ZA200101690B - Process for preparing 3-isochromanone. - Google Patents
Process for preparing 3-isochromanone. Download PDFInfo
- Publication number
- ZA200101690B ZA200101690B ZA200101690A ZA200101690A ZA200101690B ZA 200101690 B ZA200101690 B ZA 200101690B ZA 200101690 A ZA200101690 A ZA 200101690A ZA 200101690 A ZA200101690 A ZA 200101690A ZA 200101690 B ZA200101690 B ZA 200101690B
- Authority
- ZA
- South Africa
- Prior art keywords
- process according
- xylene
- catalyst
- dihalide
- strength
- Prior art date
Links
- ILHLUZUMRJQEAH-UHFFFAOYSA-N 1,4-dihydroisochromen-3-one Chemical compound C1=CC=C2COC(=O)CC2=C1 ILHLUZUMRJQEAH-UHFFFAOYSA-N 0.000 title claims description 34
- 238000004519 manufacturing process Methods 0.000 title description 5
- 239000003054 catalyst Substances 0.000 claims description 50
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 44
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 43
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 22
- 229910052763 palladium Inorganic materials 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 14
- 150000003509 tertiary alcohols Chemical class 0.000 claims description 13
- 239000003446 ligand Substances 0.000 claims description 10
- 239000003444 phase transfer catalyst Substances 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 3
- 150000007529 inorganic bases 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
- 125000002723 alicyclic group Chemical group 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 26
- 239000012071 phase Substances 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 239000008346 aqueous phase Substances 0.000 description 17
- 239000008096 xylene Substances 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 15
- 239000010410 layer Substances 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 239000007789 gas Substances 0.000 description 11
- 229940078552 o-xylene Drugs 0.000 description 11
- 230000005587 bubbling Effects 0.000 description 10
- 239000007858 starting material Substances 0.000 description 9
- 238000010626 work up procedure Methods 0.000 description 9
- 101150003085 Pdcl gene Proteins 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 6
- 238000013019 agitation Methods 0.000 description 5
- 238000005810 carbonylation reaction Methods 0.000 description 5
- 239000000155 melt Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000002699 waste material Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
- 150000004714 phosphonium salts Chemical class 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical group CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- 229910001026 inconel Inorganic materials 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 150000002940 palladium Chemical class 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000003512 tertiary amines Chemical group 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000013022 venting Methods 0.000 description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
- IKECULIHBUCAKR-UHFFFAOYSA-N 2,3-dimethylbutan-2-ol Chemical compound CC(C)C(C)(C)O IKECULIHBUCAKR-UHFFFAOYSA-N 0.000 description 1
- STQJRJBXGGJDFO-UHFFFAOYSA-N 2,3-dimethylbutane-2,3-diol Chemical compound CC(C)(O)C(C)(C)O.CC(C)(O)C(C)(C)O STQJRJBXGGJDFO-UHFFFAOYSA-N 0.000 description 1
- DBTGFWMBFZBBEF-UHFFFAOYSA-N 2,4-dimethylpentane-2,4-diol Chemical compound CC(C)(O)CC(C)(C)O DBTGFWMBFZBBEF-UHFFFAOYSA-N 0.000 description 1
- SUBFZYQWYBUTGO-UHFFFAOYSA-N 2-ethyl-n,n-di(propan-2-yl)butan-1-amine Chemical compound CCC(CC)CN(C(C)C)C(C)C SUBFZYQWYBUTGO-UHFFFAOYSA-N 0.000 description 1
- -1 2-ethylcyclohexyl Chemical group 0.000 description 1
- GGAIWRNUQIHLRE-UHFFFAOYSA-N 2-methyl-n,n-di(propan-2-yl)propan-1-amine Chemical compound CC(C)CN(C(C)C)C(C)C GGAIWRNUQIHLRE-UHFFFAOYSA-N 0.000 description 1
- KRIMXCDMVRMCTC-UHFFFAOYSA-N 2-methylhexan-2-ol Chemical compound CCCCC(C)(C)O KRIMXCDMVRMCTC-UHFFFAOYSA-N 0.000 description 1
- ALRXDIKPRCRYAU-UHFFFAOYSA-N 2-methylpropan-2-ol Chemical compound CC(C)(C)O.CC(C)(C)O ALRXDIKPRCRYAU-UHFFFAOYSA-N 0.000 description 1
- KYWJZCSJMOILIZ-UHFFFAOYSA-N 3-methylhexan-3-ol Chemical compound CCCC(C)(O)CC KYWJZCSJMOILIZ-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 1
- GSCCALZHGUWNJW-UHFFFAOYSA-N N-Cyclohexyl-N-methylcyclohexanamine Chemical compound C1CCCCC1N(C)C1CCCCC1 GSCCALZHGUWNJW-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229930182692 Strobilurin Natural products 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000007083 alkoxycarbonylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JBIROUFYLSSYDX-UHFFFAOYSA-M benzododecinium chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 JBIROUFYLSSYDX-UHFFFAOYSA-M 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- OCTAKUVKMMLTHX-UHFFFAOYSA-M di(icosyl)-dimethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCCCC OCTAKUVKMMLTHX-UHFFFAOYSA-M 0.000 description 1
- FXORZKOZOQWVMQ-UHFFFAOYSA-L dichloropalladium;triphenylphosphane Chemical compound Cl[Pd]Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 FXORZKOZOQWVMQ-UHFFFAOYSA-L 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- ZCPCLAPUXMZUCD-UHFFFAOYSA-M dihexadecyl(dimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCC ZCPCLAPUXMZUCD-UHFFFAOYSA-M 0.000 description 1
- JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- OXQMIXBVXHWDPX-UHFFFAOYSA-N n,n,2-trimethylpropan-2-amine Chemical compound CN(C)C(C)(C)C OXQMIXBVXHWDPX-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
- ISRXMEYARGEVIU-UHFFFAOYSA-N n-methyl-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(C)C(C)C ISRXMEYARGEVIU-UHFFFAOYSA-N 0.000 description 1
- MTEWAFVECQBILW-UHFFFAOYSA-N n-tert-butylcyclohexanamine Chemical compound CC(C)(C)NC1CCCCC1 MTEWAFVECQBILW-UHFFFAOYSA-N 0.000 description 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- KGYLMXMMQNTWEM-UHFFFAOYSA-J tetrachloropalladium Chemical compound Cl[Pd](Cl)(Cl)Cl KGYLMXMMQNTWEM-UHFFFAOYSA-J 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
¢ WO 00/17186 PCT/GB99/02783
PROCESS FOR PREPARING 3-ISOCHROMANONE
This invention relates to a chemical process and more particularly to a process for preparing 3-isochromanone which is useful in the manufacture of certain agricultural products. 3-Isochromanone is a well known compound and a number of methods for its preparation are described in the chemical literature. In particular, a process is described in
WQ097/00850 which comprises reacting an o-xylene-a.,a'-dihalide derivative with carbon monoxide and water in an organic solvent in the presence of a catalyst and a hydrogen halide capturing agent followed by treatment with an acid. In this process the hydrogen halide capturing agent is preferably an inorganic base. The use of amines in palladium-catalyzed carbonylation reactions are discussed in J. Org. Chem. [1993] 58, 1538-45 and in US 4,713,484. These references relate, however, to the alkoxycarbonylation of allylphosphates and acetates and to the preparation of carboxylic acid salts.
Thus, according to the present invention, there is provided an improved process for the preparation of 3-isochromanone which comprises contacting an o-xylene-a,a'-dihalide with carbon monoxide in the presence of a catalyst and a hindered amine base in a liquid medium comprising water and a tertiary alcohol.
The o-xylene-a,a'-dihalide starting material has the general formula (I):
CHX
CX ®
CHX where X is a halogen atom such as chlorine, bromine or iodine, especially chlorine or bromine. o-Xylene-a,a'-dichloride is a particularly convenient starting material.
The process of the invention is carried out in a liquid medium comprising water and a tertiary alcohol. Suitable tertiary alcohols are monohydric, dilrydric or polyhydric alcohols of formula (II):
R'
R—C—oH (I) i OR in which R', R* and R’ are independently C,, alkyl (suitably Ci. alkyl and typically C, alkyl), one or more of R', R? and R® being optionally substituted with a phenyl ring or a hydroxyl group, the hydroxy! group being attached to a carbon atom which is itself directly attached to three other carbon atoms.
Of particular interest are aliphatic monohydric and dihydric tertiary alcohols of formula (II) in which R', R? and R’ are independently C, , alkyl, where C,. alkyl includes methyl, ethyl, n- and iso-propyl and n-, iso-, sec- and tert-butyl, one of R', R? and R® being optionally substituted with a hydroxyl group attached to a carbon atom which is itself directly attached to three other carbon atoms. Examples are 2-methyl propan-2-ol (tert- butanol), 2-methy] butan-2-ol (tert-amyl alcohol), 2,3- dimethylbutan-2-ol, 2-methyl pentan- 2-0l, 2-methylhexan-2-ol and 3-methylhexan-3-ol, 2,3-dimethylbutane-2,3-diol (pinacol) and 2,4-dimethylpentane-2,4-diol. Of most interest are monohydric alcohols of formula (II) in which R', R? and R® are independently C,, alkyl. Tert-Butanol and tert-amyl alcohol are preferred, if only for their commercial availability.
The liquid medium will usually comprise two phases, at least for part of the reaction, depending on the water solubility of the tertiary alcohol. When two phases are present, vigourous agitation is desirable.
Suitably the molar ratio of water:tertiary alcohol is in the range of 1:50 to 50:1, preferably 1:1 to 20:1 and typically 1:1 to 10:1, for example about 2:1 to 7:1. .
There will usually be a molar excess of water used in relation to the quantity of o-
Xylene-a,a’-dihalide starting material. Preferably the molar ratio of water:o-xylene-o-o'- dihalide will be in the range of 100:1 to 1:1 typically 50:1 to 4:1, for example about 30:1 to 5:1.
The carbon monoxide will normally be dispersed into the liquid medium either at atmospheric pressure or at pressures up to 100 atmospheres, for example at from 1 to 10 atmospheres. The pressure chosen will depend on the equipment in which the reaction is carried out and the required reaction rates and yield.
Any suitable carbonylation catalyst may be used in the process of the invention, particularly Group VIII (first, second and third triads) metal catalysts, for example palladium, cobalt or iron catalysts. Especially suitable are palladium catalysts, for example v | WO 00/17186 PCT/GB99/02783 palladium (0) and palladium (II) catalysts, which may be water-soluble or water-insoluble, supported ona carrier, such as carbon, silica or calcium carbonate, a polymer or other inert solid, or unsupported. Supported catalysts have the advantage of facilitating catalyst recovery and recycling. Ligands such as triphenylphosphine may be used in conjunction with certain palladium catalysts or it may be beneficial to pre-reduce the catalyst with hydrogen, or another suitable reducing agent.
Suitable water-soluble palladium catalysts in the form of phoshine complexes are described, for example, by J. Kiji et al in Chem. Lett., 957-960 (1988). Suitable water- insoluble palladium complexes include bis(triphenylphosphine)palladium dichloride and tetrakis(triphenylphosphine)palladium (0) which are described by L. Cassar et al in J.
Organometallic Chem., 121 (1976), C55-56, in DE-A-2526046 and by X. Huang et al in
Chem. & Ind., 3 Sep 1990, 548. Palladium (II) catalysed carbonylation reactions are also discussed by V. Grushin et al in Organometallics, 12 (5), 1890-1901 (1993). The use of a supported carbonylation catalyst in the form of palladium-black is described by T. Ito et al in
Bull. Chem. Soc. Japan, 48 (7), 2091-2094 (1975). The use of soluble triphenylphosphine ligands to activate palladium catalysts is described by D. Bergbreiter et al in J. Mol.
Catalysis, 74 (1992), 409-419. Typical examples of suitable catalysts are palladium chloride (as a solid or in solution in hydrochloric acid or as an aqueous sodium chloride solution), dihydrotetrachloropalladium, disodium tetrachloropalladium, tetrakis(triphenylphosphine) . 20 palladium (0), dichlorobis(triphenylphosphine) palladium (II), palladium/carbon, palladium on calcium carbonate and palladium on Montmorillonite™. Other suitable catalysts and ligands, mcluding water soluble ones, are described in WO 97/00850. The ligands may be used in amounts up to 1000 mole equivalents of palladium, and suitably in the range of from 1 to 200 mole equivalents of palladium, for exampie 10 to 30 mole equivalents. The amount of palladium catalyst used may be in the range of 0.000001 to 0.5 mole equivalents of the o- xylene-a,a'-dihalide.
Where a ligand such as triphenylphosphine is used in combination with a palladium catalyst, the ligand may be added with the catalyst to the reaction mixture or a catalyst-ligand mixture may be preformed for use in the reaction. For example, a melt of triphenylphosphine and palladium chloride (PdCl,) or sodium chloropalladite (Na,PdCl,) may be solidified and ground into a powder for use in the reaction. It has been found that preformed catalyst-ligand mixtures can speed the uptake of carbon monoxide during reaction and may provide yield benefits. Typically the mole ratio of palladium to phosphorous is 1:10 to 1:30, for example 1:11 or 1:22.
The hindered amine base will usually be one which has at least two aliphatic, prefer- ably branched aliphatic, or cycloaliphatic groups or one in which the N atom is in a cycloali- phatic or aromatic ring, substituted in a manner that induces steric crowding around the N atom. Typically it will be of low water solubility and have a pK, of the conjugate acid of about 10. Thus, it may be a heteroaromatic base such as pyridine or a substituted pyridine, for example 2,6-dimethylpyridine. Or it may be a secondary amine, providing it is suffici- ently sterically hindered. An example of a suitable secondary amine is 2,2,6,6-tetramethyl- piperidine. Preferably, however, it is a tertiary amine of formula R'R?R°N wherein R', R? and
R® are independently C,_, alkyl (especially C, alkyl) C,; cycloalkyl, aryl (especially phenyl, but also pyridyl) or aryl(C, )alkyl (especially benzyl), or wherein two or three of R', R? and
R’ join together with the nitrogen atom to which they are attached to form one, two or three, 5-, 6- or 7- membered alicyclic rings optionally fused and optionally containing a second ring nitrogen atom.
Alkyl groups are straight or branched chain and, unless stated otherwise, contain from 1 to 10, especially from 1 to 6, particularly from 1 to 4, carbon atoms. Examples are methyl, ethyl, iso-propyl, n-propyl, n-butyl, sec-butyl and tert-butyl. Cycloalkyl groups comprise 3 to 6 carbon atoms and are optionally substituted by C, , alkyl. Examples are cyclohexyl, 2- } methylcyclohexyl and 2-ethylcyclohexyl.
Suitable tertiary amines of formula R'R’R’N are, for example, N,N-diisopropylethyl- amine (Hiinig’s base), N,N-dimethylaniline, triethylamine, t-butyldimethylamine, N,N- diisopropylmethylamine, N,N-diisopropylisobutylamine, N,N-diisopropyl-2- ethylbutylamine, tri-n-butylamine, N,N-dicyclohexylmethylamine, N,N- dicyclohexylethylamine, N-tert-butylcyclohexylamine, N,N-dimethylcyclohexylamine, 1,5- diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclof2.2.2)-octane or 2- or 4-dimethylamino- pyridine.
There will usually be a molar excess of hindered amine base used in relation to the quantity of o-xylene-c,at'-dihalide starting material. Preferably the molar ratio of amine:o- xylene-o,,c’-dihalide will be in the range of 10:1 to 1:1, typically 5:1 to 2:1, for example 4:1 _
¢ WO 00/17186 PCT/GB99/02783 to 2.5:1. However, it may be possible to reduce the ratio of amine: o-xylene-a,a/'-dihalide to below 1:1, even as low as about 1:100, provided that an inorganic base such as an alkali metal hydroxide, for example sodium or potassium hydroxide, is used in addition. The total amount of base should remain at 1, and preferably at 2 or more, moles per mole of o-xylene- o,a'-dihalide.
When the process is carried out in a two-phase system, it may be advantageous to include a phase transfer catalyst. By the term "phase transfer catalyst" is meant a substance which, being at least partly present in or wetted by a first (usually organic) phase, promotes reaction between a reactant in the first phase and a reactant which it transfers to the first phase from a second (usually aqueous but sometimes solid) phase. After reaction, the phase transfer catalyst is released for transferring further reactant. Phase transfer catalysts are reviewed by E. V. Dehmlow in Angewante Chemie (International Edition), 13 (3), 170 (1974). Other reviews are by Jozef Dockx in Synthesis (1973), 441-456 and by C. M. Starks in JACS., (93) 1, Jan 13 1971, 195-199.
Suitably the phase transfer catalyst is a quaternary ammonium or phosphonium salt preferably containing bulky organic groups, usually alkyl or aralkyl groups, to make it soluble in the organic phase. It is preferred that the phase catalyst is a tetraalkyl or aralkyl (eg benzyl) trialkyl ammonium or phosphonium salt in which the total number of carbon atoms attached to each nitrogen or phosphorus atom is at least 4. There is little advantage in the number being above 70. It is especially preferred that the number should be in the range of from 16 to 40. } Examples of quaternary ammonium salts are: tetramethylammonium chloride, cetyltrimethylammonium bromide, dicetyldimethylammonium chloride, octyltributyl- ammonium bromide, trioctylmethylammonium chloride (available as Aliquat™ 336), benzyldimethyllaurylammonium chloride, benzyltriethylammonium chloride, dilauryl- dimethrylammonium chioride, tetrabutylammoniom bromide and dieicosyldimethyl- ammonium chloride. Examples of quaternary phosphonium salts are cetyltripropylphos- phonium bromide and triphenylethylphosphonium bromide. Other phase transfer catalysts which may be suitable include crown ethers and polyethylene glycol variants. If used, the phase transfer catalyst may be present in an amount ranging from 0.001 to 0.5 mole equivalents of the o-xylene-o,or'-dihalide.
WO oI17186 PCT/GB99/02783 >
The process may be carried out at any suitable temperature within a range of from 20°C to 120°C, preferably from 60°C to 100°C, typically from 70°C to 90°C, for example at about 70°C.
After reaction is complete, the 3-isochromanone may be extracted by the addition of aqueous base to form a salt of the corresponding hydroxy acid. From the remaining organic phase the tertiary alcohol and amine may be recovered by distillation, the residues providing a source of catalyst for recovery. From the aqueous layer the 3-isochromanone may be regenerated by suitable pH adjustment, e.g. by acidification with, for example, hydrochloric acid, and extracted into a suitable solvent such as xylene. Carrying out the basification with degassed aqueous base under a blanket of an inert gas such as nitrogen or carbon monoxide, may reduce the formation of tarry material. The tertiary alcohol and amine may be recovered for re-use by, for example, distillation from the aqueous base layer before regeneration of the 3-isochromanone. The catalyst may also be recovered for re-use.
The 3-isochromanone may be recovered at the end of reaction by distillation. Thus, in a first method, the reaction mixture is treated with a base such as an alkali metal hydroxide, the aqueous layer separated, the 3-isochromanone regenerated by pH adjustment and extracted into a suitable solvent such as xylene, as described above. The organic extract is then distilled to remove the solvent and to recover the 3-isochromanone. Alternatively, in a second method, the end-of-reaction mixture is acidified to transfer the amine into the aqueous phase. The resulting organic phase containing the 3-isochromanone, the tertiary : alcohol and catalyst is then distilled to recover separately the tertiary alcohol and 3- isochromanone. The catalyst may be recovered from the still residues, or it may be possible : to precipitate out a salt of the catalyst, for example a palladium salt, during the acidification, and recover it by filtration prior to distillation. 3-Isochromanone is useful, inter alia, as an intermediate in the manufacture of agricultural products, especially fungicides of the strobilurin type, for example those described in EP-A-278595.
The invention is illustrated by the following Examples in which : g = grammes gc = gas chromatography mmol = millimoles °C = degrees centigrade psi = pounds per square inch JRV = jacketed reaction vessel
¢ | WO 00/17186 PCT/GB99/02783
Pressures recorded in ‘bar.g’ units are gauge measurements, not absolute. Thus, for example, 4 bar.g is equivalent to 5 bar absolute.
EXAMPLE 1 0-Xylene-a,a’-dichloride (7.0g, 39.9mmol) N,N-diisopropylethylamine (15.63g, 119.7mmol) palladium chloride (PdCl,) catalyst (0.021 g, 0.1197mmol), water (7.18g, 399 mmol) and triphenylphosphine (0.47g, 1.76mmol) and tert-butanol (11.9g, 159.6 mmol) were charged to a 100ml round bottom flask and carbon monoxide bubbled through via a syringe needle. The reaction mixture was heated to 70°C with fast agitation while bubbling carbon monoxide through. A sample tested by qualitative gc analysis after 3 hours showed the reaction to be complete.
Sodium hydroxide (6.38g at 100% strength) and water (16.5g) were added to the reaction mixture, which was then stirred at 60°C for 1 hour before separating an organic layer
A (26.66g) and an aqueous layer. Concentrated hydrochloric acid (12.31g at 35.5% strength) and o-xylene (21g) were added to the aqueous layer, which was stirred at 60°C for 1 hour before separating a xylene solution B (26.94g) and an aqueous layer C (40.35g).
Quantitative gc analysis showed 3-isochromanone present as follows:
Organic layer A 0.04% (0.18% yield)
Xylene solution B 15.01% (68.48% yield)
Aqueous layer C 0.2% (1.4% yield) ] 20 Total yield of 3-isochromanone 70.06%
EXAMPLE 2
Palladium chloride (0.043g, 0.24mmol), tripheny] phosphine (0.93g, 4mmol), N N- diisopropylethylamine (31g, 240mmol), water (14.4g, 800mmol), o-xylene-a, a' dichloride (14g, 80mmol) and tert-amyl alcohol (33.8g, 384 mmol) were charged to a 310 ml PARR reactor, fitted with an agitator and carbon monoxide charging system. The stirrer was switched on after the temperature was adjusted to 70°C and the pressure increased to 4 bar.g (60 psig). The vessel pressure was maintained at 60 psig using carbon monoxide and the temperature between 70-75°C by heating/cooling. When the carbon monoxide uptake ceased, the pressure was released back to atmosphere and the 3-isochromanone product was extracted from the organic phase using aqueous sodium hydroxide (12.8g at 100% strength,
320mmol). The 3-isochromanone was regenerated by addition of hydrochloric acid (7.3g at 35.5% strength, 200 mmol) and extracted into o-xylene (42.5g, 400mmol). The resultant solution was analysed for 3-isochromanonc and found to contain 16.8 %w/w. This represents a yield of 75.4% of 3-isochromanone from xXylene-a o' dichloride.
EXAMPLE 3 o-Xylene-a,a'-dichloride (14.7g at 95% strength, 80mmol), N,N-diisopropyl- ethylamine (31.4g at 99% strength, 250mmol), an aqueous solution of dihydrotetrachloropalladium (H,PdCl,) catalyst (0.1271g at 53.8% strength, 0.27mmol), tert- amy! alcohol (28.2g at 95% strength, 300mmol), water (14.4g, 800mmol) and triphenylphosphine (0.93g at 99% strength, 3.5mmol) were charged to a 300ml Inconel ™ autoclave. The autoclave was purged three times at 5 bar. g with carbon monoxide gas before being finally pressurised to about 4 bar.g. The reaction mixture was briskly agitated (~ 900rpm) and heated to 70°C. Once at temperature, the reaction mixture was stirred at 70°C for approximately 4 hours, the pressure being maintained at about 4 bar, g and the rate of uptake of carbon monoxide gas noted. The reaction was adjudged complete when no further carbon monoxide was seen to be consumed. The reaction mixture was then rapidly cooled to below 40°C and sampled to test for the presence of starting material by gc. Water (33g) and sodium hydroxide (27.4g at 47% strength) were charged in one portion to the open autoclave, which was then sealed and purged with carbon monoxide gas three times at 5 bar.g before finally being pressurised to 1bar.g. The reaction mixture was then stirred at 60°C under 1-2 . bar.g (CO pressure) for approximately 1 hour. The two phases were then transferred to a hot separator (in air) and separated at 60°C, the aqueous phase being drawn off for further work- . up.
The aqueous phase was added cautiously to a stored solution of o-xylene (41.4g) and concentrated hydrochloric acid (19.8g at 36% strength) at 60°C (in air). The mixture was then stirred for 1 hour at 60°C before being separated to give an aqueous waste stream and a xylene solution containing the product, 3-isochromanone; yield 83.7%.
A repeat experiment gave a yield of 83.9%.
EXAMPLE 4 0-Xylene-a,a'-dichloride (14.7g at 95% strength, 80mmol), N,N-diisopropyl- ethylamine (25.5¢ at 99% strength, 200mmol), an aqueous solution of
¢ WO 0017186 PCT/GB99/02783 dihydrotetrachloropalladium (H,PdCl,) catalyst (0.0586 at 53.8% strength, 0.126mmol), tert- amyl alcohol (14.1g, 163mmol,) water (28.8g, 1600mmol) and triphenylphosphine (2. 1g at 95% strength, 8.0mmol) were charged to 300ml Inconol ™ autoclave. The autoclave was purged three times at 5 bar.g with carbon monoxide gas before finally being pressurised to } about 4 bar.g. The reaction mixture was briskly agitated (~ 900rpm) and heated to 70°C.
Once at temperature, the reaction mixture was stirred at 70°C for approximately 4 hours, the pressure being maintained at about 4 bar.g and the rate of uptake of carbon monoxide gas noted. The reaction was adjudged complete when no further carbon monoxide was seen to be consumed. The reaction mixture was then rapidly cooled to below 40°C and sampled to test for the presence of starting material by gc. Water (33g) and sodium hydroxide (27.4g at 47% strength) were charged in one portion to the open autoclave, which was then sealed and purged with carbon monoxide gas three times at 5 bar.g before finally being pressurised to 1 : bar.g The reaction mixture was then stirred at 60°C under 1-2 bar.g (CO pressure) for : approximately 1 hour. The two phases were then transferred to a hot separator (in air) and separated at 60°C, the aqueous phase being drawn off for further work-up.
The aqueous phase was added cautiously to a stirred solution of o-xylene (41.4g) and concentrated hydrochloric acid (19.8g at 36% strength) at 60°C (in air). The mixture was then stirred for 1 hour at 60°C before being separated to give an aqueous waste stream and a xylene solution containing the product, 3- isochromanone; yield 75.8%. ) 20 EXAMPLE 5 o-Xylene-a,a’-dichloride (14.7g at 95% strength, 80mmol), N,N-diisopropyl- ethylamine (29.24g at 99% strength, 224 mmol), an aqueous solution of dihydrotetrachloropalladium (H,PdCl,) catalyst (0.075g at 53.8% strength, 0.16mmol), tert- amy] alcohol (21.37g at 99% strength, 240mmol), water (25.2g, 1400mmol) and triphenylphosphine (2.11g at 99% strength, 8mmol) were charged to a 310ml PARR autoclave fitted with an agitator and carbon monoxide charging system. The autoclave was pressurised to 60 psi with carbon monoxide and this pressure was maintained throughout the reaction, which was carried out at 70°C. The reaction was adjudged complete when no further carbon monoxide was seen to be consumed.
The contents of the autoclave were transferred to a beaker where a sample of the reaction mixture was withdrawn. The autoclave was evacuated and the reaction mixture
WO OWITISE PCT/GB99/02783 recharged to the autoclave by vacuum displacement. Sodium hydroxide solution was prepared in the same beaker with pearl sodium hydroxide (12.8g at 100% strength) and water (22.32g). This was also transferred to the autoclave by vacuum displacement. The mixture was now stirred at 60°C for 1 hour at 15 psi before transferring the contents to a separating funnel. The two phases were separated to give an aqueous layer, which was carried forward to the acid work up, and an organic layer of 46.99g. The aqueous layer was added to a stirred mixture of xylene (42.46g) at 60°C and concentrated hydrochloric acid (20.56g at 35.5% strength). This mixture was stirred at 60°C for one hour before being separated to give an aqueous layer (77.56g) and a xylene solution (5 3.25g). Quantitive analysis showed 46.99¢ 3-isochromanone at 0.03% (0.12% yield) in the organic layer, 77.56g 3- isochromanone at 0.19% (0.25% yield) in the aqueous layer and 53.25g 3-isochromanone at 18.04% (81.13% yield) in the xylene solution: total chemical yield 82.5%.
EXAMPLE 6 o-Xylene-a,a'-dichloride (14.7g at 95% strength, 80mmol), N,N-diisopropyl- ethylamine (31.4g at 99% strength, 240 mmol, nitrogen degassed), tert-amyl alcohol (33.8g at 100% strength, 384mmol, nitrogen degassed), palladium chloride (PACl,) catalyst (0.043g at 99% strength, 0.24 mmol), triphenylphosphine (2. 12g at 99% strength, 8mmol) and water (14.4g, 800mmol, nitrogen degassed), were charged to a 310 Inconel ™ autoclave. The autoclave was purged three times at 5 bar.g with carbon monoxide (technical grade), before being finally pressurised to 4 bar.g. The reaction liquors were agitated at 1000rm and heated to 70°C. The reaction temperature was maintained at 70°C for approximately 4 hours maintaining the carbon monoxide pressure at approximately 4 bar. g throughout the reaction period, noting the rate of uptake of carbon monoxide. Reaction was deemed to be complete when no further carbon monoxide was seen to be consumed. A stirred sample of reaction liquors was removed from the autoclave and tested by gc for the presence of o-xylene-o.,o'- dichloride.
The autoclave was cooled to 60°C, agitation was stopped and the autoclave vented to approximately 1 bar.g. This residual pressure was used to discharge the reaction liquors (clear, amber, single phase) to a jacketed reaction vessel (JRV), which had been previously brought to 60°C and purged with nitrogen. A positive flow of nitrogen was maintained throughout the workup in the JRV to eliminate oxygen incursion. Aqueous sodium hydroxide (60.9g at 21% strength, nitrogen degassed) was added to the stirred reaction liquors via a balanced dropping funnel which had been purged with nitrogen. The resulting liquors were stirred for approximately 1 hour then allowed to settle enabling a phase separation to take place. This consisted of an upper clear red organic phase, a lower clear red aqueous base phase and a slight black dispersion located at the interface. The lower aqueous base phase was weighed off and stored for workup later. The black dispersion was seen to adhere to the walls of the JRV on discharge of the lower phase. Air was then blown over the stirred upper organic phase allowing air incursion. Within 1 to 2 minutes severe tarring of the organic phase was seen confirming that oxygen exclusion was in fact needed during workup to avoid tarring. The organic phase was then discharged. The aqueous base phase was reintroduced in air to a clean JRV which had been heated to 60°C and agitated at 400rpm. o-Xylene (42.5g at 100 % strength, 400mmol) was introduced to the JRV followed by cautious addition of hydrochloric acid (20.3g at 36% strength, 0.2mmol). Fuming was evident and the liquors were allowed to stir for approximately 1 hour. The liquors were then allowed to stand at 60°C enabling two phases to be separated. The lower clear acidic aqueous phase was weighed off, followed by the upper clear red/amber o-xylene solution of 3-isochromanone (approximately 18%w/w). The previously recovered organic phase, acidic aqueous phase and o-Xylene solution were analysed by gc for 3-isochromanone; yield: organic phase 0.37%, acidic aqueous phase 1.56%, o-xylene solution 73.9%: total 75.8%.
EXAMPLE 7 o-Xylene-a,a'-dichioride (7.35g at 95% strength, 40mmol), N,N-diisopropyl- ethyllamine (15.7g at 99% strength, 120mmol), an aqueous solution of dihydrotetrachloropalladium (H,PdCl,) catalyst (0.0651g at 53.8% strength, 0.14mmol), tert- amyl alcohol (14.1g at 95% strength, 150mmol), water (14.4g, 800mmol) and triphenylphosphine (1.1g at 99% strength, 4mmol) were charged to a 100ml round bottom flask. The vessel was sealed and vacuum purged with carbon monoxide gas three times. The contents of the reaction vessel were briskly agitated (~900rpm) and heated to 70°C, with a steady bubbling of carbon monoxide through the mixture. Once at temperature, the reaction mixture was stirred at 70°C for approximately 2.25 hours, maintaining the steady bubbling.
The reaction mixture was sampled to test for the presence of starting material by gc.
Sodium hydroxide solution (30.2g at 21% strength) was charged in one portion to the flask, which was sealed. Carbon monoxide was then bubbled through the mixture again.
The reaction mixture was stirred at 60°C, with steady bubbling for approximately 1 hour.
The two phases were transferred to a hot separator (in air) and separated at 60°C, the aqueous phase being drawn off for further work-up. The organic phase was retained for a recycle reaction (see Recycle 1). .
The aqueous phase was added cautiously to a stirred solution of xylene (20.7g) and concentrated hydrochloric acid (9.9g at 36% strength) at 60°C (in air). The mixture was stirred for 1 hour at 60°C before separating to give an aqueous waste stream and a xylene solution containing the product, 3-isochromanone.
Recycle 1
The organic phase obtained above was charged to a 100ml round bottom flask. The same amounts of o-xylene-a,a'-dichloride, triphenylphosphine, water and palladate catalyst as above were charged to the same flask. The vessel was sealed and vacuum purged with carbon monoxide gas three times. The contents of the reaction vessel were briskly agitated (~ 900rpm) and heated to 70°C, with a steady bubbling of carbon monoxide through the mixture. Once at temperature, the reaction mixture was stirred at 70°C for approximately 2 hours, maintaining the steady bubbling. The reaction mixture was sampled to test for the presence of starting material by gc.
Sodium hydroxide solution (30.2g at 21% strength) was charged in one portion to the flask, . which was sealed. Carbon monoxide gas was bubbled through the mixture again. The reaction mixture was stirred at 60°C, with steady bubbling for approximately 1 hour. The two phases were transferred to 2 hot separator (in air) and separated at 60°C, the aqueous phase being drawn off for further work-up. The organic phase was retained for a recycle reaction (see Recycle 2).
The aqueous phase was added cautiously to a stirred solution of xylene (20.7g) and concentrated hydrochloric acid (9.9¢ at 36% strength) at 60°C (in air). The mixture was stirred for 1 hour at 60°C before separating to give an aqueous waste stream and a xylene solution containing the product, 3-isochromanone.
Recycle 2 ~The organic phase obtained from Recycle 1 was charged to a 100m] round bottom flask. The same amounts of o-xylene-a,a'-dichloride, triphenylphosphine, and water as above were charged to the same flask. The vessel was sealed and vacuum purged with carbon monoxide gas three times. The contents of the reaction vessel were briskly agitated (~ 900rpm) and heated to 70°C, with a steady bubbling of carbon monoxide through the mixture. Once at temperature, the reaction mixture was stirred at 70°C for approximately 2 hours, maintaining the steady bubbling. The reaction mixture was sampled to test for the presence of starting material by gc.
Sodium hydroxide solution was charged in one portion to the flask, which was sealed.
Carbon monoxide gas was bubbled through the mixture again. The reaction mixture was stirred at 60°C, with steady bubbling for approximately 1 hour. The two phases were transferred to a hot separator (in air) and separated at 60°C, the aqueous phase being drawn : off for further work-up (Note: tarring observed at this point).
The aqueous phase was added cautiously to a stirred solution of xylene (20.7g) and concentrated hydrochloric acid (9.9g at 36% strength) at 60°C (in air). The mixture was stirred for 1 hour at 60°C before separating to give an aqueous waste stream and a xylene solution containing the product, 3-isochromanone.
Yields: Initial experiment 82.3%; Recycle 1 69.9%; Recycle 2 73.7%. } 20 EXAMPLE 8 o-Xylene-a,a’-dichloride (14.24g at 98.3% strength, 80mmol) N,N-diisopropy}- ethylamine (31.33g at 99% strength, 240mmol), t-amy! alcohol (21.37 at 99% strength, 240mmol), water (28.8g, 1600mmol) and catalyst mixture preformed as described below (1.065g to give 3.52mmol triphenylphosphine and 0.16mmol catalyst) were charged to a 310ml Hastelloy™ autoclave. The autoclave was purged three times with carbon monoxide (premium grade) at 75psi before being finally pressurised to 30 psi. The reaction liquors were agitated at 1000rpm whilst heating to 70°C. The reaction temperature was held at 70°C, maintaining the pressure at 30 psi throughout the reaction period. Reaction was deemed to be complete when carbon monoxide uptake ceased. The vessel was vented to ~15psi and the mixture heated to 100°C to facilitate the precipitation of palladium. The reaction was stirred at 500 rpm at 100°C for one hour before transferring to a nitrogen-blanketed JRV. Aqueous sodium hydroxide (60.59g at 21% strength) was added to the JRV and stirred at 60°C for one hour, maintaining the nitrogen blanket. Separation was carried out to give a lower aqueous layer which was retained for further work-up and an upper organic layer (48.32g). The aqueous layer was recharged to the vessel along with xylene (42.46g) and concentrated hydrochloric acid (20.56g at 35.5% strength). This mixture was stirred at 60°C for one hour before separating to give a lower aqueous layer (97.0g; 3-isochromanone strength 0.22%; 1.8% yield) and an upper xylene solution of 3-isochromanone. (52.59g; 3-isochromanone strength 17.84%; 79.15% yield). Total chemical yield by quantative gc analysis, 80.95%.
Preparation of Preformed Catalyst Mixture
Triphenylphosphine (10.1010g, 38.lmmol) was charged to a 3-necked 100ml round bottom flask and heated to 90°C with rapid agitation to produce a melt. Sodium chloropalladite (Na,PdCl,) solution (1.4594g, 1.732mmol) was added dropwise to the melt ‘and the reaction mixture was agitated until the catalyst mixture was produced as a yellow slurry. The mixture was allowed to cool and the catalyst solidified. The solid was removed from the flask and powdered using a mortar and pestle. This catalyst was used directly in the above carbonylation reaction. Assuming a quantitative chemical yield of 100%, the catalyst had a palladium strength of 1.60% w/w (with a palladium to phosphorous mole ratio of 1:22)
EXAMPLE 9
A reactor vessel was purged and vented four times using nitrogen at a pressure of 1 barG. To the reactor vessel was charged tertiary-amyl alcohol (48kg, 0.55kg mol), de- } lonised water (92kg, Skg mol) o-xylene-o,o’-dichloride (45kg, 0.25kg mol), tertiary-amyl alcohol (10kg, 0.11kg mol) as a line wash for residual o-xylene-o,o'-dichloride and the . palladium chloride-triphenylphosphine catalyst species formed prior to addition using the following method.
Preparation of Catalyst
Triphenylphosphine (1.50kg, 0.0057kg mol) was charged to a 2-litre reaction vessel and heated to 90°C with rapid agitation to produce a melt. Palladium chloride in hydrochloric acid solution (0.125kg, 0.00025kg mol) was added dropwise to the melt and the reaction mixture was agitated until the catalyst was produced as a yellow slurry. The 2-litre reaction vessel was removed from the source of heat and the yellow slurry poured into a pyrex dish. The catalyst readily solidified and was subsequently broken up using a mortar and pestle for use as a powder in the reaction. The above process was repeated for a second charge of triphenylphosphine (1.5kg, 0.005 7kg mol), and assuming a quantitative chemical yield of 100% the catalyst had a palladium strength of 1.66%.
The reactor vessel was purged and vented four times using nitrogen at a pressure of 1 barG. To the reactor vessel was charged N,N-diisopropylethylamine (99kg, 0.75kg mol) and - tertiary-amyl alcohol (10kg, 0.11kg mol) as a line wash for residual N,N- diisopropylethylamine. The reactor vessel was purged and vented four times using nitrogen at a pressure of 1 barG, followed by being purged and vented twice using carbon monoxide at a pressure of 4 barG. The reactor vessel was heated to 40°C at a pressure of 3-3.5 barG under carbon monoxide. The exotherm from the reaction raised the batch temperature to 70°C. The batch was then controlled at 70°C to within +5°C using pressurised hot water until the carbon monoxide uptake ceased (ca 10kg). The pressure of the reactor vessel was reduced by venting the carbon monoxide to the atmosphere, and the temperature of the reactor vessel was reduced to 40°C. The reactor vessel was purged and vented four times using nitrogen at a pressure of 1 barG. The contents of the reactor vessel were analysed for the end of reaction by gc.
The reactor vessel was purged and vented twice using carbon monoxide at a pressure of 4 barG and left at a pressure of 1 barG using carbon monoxide. The reactor vessel was heated to 100°C and held at this temperature for 1 hour, and the pressure of the reactor vessel ] 20 was reduced by venting the carbon monoxide to the atmosphere. The reactor vessel was cooled to 55-60°C and purged and vented four times using nitrogen at a pressure of 1 barG. } To the reactor vessel was charged de-ionised water (108kg, 6kg mol) and 47% sodium hydroxide (87kg, 1.025kg mol). The reactor vessel was held at 55-60°C for 30 minutes and the contents then allowed to settle for 1 hour after stirring was stopped. The lower aqueous phase was separated and filtered via a Pall screening cartridge, and after stirring was started the organic phase was discharged to an earthed drum.
The aqueous phase distilled under a vacuum of SOmmHg at a temperature of 55°C until a change in distillate appearance was apparent. The distillate was then discharged to an earthed drum. To the remaining aqueous phase was charged o-xylene (130kg, 1.28kg mol) and hydrochloric acid (65kg, 0.64kg mol) maintaining the reactor vessel at a temperature of 5 5-60°C throughout the course of the addition. The reactor vessel was stirred
© WO 00117186 PCT/GBY9/02783 for 1 hour at 55-60°C and then analysed for pH (<2). The contents were then allowed to settle for 1 hour after stirring was stopped, and the aqueous and o-xylene phases were separated to individual earthed drums.
The solution of 3-isochromanone in o-xylene (166.5kg) was analysed as 18.37% w/w/ strength (30.5%g at 100% weight). This represents anisolated yield of 82.58%. The chemical yield for the process was analysed to be 84.53%.
Claims (15)
1. A process for the preparation of 3-isochromanone which comprises contacting an o- Xylene-a,a'-dihalide with carbon monoxide, in the presence of a catalyst and a hindered amine base in a liquid medium comprising water and a tertiary alcohol.
2. A process according to claim 1 in which the o-xylene-a,a'-dihalide is o-xylene-a,a'- dichloride.
3. A process according to claim 1 or 2 in which in the tertiary alcohol is an alcohol of formula (II): R’ Re~C—on R? in which R', R? and R® are independently C, 4 alkyl, one or more of R', R? and R® being optionally substituted with a phenyl ring or a hydroxy! group, the hydroxyl group being attached to a carbon atom which is itself directly attached to three other carbon atoms.
: 4. A process according to claim 3 in which the tertiary alcohol is tert-amyl alcohol or tert-butanol. : 20
5. A process according to claim 3 or 4 in which the molar ratio of water:tertiary alcohol is in the range of 1:50 to 50:1.
6. A process according to claim 3 or 4 in which the molar ratio of water:o-xylene-a.a'- dihalide is in the range of 100:1 to 1:1.
7. A process according to any one of the preceding claims in which the amine base is an amine of formula R'R’R°N wherein R',R? and R? are independently C, ,, alkyl,
C;4 cycloalkyl, aryl or aryl(C, ,)alkyl or wherein two or three of R', R? and R? join together with the nitrogen atom to which they are attached to form one, two or three, 5-, 6- or 7- membered alicyclic rings optionally fused and optionally containing a second ring nitrogen atom.
8. A process according to any one of the preceding claims in which the molar ratio of amine base:o-xylene-a,o’-dihalide is in the range of 10:1 to 1:1.
9. A process according to any one of claims 1 to 7 in which an inorganic base is used in conjunction with the amine base, the total amount of base used being at least 1 mole per mole of o-xylene-at,a'-dihalide.
10. A process according to any one of the preceding claims in which the catalyst is a palladium catalyst.
11. A process according to any one of the preceding claims in which the catalyst is present in the amount of 0.000001 to 0.5 mole equivalents of the o-xylene-o,a'- dihalide.
12. A process according to claim 10 in which a triphenylphosphine ligand is used in . combination with the palladium catalyst in the range of from 1 to 200 mole equivalents of phosphorous to palladium. .
13. A process according to claim 12 in which the triphenylphosphine ligand and palladium catalyst are used in a preformed mixture.
14. A process according to any one of the preceding claims in which there is present a phase transfer catalyst.
15. A process according to any one of the preceding claims which is carried out at a temperature of from 20°C to 200°C.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9820465.4A GB9820465D0 (en) | 1998-09-18 | 1998-09-18 | Chemical process |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200101690B true ZA200101690B (en) | 2002-05-28 |
Family
ID=27676585
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200101690A ZA200101690B (en) | 1998-09-18 | 2001-02-28 | Process for preparing 3-isochromanone. |
Country Status (1)
Country | Link |
---|---|
ZA (1) | ZA200101690B (en) |
-
2001
- 2001-02-28 ZA ZA200101690A patent/ZA200101690B/en unknown
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103370310A (en) | 3-hydroxy-6h-benzo[c]chromen-6-one derivative and method for producing same | |
KR20070115896A (en) | Process for producing (z)-1-phenyl-1-(n,n-diethylaminocarbonyl)-2-phthalimidomethylcyclopropane | |
US6888008B2 (en) | Process for preparing 3-isochromanone | |
ZA200101690B (en) | Process for preparing 3-isochromanone. | |
Grigg et al. | Palladium catalysed reaction of allene with phenols. Phenoxymethyl-1, 3-dienes and their further reactions | |
KR100661529B1 (en) | Process for preparing 3-isochromanone | |
EP1015442B1 (en) | Process for preparing 3-isochromanone | |
CN110885329B (en) | Synthetic method of 1, 7-naphthyridine derivative | |
CN110240561B (en) | Low-cost preparation method of 3-hydroxypyridine | |
JP2000143656A (en) | Production of d,l-alpha-tocopherol | |
US6184392B1 (en) | Process for preparing 3-isochromanone | |
AU2003219316B2 (en) | Process for the preparation of 3-isochromanone | |
KR101703771B1 (en) | Production method of halogen-substituted phthalide | |
US6518430B1 (en) | Process for the preparation of 5-(substituted)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-F]quinolines and derivatives thereof | |
CN117447382A (en) | Preparation method of tetrahydropyrrolo cyclopropane | |
Chapelat | Asymmetric synthesis of 2, 2-disubstituted chromanols. novel approaches to vitamin E analogues | |
Ripberger | Stereoselective Bond Formation in the Total Synthesis of Rubriflordilactone B | |
JPH05331102A (en) | Production of optically active citronellic acid derivative or its antipode |