USRE37188E1 - Processes for the preparation of cyclopropanecarboxylic acid and derivatives thereof - Google Patents
Processes for the preparation of cyclopropanecarboxylic acid and derivatives thereof Download PDFInfo
- Publication number
- USRE37188E1 USRE37188E1 US09/289,387 US28938799A USRE37188E US RE37188 E1 USRE37188 E1 US RE37188E1 US 28938799 A US28938799 A US 28938799A US RE37188 E USRE37188 E US RE37188E
- Authority
- US
- United States
- Prior art keywords
- cyclopropanecarboxylic acid
- cyclopropanecarboxamide
- temperature
- pressure
- preparation
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 62
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 230000008569 process Effects 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 claims abstract description 24
- 230000003647 oxidation Effects 0.000 claims abstract description 19
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 19
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910001882 dioxygen Inorganic materials 0.000 claims abstract description 9
- 150000001408 amides Chemical class 0.000 claims abstract description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 34
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 26
- 239000003054 catalyst Substances 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 19
- -1 cyclopropanecarboxylate ester Chemical class 0.000 claims description 19
- 229910021529 ammonia Inorganic materials 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003570 air Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 150000002440 hydroxy compounds Chemical class 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000013022 venting Methods 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims 1
- 150000002148 esters Chemical class 0.000 abstract description 6
- 239000002253 acid Substances 0.000 abstract description 4
- 230000003197 catalytic effect Effects 0.000 abstract description 4
- 150000001805 chlorine compounds Chemical class 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 17
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 10
- 239000011347 resin Substances 0.000 description 10
- 229920005989 resin Polymers 0.000 description 10
- 239000007789 gas Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical group C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 8
- MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 description 8
- 238000004817 gas chromatography Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 238000002955 isolation Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000005886 esterification reaction Methods 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000032050 esterification Effects 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- IPLKGJHGWCVSOG-UHFFFAOYSA-N 4-chlorobutanoic acid Chemical compound OC(=O)CCCCl IPLKGJHGWCVSOG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000007112 amidation reaction Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000012320 chlorinating reagent Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 4
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 4
- 0 *OC(=O)C1CC1 Chemical compound *OC(=O)C1CC1 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 230000009435 amidation Effects 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 150000003738 xylenes Chemical class 0.000 description 3
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 2
- ARGCQEVBJHPOGB-UHFFFAOYSA-N 2,5-dihydrofuran Chemical compound C1OCC=C1 ARGCQEVBJHPOGB-UHFFFAOYSA-N 0.000 description 2
- ZFCFBWSVQWGOJJ-UHFFFAOYSA-N 4-chlorobutanenitrile Chemical compound ClCCCC#N ZFCFBWSVQWGOJJ-UHFFFAOYSA-N 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- GXBYFVGCMPJVJX-UHFFFAOYSA-N Epoxybutene Chemical compound C=CC1CO1 GXBYFVGCMPJVJX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- WYYQVWLEPYFFLP-UHFFFAOYSA-K chromium(3+);triacetate Chemical compound [Cr+3].CC([O-])=O.CC([O-])=O.CC([O-])=O WYYQVWLEPYFFLP-UHFFFAOYSA-K 0.000 description 2
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- LDDOSDVZPSGLFZ-UHFFFAOYSA-N ethyl cyclopropanecarboxylate Chemical compound CCOC(=O)C1CC1 LDDOSDVZPSGLFZ-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- PKAHQJNJPDVTDP-UHFFFAOYSA-N methyl cyclopropanecarboxylate Chemical compound COC(=O)C1CC1 PKAHQJNJPDVTDP-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- FARHYDJOXLCMRP-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]pyrazol-3-yl]oxyacetic acid Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(N1CC2=C(CC1)NN=N2)=O)OCC(=O)O FARHYDJOXLCMRP-UHFFFAOYSA-N 0.000 description 1
- ZIODMHXAGZXTJF-UHFFFAOYSA-N 2-methylpropyl cyclopropanecarboxylate Chemical compound CC(C)COC(=O)C1CC1 ZIODMHXAGZXTJF-UHFFFAOYSA-N 0.000 description 1
- TXQPIYKVIOKFAB-UHFFFAOYSA-N 4,4,5,5-tetrachloro-1,3-dioxolan-2-one Chemical compound ClC1(Cl)OC(=O)OC1(Cl)Cl TXQPIYKVIOKFAB-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical group CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- XYQQGESWGNLKIO-UHFFFAOYSA-N acetic acid;chromium;dihydrate Chemical compound O.O.[Cr].[Cr].[Cr].CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O XYQQGESWGNLKIO-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229940011182 cobalt acetate Drugs 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- BEGBSFPALGFMJI-UHFFFAOYSA-N ethene;sodium Chemical group [Na].C=C BEGBSFPALGFMJI-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- ZZUYIRISBMWFMV-UHFFFAOYSA-N methyl 4-chlorobutanoate Chemical compound COC(=O)CCCCl ZZUYIRISBMWFMV-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012508 resin bead Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- JYCDILBEUUCCQD-UHFFFAOYSA-N sodium;2-methylpropan-1-olate Chemical compound [Na+].CC(C)C[O-] JYCDILBEUUCCQD-UHFFFAOYSA-N 0.000 description 1
- HQIZDGAMCWYBKS-UHFFFAOYSA-M sodium;cyclopropanecarboxylate Chemical compound [Na+].[O-]C(=O)C1CC1 HQIZDGAMCWYBKS-UHFFFAOYSA-M 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/04—Saturated compounds having a carboxyl group bound to a three or four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/21—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen
- C07C51/23—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen of oxygen-containing groups to carboxyl groups
- C07C51/235—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen of oxygen-containing groups to carboxyl groups of —CHO groups or primary alcohol groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Definitions
- Cyclopropanecarboxylic acid and its derivatives, especially cyclopropylamine, are useful in the synthesis of pharmaceuticals and pesticides. See, for example, European Patent Publications EP 237,955 A2, EP 273,862 A2 and EP 430,847 A1.
- cyclopropanecarboxylic acid by a three-step process consisting of (1) the reaction of a metal cyanide with 1-bromo-3-chloropropane to obtain 4-chlorobutyronitrile, the cyclization of the 4-chlorobutyronitrile to obtain cyclopropanenitrile, and (3) the hydrolysis of the cyclopropanenitrile to obtain cyclopropanecarboxylic acid is disclosed in Japanese Patent Kokai 04077453, Org. Synthesis, Coll. Vol. 1, 156 (1941) and Org. Synthesis, Coll. Vol. 3, 221 (1955). This process requires handling of an extremely toxic metal cyanide and extensive extractions in the isolation of the product.
- U.S. Pat. No. 4,590,292 describes a route to cyclopropanecarboxamide from ⁇ -butyrolactone via a four step process.
- ⁇ -Butyrolactone is cleaved with hydrogen chloride gas in the presence of aqueous sulfuric acid solution to form 4-chlorobutyric acid which is converted into a chlorobutyrate ester.
- the chlorobutyrate ester is cyclized by sodium hydroxide in the presence of a phase transfer catalyst to yield a cyclopropanecarboxylate ester.
- This ester is treated with ammonia in the presence of a sodium alkoxide as a catalyst to form cyclopropanecarboxamide.
- U.S. Pat. No. 5,068,428 (equivalent of European Patent Specification EP 365,970) discloses a process for the production of cyclopropanecarboxamide by the amidation of isobutyl cyclopropanecarboxylate in the presence of sodium isobutoxide/isobutanol.
- the isolation of the product from the reaction mixture is not trivial with a moist, salt-containing product usually being obtained.
- the process has limitations similar to those described in U.S. Pat. No. 4,590,292.
- the present invention pertains to the preparation of cyclopropanecarboxylic acid by the non-catalytic, oxidation of cyclopropanecarboxaldehyde which may be obtained by the thermal isomerization or rearrangement of 2,3-dihydrofuran.
- U.S. Pat. No. 4,275,238 describes passing 2,3-dihydrofuran through a column at 480° C. to obtain cyclopropanecarboxaldehyde having a purity of 90% purity and containing 6.2-6.7% crotonaidehyde.
- Wilson J. Amer. Chem. Soc. 69, 3002 (1947).
- 2,3-Dihydrofuran may be obtained according to the process described in U.S. Pat. No. 5,254,701 by the isomerization of 2,5-dihydrofuran which in turn can be produced by the isomerization of 3,4-epoxy-1-butene as described in U.S. Pat. Nos. 3,932,468, 3,996,248 and 5,082,956.
- U.S. Pat. Nos. 4,897,498 and 4,950,773 describe the preparation of 3,4-epoxy-1-butene by selective monoepoxidation of butadiene.
- the molecular oxygen used in the process of our invention may be provided as substantially pure oxygen, air, oxygen-enriched air or oxygen diluted with one or more inert gases.
- the source of the molecular oxygen is air.
- air or other oxygen-containing gas is fed with sufficient agitation to the liquid cyclopropanecarboxaldehyde at a rate which results in complete, or substantially complete, conversion of the cyclopropanecarboxaldehyde in from about 2 to 12 hours.
- Agitation may be provided by mechanical stirrers or by sparging air into a columnar oxidation vessel.
- the second step of the process of this invention may be carried out in a batch, semi-continuous or continuous mode of operation.
- the oxidation process of the present invention is non-catalytic and proceeds at good rates and selectivities in the absence of a catalyst and, therefore, preferably is carried out in the absence of an added oxidation catalyst.
- a catalyst in the process.
- catalysts include transition metals and compounds thereof such as cobalt acetate, chromium acetate, platinum and chromium acetate hydroxide and alkali metal carboxylate salts such as sodium acetate and sodium, cyclopropanecarboxylate.
- an inert, organic solvent also may be utilized.
- solvents examples include aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, toluene, xylene and mixed xylene isomers; ethers such as tetrahydrofuran; alcohols such as methanol and ethanol; or the oxidation product.
- a preferred embodiment of our invention comprises a process for the preparation of cyclopropanecarboxylic acid which comprises the steps of
- hydroxy compound reactants include compounds having the structural formula R—OH wherein R is (i) a linear or branched alkyl, alkenyl or alkynyl radical containing up to about 30 carbon atoms, (ii) a cycloalkyl or cycloalkenyl radical containing 3 to 7 carbon atoms, (iii) a carbocyclic aromatic or heterocyclic aromatic radical which may carry one or more substituents, or (iv) a 5- or 6-membered non-aromatic heterocyclic radical comprising one or more hetero atoms.
- R is (i) a linear or branched alkyl, alkenyl or alkynyl radical containing up to about 30 carbon atoms, (ii) a cycloalkyl or cycloalkenyl radical containing 3 to 7 carbon atoms, (iii) a carbocyclic aromatic or heterocyclic aromatic radical which may carry one or more substituents, or (iv) a 5- or 6-
- These solid acidic resins are easily separated from the product mixture by filtration and the recovered resins are reusable.
- the process may be operated batchwise, semi-continuously or continuously. For example, in semi-continuous or continuous operation, cyclopropanecarboxylic acid and an alcohol may be fed to a packed column of the solid acid resin. Recovery and isolation of excess alcohol and the ester product may be accomplished by distillation.
- the esterification reaction optionally may be performed in the presence of an organic solvent which forms an azeotrope (constant boiling mixture) with water and thus facilitate the removal of by-product water by azeotropic distillation during the esterification process.
- organic solvent which forms an azeotrope (constant boiling mixture) with water and thus facilitate the removal of by-product water by azeotropic distillation during the esterification process.
- solvents include aromatic hydrocarbons such as benzene, toluene, xylene and mixed xylene isomers.
- Cyclopropanecarbonyl chloride may be prepared by contacting cyclopropanecarboxylic acid with a chlorinating agent at a temperature of about 10° to 120° C.
- chlorinating agents include thionyl chloride (see procedure described in J. Chem. Soc. Perkin I, pp. 146-147 1976), tetrachloroethylene carbonate (European Patent Specification EP 315,517), phosphorus pentachloride, phosphorus trichloride, oxalyl chloride or phosgene.
- the mole ratio of the chlorinating agent to cyclopropanecarboxylic acid normally is at least 1:1 and preferably is about 1.1:1 to 1.2:1.
- the reaction of cyclopropanecarboxylic acid and the chlorinating agent normally is carried out in the absence of either a solvent or a catalyst.
- the chlorination preferably utilizes thionyl chloride at a temperature of about 50° to 100° C.
- cyclopropanecarbonyl chloride having a purity of at least 98% may be recovered by distillation in yields in the range of 90 to 96%.
- Cyclopropanecarboxamide may be obtained by contacting cyclopropanecarboxylic acid with ammonia at a temperature of about 20° to 400° C., preferably 180° to 260° C., and a pressure in the range of 1 to 345 bar absolute.
- the pressure employed usually depends on the size of the reactor used and preferably is in the range of about 10 to 100 bar absolute. Satisfactory yields usually are achieved using reaction times of about 1 to 10 hours.
- the amount of ammonia employed in the reaction is in the range of 1 to 50 moles, preferably 3 to 6 moles, per mole of cyclopropanecarboxylic acid.
- the reaction batch is worked up by venting the reactor with nitrogen at 100° to 150° C.
- the reaction of cyclopropanecarboxylic acid with ammonia preferably is carried out in the absence of solvent and catalyst.
- the exclusion of catalyst and solvents not only provides cost advantages but also simplifies the isolation of the product to give pure cyclopropanecarboxamide suitable for uses in pharmaceuticals and agrochemicals.
- the amidation reaction optionally may be carried out in the presence of an inert, organic solvent.
- solvents include aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, toluene, xylene and mixed xylene isomers, ethers such as tetrahydrofuran, alcohols such as methanol and ethanol.
- a particularly useful procedure for the preparation cyclopropanecarboxamide comprises the steps of:
- Cyclopropanecarboxaldehyde (105 g, 95% purity, containing 4-4.5% crotonaldehyde) is placed in a steam-jacketed vessel equipped with a mechanical stirrer and a gas inlet at the base of the vessel which then is heated with steam (95°-100° C.). Air is introduced at a rate of 400 mL/minute with agitation for a period of about 8 hours after which time consumption of the cyclopropanecarboxaldehyde is complete as shown by gas chromatography. Distillation of the crude product under reduced pressure gives cyclopropanecarboxylic acid (113 g, 98% purity) in 90% yield.
- Example 1 The procedure described in Example 1 is repeated using 45 g of cyclopropanecarboxaldehyde (except Example 4 in which 56 g of cyclopropanecarboxaldehyde is used) and varying air flow rates and reaction temperatures.
- the materials listed below are used in Examples 4, 6 and 7;
- Example 6 0.5 g of platinum on carbon
- Example 7 22.5 mg cobaltous acetate and 22.5 mg of chromium (III) acetate hydroxide.
- cyclopropanecarboxylic acid 8.6 g
- ethanol 23 mL
- concentrated sulfuric acid 2 drops
- the mixture is refluxed (approximately 85° C.) for 16 hours.
- GC analysis shows that 98% of the cyclopropanecarboxylic acid has been consumed and a 98% yield of ethyl cyclopropanecarboxylate is obtained.
- Amberlyst-15 and Nafion-H acidic ion exchange resins are evaluated as catalysts for the esterification of cyclopropanecarboxylic acid with methanol and ethanol to produce methyl and ethyl cyclopropanecarboxylate.
- 2 g of the ion exchange resin, 20 g of cyclopropanecarboxylic acid, and 100 mL of either methanol or ethanol are heated at reflux for a reaction time of up to 20 hours.
- the consumption of the cyclopropanecarboxylic acid is monitored every 2 hours by GC analysis.
- the materials used in each of Examples 10-13 are:
- Example 13 Nafion-H resin and ethanol.
- the results obtained are shown in Table II wherein Total Reaction Time is the hours of reaction time at which the reaction mixtures is sampled for GC analysis and the Percent Completion is the mole percent of cyclopropanecarboxylic acid consumed at the time of each analysis.
- cyclopropanecarboxylic acid 8.6 g, 95% assay.
- thionyl chloride (13.1 g) dropwise through the addition funnel while stirring.
- the reaction mixture is heated at 80° C. for 30 minutes after which period of time liberation of gas stopped.
- the mixture is fractionated under reduced pressure to give cyclopropanecarbonyl chloride as a colorless oil (9.4 g, 90% yield, 98% purity by GC).
- cyclopropanecarboxylic acid 131.6 g, 95% assay.
- thionyl chloride 218.9 g
- the reaction mixture is heated at 80° C. for 30 minutes (liberation of gas stopped).
- the mixture is fractionated under reduced pressure to give cyclopropanecarbonyl chloride as a colorless oil (164.2 g, 96% yield, 98% purity by GC).
- a 300-mL autoclave is charged with cyclopropanecarboxylic acid (129 g, 98% assay) and ammonia (100 ml), sealed and heated to 240° C.
- the contents of the autoclave are heated with stirring at 240° C. and 41-44 bar absolute for 2 hours.
- the reaction mixture is cooled to 150° C., the autoclave is vented and nitrogen is circulated through the autoclave at atmospheric pressure.
- the reaction mixture is allowed to cool to room temperature and the cyclopropanecarboxamide product (119 g, 95% yield, 93% purity by GC) is collected as a solid.
- GC analysis indicated 94% consumption of the cyclopropanecarboxylic acid.
- the product is washed with heptane and suction filtered to give cyclopropanecarboxamide having a purity of 99%.
Abstract
Disclosed is a process for the preparation of cyclopropanecarboxylic acid by the non-catalytic, oxidation of cyclopropanecarboxaldehyde using molecular oxygen as the oxidant. Also disclosed are processes for the preparation of amides, esters and acid chlorides from cyclopropanecarboxylic acid.
Description
This is a divisional application of application Ser. No. 08/315,462, filed Sep. 30, 1994 now U.S. Pat. No. 5,504,245.
This invention pertains a process for the preparation of cyclopropanecarboxylic acid by the non-catalytic, oxidation of cyclopropanecarboxaldehyde. This invention also pertains to processes for the preparation of esters and the amide and acid chloride of cyclopropanecarboxylic acid.
Cyclopropanecarboxylic acid and its derivatives, especially cyclopropylamine, are useful in the synthesis of pharmaceuticals and pesticides. See, for example, European Patent Publications EP 237,955 A2, EP 273,862 A2 and EP 430,847 A1. The synthesis of cyclopropanecarboxylic acid by a three-step process consisting of (1) the reaction of a metal cyanide with 1-bromo-3-chloropropane to obtain 4-chlorobutyronitrile, the cyclization of the 4-chlorobutyronitrile to obtain cyclopropanenitrile, and (3) the hydrolysis of the cyclopropanenitrile to obtain cyclopropanecarboxylic acid is disclosed in Japanese Patent Kokai 04077453, Org. Synthesis, Coll. Vol. 1, 156 (1941) and Org. Synthesis, Coll. Vol. 3, 221 (1955). This process requires handling of an extremely toxic metal cyanide and extensive extractions in the isolation of the product. Additional processes for the synthesis of cyclopropanecarboxylic acid on a laboratory scale are described by J. Tu et al., Youji Huaxue 12, pp. 48-50 (1992); J. Yang et al., Huaxue Shijie 31, pp. 356-358 (1990); M. A. Cohen et al., Tetrahedron Letter 31, 7223-7226 (1990); C. W. Jefford et al., J. Chem. Soc. Chem. Commun., pp. 634-635 (1988); S. C. Bunce et al. Org. Prep. Proced. Int., 6, pp. 193-196 (1974); G. M. Lampan et al., J. Chem. Eng. Data. 14, pp. 396-397 (1969). While convenient for laboratory use, the procedures in these cited articles are not suitable for large-scale commercial use due to low yields and/or the use of expensive reagents.
U.S. Pat. No. 3,711,549 discloses the preparation of methyl cyclopropanecarboxylate by the steps of (1) converting γ-butyrolactone to 4-chlorobutyric acid by cleaving γ-butyrolactone in the presence of zinc chloride at 120° C. and 20.7 bars, (2) reacting the 4-chlorobutyric acid with methanol, and (3) cyclizing the methyl 4-chlorobutyrate. The cyclization reaction requires preesterification of the acid since the cyclization condition otherwise would result in conjugative polymerization of the butyric acid moiety or ring closure to reform gamma-butyrolactone. The process of U.S. Pat. No. 3,711,549 requires handling strongly corrosive and hazardous hydrogen chloride in the gaseous state at elevated temperatures and pressures. The process also involves the use of sodium metal in the manufacture of the fresh sodium methoxide needed for the ring closure of 4-chlorobutyrate ester to yield cyclopropanecarboxylate ester. The mentioned requirements of the process described in U.S. Pat. No. 3,711,549 present serious problems with respect to safety in equipment design and material handling.
U.S. Pat. No. 4,590,292 describes a route to cyclopropanecarboxamide from γ-butyrolactone via a four step process. γ-Butyrolactone is cleaved with hydrogen chloride gas in the presence of aqueous sulfuric acid solution to form 4-chlorobutyric acid which is converted into a chlorobutyrate ester. The chlorobutyrate ester is cyclized by sodium hydroxide in the presence of a phase transfer catalyst to yield a cyclopropanecarboxylate ester. This ester is treated with ammonia in the presence of a sodium alkoxide as a catalyst to form cyclopropanecarboxamide. Like the process of U.S. Pat. No. 3,711,549, this process requires the handling of hydrogen chloride gas at elevated temperatures and pressures. To facilitate ring closure of the 4-chlorobutyrate ester to yield the cyclopropanecarboxylate ester, the use of a secondary or tertiary alcohol in the esterification of 4-chlorobutyric acid is essential. Otherwise hydrolysis of the ester becomes a major competitive reaction leading to low yields (U.S. Pat. No. 3,711,549). It is known that esterification using hindered alcohols presents difficulties in driving the reaction to completion. Long reaction times and continuous removal of water (azeotrope with a organic solvent) are required, which leads to higher costs in manufacturing. The cyclization step of this process requires the handling of a chlorinated solvent such as dichloromethane in order to perform the phase transfer-catalyzed cyclization. In the amidation step of the process of U.S. Pat. No. 4,590,292, typically more than 20 mole percent of sodium alkoxide is needed for effective reaction rates. As a result, the isolation of the product from the reaction mixture is difficult and, based on the examples given, the product usually is obtained as a solution of methanol. In the case of the isolation of a pure product, less than a 46% yield is reported. Recycling and repeating the amidation of the mother liquid is required in order to gain higher yields. Since large amounts of catalyst (sodium ethylene glycoxide) are needed, the preparation of the catalyst constitutes an additional step of the process. It is apparent that the process disclosed in U.S. Pat. No. 4,590,292 poses problems with regard to safety and economics.
U.S. Pat. No. 5,068,428 (equivalent of European Patent Specification EP 365,970) discloses a process for the production of cyclopropanecarboxamide by the amidation of isobutyl cyclopropanecarboxylate in the presence of sodium isobutoxide/isobutanol. The isolation of the product from the reaction mixture is not trivial with a moist, salt-containing product usually being obtained. The process has limitations similar to those described in U.S. Pat. No. 4,590,292.
The present invention pertains to the preparation of cyclopropanecarboxylic acid by the non-catalytic, oxidation of cyclopropanecarboxaldehyde which may be obtained by the thermal isomerization or rearrangement of 2,3-dihydrofuran. For example, U.S. Pat. No. 4,275,238 describes passing 2,3-dihydrofuran through a column at 480° C. to obtain cyclopropanecarboxaldehyde having a purity of 90% purity and containing 6.2-6.7% crotonaidehyde. A similar procedure is described by Wilson, J. Amer. Chem. Soc. 69, 3002 (1947). 2,3-Dihydrofuran may be obtained according to the process described in U.S. Pat. No. 5,254,701 by the isomerization of 2,5-dihydrofuran which in turn can be produced by the isomerization of 3,4-epoxy-1-butene as described in U.S. Pat. Nos. 3,932,468, 3,996,248 and 5,082,956. U.S. Pat. Nos. 4,897,498 and 4,950,773 describe the preparation of 3,4-epoxy-1-butene by selective monoepoxidation of butadiene.
The process of the present invention comprises the preparation of cyclopropanecarboxylic acid by contacting cyclopropanecarboxaldehyde with molecular oxygen at elevated temperature. We have discovered that the novel oxidation process proceeds at an acceptable rate in the absence of a catalyst and a solvent which reduces operating costs and greatly simplifies both isolation of the carboxylic acid product and the equipment required for the operation of the process. The rate of oxidation of cyclopropanecarboxaldehyde to cyclopropanecarboxylic acid has been found to be dependent primarily upon oxygen mass transfer rather than any catalyst action. Since the oxidation of an aldehyde to a carboxylic acid is a free radical process [see, for example, Riley et al., J. Org. Chem. 52, 287 (1987)], partial or complete decomposition of the cyclopropane ring was a potential problem of the oxidation process. Another advantage provided by the oxidation process is that it causes the decomposition of crotonaldehyde, an inevitable impurity of cyclopropanecarboxaldehyde obtained from 2,3-dihydrofuran. Since the boiling points of cyclopropanecarboxylic acid and crotonic acid are 182°-184° C. and 180°-181° C., respectively, the conversion of the crotonaldehyde impurity to crotonic acid during the oxidation of cyclopropanecarboxaldehyde to cyclopropanecarboxylic acid would present a very difficult purification problem.
The elevated temperatures which may be employed in the operation of the present oxidation process are in the range of about 10° to 200° C. although temperatures in the range of about 50° to 100° C. are preferred. Process pressures of about 0.5 to 50 bar absolute may be used with pressures of about 1 to 10 bar absolute being preferred.
The molecular oxygen used in the process of our invention may be provided as substantially pure oxygen, air, oxygen-enriched air or oxygen diluted with one or more inert gases. Normally, the source of the molecular oxygen is air. In the operation of the process air or other oxygen-containing gas is fed with sufficient agitation to the liquid cyclopropanecarboxaldehyde at a rate which results in complete, or substantially complete, conversion of the cyclopropanecarboxaldehyde in from about 2 to 12 hours. Agitation may be provided by mechanical stirrers or by sparging air into a columnar oxidation vessel. The second step of the process of this invention may be carried out in a batch, semi-continuous or continuous mode of operation.
The oxidation process of the present invention is non-catalytic and proceeds at good rates and selectivities in the absence of a catalyst and, therefore, preferably is carried out in the absence of an added oxidation catalyst. However, it is possible to employ a catalyst in the process. Examples of such catalysts include transition metals and compounds thereof such as cobalt acetate, chromium acetate, platinum and chromium acetate hydroxide and alkali metal carboxylate salts such as sodium acetate and sodium, cyclopropanecarboxylate. Although not essential to the successful operation of the process, an inert, organic solvent also may be utilized. Examples of such solvents include aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, toluene, xylene and mixed xylene isomers; ethers such as tetrahydrofuran; alcohols such as methanol and ethanol; or the oxidation product. A preferred embodiment of our invention comprises a process for the preparation of cyclopropanecarboxylic acid which comprises the steps of
(1) contacting a mixture of 99.5 to 70 weight percent cyclopropanecarboxaldehyde and 0.5 to 30 weight percent crotonaldehyde with molecular oxygen at a temperature of about 50° to 100° C. and a pressure of about 1 to 10 bar absolute; and
(2) recovering cyclopropanecarboxylic acid free of crotonic acid.
As mentioned hereinabove, crotonaldehyde is an inevitable impurity of cyclopropanecarboxaldehyde obtained from 2,3-dihydrofuran. The oxidation process of this invention causes decomposition of crotonaldehyde and/or crotonic acid and thus purification of the cyclopropanecarboxylic acid is greatly simplified. In this embodiment of the invention the cyclopropanecarboxaldehyde/crotonaldehyde mixture more typically comprises 99 to 85 weight percent cyclopropanecarboxaldehyde and 1 to 15 weight percent crotonaldehyde.
The cyclopropanecarboxylic acid obtained from the oxidation process may be converted to various derivatives such as esters, acid chlorides and amides. Cyclopropanecarboxylate esters, e.g., compounds having the structure
wherein R is defined below, are prepared by reacting cyclopropanecarboxylic acid with various hydroxy compounds at a temperature of about 20° to 200° C., preferably about 60 to 150° C., in the presence of an acidic esterification catalyst. Examples of typical hydroxy compounds include aliphatic, cycloaliphatic and non-aromatic heterocyclic alcohols containing up to about 30, preferably up to about 12, carbon atoms; aromatic, carbocyclic and heterocyclic hydroxy compounds containing 4 to 14 ring carbon atoms such as phenols, napthols and the like. Examples of the hydroxy compound reactants include compounds having the structural formula R—OH wherein R is (i) a linear or branched alkyl, alkenyl or alkynyl radical containing up to about 30 carbon atoms, (ii) a cycloalkyl or cycloalkenyl radical containing 3 to 7 carbon atoms, (iii) a carbocyclic aromatic or heterocyclic aromatic radical which may carry one or more substituents, or (iv) a 5- or 6-membered non-aromatic heterocyclic radical comprising one or more hetero atoms. Exemplary compounds contemplated for use in the practice of the present invention include methanol, ethanol, propanol, isopropanol, butanol, 2-butanol, isobutanol, t-butanol, phenol and benzyl alcohol. Primary and secondary alkanols containing up to about 8 carbon atoms constitute the preferred hydroxy compound reactants.
The alcohol is generally employed in a quantity of 1 to 200 equivalents per equivalent of cyclopropanecarboxylic acid to be converted, preferably 5 to 20 equivalents. Acids which can be used as catalyst for this transformation are: (1) inorganic acids such as sulfuric acid, hydrochloric acid and phosphoric acid; (2) organic acids such as trifluoroacetic acid, p-toluenesulfonic acid, methylsulfonic acid and cyclopropanecarboxylic acid itself. Particularly useful for this reaction is the use of insoluble, acidic, ion exchange resins such as sulfonated polystyrene resins, e.g. Amberlyst XN-1010 and Amberlyst-15 resin beads, and sulfonated polyfluorocarbon resins, e.g., Nafion-H resin. These solid acidic resins are easily separated from the product mixture by filtration and the recovered resins are reusable. The process may be operated batchwise, semi-continuously or continuously. For example, in semi-continuous or continuous operation, cyclopropanecarboxylic acid and an alcohol may be fed to a packed column of the solid acid resin. Recovery and isolation of excess alcohol and the ester product may be accomplished by distillation.
The esterification reaction optionally may be performed in the presence of an organic solvent which forms an azeotrope (constant boiling mixture) with water and thus facilitate the removal of by-product water by azeotropic distillation during the esterification process. Examples of such solvents include aromatic hydrocarbons such as benzene, toluene, xylene and mixed xylene isomers.
Cyclopropanecarbonyl chloride may be prepared by contacting cyclopropanecarboxylic acid with a chlorinating agent at a temperature of about 10° to 120° C. Examples of chlorinating agents include thionyl chloride (see procedure described in J. Chem. Soc. Perkin I, pp. 146-147 1976), tetrachloroethylene carbonate (European Patent Specification EP 315,517), phosphorus pentachloride, phosphorus trichloride, oxalyl chloride or phosgene. The mole ratio of the chlorinating agent to cyclopropanecarboxylic acid normally is at least 1:1 and preferably is about 1.1:1 to 1.2:1. The reaction of cyclopropanecarboxylic acid and the chlorinating agent normally is carried out in the absence of either a solvent or a catalyst. The chlorination preferably utilizes thionyl chloride at a temperature of about 50° to 100° C. Upon completion of the reaction (when liberation of gas has stopped), cyclopropanecarbonyl chloride having a purity of at least 98% may be recovered by distillation in yields in the range of 90 to 96%.
Cyclopropanecarboxamide may be obtained by contacting cyclopropanecarboxylic acid with ammonia at a temperature of about 20° to 400° C., preferably 180° to 260° C., and a pressure in the range of 1 to 345 bar absolute. The pressure employed usually depends on the size of the reactor used and preferably is in the range of about 10 to 100 bar absolute. Satisfactory yields usually are achieved using reaction times of about 1 to 10 hours. The amount of ammonia employed in the reaction is in the range of 1 to 50 moles, preferably 3 to 6 moles, per mole of cyclopropanecarboxylic acid. The reaction batch is worked up by venting the reactor with nitrogen at 100° to 150° C. to remove the water along with the excess ammonia. After cooling to room temperature, the product is obtained as a solid which is washed with heptane and collected by filtration to give 99% pure cyclopropanecarboxamide. Such a procedure typically gives an isolated yield of cyclopropanecarboxamide of about 90% at more than 96% conversion of cyclopropanecarboxylic acid.
The reaction of cyclopropanecarboxylic acid with ammonia preferably is carried out in the absence of solvent and catalyst. The exclusion of catalyst and solvents not only provides cost advantages but also simplifies the isolation of the product to give pure cyclopropanecarboxamide suitable for uses in pharmaceuticals and agrochemicals. However, the amidation reaction optionally may be carried out in the presence of an inert, organic solvent. Examples of such solvents include aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, toluene, xylene and mixed xylene isomers, ethers such as tetrahydrofuran, alcohols such as methanol and ethanol.
A particularly useful procedure for the preparation cyclopropanecarboxamide comprises the steps of:
(1) contacting cyclopropanecarboxylic acid with ammonia in a reactor at a temperature of 200° to 260° C., preferably 230° to 240° C., and a pressure of 10 to 100 bar absolute in the absence of both a catalyst and a solvent to form a metal of cyclopropanecarboxamide;
(2) venting the reactor at temperature above the melting point (120°-122° C.) of cyclopropanecarboxamide, preferably at 130° to 150° C., to reduce the pressure to about atmospheric pressure and remove excess ammonia and water of reaction from the cyclopropanecarboxamide; and
(3) obtaining from the reactor cyclopropanecarboxamide essentially free, e.g., containing less than 0.5 weight percent of each, of water and ammonia. This procedure simplifies the purification of cyclopropanecarboxamide and avoids a potential loss in yield due to the presence of water in which the cyclopropanecarboxamide is soluble.
The processes provided by the present invention are further illustrated by the following examples. Gas chromatographic (GC) analyses were performed on a Hewlett-Packard 5890 series II gas chromatography with a 30 meter DB-Wax and a 30 meter DB-17 capillary coles. The identities of the products obtained were confirmed by nuclear magnetic spectrometry and gas chromatography-mass spectrometry comparing to authentic samples purchased from Aldrich chemical company.
Cyclopropanecarboxaldehyde (105 g, 95% purity, containing 4-4.5% crotonaldehyde) is placed in a steam-jacketed vessel equipped with a mechanical stirrer and a gas inlet at the base of the vessel which then is heated with steam (95°-100° C.). Air is introduced at a rate of 400 mL/minute with agitation for a period of about 8 hours after which time consumption of the cyclopropanecarboxaldehyde is complete as shown by gas chromatography. Distillation of the crude product under reduced pressure gives cyclopropanecarboxylic acid (113 g, 98% purity) in 90% yield.
The procedure described in Example 1 is repeated using 45 g of cyclopropanecarboxaldehyde (except Example 4 in which 56 g of cyclopropanecarboxaldehyde is used) and varying air flow rates and reaction temperatures. The materials listed below are used in Examples 4, 6 and 7;
Example 4 - 2.16 g of sodium cyclopropanecarboxylate
Example 6 - 0.5 g of platinum on carbon
Example 7 - 22.5 mg cobaltous acetate and 22.5 mg of chromium (III) acetate hydroxide.
The results obtained are shown in Table I wherein Flow Rate is the rate in mL per minute at which air is fed to the gas saturator; Reaction Temperature is the temperature in °C. at which the slightly exothermic oxidation is carried out; and Completion Time is the period of time in hours required to consume all of the cyclopropanecarboxaldehyde. The purity of the cyclopropanecarboxaldehyde obtained was 98% or greater.
TABLE I | ||||
Reaction | Completion | Isolated | ||
Example | Flow Rate | Temperature | Time | Yield, % |
2 | 400 | 25 | 8 | 85 |
3 | 400 | 95-100 | 5 | 88 |
4 | 200 | 95-100 | 8 | 85 |
5 | 200 | 25 | 12 | 75 |
6 | 200 | 25 | 12 | 68 |
7 | 200 | 25 | 10 | 92 |
To a 10-mL, three-necked flask equipped with a condenser, a magnetic stir bar and a thermometer is charged cyclopropanecarboxylic acid (1 g), methanol (5 mL) and 1 drop of concentrated sulfuric acid. The mixture is refluxed (approximately 70° C.) for 3 hours. GC analysis shows complete consumption of the cyclopropanecarboxylic acid and that a quantitative yield of methyl cyclopropanecarboxylate is obtained.
To a 10-mL, three-necked flask equipped with a condenser, a magnetic stir bar and a thermometer is charged cyclopropanecarboxylic acid (8.6 g), ethanol (23 mL) and 2 drops of concentrated sulfuric acid. The mixture is refluxed (approximately 85° C.) for 16 hours. GC analysis shows that 98% of the cyclopropanecarboxylic acid has been consumed and a 98% yield of ethyl cyclopropanecarboxylate is obtained.
In these examples Amberlyst-15 and Nafion-H acidic ion exchange resins are evaluated as catalysts for the esterification of cyclopropanecarboxylic acid with methanol and ethanol to produce methyl and ethyl cyclopropanecarboxylate. In each example, 2 g of the ion exchange resin, 20 g of cyclopropanecarboxylic acid, and 100 mL of either methanol or ethanol are heated at reflux for a reaction time of up to 20 hours. The consumption of the cyclopropanecarboxylic acid is monitored every 2 hours by GC analysis. In addition to cyclopropanecarboxylic acid, the materials used in each of Examples 10-13 are:
Example 10 - Amberlyst-15 resin and methanol
Example 11 - Nafion-H resin and methanol
Example 12 - Amberlyst-15 resin and ethanol
Example 13 - Nafion-H resin and ethanol. The results obtained are shown in Table II wherein Total Reaction Time is the hours of reaction time at which the reaction mixtures is sampled for GC analysis and the Percent Completion is the mole percent of cyclopropanecarboxylic acid consumed at the time of each analysis.
TABLE II | ||
Percent Completion |
Total | Example | Example | Example | Example |
Reaction Time | 10 | 11 | 12 | 13 |
2 | 50.85 | 76.70 | 28.57 | 39.09 |
4 | 68.66 | 83.38 | 42.48 | 58.30 |
6 | 71.21 | 88.27 | 51.95 | 67.70 |
8 | 85.09 | 93.18 | 67.18 | 75.73 |
10 | 87.54 | 96.07 | 66.78 | 80.07 |
12 | 90.30 | 96.21 | 71.46 | 83.84 |
14 | 92.78 | 96.78 | 76.11 | 86.02 |
16 | 94.00 | 96.94 | 79.10 | 89.12 |
18 | 94.28 | — | 81.33 | — |
20 | 95.61 | 97.88 | 81.80 | — |
To a 50 mL flask equipped with a condensate and an addition funnel is placed cyclopropanecarboxylic acid (8.6 g, 95% assay). To this is added thionyl chloride (13.1 g) dropwise through the addition funnel while stirring. After completion of the addition, the reaction mixture is heated at 80° C. for 30 minutes after which period of time liberation of gas stopped. The mixture is fractionated under reduced pressure to give cyclopropanecarbonyl chloride as a colorless oil (9.4 g, 90% yield, 98% purity by GC).
To a 500 mL flask equipped with a condenser and an addition funnel, is placed cyclopropanecarboxylic acid (131.6 g, 95% assay). To this is added thionyl chloride (218.9 g) dropwise through the addition funnel while stirring. After completion of the addition over a period of 1.5 hours, the reaction mixture is heated at 80° C. for 30 minutes (liberation of gas stopped). The mixture is fractionated under reduced pressure to give cyclopropanecarbonyl chloride as a colorless oil (164.2 g, 96% yield, 98% purity by GC).
A 300-mL autoclave is charged with cyclopropanecarboxylic acid (86 g, 95% assay) and ammonia (100 ml), sealed and heated to 240° C. The contents of the autoclave are maintained at 240° C. and 42 to 45 bar absolute for 2 hours. The reaction mixture is cooled to 150° C., the autoclave is vented and nitrogen is circulated through the autoclave at atmospheric pressure. The reaction mixture is allowed to cool to room temperature and the cyclopropanecarboxamide product is collected as solids. GC analysis indicated 96% consumption of the cyclopropanecarboxylic acid. The product is washed with heptane and suction filtered to give 73 g of cyclopropanecarboxamide having a purity of 99% (m.p. 120°-122° C.) in a 90% isolated yield.
A 300-mL autoclave is charged with cyclopropanecarboxylic acid (129 g, 98% assay) and ammonia (100 ml), sealed and heated to 240° C. The contents of the autoclave are heated with stirring at 240° C. and 41-44 bar absolute for 2 hours. The reaction mixture is cooled to 150° C., the autoclave is vented and nitrogen is circulated through the autoclave at atmospheric pressure. The reaction mixture is allowed to cool to room temperature and the cyclopropanecarboxamide product (119 g, 95% yield, 93% purity by GC) is collected as a solid. GC analysis indicated 94% consumption of the cyclopropanecarboxylic acid. The product is washed with heptane and suction filtered to give cyclopropanecarboxamide having a purity of 99%.
The invention has been described in detail with particular reference to preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention.
Claims (14)
1. Process for the preparation of cyclopropanecarboxylic acid which comprises contacting cyclopropanecarboxaldehyde with molecular oxygen at a temperature of about 10° to 200° C. wherein in a second step the cyclopropanecarboxylic acid is reacted with a hydroxy compound having the structure R—OH in the presence of an acidic catalyst to produce a cyclopropanecarboxylate ester having the structure:
wherein R is (i) a linear or branched alkyl, alkenyl or alkynyl radical containing up to about 30 carbon atoms, (ii) a cycloalkyl or cycloalkenyl radical containing 3 to 7 carbon atoms, (iii) a carbocyclic aromatic or heterocyclic aromatic radical which may carry one or more substituents, or (iv) a 5- or 6-membered non-aromatic heterocyclic radical comprising one or more hetero atoms.
2. Process for the preparation of cyclopropanecarboxylic acid which comprises contacting cyclopropanecarboxaldehyde with molecular oxygen provided as substantially pure oxygen, air, or oxygen-enriched air at a temperature of about 50° to 100° C. and a pressure of about 1 to 10 bar absolute in the absence of an oxidation catalyst wherein in a second step the cyclopropanecarboxylic acid is reacted with a primary or secondary alkanol containing up to about 8 carbon atoms at a temperature of about 60° to 150° C. in the presence of an acidic catalyst to produce an alkyl cyclopropanecarboxylate.
3. Process for the preparation of cyclopropanecarboxylic acid which comprises contacting cyclopropanecarboxaldehyde with molecular oxygen at a temperature of about 10° to 200° C. wherein in a second step the cyclopropanecarboxylic acid is reacted with ammonia at a temperature of about 20° to 400° C. and a pressure of about 1 to 345 bar absolute to produce cyclopropanecarboxamide.
4. Process for the preparation of cyclopropanecarboxylic acid which comprises contacting cyclopropanecarboxaldehyde with molecular oxygen provided as substantially pure oxygen, air, or oxygen-enriched air at a temperature of about 50° to 100° C. and a pressure of about 1 to 10 bar absolute in the absence of an oxidation catalyst wherein in a second step the cyclopropanecarboxylic acid is reacted with ammonia at a temperature of about 180° to 260° C. and a pressure of about 10 to 100 bar absolute to produce cyclopropanecarboxamide.
5. Process for the preparation cyclopropanecarboxamide which comprises the steps of:
(1) contacting cyclopropanecarboxylic acid with ammonia in a reactor at a temperature of 200° to 260° C. and a pressure of 10 to 100 bar absolute in the absence of both a catalyst and a solvent to form a melt of cyclopropanecarboxamide;
(2) venting the reactor at a temperature above the melting point of cyclopropanecarboxamide to reduce the pressure to about atmospheric pressure and remove excess ammonia and water of reaction from the cyclopropanecarboxamide; and
(3) obtaining from the reactor cyclopropanecarboxamide essentially free of water and ammonia.
6. Process according to claim 5 wherein step (1) is performed at 230° to 240° C. and step (2) is performed at 130° to 150° C.
7. A process for the preparation of cyclopropanecarboxamide which comprises reacting cyclopropanecarboxylic acid with ammonia at a pressure of 1 to 345 bar in the presence of an organic solvent to give the amide.
8. The process of claim 7, which is carried out in the absence of a catalyst.
9. The process of claim 7, wherein at least one solvent selected from the group consisting of aromatic hydrocarbons and aliphatic hydrocarbons is used as the solvent.
10. The process of claim 7, wherein the at least one solvent selected from the group consisting of cyclohexane, heptane, toluene, and xylene is used as the solvent.
11. The process of claim 7, wherein at least one solvent selected from the group consisting of ethers and alcohols is used as the solvent.
12. The process of claim 7, which is carried out at a pressure of 1 to 100 bar.
13. The process of claim 7, wherein the reaction with ammonia is carried out in a temperature range from 20° to 400° C.
14. The process of claim 7, wherein the amide is collected as a solids, washed and isolated by filtration.
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US08/315,462 US5504245A (en) | 1994-09-30 | 1994-09-30 | Processes for the preparation of cyclopropanecarboxylic acid and derivatives thereof |
US08/562,948 US5663418A (en) | 1994-09-30 | 1995-11-27 | Processes for the preparation of cyclopropanecarboxylic acid and derivatives thereof |
US09/289,387 USRE37188E1 (en) | 1994-09-30 | 1999-04-12 | Processes for the preparation of cyclopropanecarboxylic acid and derivatives thereof |
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DE19547635A1 (en) | 1995-12-20 | 1997-06-26 | Bayer Ag | Process for the preparation of cyclopropanecarboxamides |
US5633401A (en) * | 1996-04-01 | 1997-05-27 | Eastman Chemical Company | Process for decolorizing cyclopropanecarboxylic acid |
DE19738072A1 (en) | 1997-09-01 | 1999-03-04 | Huels Chemische Werke Ag | Process for the preparation of cyclopropanecarboxylic acid esters of lower alcohols |
US6552217B2 (en) * | 2000-08-01 | 2003-04-22 | Eastman Chemical Company | Process for the preparation of alkyl 1-methylcyclopropanecarboxylate |
PT2292379E (en) * | 2005-03-15 | 2012-03-30 | Htc Sweden Ab | A method for cleaning a polished hard floor surface of stone or stone-like material |
US10065283B2 (en) | 2005-03-15 | 2018-09-04 | Twister Cleaning Technology Ab | Method and tool for maintenance of hard surfaces, and a method for manufacturing such a tool |
CN107118119B (en) * | 2017-05-27 | 2019-08-02 | 大丰跃龙化学有限公司 | A kind of environmentally friendly synthetic method of cyclopropyl formamide |
CN114213234A (en) * | 2021-12-27 | 2022-03-22 | 内蒙古源宏精细化工有限公司 | Synthesis method of cyclopropyl formic acid |
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US3047599A (en) * | 1958-12-22 | 1962-07-31 | Ruhrchemie Ag | Process for the production of mixtures of isomeric aliphatic or cycloaliphatic carboxylic acids having molecular sizes of from c to c |
GB955421A (en) * | 1960-02-04 | 1964-04-15 | Ici Ltd | Improvements in and relating to the oxidation of aldehydes |
FR1507192A (en) * | 1966-08-26 | 1967-12-29 | Roussel Uclaf | Novel aryl allylsulfones and method of preparation |
US3711549A (en) * | 1970-05-19 | 1973-01-16 | Gulf Research Development Co | Process for manufacturing cyclopropylamine |
US4518797A (en) * | 1978-10-23 | 1985-05-21 | Shell Oil Company | Cyclopropanecarboxylate pesticides and their preparation |
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US20090253870A1 (en) * | 2001-08-27 | 2009-10-08 | Akikazu Matsumoto | Photoresponsive polymer,built-up type diacetylene polymer, crystal of ammonium carboxylate, and method of manufacturing them |
US7750084B2 (en) | 2001-08-27 | 2010-07-06 | Japan Science And Technology Agency | Photoresponsive polymer, built-up type diacetylene polymer, crystal of ammonium carboxylate, and method for manufacturing them |
US7981968B2 (en) | 2001-08-27 | 2011-07-19 | Japan Science And Technology Agency | Photoresponsive polymer, built-up type diacetylene polymer, crystal of ammonium carboxylate, and method of manufacturing them |
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WO1996010554A1 (en) | 1996-04-11 |
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US5663418A (en) | 1997-09-02 |
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ZA958249B (en) | 1996-04-24 |
PL319409A1 (en) | 1997-08-04 |
NO971340L (en) | 1997-04-30 |
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US5504245A (en) | 1996-04-02 |
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