic system, system comprising at least one group R ', said cyclic residue being able to carry one or more substituents, - R "represents one or more substituents, identical or different, of electron donor nature possibly linked to each other, and
- n est un nombre entier différent de zéro, inférieur ou égal à 4.
Le caractère électrodonneur des radicaux R' est apprécié dans le cadre de la présente invention selon l'échelle d'électronégativité établie par Jerry March- n is an integer other than zero, less than or equal to 4. The electron donor character of the radicals R ′ is appreciated in the context of the present invention according to the electronegativity scale established by Jerry March
"Advanced Organic Chemistry", 4ème édition, John Wiley and Sons, 1992, pp."Advanced Organic Chemistry", 4th edition, John Wiley and Sons, 1992, pp.
14 et suivantes. Le caractère électronégatif d'un radical est évalué au regard de celui de l'atome d'hydrogène dont la valeur est de 2, 176.14 and following. The electronegative character of a radical is evaluated with regard to that of the hydrogen atom whose value is 2.176.
A titre illustratif des radicaux pouvant être représentés par R' dans la formule générale (II), on peut notamment citer :By way of illustration of the radicals which can be represented by R 'in the general formula (II), there may be mentioned in particular:
- un radical al yle linéaire ou ramifié ayant de 1 à 12 atomes de carbone, la chaîne hydrocarbonée pouvant être éventuellement interrompue par un hétéroatome (par exemple l'oxygène), par un groupe fonctionnel (par exemple -CO-) et/ou porteuse d'un substituant comme par exemple un substituant cyclique aromatique ou non. Il peut notamment s'agir d'un radical alkyle, linéaire ou ramifié, ayant de 1 à 6 atomes de carbone, de préférence de 1 à 4 atomes de carbone, tel que méthyle, éthyle, propyle, isopropyle, butyle, isobutyle, sec- butyle, tert-butyle ou d'un radical alcényle linéaire ou ramifié ayant de 2 à 6 atomes de carbone, de préférence, de 2 à 4 atomes de carbone, tel que vinyle, allyle ou d'un radical arylalkyle en C, à C12 comme le benzyle,a linear or branched al yl radical having from 1 to 12 carbon atoms, the hydrocarbon chain possibly being interrupted by a heteroatom (for example oxygen), by a functional group (for example -CO-) and / or carrier a substituent such as for example a cyclic substituent, aromatic or not. It may especially be an alkyl radical, linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, dry - butyl, tert-butyl or of a linear or branched alkenyl radical having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl or from a C arylalkyl radical, to C 12 like benzyl,
- un radical carbocyclique saturé ou comprenant 1 ou 2 insaturations dans le cycle, ayant généralement de 3 à 8 atomes de carbone, de préférence, 6 atomes de carbone dans le cycle, ledit cycle pouvant être substitué avec des substituants tels que R'. Il peut notamment s'agir d'un groupe cycloalkyle ayant de 3 à 8 atomes de carbone comme un groupe cyclohexyle et- A carbocyclic radical saturated or comprising 1 or 2 unsaturations in the ring, generally having 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring, said ring being able to be substituted with substituents such as R '. It may especially be a cycloalkyl group having 3 to 8 carbon atoms such as a cyclohexyl group and
- un radical carbocyclique aromatique, de préférence monocyclique ayant généralement au moins 4 atomes de carbone, de préférence, 6 atomes de carbone dans le cycle, ledit cycle pouvant être substitué. Il peut notamment s'agir du phényle;an aromatic carbocyclic radical, preferably a monocyclic radical, generally having at least 4 carbon atoms, preferably 6 carbon atoms in the ring, said ring possibly being substituted. It can in particular be phenyl;
- Z(R^ avec Z représentant un atome d'oxygène ou de soufre et R répondant à la définition proposée pour R' ci-dessus et de préférence figurant- Z (R ^ with Z representing an oxygen or sulfur atom and R meeting the definition proposed for R 'above and preferably appearing
• Un atome d'hydrogène, • un radical alkyle, linéaire ou ramifié en C1 à C6 et de préférence en C, à C4 tel que méthyle, éthyle, propyle, isopropyle, butyle, isobutyle, sec-butyle, tert-butyle ;• A hydrogen atom, • an alkyl radical, linear or branched at C 1 to C 6 and preferably at C, to C 4 such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl;
• un radical cycloalkyle en C3 à C8 tel que le cyclohexyle ;
• un radical aryle en C5 à C12, condensé ou non tel que le phényle;• a C 3 to C 8 cycloalkyl radical such as cyclohexyl; • a C 5 to C 12 aryl radical, condensed or not, such as phenyl;
• un radical arylalkyle en C, à C12 comme le benzyle, et - - -" • un radical trialkylsilyle.• a C 1 to C 12 arylalkyl radical such as benzyl, and - - - " • a trialkylsilyl radical.
- R OORL - R2CO-N(R3)2,- R OOR L - R 2 CO-N (R 3 ) 2 ,
- R2-N(R3)2,- R 2 -N (R 3 ) 2 ,
- R2-CF3 ; avec R2 représentant un lien valentiel ou un radical hydrocarboné divalent linéaire ou ramifié, saturé ou insaturé ayant de 1 à 6 atomes de carbone tel que, par exemple, méthylène, éthylene, propylene, isopropylène ou isopropylidène et les radicaux R3, identiques ou différents, représentant un atome d'hydrogène ou un radical alkyle linéaire ou ramifié ayant de 1 à 6 atomes de carbone ou encore- R 2 -CF 3 ; with R 2 representing a valential bond or a divalent linear or branched, saturated or unsaturated hydrocarbon radical having from 1 to 6 carbon atoms such as, for example, methylene, ethylene, propylene, isopropylene or isopropylidene and the radicals R 3 , which are identical or different, representing a hydrogen atom or a linear or branched alkyl radical having from 1 to 6 carbon atoms or else
- deux groupes R' peuvent être liés et former des groupes alkylènedioxy ou alkylènedithio, de préférence, un groupe méthylènedioxy, éthylènedioxy, méthylènedithio ou éthylènedithio.- Two R ′ groups can be linked and form alkylenedioxy or alkylenedithio groups, preferably a methylenedioxy, ethylenedioxy, methylenedithio or ethylenedithio group.
Il est entendu que la liste des exemples de substituants R' figurant ci- dessus ne présente pas de caractère limitatif. N'importe quel substituant peut être présent sur le cycle dans la mesure où il demeure inerte dans les conditions réactionnelles c'est-à-dire qu'il n'interfère pas avec la réaction d'orthométallation. Dans la formule générale (II) des dérivés aromatiques, le reste A peut représenter le reste d'un composé carbocyclique aromatique, monocyclique ayant au moins 4 atomes de carbone et de préférence 6 atomes de carbone ou le reste d'un composé carbocyclique polycyclique qui peut être constitué par au moins 2 carbocycles aromatiques et formant entre eux des systèmes ortho- ou ortho- et péricondensés ou par au moins 2 carbocycles dont au moins l'un d'entre eux est aromatique et formant entre eux des systèmes ortho- ou ortho- et péricondensés. On peut citer plus particulièrement, un reste naphtalénique.It is understood that the list of examples of substituents R ′ appearing above does not have any limiting nature. Any substituent can be present on the cycle insofar as it remains inert under the reaction conditions, that is to say that it does not interfere with the orthometallation reaction. In the general formula (II) of the aromatic derivatives, the residue A can represent the remainder of an aromatic, monocyclic carbocyclic compound having at least 4 carbon atoms and preferably 6 carbon atoms or the remainder of a polycyclic carbocyclic compound which can be constituted by at least 2 aromatic carbocycles and forming between them ortho- or ortho- and pericondensed systems or by at least 2 carbocycles of which at least one of them is aromatic and forming between them ortho- or ortho systems - and pericondensed. Mention may more particularly be made of a naphthalene residue.
Le reste A peut porter un ou plusieurs radicaux R' sur le noyau aromatique.The remainder A can carry one or more radicals R 'on the aromatic nucleus.
Le procédé de l'invention s'applique tout particulièrement aux dérivés aromatiques carbocycliques substitués par au moins un radical électrodonneur figuré par un groupe OR
Dans le présent texte, on désigne, de manière simplifiée, par "groupes alkoxy", les groupes du type -0-Rτ dans lesquels R, a la signification donnée précédemment. R^ représente donc aussi bien un radical aliphatique acyclique ou cycloaliphatique, saturé, insaturé ou aromatique qu'un radical aliphatique saturé ou insaturé porteur d'un substituant cyclique, aromatique ou non, ou encore un radical trialkylsilyle.The process of the invention applies very particularly to aromatic carbocyclic derivatives substituted by at least one electron donor radical represented by an OR group In the present text, "alkoxy groups" denote, in a simplified manner, groups of the type -0-Rτ in which R, has the meaning given above. R ^ therefore represents both an acyclic or cycloaliphatic, saturated, unsaturated or aromatic aliphatic radical as a saturated or unsaturated aliphatic radical carrying a cyclic substituent, aromatic or not, or a trialkylsilyl radical.
L'éther aromatique carbocyclique qui intervient dans le procédé de l'invention répond de préférence à la formule (II) dans laquelle R^ dans OR, représente un radical aliphatique acyclique, saturé ou insaturé, linéaire ou ramifié.The carbocyclic aromatic ether which is involved in the process of the invention preferably corresponds to formula (II) in which R 1 in OR represents an acyclic aliphatic radical, saturated or unsaturated, linear or branched.
Plus préférentiellement, R1 de l'éther aromatique représente un radical alkyle linéaire ou ramifié ayant de 1 à 12 atomes de carbone, de préférence de 1 à 6 atomes de carbone, la chaîne hydrocarbonée pouvant être éventuellement interrompue par un hétéroatome (par exemple l'oxygène), par un groupe fonctionnel (par exemple -CO-) et/ou porteuse d'un substituant.More preferably, R 1 of the aromatic ether represents a linear or branched alkyl radical having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms, the hydrocarbon chain possibly being interrupted by a hetero atom (for example l 'oxygen), by a functional group (for example -CO-) and / or carrying a substituent.
Le radical aliphatique acyclique, saturé ou insaturé, linéaire ou ramifié, peut être éventuellement porteur d'un substituant cyclique. Par cycle, on entend de préférence, un cycle carbocyclique saturé, insaturé ou aromatique, de préférence cycloaliphatique ou aromatique notamment cycloaliphatique comprenant 6 atomes de carbone dans le cycle ou benzénique.The acyclic aliphatic radical, saturated or unsaturated, linear or branched, may optionally carry a cyclic substituent. The term “ring” is preferably understood to mean a saturated, unsaturated or aromatic carbocyclic ring, preferably cycloaliphatic or aromatic, in particular cycloaliphatic ring comprising 6 carbon atoms in the ring or benzene.
Le radical aliphatique acyclique peut être relié au cycle par un lien valentiel, un hétéroatome ou un groupe fonctionnel comme illustrés dans le cas de la définition de R'.The acyclic aliphatic radical can be linked to the cycle by a valential bond, a heteroatom or a functional group as illustrated in the case of the definition of R '.
Le cycle peut être éventuellement substitué et à titre d'exemples de substituants cycliques, on peut envisager, entre autres, les substituants tels que R' dont la signification est précisée pour la formule (lia).The ring can be optionally substituted and, by way of examples of cyclic substituents, it is possible, among others, to consider substituents such as R ′, the meaning of which is specified for the formula (IIa).
R peut représenter également un radical carbocyclique saturé ou comprenant 1 ou 2 insaturations dans le cycle, ayant généralement de 3 à 8 atomes de carbone, de préférence, 6 atomes de carbone dans le cycle, ledit cycle pouvant être substitué avec des substituants tels que ceux proposés pourR can also represent a saturated carbocyclic radical or comprising 1 or 2 unsaturations in the ring, generally having 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring, said ring being able to be substituted with substituents such as those proposed for
R'.R '.
RT peut représenter également un radical carbocyclique aromatique, de préférence monocyclique ayant généralement au moins 4 atomes de carbone, de
préférence, 6 atomes de carbone dans le cycle, ledit cycle pouvant être substitué avec des substituants tels que ceux proposés pour R'.R T can also represent an aromatic carbocyclic radical, preferably a monocyclic radical generally having at least 4 carbon atoms, of preferably 6 carbon atoms in the ring, said ring being able to be substituted with substituents such as those proposed for R '.
Le procédé de l'invention s'applique tout particulièrement aux éthers aromatiques de formule (II) dans laquelle R, représente un radical alkyle linéaire ou ramifié ayant de 1 à 4 atomes de carbone, un radical arylalkyle ou un radical trialkylsilyle.The process of the invention is particularly applicable to aromatic ethers of formula (II) in which R represents a linear or branched alkyl radical having from 1 to 4 carbon atoms, an arylalkyl radical or a trialkylsilyl radical.
Comme exemples de radicaux R^ préférés selon l'invention, on peut citer les radicaux méthyle ou éthyle, benzyle et triméthysilyle.As examples of preferred R 1 radicals according to the invention, mention may be made of methyl or ethyl, benzyl and trimethysilyl radicals.
Le procédé de l'invention s'applique plus particulièrement aux éthers aromatiques de formule (lia) :The process of the invention applies more particularly to aromatic ethers of formula (IIa):
Dans la formule (Ma), R, représente préférentiellement un radical alkyle, linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, de préférence, un radical méthyle ou éthyle ou un radical arylalkyle ou un radical trialkylsilyle et R' et n sont tels que définis ci-dessus.In the formula (Ma), R preferably represents an alkyl radical, linear or branched, having from 1 to 4 carbon atoms, preferably a methyl or ethyl radical or an arylalkyl radical or a trialkylsilyl radical and R 'and n are as defined above.
Interviennent préférentiellement dans le procédé de l'invention des éthers aromatiques de formule (II) ou (lia) dans lesquelles :The aromatic ethers of formula (II) or (IIa) are preferably used in the process of the invention in which:
- n varie de 0 à 2,- n varies from 0 to 2,
- R représente un radical alkyle, linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, ou un radical arylalkyle et de préférence benzyle ou un radical trialkylsilyle,R represents an alkyl radical, linear or branched, having from 1 to 4 carbon atoms, or an arylalkyl and preferably benzyl radical or a trialkylsilyl radical,
- R' représente un radical alkoxy, linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, de préférence, un radical méthoxy ou éthoxy ou un radical OR1 avec R, tel que défini ci-dessus.- R 'represents an alkoxy radical, linear or branched, having from 1 to 4 carbon atoms, preferably a methoxy or ethoxy radical or an OR 1 radical with R, as defined above.
A titre illustratif de composés répondant à la formule (II) ou (lia), on peut mentionner plus particulièrement :
- les monoéthers tels que l'anisole, l'éthoxybenzène (phénétole), le propoxybenzène, l'isopropoxybenzène, le butoxybenzène, l'isobutoxybenzène, le benzyloxybenzène, le 1-méthoxynaphtalène, le 2-méthoxynaphtalène, le 2- éthoxynaphtalène ; les monoéthers substitués tels que le 1-méthoxy-2- allyloxybenzène, le phénoxytriméthylsilane ;By way of illustration of compounds corresponding to formula (II) or (IIa), there may be mentioned more particularly: - monoethers such as anisole, ethoxybenzene (phenetole), propoxybenzene, isopropoxybenzene, butoxybenzene, isobutoxybenzene, benzyloxybenzene, 1-methoxynaphthalene, 2-methoxynaphthalene, 2-ethoxynaphthalene; substituted monoethers such as 1-methoxy-2-allyloxybenzene, phenoxytrimethylsilane;
- les diéthers comme le vératrole, le 1 ,3-diméthoxybenzène, le 1 ,4- diméthoxybenzène, le 1 ,2-diéthoxybenzène, le 1 ,3-diéthoxybenzène, le 1 ,2- diméthoxybenzène, le 1 ,3-dipropoxybenzène, le 1 ,2-méthylènedioxybenzène, le 1 ,2-éthylènedioxybenzène ; le 1 ,3-dibenzyloxybenzène ; le 1 ,3-diphénol-bis- triméthylsilylé ;- diethers such as veratrole, 1,3-dimethoxybenzene, 1,4-dimethoxybenzene, 1,2-diethoxybenzene, 1,3-diethoxybenzene, 1,2-dimethoxybenzene, 1,3-dipropoxybenzene, 1, 2-methylenedioxybenzene, 1, 2-ethylenedioxybenzene; 1,3-dibenzyloxybenzene; 1,3-diphenol-bis-trimethylsilyl;
- les triéthers comme le 1 ,3,5-triméthoxybenzène et le 1 ,3,5- triéthoxybenzène.- triethers such as 1, 3,5-trimethoxybenzene and 1, 3,5-triethoxybenzene.
Les composés auxquels s'applique de manière plus particulièrement intéressante le procédé selon l'invention sont le 1 ,3-diméthoxybenzène, l'anisole, le 1 ,4-diméthoxybenzène, le 1 ,2-diméthoxybenzène et le 1 ,3- dibenzyloxybenzène, le 1 ,3-diphénol-bis-terbutyldiméthylsilylé.The compounds to which the process according to the invention applies more particularly advantageously are 1,3-dimethoxybenzene, anisole, 1,4-dimethoxybenzene, 1,2-dimethoxybenzene and 1,3-dibenzyloxybenzene, 1,3-diphenol-bis-terbutyldimethylsilylated.
Pour ce qui est du composé de formule générale (I), conviennent tout particulièrement à l'invention les composés dans lesquels R représente un groupement alkyle linéaire ou ramifié en C à C10, cycloalkyle en C3 à C10, aryle en C6 à C12 ou alkylaryle en C7 à C15 comme par exemple un radical benzyle.As regards the compound of general formula (I), the compounds in which R represents a linear or branched C 10 -C 10 alkyl group, C 3 -C 10 cycloalkyl, C 6 aryl, are very particularly suitable for the invention. to C 12 or C 7 to C 15 alkylaryl such as for example a benzyl radical.
Plus préférentiellement, il s'agit d'un groupement alkyle en C à C10 et plus préférentiellement d'un groupement alkyle en C3 à C10 avec la chaîne alkyle pouvant le cas échéant être interrompue par un ou plusieurs atomes d'oxygène. II s'agit plus préférentiellement d'un chloroalcane et de préférence du chlorobutane ou chlorooctane.More preferably, it is a C 10 to 10 alkyl group and more preferably a C 3 to C 10 alkyl group with the alkyl chain possibly being interrupted by one or more oxygen atoms. It is more preferably a chloroalkane and preferably chlorobutane or chlorooctane.
En ce qui concerne le métal alcalin employé selon l'invention, il peut s'agir du sodium, lithium ou potassium. Le procédé revendiqué est plus particulièrement intéressant lorsque le sodium est utilisé à titre de métal alcalin.As regards the alkali metal used according to the invention, it may be sodium, lithium or potassium. The claimed process is more particularly advantageous when sodium is used as an alkali metal.
En effet, il est vraisemblable que par réaction du composé de formule générale (I) sur le métal alcalin, on génère le carbanion R" qui, par réaction avec
le dérivé aromatique carbocyclique de formule générale (II) ou (lia), conduit à la métallation de celui-ci. Or, dans le cas du procédé revendiqué, le carbanion R" est avantageusement généré en présence d'un dérivé aromatique carbocyclique et donc réagit de suite avec celui-ci. En conséquence, le procédé revendiqué permet de réduire significativement les risques de réactions parasites de dimérisation, plus particulièrement observées en présence de sodium, et consistant en une réaction du carbanion R" sur un composé de formule généraleIndeed, it is likely that by reaction of the compound of general formula (I) with the alkali metal, the carbanion R " is generated which, by reaction with the aromatic carbocyclic derivative of general formula (II) or (IIa), leads to the metallation thereof. However, in the case of the claimed process, the carbanion R ″ is advantageously generated in the presence of a carbocyclic aromatic derivative and therefore reacts immediately with it. Consequently, the claimed process makes it possible to significantly reduce the risks of parasitic reactions of dimerization, more particularly observed in the presence of sodium, and consisting of a reaction of carbanion R " on a compound of general formula
Ce métal alcalin peut être introduit pour la réaction de métallation soit sous la forme d'une dispersion, soit à l'état fondu.This alkali metal can be introduced for the metallation reaction either in the form of a dispersion or in the molten state.
Généralement, on privilégie la forme dispersée qui est plus avantageuse en terme de réactivité. Cette forme dispersée, disponible commercialement, peut également être obtenue in situ par agitation vigoureuse du métal préalablement fondu.Generally, the dispersed form is preferred, which is more advantageous in terms of reactivity. This dispersed form, available commercially, can also be obtained in situ by vigorous stirring of the previously molten metal.
Le composé de formule générale (I) est généralement introduit à raison d'au moins un équivalent du dérivé aromatique carbocyclique et de préférence entre environ 1 à 2 équivalents. Le métal alcalin est pour sa part présent entre environ 2 à 4 équivalents du dérivé aromatique carbocyclique et de préférence entre environ 2 à 2,5 équivalents.The compound of general formula (I) is generally introduced in an amount of at least one equivalent of the aromatic carbocyclic derivative and preferably between approximately 1 to 2 equivalents. The alkali metal is for its part present between approximately 2 to 4 equivalents of the aromatic carbocyclic derivative and preferably between approximately 2 to 2.5 equivalents.
La réaction du dérivé aromatique carbocyclique avec le composé de formule (I) et le métal alcalin est conduite au sein d'un liquide aprotique organique inerte dans les conditions réactionnelles appropriées. Comme exemples de solvants convenant à la présente invention, on peut citer en particulier les hydrocarbures aliphatiques ou aromatiques, les éther- oxydes aliphatiques, cycloaliphatiques ou aromatiques.The reaction of the aromatic carbocyclic derivative with the compound of formula (I) and the alkali metal is carried out in an inert organic aprotic liquid under the appropriate reaction conditions. As examples of solvents suitable for the present invention, there may be mentioned in particular aliphatic or aromatic hydrocarbons, aliphatic, cycloaliphatic or aromatic ether-oxides.
A titre d'exemples d'hydrocarbures aliphatiques ou cycloaliphatiques, on peut citer plus particulièrement les paraffines telles que notamment, l'hexane, l'heptane, l'octane, le nonane, le décane, le undécane, le dodécane, le tétradécane ou le cyclohexane, et les hydrocarbures aromatiques comme notamment le benzène, le toluène, les xylènes, le cumène, les coupes
pétrolières constituées de mélange d'alkylbenzènes, notamment les coupes de type Solvesso®.As examples of aliphatic or cycloaliphatic hydrocarbons, there may be mentioned more particularly paraffins such as, in particular, hexane, heptane, octane, nonane, decane, undecane, dodecane, tetradecane or cyclohexane, and aromatic hydrocarbons such as benzene, toluene, xylenes, cumene, cuts petroleum based on a mixture of alkylbenzenes, in particular the Solvesso® type cuts.
On peut utiliser également à titre de solvants organiques, les éther-oxydes aliphatiques, cycloaliphatiques ou aromatiques et, plus particulièrement, l'oxyde de diéthyle, l'oxyde de dipropyle, l'oxyde de diisopropyle, l'oxyde de dibutyle, le méthyltertiobutyléther, l'oxyde de dipentyle, l'oxyde de diisopentyle, le diméthyléther de l'éthylèneglycol (ou 1 ,2-diméthoxyéthane), le diméthyléther du diéthylèneglycol (ou 1 ,5-diméthoxy 3-oxapentane) ; l'oxyde de phényle, l'oxyde de benzyle ; le dioxane, le tétrahydrofurane (THF). Les solvants préférés sont des hydrocarbures aromatiques anhydres comme le toluène, le THF, les xylènes et analogues anhydres.It is also possible to use, as organic solvents, aliphatic, cycloaliphatic or aromatic ether-oxides and, more particularly, diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, methyltertiobutyl ether , dipentyl oxide, diisopentyl oxide, dimethyl ether of ethylene glycol (or 1,2-dimethoxyethane), dimethyl ether of diethylene glycol (or 1,5-dimethoxy 3-oxapentane); phenyl oxide, benzyl oxide; dioxane, tetrahydrofuran (THF). Preferred solvents are anhydrous aromatic hydrocarbons such as toluene, THF, xylenes and the like.
On peut également utiliser un mélange de solvants organiques. Bien entendu le solvant retenu doit demeurer inerte dans les conditions réactionnelles.It is also possible to use a mixture of organic solvents. Of course, the solvent retained must remain inert under the reaction conditions.
La concentration du dérivé aromatique carbocyclique dans le milieu peut varier dans de larges limites. Ainsi, elle peut être comprise entre 5 et 40 % en poids du milieu et, de préférence, est de l'ordre de 20 % en poids.The concentration of the aromatic carbocyclic derivative in the medium can vary within wide limits. Thus, it can be between 5 and 40% by weight of the medium and, preferably, is of the order of 20% by weight.
D'un point de vue pratique, la réaction d'orthométallation est conduite en chargeant tout d'abord le métal alcalin dans le solvant organique. L'ensemble est alors maintenu sous agitation. En revanche, l'addition consécutive du dérivé aromatique carbocyclique peut être réalisée selon deux variantes.From a practical point of view, the orthometallation reaction is carried out by first loading the alkali metal into the organic solvent. The whole is then kept under stirring. On the other hand, the consecutive addition of the aromatic carbocyclic derivative can be carried out according to two variants.
Selon une première variante, on introduit celui sous la forme d'un mélange avec le composé de formule générale (I). L'addition de ce mélange au milieu réactionnel est de préférence réalisée de manière progressive.According to a first variant, that is introduced in the form of a mixture with the compound of general formula (I). The addition of this mixture to the reaction medium is preferably carried out gradually.
L'autre variante de préférence retenue, consiste à ajouter de manière successive le dérivé aromatique carbocyclique puis le composé de formule générale (I).The other preferably preferred variant consists in successively adding the aromatic carbocyclic derivative then the compound of general formula (I).
Généralement, l'introduction des différents composés est réalisée à une température comprise entre -20° C et 50° C et, de préférence, à température ambiante. Un chauffage ultérieur du milieu réactionnel à une température entre 20° C et 100° C et plus préférentiellement entre 40° C et 60° C peut le cas échéant être avantageux.
Généralement, la réaction est conduite à pression atmosphérique. On préfère conduire la réaction sous atmosphère contrôlée de gaz inertes tels que l'azote ou les gaz rares comme l'argon.Generally, the introduction of the various compounds is carried out at a temperature between -20 ° C and 50 ° C and, preferably, at room temperature. Subsequent heating of the reaction medium to a temperature between 20 ° C and 100 ° C and more preferably between 40 ° C and 60 ° C may if necessary be advantageous. Generally, the reaction is carried out at atmospheric pressure. It is preferred to carry out the reaction under a controlled atmosphere of inert gases such as nitrogen or rare gases such as argon.
Le déroulement de la réaction de métallation peut le cas échéant être contrôlé par visualisation de la disparition du métal alcalin. A la fin de la réaction, la forme métallée du dérivé aromatique carbocyclique est présente dans le milieu réactionnel sous une forme solubilisée. Le cas échéant, l'excès de métal alcalin est neutralisé.The progress of the metallation reaction can if necessary be monitored by visualization of the disappearance of the alkali metal. At the end of the reaction, the metallic form of the aromatic carbocyclic derivative is present in the reaction medium in a solubilized form. If necessary, the excess of alkali metal is neutralized.
Le produit de la réaction d'orthométallation n'est pas isolé et utilisé tel quel pour conduire à des dérivés du composé de formule générale (II) ou (lia).The product of the orthometallation reaction is not isolated and used as such to lead to derivatives of the compound of general formula (II) or (IIa).
Généralement, on introduit dans le milieu réactionnel un composé organique capable d'interagir par substitution électrophile avec ledit produit de métallation.Generally, an organic compound capable of interacting by electrophilic substitution with said metallation product is introduced into the reaction medium.
A titre représentatif et non limitatif de ce type de composés organiques, on peut notamment citer les composés suivants :As a representative and non-limiting example of this type of organic compound, the following compounds may be mentioned:
- S02, - S0 2,
- C02,- C0 2 ,
- CS2, - CS 2,
- (R5)2NCHO, - (CH20)n. avec n' étant un entier variant de 1 à 3,- (R 5 ) 2 NCHO, - (CH 2 0) n . with n being an integer varying from 1 to 3,
- paraformaldéhyde,- paraformaldehyde,
- (R50)2S02( - (R 5 0) 2 S0 2 (
- R5SiX\- R 5 SiX \
- ArCH2X\ - R5-S-S-R5 - ArCH 2 X \ - R 5 -SSR 5
- R5S02-0-02SR5l - R 5 S0 2 -0-0 2 SR 5l
- R5X\- R 5 X \
- B(OR5)3, - B (OR 5 ) 3,
- R5so2x\ - ArCOX' , avec R5 représentant un radical alkyle en C, à C12, linéaire ou ramifié, ou cycloalkyle en C3 à C12, ou un radical trifluorométhyle et X' représentant un atome d'halogène comme le chlore ou le brome.
La réaction en soi peut être réalisée de manière conventionnelle.- R 5 so 2 x \ - ArCOX ', with R 5 representing a C 1 to C 12 alkyl radical, linear or branched, or C 3 to C 12 cycloalkyl, or a trifluoromethyl radical and X' representing an atom of halogen such as chlorine or bromine. The reaction per se can be carried out in a conventional manner.
Le dérivé électrophile est classiquement introduit à raison d'environ 1 ,0 à 2 équivalents par rapport au dérivé aromatique carbocyclique métallé et de préférence d'environ 1 à 1 ,5.The electrophilic derivative is conventionally introduced in an amount of approximately 1.0 to 2 equivalents relative to the aromatic carbocyclic metallized derivative and preferably of approximately 1 to 1.5.
La réaction peut être conduite à une température comprise entre 20° C et 80° C et de préférence entre 20° C et 50° C. Elle est généralement effectuée à pression atmosphérique et sous atmosphère interte.The reaction can be carried out at a temperature between 20 ° C and 80 ° C and preferably between 20 ° C and 50 ° C. It is generally carried out at atmospheric pressure and under an intimate atmosphere.
Le produit réactionnel peut être isolé à l'issue de la réaction de substitution par toute technique classique de type extraction par exemple.The reaction product can be isolated at the end of the substitution reaction by any conventional extraction type technique for example.
Un mode de réalisation particulier de l'invention concerne notamment la préparation de l'acide 2,6-diméthoxybenzoïque à partir du 1 ,3- diméthoxybenzène.A particular embodiment of the invention relates in particular to the preparation of 2,6-dimethoxybenzoic acid from 1,3-dimethoxybenzene.
Plus précisément, la présente invention a pour objet un procédé de préparation de l'acide 2,6-diméthoxybenzoïque à partir du 1 ,3-diméthoxybenzène via l'orthométallation de ce dernier, caractérisé en ce que ladite métallation est réalisée en faisant réagir le 1 ,3-diméthoxybenzène avec un métal alcalin en présence d'un composé de formule générale (I) :More specifically, the subject of the present invention is a process for the preparation of 2,6-dimethoxybenzoic acid from 1,3-dimethoxybenzene via the orthometallation of the latter, characterized in that said metallation is carried out by reacting the 1, 3-dimethoxybenzene with an alkali metal in the presence of a compound of general formula (I):
RX (I) dans laquelle :RX (I) in which:
- R représente un radical hydrocarboné ayant de 1 à 20 atomes de carbone qui peut être un radical aliphatique acyclique saturé ou insaturé, linéaire ou ramifié ; un radical cycloaliphatique saturé, insaturé, monocyclique ou polycyclique ; un radical aliphatique saturé ou insaturé, linéaire ou ramifié porteur d'un substituant cyclique ; et- R represents a hydrocarbon radical having from 1 to 20 carbon atoms which can be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical carrying a cyclic substituent; and
- X représente un atome de brome ou de chlore.- X represents a bromine or chlorine atom.
Le métal alcalin est tel que défini précédemment. De préférence, il s'agit du sodium.The alkali metal is as defined above. Preferably, it is sodium.
Selon un mode de réalisation de l'invention, il est associé à du chlorooctane.According to one embodiment of the invention, it is associated with chlorooctane.
Pour ce qui est de la stoechiométrie et des paramètres opératoires convenant à la réalisation de ladite réaction de métallation, on se reportera aux informations présentées précédemment.
Les exemples figurant ci-après sont présentés à titre illustratif et non limitatif de la présente invention.As regards the stoichiometry and the operating parameters suitable for carrying out said metallation reaction, reference will be made to the information presented above. The examples given below are presented by way of illustration and without implied limitation of the present invention.
EXEMPLE 1 : Préparation de l'acide 2,6-diméthoxybenzoïqueEXAMPLE 1 Preparation of 2,6-dimethoxybenzoic acid
Dans un réacteur, on introduit 5,90 g (0,256 M) de sodium et 200 ml de toluène anhydre. Le mélange est porté à reflux pendant 30 mn puis agité vigoureusement à température ambiante.5.90 g (0.256 M) of sodium and 200 ml of anhydrous toluene are introduced into a reactor. The mixture is brought to reflux for 30 min and then vigorously stirred at room temperature.
On ajoute alors successivement 12,6 g (0,09 M) de 1 ,3-diméthoxybenzène et 17,7 g (0,119 M) de chlorooctane. Après 2 h d'agitation à température ambiante, environ 35 g de C02 sont ajoutés et la réaction est agitée pendant 12 h à température ambiante.12.6 g (0.09 M) of 1,3-dimethoxybenzene and 17.7 g (0.119 M) of chlorooctane are then added successively. After 2 h of stirring at room temperature, approximately 35 g of CO 2 are added and the reaction is stirred for 12 h at room temperature.
L'excès de sodium est ensuite neutralisé par 10 ml de méthanol.The excess sodium is then neutralized with 10 ml of methanol.
Après acidification au moyen d'une solution concentrée d'acide chlorhydrique, le milieu est concentré sous pression partielle.After acidification using a concentrated hydrochloric acid solution, the medium is concentrated under partial pressure.
Le résidu est dissous dans l'acétone. Les sels inorganiques sont éliminés par filtration.The residue is dissolved in acetone. The inorganic salts are removed by filtration.
La recristallisation est réalisée dans un mélange acétone/hexane. On obtient alors 11 ,3 g d'acide 2,6-diméthoxy benzoïque (rendement = 68 %).Recrystallization is carried out in an acetone / hexane mixture. 11.3 g of 2,6-dimethoxy benzoic acid are then obtained (yield = 68%).
Caractéristiques du produit obtenu : RMN1H (DMSO d6) = 3,89 ppm (s, 6H)Characteristics of the product obtained: 1 H NMR (DMSO d 6 ) = 3.89 ppm (s, 6H)
6,60 ppm (d, 2H)6.60 ppm (d, 2H)
7,34 ppm (t, 1 H) 8-9 ppm (s, 1 H).7.34 ppm (t, 1 H) 8-9 ppm (s, 1 H).
En substituant du chloropropane au chlorooctane on obtient l'acide 2,6- diméthoxybenzoïque avec un rendement de 71 %.By substituting chloropropane for chlorooctane, 2,6-dimethoxybenzoic acid is obtained with a yield of 71%.
EXEMPLES 2-8 :EXAMPLES 2-8:
Préparation de composés aryliques 2,6-diméthoxy substitués
L'orthométallation du 1 ,3-diméthoxybenzène est réalisée dans les mêmes conditions que l'exemple 1 , en présence de chlorooctane. La nature de l'électrophile utilisé est ensuite différente :
Preparation of substituted 2,6-dimethoxy aryl compounds The orthometallation of 1,3-dimethoxybenzene is carried out under the same conditions as in Example 1, in the presence of chlorooctane. The nature of the electrophile used is then different:
EXEMPLE 9 : Essai comparatif EXAMPLE 9 Comparative test
On reproduit l'exemple 4 en substituant du chlorobenzène au chlorooctarfe.Example 4 is reproduced by substituting chlorobenzene for chlorooctarfe.
Le rendement isolé en 2,6-diméthoxytoluène est de 34% avec formation de 36% d'un produit secondaire, le 2,6-diméthoxybiphényle.The isolated yield of 2,6-dimethoxytoluene is 34% with the formation of 36% of a secondary product, 2,6-dimethoxybiphenyl.
EXEMPLES 10-12 :EXAMPLES 10-12:
Préparation de dérivés de l'acide benzoïquePreparation of benzoic acid derivatives
La réaction d'orthométallation est conduite comme dans l'exemple 1 , en utilisant des substrats différents et C02 comme électrophile.The orthometallation reaction is carried out as in Example 1, using different substrates and C0 2 as electrophilic.
(*) : utilisation d'une suspension commerciale de Na/toluène.
( * ): use of a commercial suspension of Na / toluene.
Claims
1. Procédé d'orthométallation d'un dérivé aromatique carbocyclique portant au moins un groupement électrodonneur, caractérisé en ce que l'on fait réagir ledit dérivé aromatique carbocyclique avec une quantité efficace d'au moins un métal alcalin en présence d'un composé de formule (I) :1. Method for orthometallation of a carbocyclic aromatic derivative carrying at least one electron donor group, characterized in that said carbocyclic aromatic derivative is reacted with an effective amount of at least one alkali metal in the presence of a compound of formula (I):
RX (I) dans laquelleRX (I) in which
- R représente un radical hydrocarboné ayant de 1 à 20 atomes de carbone qui peut être un radical aliphatique acyclique saturé ou insaturé, linéaire ou ramifié ; un radical cycloaliphatique saturé, insaturé, monocyclique ou polycyclique ; un radical aliphatique saturé ou insaturé, linéaire ou ramifié porteur d'un substituant cyclique et- R represents a hydrocarbon radical having from 1 to 20 carbon atoms which can be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical carrying a cyclic substituent and
- X représente un atome de brome ou de chlore.- X represents a bromine or chlorine atom.
2. Procédé selon la revendication 1 , caractérisé en ce que le dérivé aromatique carbocyclique répond à la formule générale (II):2. Method according to claim 1, characterized in that the aromatic carbocyclic derivative corresponds to the general formula (II):
dans laquelle : - A symbolise le reste d'un cycle formant tout ou partie d'un système carbocyclique aromatique, monocyclique ou polycyclique, système comprenant au moins un groupement R', ledit reste cyclique pouvant porter un ou plusieurs substituants, in which: - A symbolizes the remainder of a cycle forming all or part of an aromatic, monocyclic or polycyclic carbocyclic system, system comprising at least one group R ′, said cyclic residue being able to carry one or more substituents,
- R' représente un ou plusieurs substituants, identiques ou différents, à caractère électrodonneur, éventuellement liés entre eux, etR 'represents one or more substituents, identical or different, of electron-donating nature, optionally linked together, and
- n est un nombre entier différent de zéro, inférieur ou égal à 4.- n is an integer other than zero, less than or equal to 4.
3. Procédé selon la revendication 2, caractérisé en ce que R' est au moins un radical choisi parmi :3. Method according to claim 2, characterized in that R 'is at least one radical chosen from:
- un radical alkyle linéaire ou ramifié ayant de 1 à 12 atomes de carbone, la chaîne hydrocarbonée pouvant être éventuellement interrompue par un hétéroatome, par un groupe fonctionnel et/ou porteur d'un substituant comme un substituant cyclique, aromatique ou non,
- un radical carbocyclique saturé ou comprenant 1 ou 2 insaturations dans le cycle, ayant généralement de 3 à 8 atomes de carbone, de préférence, 6 atomes de carbone dans le cycle, ledit cycle pouvant être substitué avec des substituants tels que R' et - un radical carbocyclique aromatique, de préférence monocyclique ayant généralement au moins 4 atomes de carbone, de préférence, 6 atomes de carbone dans le cycle, ledit cycle pouvant être substitué tels que R',a linear or branched alkyl radical having from 1 to 12 carbon atoms, the hydrocarbon chain possibly being interrupted by a heteroatom, by a functional group and / or carrying a substituent such as a cyclic substituent, aromatic or not, - a carbocyclic radical saturated or comprising 1 or 2 unsaturations in the ring, generally having 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring, said ring being able to be substituted with substituents such as R 'and - an aromatic carbocyclic radical, preferably a monocyclic radical generally having at least 4 carbon atoms, preferably 6 carbon atoms in the ring, said ring being able to be substituted such as R ′,
- Z(R avec Z représentant un atome d'oxygène ou de soufre et R, répondant à la définition proposée pour R' ci-dessus et de préférence figurant • un atome d'hydrogène,- Z (R with Z representing an oxygen or sulfur atom and R, corresponding to the definition proposed for R 'above and preferably appearing • a hydrogen atom,
• un radical alkyle, linéaire ou ramifié en C, à C6 et de préférence en C à C4 tel que méthyle, éthyle, propyle, isopropyle, butyle, isobutyle, sec-butyle, tert-butyle ;• an alkyl radical, linear or branched at C, C 6 and preferably C 4 to C 4 such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl;
• un radical cycloalkyle en C3 à C8 tel que le cyclohexyle ; • un radical aryle en C5 à C12, condensé ou non tel que le phényle;• a C 3 to C 8 cycloalkyl radical such as cyclohexyl; • a C 5 to C 12 aryl radical, condensed or not, such as phenyl;
• un radical arylalkyle en C, à C12 comme le benzyle, etA C 1 to C 12 arylalkyl radical such as benzyl, and
• un radical trialkylsilyle.• a trialkylsilyl radical.
- RsCOOR,,- RsCOOR ,,
- R2CO-N(R3)2, - R2-N(R3)2,- R 2 CO-N (R 3 ) 2 , - R 2 -N (R 3 ) 2 ,
- R2-CF3 ; avec R2 représentant un lien valentiel ou un radical hydrocarboné divalent linéaire ou ramifié, saturé ou insaturé ayant de 1 à 6 atomes de carbone et les radicaux R3, identiques ou différents, représentant un atome d'hydrogène ou un radical alkyle linéaire ou ramifié ayant de 1 à 6 atomes de carbone ou encore- R 2 -CF 3 ; with R 2 representing a valential bond or a divalent linear or branched, saturated or unsaturated hydrocarbon radical having from 1 to 6 carbon atoms and the radicals R 3 , identical or different, representing a hydrogen atom or a linear or branched alkyl radical having 1 to 6 carbon atoms or
- deux groupes R' peuvent être liés et former des groupes alkylènedioxy ou alkylènedithio.- two R ′ groups can be linked and form alkylenedioxy or alkylenedithio groups.
4. Procédé selon la revendication 2 ou 3, caractérisé en ce que le reste A représente le reste d'un composé carbocyclique aromatique, monocyclique ayant au moins 4 atomes de carbone et de préférence 6 atomes de carbone ou le reste d'un composé carbocyclique polycyclique qui peut être constitué par au moins 2 carbocycles aromatiques et formant entre eux des systèmes ortho- ou ortho- et
péricondensés ou par au moins 2 carbocycles dont au moins l'un d'entre eux est aromatique et formant entre eux des systèmes ortho- ou ortho- et péricondensés.4. Method according to claim 2 or 3, characterized in that the residue A represents the remainder of an aromatic, monocyclic carbocyclic compound having at least 4 carbon atoms and preferably 6 carbon atoms or the remainder of a carbocyclic compound polycyclic which can consist of at least 2 aromatic carbocycles and form between them ortho- or ortho- and pericondensed or by at least 2 carbocycles of which at least one of them is aromatic and forming between them ortho- or ortho- and pericondensed systems.
5. Procédé selon l'une des revendications précédentes, caractérisé en ce que le substituant électrodonneur représenté par R' est au moins un groupe OR, avec R1 tel que défini en revendication 3.5. Method according to one of the preceding claims, characterized in that the electron donor substituent represented by R 'is at least one OR group, with R 1 as defined in claim 3.
6. Procédé selon la revendication 5, caractérisé en ce qu'il s'agit d'un groupe OR, avec R, représentant un radical alkyle linéaire ou ramifié ayant de 1 à 4 atomes de carbone, un radical arylalkyle ou un radical trialkylsilyle.6. Method according to claim 5, characterized in that it is an OR group, with R, representing a linear or branched alkyl radical having from 1 to 4 carbon atoms, an arylalkyl radical or a trialkylsilyl radical.
7. Procédé selon l'une des revendications précédentes, caractérisé en ce que le dérivé aromatique carbocyclique répond à la formule générale (Ma) :7. Method according to one of the preceding claims, characterized in that the aromatic carbocyclic derivative corresponds to the general formula (Ma):
dans laquelle R, représente un radical alkyle, linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, ou un radical arylalkyle ou un radical trialkylsilyle et R' et n sont tels que définis à la revendication 3. in which R represents a linear or branched alkyl radical having from 1 to 4 carbon atoms, or an arylalkyl radical or a trialkylsilyl radical and R 'and n are as defined in claim 3.
8. Procédé selon la revendication 7, caractérisé en ce que :8. Method according to claim 7, characterized in that:
- n varie de 0 à 2, - R, représente un radical alkyle, linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, un radical arylalkyle ou un radical trialkylsilyle,- n varies from 0 to 2, - R, represents an alkyl radical, linear or branched, having from 1 to 4 carbon atoms, an arylalkyl radical or a trialkylsilyl radical,
- R' représente un radical alkoxy, linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, de préférence, un radical méthoxy ou éthoxy ou un radical OR, avec R, tel que défini ci-dessus. - R 'represents an alkoxy radical, linear or branched, having from 1 to 4 carbon atoms, preferably, a methoxy or ethoxy radical or an OR radical, with R, as defined above.
9. Procédé selon l'une des revendications précédentes, caractérisé en ce que le dérivé aromatique est de formule (II) ou (lia) et est choisi parmi :9. Method according to one of the preceding claims, characterized in that the aromatic derivative is of formula (II) or (IIa) and is chosen from:
- les monoéthers tels que l'anisole, l'éthoxybenzène (phénétole), le propoxybenzène, l'isopropoxybenzène, le butoxybenzène, l'isobutoxybenzène, le 1-méthoxynaphtalène, le 2-méthoxynaphtalène, le 2-éthoxynaphtalène ; les monoéthers substitués tels que le 1-méthoxy-2-allyloxybenzène ; le benzyloxybenzène ; le phénoxytriméthylsilane ;- monoethers such as anisole, ethoxybenzene (phenetole), propoxybenzene, isopropoxybenzene, butoxybenzene, isobutoxybenzene, 1-methoxynaphthalene, 2-methoxynaphthalene, 2-ethoxynaphthalene; substituted monoethers such as 1-methoxy-2-allyloxybenzene; benzyloxybenzene; phenoxytrimethylsilane;
- les diéthers comme le vératrole, le 1 ,3-diméthoxybenzène, le 1 ,4- diméthoxybenzène, le 1 ,2-diéthoxybenzène, le 1 ,3-diéthoxybenzène, le 1 ,2-
diméthoxybenzène, le 1 ,3-dipropoxybenzène, le 1 ,2-méthylènedioxybenzène, le 1 ,2-éthylènedioxybenzène ; le 1 ,3-dibenzyloxybenzène ; le 1 ,3-diphénol-bis- triméthylsil té ;- diethers such as veratrole, 1, 3-dimethoxybenzene, 1, 4-dimethoxybenzene, 1, 2-diethoxybenzene, 1, 3-diethoxybenzene, 1, 2- dimethoxybenzene, 1,3-dipropoxybenzene, 1,2-methylenedioxybenzene, 1,2-ethylenedioxybenzene; 1,3-dibenzyloxybenzene; 1,3-diphenol-bis-trimethylsil t;
- les triéthers comme le 1 ,3,5-triméthoxybenzène et le 1 ,3,5- triéthoxybenzène.- triethers such as 1, 3,5-trimethoxybenzene and 1, 3,5-triethoxybenzene.
10. Procédé selon l'une des revendications précédentes, caractérisé en ce que dans le composé de formule générale (I) R représente un groupement choisi parmi les alkyle linéaire ou ramifié en C, à C10, cycloalkyle en C3 à C10, aryle en C6 à C12 ou alkylaryle en C7 à C15 . 10. Method according to one of the preceding claims, characterized in that in the compound of general formula (I) R represents a group chosen from linear or branched C 1 to C 10 alkyl, C 3 to C 10 cycloalkyl, C 6 to C 12 aryl or C 7 to C 15 alkylaryl.
11. Procédé selon l'une des revendications précédentes, caractérisé en ce que le composé de formule générale (I) est un chloroalcane et de préférence le chlorooctane ou chlorobutane.11. Method according to one of the preceding claims, characterized in that the compound of general formula (I) is a chloroalkane and preferably chlorooctane or chlorobutane.
12. Procédé selon l'une des revendications précédentes, caractérisé en ce que le métal alcalin est choisi parmi le lithium, sodium et potassium. 12. Method according to one of the preceding claims, characterized in that the alkali metal is chosen from lithium, sodium and potassium.
13. Procédé selon la revendication 12, caractérisé en ce qu'il s'agit du sodium de préférence sous une forme dispersée.13. The method of claim 12, characterized in that it is preferably sodium in a dispersed form.
14. Procédé selon l'une quelconque des revendications précédentes, caractérisé en ce que le composé de formule générale (I) est introduit à raison d'au moins un équivalent du dérivé aromatique carbocyclique et, de préférence, entre environ 1 à 2 équivalents.14. Method according to any one of the preceding claims, characterized in that the compound of general formula (I) is introduced in an amount of at least one equivalent of the aromatic carbocyclic derivative and, preferably, between approximately 1 to 2 equivalents.
15. Procédé selon l'une quelconque des revendications précédentes, caractérisé en ce que le métal alcalin est présent entre environ 2 à 4 équivalents du dérivé aromatique carbocyclique et de préférence entre environ 2 à 2,5 équivalents. 15. Method according to any one of the preceding claims, characterized in that the alkali metal is present between approximately 2 to 4 equivalents of the aromatic carbocyclic derivative and preferably between approximately 2 to 2.5 equivalents.
16. Procédé selon l'une quelconque des revendications précédentes, caractérisé en ce que la réaction de l'éther aromatique carbocyclique avec le composé de formule (I) et le métal alcalin est conduite au sein d'un liquide aprotique organique inerte dans les conditions réactionnelles appropriées.16. Method according to any one of the preceding claims, characterized in that the reaction of the carbocyclic aromatic ether with the compound of formula (I) and the alkali metal is carried out in an aprotic organic liquid inert under the conditions appropriate reaction.
17. Procédé selon la revendication 16, caractérisé en ce que le solvant est choisi parmi le toluène le THF, les xylènes et analogues anhydres.17. The method of claim 16, characterized in that the solvent is chosen from toluene THF, xylenes and anhydrous analogs.
18. Procédé selon l'une des revendications précédentes, caractérisé en ce que la concentration du dérivé aromatique est comprise entre 5 et 40 % en poids du milieu et de préférence est de l'ordre de 20 % en poids.
18. Method according to one of the preceding claims, characterized in that the concentration of the aromatic derivative is between 5 and 40% by weight of the medium and preferably is of the order of 20% by weight.
19. Procédé selon l'une des revendications précédentes, caractérisé en ce que la réaction d'orthométallation est conduite en chargeant tout d'abord le métal alcalin dans le solvant organique.19. Method according to one of the preceding claims, characterized in that the orthometallation reaction is carried out by first charging the alkali metal in the organic solvent.
20. Procédé selon la revendication 19, caractérisé en ce qu'on introduit ensuite le dérivé carbocyclique aromatique en mélange avec le composé de formule générale (I).20. Method according to claim 19, characterized in that the aromatic carbocyclic derivative is then introduced in admixture with the compound of general formula (I).
21. Procédé selon la revendication 19, caractérisé en ce qu'on ajoute successivement le dérivé aromatique carbocyclique puis le composé de formule générale (I). 21. The method of claim 19, characterized in that successively adds the aromatic carbocyclic derivative then the compound of general formula (I).
22. Procédé selon l'une quelconque des revendications 1 à 21 , caractérisé en ce que le produit de la réaction de métallation n'est pas isolé et est mis en présence in situ avec un composé organique capable de réagir avec lui par substitution électrophile.22. Method according to any one of claims 1 to 21, characterized in that the product of the metallation reaction is not isolated and is brought into presence in situ with an organic compound capable of reacting with it by electrophilic substitution.
23. Procédé de préparation de l'acide 2,6-diméthoxybenzoïque à partir du 1 ,3-diméthoxybenzène via l'orthométallation de ce dernier, caractérisé en ce que ladite métallation est réalisée en faisant réagir le 1 ,3-diméthoxybenzène avec un métal alcalin en présence d'un composé de formule générale (I) :23. Process for the preparation of 2,6-dimethoxybenzoic acid from 1,3-dimethoxybenzene via the orthometallation of the latter, characterized in that said metallation is carried out by reacting 1,3-dimethoxybenzene with a metal alkaline in the presence of a compound of general formula (I):
RX (I) dans laquelle : - R représente un radical hydrocarboné ayant de 1 à 20 atomes de carbone qui peut être un radical aliphatique acyclique saturé ou insaturé, linéaire ou ramifié ; un radical cycloaliphatique saturé, insaturé, monocyclique ou polycyclique ; un radical aliphatique saturé ou insaturé, linéaire ou ramifié porteur d'un substituant cyclique ; et - X représente un atome de brome ou de chlore.RX (I) in which: - R represents a hydrocarbon radical having from 1 to 20 carbon atoms which may be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical carrying a cyclic substituent; and - X represents a bromine or chlorine atom.
24. Procédé selon la revendication 23, caractérisé en ce que le composé de formule générale (I) est le chlorooctane.24. The method of claim 23, characterized in that the compound of general formula (I) is chlorooctane.
25. Procédé selon la revendication 23 ou 24, caractérisé en ce que le métal alcalin est le sodium.
25. The method of claim 23 or 24, characterized in that the alkali metal is sodium.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9806191A FR2778656B1 (en) | 1998-05-15 | 1998-05-15 | PROCESS FOR ORTHOMETALLATION OF A CARBOCYCLIC AROMATIC DERIVATIVE CARRYING AT LEAST ONE ELECTRONIC DONOR |
FR9806191 | 1998-05-15 | ||
PCT/FR1999/001163 WO1999059941A1 (en) | 1998-05-15 | 1999-05-14 | Method for orthometalation of a carbocyclic aromatic derivative bearing at least an electron donor group |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1077911A1 true EP1077911A1 (en) | 2001-02-28 |
Family
ID=9526421
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99919335A Withdrawn EP1077911A1 (en) | 1998-05-15 | 1999-05-14 | Method for orthometalation of a carbocyclic aromatic derivative bearing at least an electron donor group |
Country Status (6)
Country | Link |
---|---|
US (1) | US6384273B1 (en) |
EP (1) | EP1077911A1 (en) |
JP (1) | JP2002515465A (en) |
AU (1) | AU3714599A (en) |
FR (1) | FR2778656B1 (en) |
WO (1) | WO1999059941A1 (en) |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4845277A (en) * | 1988-08-22 | 1989-07-04 | Mine Safety Appliances Company | Method of preparing dialkoxybenzoic acid |
-
1998
- 1998-05-15 FR FR9806191A patent/FR2778656B1/en not_active Expired - Fee Related
-
1999
- 1999-05-14 US US09/700,467 patent/US6384273B1/en not_active Expired - Fee Related
- 1999-05-14 JP JP2000549561A patent/JP2002515465A/en not_active Withdrawn
- 1999-05-14 AU AU37145/99A patent/AU3714599A/en not_active Abandoned
- 1999-05-14 EP EP99919335A patent/EP1077911A1/en not_active Withdrawn
- 1999-05-14 WO PCT/FR1999/001163 patent/WO1999059941A1/en not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO9959941A1 * |
Also Published As
Publication number | Publication date |
---|---|
US6384273B1 (en) | 2002-05-07 |
JP2002515465A (en) | 2002-05-28 |
WO1999059941A1 (en) | 1999-11-25 |
FR2778656A1 (en) | 1999-11-19 |
AU3714599A (en) | 1999-12-06 |
FR2778656B1 (en) | 2000-12-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2005082820A1 (en) | Method for preparation of a fluoroaromatic compound from an aminoaromatic amine compound. | |
EP1144346B1 (en) | Method for preparing beta-phosphorous nitroxide radicals | |
CA1082742A (en) | Hydroxylation of aromatic compositions | |
EP0877726A1 (en) | Aromatic compound acylation method | |
EP0021927A1 (en) | Process for the preparation of aryl ethers | |
WO1999059941A1 (en) | Method for orthometalation of a carbocyclic aromatic derivative bearing at least an electron donor group | |
EP0200657B1 (en) | Process for the preparation of trifluoroethoxy- or trifluoroethylthiobenzenes | |
FR2944012A1 (en) | PROCESS FOR HYDROXYLATION OF PHENOLS AND ETHERS OF PHENOLS | |
FR2793792A1 (en) | PROCESS FOR ALPHA-METALLATION OF A HETEROCYCLIC, MONOCYCLIC OR POLYCYCLIC DERIVATIVE AND HAVING AT LEAST ONE HATEROCYCLE WITH 5 ATOMS, UNSATURATED OR AROMATIC | |
FR2889524A1 (en) | PROCESS FOR FORMING A CARBON-NITROGEN BOND | |
EP1250303A1 (en) | Method for preparing alpha-halogenated ketones | |
CA1077952A (en) | Process for the preparation of acetal halides from esters | |
CH618423A5 (en) | ||
FR2798928A1 (en) | PROCESS FOR THE PREPARATION OF SUBSTITUTED ALKYNIC MIXED ETHERS | |
EP0117186B1 (en) | Process for the preparation of cyclopropane derivatives | |
EP0931057B1 (en) | Method for preparing 4-methyl-biphenyl derivatives | |
EP0382641B1 (en) | Process for the preparation of ditertioalkyl dicarbonate | |
CH617674A5 (en) | ||
FR2787787A1 (en) | PROCESS FOR THE PREPARATION OF DIPHENYL AROMATIC THIOETHERS | |
FR2761680A1 (en) | INHIBITOR COMPOSITION OF THE RADICAL POLYMERIZATION OF ETHYLENICALLY UNSATURATED MONOMERS AND METHOD OF INHIBITING THE RADICAL POLYMERIZATION OF SAID MONOMERS | |
EP0002142A1 (en) | Complexes of boranes, their preparation, and their use in hydroboration and reduction reactions | |
EP0606182A1 (en) | Process for the preparation of an aromatic o-dihydroxylated compound | |
FR2735468A1 (en) | PROCESS FOR THE PREPARATION OF A DI- OR POLYHYDROXYL AROMATIC COMPOUND | |
EP0353130A1 (en) | Process for the preparation of N-allyl and N-alkyl anilines catalysed by iodides | |
WO1998011055A1 (en) | Method for the carboxylation on an aminonaphtol |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20001110 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IE IT LI NL |
|
17Q | First examination report despatched |
Effective date: 20020828 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
18W | Application withdrawn |
Effective date: 20030514 |