CN108467342B - Method for synthesizing benzoic acid compound by oxidizing benzyl alcohol compound under assistance of ultrasonic waves - Google Patents
Method for synthesizing benzoic acid compound by oxidizing benzyl alcohol compound under assistance of ultrasonic waves Download PDFInfo
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- CN108467342B CN108467342B CN201810308573.9A CN201810308573A CN108467342B CN 108467342 B CN108467342 B CN 108467342B CN 201810308573 A CN201810308573 A CN 201810308573A CN 108467342 B CN108467342 B CN 108467342B
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- China
- Prior art keywords
- benzyl alcohol
- ultrasonic
- reaction
- benzoic acid
- diethylene glycol
- Prior art date
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- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 title claims abstract description 188
- 235000019445 benzyl alcohol Nutrition 0.000 title claims abstract description 62
- 238000000034 method Methods 0.000 title claims abstract description 31
- 230000002194 synthesizing effect Effects 0.000 title claims description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 title abstract description 68
- 235000010233 benzoic acid Nutrition 0.000 title abstract description 41
- 239000005711 Benzoic acid Substances 0.000 title abstract description 39
- -1 benzoic acid compound Chemical class 0.000 title abstract description 19
- 230000001590 oxidative effect Effects 0.000 title description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 157
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims abstract description 86
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 25
- 239000002994 raw material Substances 0.000 claims abstract description 23
- 230000003647 oxidation Effects 0.000 claims abstract description 14
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 230000035484 reaction time Effects 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 150000001559 benzoic acids Chemical class 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000006657 (C1-C10) hydrocarbyl group Chemical group 0.000 claims 1
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims 1
- IMXLQXHCHYKEEE-UHFFFAOYSA-N benzene;formic acid Chemical class OC=O.C1=CC=CC=C1 IMXLQXHCHYKEEE-UHFFFAOYSA-N 0.000 claims 1
- 230000006837 decompression Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 7
- 239000000543 intermediate Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000004134 energy conservation Methods 0.000 abstract 1
- 230000005855 radiation Effects 0.000 description 38
- 239000011259 mixed solution Substances 0.000 description 37
- 238000002360 preparation method Methods 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 230000000052 comparative effect Effects 0.000 description 13
- 239000007800 oxidant agent Substances 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Substances OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 4
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 4
- CKMXAIVXVKGGFM-UHFFFAOYSA-N p-cumic acid Chemical compound CC(C)C1=CC=C(C(O)=O)C=C1 CKMXAIVXVKGGFM-UHFFFAOYSA-N 0.000 description 4
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 description 4
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000002604 ultrasonography Methods 0.000 description 3
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N (2-methylphenyl)methanol Chemical compound CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 2
- AXCHZLOJGKSWLV-UHFFFAOYSA-N (4-phenylphenyl)methanol Chemical group C1=CC(CO)=CC=C1C1=CC=CC=C1 AXCHZLOJGKSWLV-UHFFFAOYSA-N 0.000 description 2
- RATSANVPHHXDCT-UHFFFAOYSA-N 4-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)(F)F)C=C1 RATSANVPHHXDCT-UHFFFAOYSA-N 0.000 description 2
- AQRMQSZDZHOFAD-UHFFFAOYSA-N 4-(trifluoromethyl)benzenecarbothioic s-acid Chemical compound OC(=S)C1=CC=C(C(F)(F)F)C=C1 AQRMQSZDZHOFAD-UHFFFAOYSA-N 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- TUXYZHVUPGXXQG-UHFFFAOYSA-N 4-bromobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-N 0.000 description 2
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 2
- ADCUEPOHPCPMCE-UHFFFAOYSA-N 4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1 ADCUEPOHPCPMCE-UHFFFAOYSA-N 0.000 description 2
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- GHICCUXQJBDNRN-UHFFFAOYSA-N 4-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(I)C=C1 GHICCUXQJBDNRN-UHFFFAOYSA-N 0.000 description 2
- REIDAMBAPLIATC-UHFFFAOYSA-M 4-methoxycarbonylbenzoate Chemical compound COC(=O)C1=CC=C(C([O-])=O)C=C1 REIDAMBAPLIATC-UHFFFAOYSA-M 0.000 description 2
- PJHWTWHVCOZCPU-UHFFFAOYSA-N 4-methylbenzenecarbothioic s-acid Chemical compound CC1=CC=C(C(O)=S)C=C1 PJHWTWHVCOZCPU-UHFFFAOYSA-N 0.000 description 2
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 2
- LMJXSOYPAOSIPZ-UHFFFAOYSA-N 4-sulfanylbenzoic acid Chemical compound OC(=O)C1=CC=C(S)C=C1 LMJXSOYPAOSIPZ-UHFFFAOYSA-N 0.000 description 2
- MEXUTNIFSHFQRG-UHFFFAOYSA-N 6,7,12,13-tetrahydro-5h-indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-one Chemical compound C12=C3C=CC=C[C]3NC2=C2NC3=CC=C[CH]C3=C2C2=C1C(=O)NC2 MEXUTNIFSHFQRG-UHFFFAOYSA-N 0.000 description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LODDFDHPSIYCTK-UHFFFAOYSA-N (2,4,6-trimethylphenyl)methanol Chemical compound CC1=CC(C)=C(CO)C(C)=C1 LODDFDHPSIYCTK-UHFFFAOYSA-N 0.000 description 1
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 description 1
- GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-UHFFFAOYSA-N 0.000 description 1
- CNQRHSZYVFYOIE-UHFFFAOYSA-N (4-iodophenyl)methanol Chemical compound OCC1=CC=C(I)C=C1 CNQRHSZYVFYOIE-UHFFFAOYSA-N 0.000 description 1
- MTXQKSQYMREAGJ-UHFFFAOYSA-N (4-methylsulfanylphenyl)methanol Chemical compound CSC1=CC=C(CO)C=C1 MTXQKSQYMREAGJ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SIRPHJCQZYVEES-UHFFFAOYSA-N 1-methylbenzimidazole-2-carbaldehyde Chemical compound C1=CC=C2N(C)C(C=O)=NC2=C1 SIRPHJCQZYVEES-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- PGJYYCIOYBZTPU-UHFFFAOYSA-N 2,3,4,5,6-pentafluorobenzyl alcohol Chemical compound OCC1=C(F)C(F)=C(F)C(F)=C1F PGJYYCIOYBZTPU-UHFFFAOYSA-N 0.000 description 1
- FFFIRKXTFQCCKJ-UHFFFAOYSA-N 2,4,6-trimethylbenzoic acid Chemical compound CC1=CC(C)=C(C(O)=O)C(C)=C1 FFFIRKXTFQCCKJ-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- JJCKHVUTVOPLBV-UHFFFAOYSA-N 3-Methylbenzyl alcohol Chemical compound CC1=CC=CC(CO)=C1 JJCKHVUTVOPLBV-UHFFFAOYSA-N 0.000 description 1
- XAASLEJRGFPHEV-UHFFFAOYSA-N 4-cyanobenzyl alcohol Chemical compound OCC1=CC=C(C#N)C=C1 XAASLEJRGFPHEV-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- BWVAOONFBYYRHY-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(CO)C=C1 BWVAOONFBYYRHY-UHFFFAOYSA-N 0.000 description 1
- ZLSOZAOCYJDPKX-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]methanol Chemical compound OCC1=CC=C(OC(F)(F)F)C=C1 ZLSOZAOCYJDPKX-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 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
- 238000007796 conventional method Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- CEEHFWSNEHHQPJ-UHFFFAOYSA-N ethyl 5-hydroxy-7-oxo-2-phenyl-8-prop-2-enylpyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=C2N(CC=C)C(=O)C(C(=O)OCC)=C(O)C2=CN=C1C1=CC=CC=C1 CEEHFWSNEHHQPJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical group C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- VBWFYEFYHJRJER-UHFFFAOYSA-N methyl 4-(hydroxymethyl)benzoate Chemical compound COC(=O)C1=CC=C(CO)C=C1 VBWFYEFYHJRJER-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- OIGWAXDAPKFNCQ-UHFFFAOYSA-N p-Isopropylbenzyl alcohol Natural products CC(C)C1=CC=C(CO)C=C1 OIGWAXDAPKFNCQ-UHFFFAOYSA-N 0.000 description 1
- VEDDBHYQWFOITD-UHFFFAOYSA-N para-bromobenzyl alcohol Chemical compound OCC1=CC=C(Br)C=C1 VEDDBHYQWFOITD-UHFFFAOYSA-N 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006561 solvent free reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/08—Formation or introduction of functional groups containing oxygen of carboxyl groups or salts, halides or anhydrides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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Abstract
The invention belongs to the field of synthesis of organic intermediates, and particularly discloses an ultrasonic-assisted synthesis method of a benzoic acid compound, which comprises the following steps: under the auxiliary action of ultrasonic waves, the diethylene glycol dimethyl ether promotes air oxidation of benzyl alcohol to obtain the benzoic acid compound; the raw material of the benzyl alcohol is the benzyl alcohol or a benzoic acid derivative containing one to five substituent groups at different positions on a benzene ring of the benzyl alcohol; the reaction promoter is diethylene glycol dimethyl ether. The method has the advantages of easily obtained raw materials, simple and convenient reaction conditions, short reaction time, greenness, energy conservation, high reaction selectivity and yield, excellent substrate functional group compatibility and higher application value.
Description
Technical Field
The invention belongs to the technical field of synthesis of organic intermediates, and particularly relates to a synthetic method of a benzoic acid compound.
Background
Benzoic acid is widely used in the chemical fields of food, medicine, dye and the like, and is also an important organic synthesis intermediate. At present, there are a number of reports in the literature on the synthesis of benzoic acid, including: toluene liquid phase oxidation, benzonitrile hydrolysis, toluene chlorination hydrolysis, phthalic anhydride hydrolysis, alcohol oxidation, and the like.
The toluene liquid phase oxidation method is the most main method for producing benzoic acid at present, and is usually prepared by catalyzing air oxidation toluene with catalysts such as cobalt, manganese and the like, but the reaction has low single conversion rate, needs multiple cyclic oxidation reactions, and has limited tolerance of functional groups. The chlorination hydrolysis of toluene, the hydrolysis of benzonitrile and the hydrolysis of phthalic anhydride require the use of inorganic bases for dehydrogenation, and after the reaction is finished, the acid is neutralized, and a large amount of industrial salts are generated. In addition, these methods generally have the disadvantage of limited functional group tolerance, so that many benzoic acids containing sensitive functional groups (e.g., mercapto groups, cyano groups, ester groups, etc.) cannot be passed through other methods.
The benzyl alcohol oxide is one of the important methods for preparing benzoic acid, and the oxidants used in the reaction comprise various oxidants such as hydrogen peroxide, tert-butyl peroxide, oxygen, potassium permanganate and the like. Air is the greenest and cheap oxidant, and the oxidation of benzyl alcohol by air can not only reduce the cost of the oxidant and reduce the environmental pollution, but also has higher safety than the reaction of oxidizing benzyl alcohol by oxygen.
The method for oxidizing benzyl alcohol by air mainly comprises the following steps:
(1) in 2013, the method for generating benzoic acid by oxidizing sodium benzoate with air after sodium hydroxide or sodium tert-butoxide with 2 times of chemical equivalent reacts with benzyl alcohol to generate sodium benzoate and then acidifying is reported by leigh et al, Wuhan university.
Jing Wang,Chao Liu,Jiwen Yuan,Aiwen Lei,Transition-metal-free aerobicoxidation of primary alcohols to carboxylic acids,New J.Chem.,2013,37(6):1700-1703.
(2) In 2014, Shanghai organic institute of Chinese academy of sciences and others developed a method in which 6 times of chemical equivalent of potassium hydroxide reacts with benzyl alcohol to generate potassium benzyl methoxide, and under the action of silver salt, dried air oxidizes potassium benzyl methoxide to generate potassium benzoate for reacidification.
Lei Han,Ping Xing,Biao Jiang,Selective Aerobic Oxidation of Alcoholsto Aldehydes,Carboxylic Acids,and Imines Catalyzed by a Ag-NHC Complex,Org.Lett.,2014,16(13):3428-3431
(3)2016, Shanxi university Wang super et al report that metal rhodium salt catalyzes and oxidizes benzyl alcohol to generate benzaldehyde, sodium hydroxide promotes benzaldehyde to generate Cannizzaro reaction (Cannizzaro reaction) to generate sodium benzoate, and the sodium benzoate is obtained through acidification
Xuewei Wang,Chao Wang,Yuxuan Liu,Jianliang Xiao,Acceptorlessdehydrogenation and aerobic oxidation of alcohols with a reusable binuclearrhodium(ii)catalyst in water,Green Chem.,2016,18(17):4605-4610.
However, these methods have the following disadvantages:
(1) in the three routes, a large amount of strong base is used as a reaction promoter, excessive protonic acid is required to be added for acid-base neutralization treatment after the reaction is finished, and basic sensitive functional groups such as ester groups, cyano groups and the like cannot be compatible;
(2) routes 1 and 3 require the use of large amounts of organic solvents, which adversely affects the environment when increasing the reaction cost;
(3) routes 2 and 3 require the use of noble metal catalysts and ligands, are expensive to react, and may cause problems with metal residues in the synthesis of pharmaceutical intermediates.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention aims to provide the environment-friendly low-cost preparation method for preparing the benzoic acid by oxidizing the benzyl alcohol, which has high atom economy and excellent functional group compatibility.
A method for synthesizing benzoic acid compound by oxidizing benzyl alcohol compound under the assistance of ultrasonic wave, benzyl alcohol raw material is oxidized under oxygen-containing atmosphere under the reaction accelerator, the assistance of ultrasonic wave and the temperature not lower than 60 ℃, and the benzoic acid compound is obtained;
the raw material of the benzyl alcohol is the benzyl alcohol or a benzoic acid derivative containing one to five substituent groups at different positions on a benzene ring of the benzyl alcohol;
the reaction accelerator is diethylene glycol dimethyl ether (CAS: 111-96-6).
The method of the invention originally provides a method for directly using benzyl alcohol raw material as a starting material and using cheap green oxygen-containing atmosphere (such as air) as an oxidant under the assistance of the reaction accelerator and ultrasonic waves and at the oxidation reaction temperature, and directly oxidizing the benzyl alcohol into acid by alcohol under the solvent-free condition (without adding additional reaction solvent) and without a metal catalyst; the method has the advantages of high reaction efficiency, low production cost, good functional group compatibility and environmental friendliness.
The raw material of the benzyl alcohol is at least one of the compounds with the structure shown in the formula 1:
R1～R5is alone H, C1～C10A hydrocarbon group of1～C10Hydrocarbyloxy group of (C)6～C20Aryl of (C)5～C20Heterocyclic aryl, hydroxy, mercapto, methylthio, trifluoromethylthio, cyano, C2～C30Ester group of (a), nitro group, trifluoromethyl group, halogen, alcohol methyl group or aldehyde;
or R1～R5Wherein adjacent groups together form a 5-10 membered partially or fully unsaturated cyclic structure; the cyclic structure may also contain heteroatoms and substituents.
In the present invention, said C1～C10The hydrocarbon group (C) is a saturated alkyl group having the above carbon number, an unsaturated bond or a cyclic group, for example, C1～C10And an alkyl group, an alkenyl group, an alkynyl group, a 5-6 membered cycloalkyl group, a partially unsaturated 5-6 membered cyclic group, etc.
The aryl is the phenyl with the carbon number or a condensed ring group condensed with the phenyl; the aryl group may have a substituent, such as a halogen, an alkyl group, an alkoxy group, or the like.
The aromatic heterocycle is a 5-10 membered heteroaryl with the carbon number, and the heteroatom is O, S or N.
Said C1～C10With said hydrocarbyloxy group of C1～C10The hydrocarbon group of (a) is a group bonded through oxygen and a benzene ring.
Further preferably: said R1～R5Is alone H, C1～C6Alkyl of (A), C1～C6Alkoxy group of (C)6～C10Aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms; the heteroatom is O, S or N.
Said C1～C6The alkyl group (b) is preferably a linear or branched alkyl group having 1 to 6 carbon atoms, for example, a methyl group, an ethyl group, an isopropyl group, an n-butyl group, or the like. Said C1～C6The alkoxy group is preferably a linear or branched C1-6 chainAlkanyloxy is, for example, methoxy, ethoxy, isopropoxy, and the like. C6～C10The aryl of (A) is phenyl, alkyl substituted phenyl, naphthalene ring group and the like.
Preferably, the benzyl alcohol compound is provided with a substituent group at the para position of the benzyl alcohol primary alcohol, and the substituent group is different types of substituent groups such as electron withdrawing groups, electron donating groups and the like; said R1、R2、R4、R5Is H.
The invention adopts oxygen-containing atmosphere as oxidant; the oxygen-containing atmosphere can be a mixed atmosphere containing oxygen or a pure atmosphere.
Preferably, the oxygen-containing atmosphere is air.
The invention is innovatively and directly oxidized into acid by alcohol under the condition of no metal catalyst; in order to achieve the object, the present inventors have found through studies that a benzyl alcohol raw material can be unexpectedly oxidized into a corresponding benzoic acid compound by the assistance of ultrasonic waves in cooperation with the action of a reaction accelerator, and that the reaction yield is high and the conditions are mild.
Preferably, the molar ratio of the reaction promoter to the benzyl alcohol raw material is greater than or equal to 1.
Further preferably, the reaction promoter is added in excess of the equivalent weight of the raw material of the benzyl alcohol; that is, the molar ratio of the reaction promoter to the benzyl alcohol feedstock is greater than 1.
Further preferably, the molar ratio of the reaction promoter to the raw material of the benzyl alcohol is 2-5: 1; more preferably 3-3.6: 1; most preferably 3: 1.
Preferably, the ultrasonic frequency is 15-80 KHz; further preferably 20-60 KHz; further preferably 40-60 KHz; most preferably 40 KHz. At the preferred frequencies, the yield of product is higher.
Researches show that the yield of the product is more than 90% at the preferable frequency of 20-60KHz, and the yield of the product is further improved at the further preferable frequency of 40-60 KHz.
Preferably, the power of the ultrasonic wave is 15-120W; further preferably 20 to 100W; even more preferably 30-60W; most preferably 30-40W. At the preferred powers, the product yields are higher. The research shows that the yield of the product is more than 90 percent at the preferable range of 30-60W, and the yield of the product is further improved at the further preferable range of 30-40W.
With this preferred combination of ultrasonic frequency and power, the product yield and purity is more desirable.
Preferably, the method comprises the following steps: the temperature of the oxidation reaction process is 60-100 ℃. At this preferred temperature, the product is more excellent in yield and purity.
Further research shows that under the ultrasonic and reaction accelerator, the yield of the product is obviously improved when the reaction temperature is not lower than 60 ℃; the temperature is lower than 60 ℃, and the yield of the product is obviously reduced.
Further preferably, the temperature in the oxidation reaction process is 65-80 ℃; still more preferably 65-70 ℃; most preferably 70 deg.c.
The oxidation reaction is a solvent-free reaction. The oxidation reaction of the invention does not need to add other reaction solvents except the benzyl alcohol raw material and the reaction promoter besides the metal catalyst.
In the invention, the oxidation reaction time is 30-80 minutes.
And after the oxidation reaction, performing post-treatment to obtain the carboxylic acid (carbon of primary alcohol is converted into carboxylic acid) corresponding to the benzyl alcohol raw material.
The post-treatment method of the invention can adopt the conventional method, such as removing the reaction promoter and recrystallizing to obtain the acid.
And after the reaction is finished, evaporating under reduced pressure to remove the reaction promoter, washing residues with water, and recrystallizing to obtain the benzoic acid compound.
Examples of the recrystallization method include water, a unit of C1 to C4, and a polyol.
The method of the invention originally provides an environment-friendly method for synthesizing the benzoic acid compound under the solvent-free condition by directly taking a benzyl alcohol raw material as a starting material, cheap, green and safe air as an oxidant and cheap diethylene glycol dimethyl ether as an accelerator under the assistance of the reaction accelerator and ultrasonic waves.
In the invention, the benzyl alcohol and the substituted benzyl alcohol are used as starting raw materials, and the reaction materials have wide sources; air is an oxidant which is cheap and easy to obtain; the yield of the multiple benzoic acids synthesized by the reaction promoter and the assistance of ultrasonic waves is high, the operation is simple, the reaction time is short, the reaction safety is high, and the cost is low.
Taking benzyl alcohol as an example, the reaction principle is that under the ultrasonic-assisted action, diethylene glycol dimethyl ether and hot air react to generate peroxide, the peroxide oxidizes benzyl alcohol to generate a carbon radical intermediate A, the intermediate A is coupled with hydroxyl radicals to obtain a glycol intermediate B, glycol is dehydrated to obtain benzaldehyde, and the benzaldehyde undergoes oxidation reaction again to obtain benzoic acid (see formula 1).
Has the advantages that:
1) the benzyl alcohol, the diethylene glycol dimethyl ether and the air are rich and easily obtained, and the price is low;
2) the diethylene glycol dimethyl ether with three times of chemical equivalent is used as a reaction promoter and a solvent, so that the reaction cost is reduced, the reaction is simplified, and the separation and purification cost is reduced. The diethylene glycol dimethyl ether generates peroxide in situ in the reaction, and is reduced into the diethylene glycol dimethyl ether after the reaction is finished, so that the diethylene glycol dimethyl ether can be recycled; the boiling points of the diethylene glycol dimethyl ether, the benzoic acid and the derivatives thereof are greatly different, and the diethylene glycol dimethyl ether and the benzoic acid are easy to recover;
3) ultrasonic radiation is used for assisting the reaction, so that the reaction time is shortened, and the reaction yield is improved;
4) the reaction condition is mild, and the compatibility of substrate functional groups is good;
5) the reaction system is an open reaction system, the reaction temperature is low, and the safety of the reaction process is high;
6) researches show that the yield of the product can be further improved by taking ethylene glycol dimethyl ether as a reaction promoter, and the yield of the product can be further improved by matching with an ultrasonic auxiliary method; the yield of the target product can reach 95 percent or more.
Detailed Description
The following specific examples are intended to further illustrate the present disclosure, but not to limit the scope of the claims.
In the following case, the ultrasonic reaction apparatus is an existing apparatus.
Example 1: preparation of benzoic acid:
0.54g (5mmoL) of benzyl alcohol and 2g (15mmoL) of diethylene glycol dimethyl ether were sequentially added to a 10mL round-bottomed flask, and the resulting mixture was subjected to an open reaction with ultrasonic irradiation at 40KHz/30W/70 ℃ for 30 minutes in an ultrasonic reaction apparatus. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.59g of the corresponding benzoic acid in 98% yield.
Amplification preparation:
A1L three-neck round-bottom flask, a mechanical stirrer connected with a middle ground, a 80cm snake-shaped condenser externally connected with a ground, and an external air source are sequentially added with 54g of benzyl alcohol and 200g of diethylene glycol dimethyl ether, and the obtained mixed solution is subjected to ultrasonic radiation reaction for 50 minutes at 40KHz/80W/70 ℃ in an ultrasonic reaction device. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 60g of benzoic acid, yield 99%.
Comparative example 1
The ultrasonic assisted reaction is carried out at the temperature lower than 60 ℃, and the specific steps are as follows:
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 40KHz/30W/50 ℃. And detecting a large amount of residual raw materials by using a thin-layer chromatography plate, wherein the theoretical yield of the benzoic acid is 8% by using a gas phase detection method.
Example 2
The difference compared to example 1 is that the shift reaction temperature is 60 ℃, as follows:
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 40KHz/30W/60 ℃ in an ultrasonic reaction device. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.35g of benzoic acid in 58% yield.
Example 3
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at the temperature of 17KHz/30W/70 ℃ in an ultrasonic reaction device. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.54g of benzoic acid in 88% yield.
Example 4
The difference compared to example 1 is that a lower ultrasound frequency is used, as follows:
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 20KHz/30W/70 ℃ in an ultrasonic reaction device. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.55g of benzoic acid in 90% yield.
Example 5
The difference compared to example 1 is that a higher ultrasound frequency is used, as follows:
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 60KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.56g of benzoic acid in 93% yield.
Example 6
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 80KHz/30W/70 ℃ in an ultrasonic reaction device. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.55g of benzoic acid in 90% yield.
Example 7
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 65 minutes by ultrasonic radiation at 40KHz/15W/70 ℃ in an ultrasonic reaction device. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.52g of benzoic acid in 85% yield.
Example 8
Compared with the embodiment 1, the difference is that lower ultrasonic power is adopted, and the specific steps are as follows:
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 50 minutes by ultrasonic radiation at 40KHz/20W/70 ℃ in an ultrasonic reaction device. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.54g of benzoic acid in 90% yield.
Example 9
Compared with the embodiment 1, the difference is that the higher ultrasonic power is adopted, and the specific steps are as follows:
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/60W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.59g of benzoic acid in 98% yield.
Example 10
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/120W/70 ℃. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.48g of benzoic acid in 80% yield.
Comparative example 2
The difference compared to example 1 is that mechanical agitation replaces the ultrasound-assisted operation of the present invention, as follows:
0.54g of benzyl alcohol and 2g of diethylene glycol dimethyl ether were sequentially added to a 10mL round-bottomed flask, and the resulting mixture was reacted with stirring at 70 ℃ for 15 hours in a stirring reaction apparatus. And detecting a large amount of residual raw materials by using a thin-layer chromatography plate, wherein the theoretical yield of the benzoic acid is 17% by using a gas phase detection method.
Example 11
Compared with the example 1, the difference is that the addition molar amount of the shift reaction accelerant (2:1) is as follows:
0.54g (5mmoL) of benzyl alcohol and 1.34g (10mmoL) of diethylene glycol dimethyl ether were sequentially added to a 10mL round-bottomed flask, and the resulting mixture was subjected to an open reaction with ultrasonic irradiation at 40KHz/30W/70 ℃ for 30 minutes in an ultrasonic reaction apparatus. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give benzoic acid 0.53g in 87% yield.
Example 12
Compared with the example 1, the difference is that the addition molar amount (4:1) of the shift reaction promoter is as follows:
0.54g of benzyl alcohol and 2.68g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.59g of benzoic acid in 98% yield.
Example 13
Compared with the example 1, the difference is that the addition molar amount of the shift reaction accelerant (2:1) is as follows:
0.54g of benzyl alcohol and 1.35g of ethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. . The ethylene-diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.54g of benzoic acid in 90% yield.
Comparative example 3
The difference from example 1 is that the types of the shift reaction accelerator are as follows:
0.54g of benzyl alcohol and 1.3g of 2-methyltetrahydrofuran are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 40KHz/30W/70 ℃ in an ultrasonic reaction device. The gas phase detection reaction yield is 21%, and the conversion rate of the benzyl alcohol is 28%.
Comparative example 4
The difference from example 1 is that the types of the shift reaction accelerator are as follows:
0.54g of benzyl alcohol and 1.3g of 1, 4-dioxane were sequentially added to a 10mL round-bottom flask, and the resulting mixture was subjected to an ultrasonic reaction for 60 minutes at 40KHz/30W/70 ℃ in an ultrasonic reaction apparatus. The gas phase detection reaction yield is 16%, and the conversion rate of the benzyl alcohol is 20%.
Comparative example 5
The difference from example 1 is that the types of the shift reaction accelerator are as follows:
0.54g of benzyl alcohol and 1.60g of diethylene glycol are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to ultrasonic radiation reaction for 60 minutes at 40KHz/30W/70 ℃ in an ultrasonic reaction device. No benzoic acid product was formed as determined by thin layer chromatography.
Comparative example 6
The difference from example 1 is that the types of the shift reaction accelerator are as follows:
0.54g of benzyl alcohol and 1.38g of toluene were sequentially added to a 10mL round-bottomed flask, and the resulting mixture was subjected to an open reaction with ultrasonic irradiation at 40KHz/30W/70 ℃ for 60 minutes in an ultrasonic reaction apparatus. No benzoic acid product was formed as determined by thin layer chromatography.
Comparative example 7
The difference from example 1 is that the types of the shift reaction accelerator are as follows:
0.54g of benzyl alcohol and 1.17g of dimethyl sulfoxide are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 60 minutes by ultrasonic radiation at 40KHz/30W/70 ℃ in an ultrasonic reaction device. No benzoic acid product was formed as determined by thin layer chromatography.
Example 14: preparation of 4-methylbenzoic acid:
0.61g of 4-methylbenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.66g of 4-methylbenzoic acid in 98% yield.
Example 15: preparation of 4-isopropylbenzoic acid:
0.75g of 4-isopropylbenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure, and recrystallization was carried out to obtain 0.79g of 4-isopropylbenzoic acid in 98% yield.
Example 16: preparation of 4-phenylbenzoic acid:
0.85g of 4-hydroxymethyl biphenyl (4-phenyl benzyl alcohol) and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 35 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.95g of 4-phenylbenzoic acid in 96% yield.
Example 17: preparation of 4-hydroxybenzoic acid:
0.62g of 4-hydroxybenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure, and recrystallization was carried out to obtain 0.64g of 4-hydroxybenzyl alcohol in a yield of 94%.
Example 18: preparation of 4-methoxybenzoic acid:
0.69g of 4-methoxybenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.74g of 4-methoxybenzoic acid in 98% yield.
Example 19: preparation of 4-trifluoromethoxybenzoic acid:
0.96g of 4-trifluoromethoxybenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 35 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.91g of 4-trifluoromethoxybenzoic acid in 96% yield.
Example 20: preparation of 4-mercaptobenzoic acid:
0.70g of 4-mercaptobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure, and recrystallization was carried out to obtain 0.72g of 4-mercaptobenzoic acid, yield 94%.
Example 21: preparation of 4-methylthiobenzoic acid:
0.77g of 4-methylthiobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 40KHz/30W/70 ℃ in an ultrasonic reaction device. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.79g of 4-methylthiobenzoic acid in 95% yield.
Example 22: preparation of 4-trifluoromethylthiobenzoic acid:
1.04g of 4-trifluoromethylsulfanyl benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 40 minutes by ultrasonic radiation at 40KHz/30W/70 ℃ in an ultrasonic reaction device. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 1.0g of 4-trifluoromethylthiobenzoic acid in 91% yield.
Example 23: preparation of 4-fluorobenzoic acid:
0.63g of 4-fluorobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure, and recrystallization was carried out to obtain 0.67g of 4-fluorobenzoic acid in 97% yield.
Example 24: preparation of 4-chlorobenzoic acid:
0.71g of 4-chlorobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 40KHz/30W/70 ℃ in an ultrasonic reaction device. Diethylene glycol dimethyl ether was removed under reduced pressure, and recrystallization was carried out to obtain 0.74g of 4-chlorobenzoic acid in 96% yield.
Example 25: preparation of 4-bromobenzoic acid:
0.94g of 4-bromobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.76g of 4-bromobenzoic acid in 98% yield.
Example 26: preparation of 4-iodobenzoic acid:
1.17g of 4-iodobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 1.15g of 4-iodobenzoic acid in 93% yield.
Example 27: preparation of 4-nitroformic acid:
0.76g of 4-nitrobenzol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 60 minutes by ultrasonic radiation at 40KHz/30W/70 ℃ in an ultrasonic reaction device. The conversion rate of the 4-nitrobenzol raw material is 91% by gas phase mass spectrum detection, the raw material is not consumed when the reaction time is continuously increased, and the conversion rate of the raw material is 90% by gas phase detection. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.71g of 4-nitroformic acid in 86% yield.
Example 28: preparation of 4-cyanobenzoic acid:
0.66g of 4-cyanobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.68g of 4-cyanobenzoic acid in 93% yield.
Example 29: preparation of terephthalic acid:
0.69g of terephthalyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 35 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.80g of terephthalic acid in 97% yield.
Example 30: preparation of monomethyl terephthalate:
0.83g of methyl 4- (hydroxymethyl) benzoate and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes by ultrasonic radiation at 40KHz/30W/70 ℃ in an ultrasonic reaction device. The diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.85g of monomethyl terephthalate in 94% yield.
Example 31: preparation of 2-methylbenzoic acid:
0.61g of 2-methylbenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 35 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.64g of 2-methylbenzoic acid in 94% yield.
Example 32: preparation of 3-methylbenzoic acid:
0.61g of 3-methylbenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.66g of 3-methylbenzoic acid in 97% yield.
Example 33: preparation of trimesobenzoic acid:
0.75g of 2,4, 6-trimethyl benzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure and recrystallized to give 0.76g of 2,4, 6-trimethylbenzoic acid in 93% yield.
Example 34: preparation of pentafluorobenzoic acid:
0.99g of pentafluorobenzyl alcohol and 2g of diethylene glycol dimethyl ether are sequentially added into a 10mL round-bottom flask, and the obtained mixed solution is subjected to open reaction for 30 minutes in an ultrasonic reaction device by ultrasonic radiation at 40KHz/30W/70 ℃. Diethylene glycol dimethyl ether was removed under reduced pressure, and recrystallization was carried out to obtain 0.89g of pentafluorobenzoic acid in 95% yield.
H of the products obtained in examples 1, 14 to 341NMR and C13NMR data are shown in Table 1:
as is clear from the above examples, benzoic acid compounds can be efficiently and green synthesized by the method of the present invention.
By the aid of the example 1 and the reaction temperature (comparative example 1 and example 2), the yield of the product at 40KHz/30W/70 ℃ is improved by 30 percent relative to the yield of 40KHz/30W/60 ℃, the yield is improved by 90 percent relative to the yield of 50 ℃, and the yield is not increased when the temperature is continuously increased; in view of all the energy considerations, the reaction temperature was changed to the nearest 70 deg.C
By adopting the embodiment 1 and the ultrasonic frequency and power embodiments (embodiment 1, embodiment 3-10), the yield increased by about 3-18% by adopting 40 KHz/40W;
by adopting the example 1 and the mechanical stirring to the example (the comparative example 2), the yield is improved by 57 percent by adopting 40KHz/40W ultrasonic assisted reaction, and the reaction time is shortened by only 0.5 hour from 15 hours;
compared with the comparative examples (comparative examples 3 to 7), in the reaction process, the reaction yield can be improved to 98% from 0% of that of comparative examples 9 to 10 and 41% of that of comparative example 1 by adding the reaction promoter of the invention and matching with an ultrasonic wave auxiliary synthesis method in the example 1; the effect is obvious.
In summary, diethylene glycol dimethyl ether is used as the reaction promoter, the molar ratio of the reaction promoter to the raw benzyl alcohol is 3:1, and the yield of the product is obviously improved under the preferable reaction condition of 40KHz/30W/70 ℃.
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