CN109232259A - A kind of preparation method of nitro-acetophenone - Google Patents
A kind of preparation method of nitro-acetophenone Download PDFInfo
- Publication number
- CN109232259A CN109232259A CN201811133588.2A CN201811133588A CN109232259A CN 109232259 A CN109232259 A CN 109232259A CN 201811133588 A CN201811133588 A CN 201811133588A CN 109232259 A CN109232259 A CN 109232259A
- Authority
- CN
- China
- Prior art keywords
- acid
- nitro
- preparation
- compound
- acetophenone
- 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.)
- Granted
Links
- JTWHVBNYYWFXSI-UHFFFAOYSA-N 2-nitro-1-phenylethanone Chemical compound [O-][N+](=O)CC(=O)C1=CC=CC=C1 JTWHVBNYYWFXSI-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- 239000002994 raw material Substances 0.000 claims abstract description 10
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000007062 hydrolysis Effects 0.000 claims abstract description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 26
- 238000010792 warming Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 18
- 239000012320 chlorinating reagent Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- -1 tert-pentyl ester Chemical class 0.000 claims description 15
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 235000002639 sodium chloride Nutrition 0.000 claims description 11
- WOVSUSZMYLDKRM-UHFFFAOYSA-N C(OC(C)(C)C)(OC(C)(C)C)=O.C(CC(=O)O)(=O)O Chemical compound C(OC(C)(C)C)(OC(C)(C)C)=O.C(CC(=O)O)(=O)O WOVSUSZMYLDKRM-UHFFFAOYSA-N 0.000 claims description 10
- 150000007524 organic acids Chemical class 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 150000007522 mineralic acids Chemical class 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 235000011054 acetic acid Nutrition 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000005660 chlorination reaction Methods 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 239000012044 organic layer Substances 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- AFPHTEQTJZKQAQ-UHFFFAOYSA-N 3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1 AFPHTEQTJZKQAQ-UHFFFAOYSA-N 0.000 claims description 4
- 238000006482 condensation reaction Methods 0.000 claims description 4
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 claims description 3
- UNMYWSMUMWPJLR-UHFFFAOYSA-L Calcium iodide Chemical compound [Ca+2].[I-].[I-] UNMYWSMUMWPJLR-UHFFFAOYSA-L 0.000 claims description 3
- CMEWLCATCRTSGF-UHFFFAOYSA-N N,N-dimethyl-4-nitrosoaniline Chemical compound CN(C)C1=CC=C(N=O)C=C1 CMEWLCATCRTSGF-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 150000001263 acyl chlorides Chemical class 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 229910001622 calcium bromide Inorganic materials 0.000 claims description 3
- WGEFECGEFUFIQW-UHFFFAOYSA-L calcium dibromide Chemical compound [Ca+2].[Br-].[Br-] WGEFECGEFUFIQW-UHFFFAOYSA-L 0.000 claims description 3
- 229940046413 calcium iodide Drugs 0.000 claims description 3
- 229910001640 calcium iodide Inorganic materials 0.000 claims description 3
- 239000001506 calcium phosphate Substances 0.000 claims description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 3
- 235000011010 calcium phosphates Nutrition 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 3
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 3
- 230000006837 decompression Effects 0.000 claims description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 150000003462 sulfoxides Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 238000009833 condensation Methods 0.000 abstract description 2
- 230000005494 condensation Effects 0.000 abstract description 2
- 238000007796 conventional method Methods 0.000 abstract description 2
- 238000012805 post-processing Methods 0.000 abstract 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 5
- ARKIFHPFTHVKDT-UHFFFAOYSA-N 1-(3-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=CC([N+]([O-])=O)=C1 ARKIFHPFTHVKDT-UHFFFAOYSA-N 0.000 description 4
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 description 3
- YQYGPGKTNQNXMH-UHFFFAOYSA-N 4-nitroacetophenone Chemical compound CC(=O)C1=CC=C([N+]([O-])=O)C=C1 YQYGPGKTNQNXMH-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- PXWYZLWEKCMTEZ-UHFFFAOYSA-N 1-ethyl-2-nitrobenzene Chemical compound CCC1=CC=CC=C1[N+]([O-])=O PXWYZLWEKCMTEZ-UHFFFAOYSA-N 0.000 description 2
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical group [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
- MLNKXLRYCLKJSS-RMKNXTFCSA-N (2e)-2-hydroxyimino-1-phenylethanone Chemical compound O\N=C\C(=O)C1=CC=CC=C1 MLNKXLRYCLKJSS-RMKNXTFCSA-N 0.000 description 1
- CGXJUBDTCAAXAY-UHFFFAOYSA-N 1-(3-aminophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC(N)=C1 CGXJUBDTCAAXAY-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001546 nitrifying effect Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation methods of nitro-acetophenone, using nitrobenzoic acid as raw material, obtain target product by chloride, condensation, hydrolysis three-step reaction.This method reaction condition is mild, post-processing is simple, avoids the problem of nitrification involved in conventional method and oxidation reaction condition harshness, while having many advantages, such as that pollution is small, yield is high.
Description
Technical field
The present invention relates to organic synthesis field, in particular to a kind of preparation method of nitro-acetophenone.
Background technique
Nitro-acetophenone is the important intermediate in organic synthesis and pharmaceutical synthesis field, and application is relatively more extensive such as adjacent nitre
Benzoylformaldoxime, m-nitroacetophenone and p-nitroacetophenone.Ortho-nitroacetophenone is used for sensitizer processed, it can also be used to diabetes processed
Drug Li Gelieting etc.;M-nitroacetophenone through reduction can m-aminophenyl ethyl ketone processed, medical industry be used for adrenaline drug processed
Deng;P-nitroacetophenone is also used for pesticide, dyestuff, perfume (or spice) for broad-spectrum antibacterials antibiotic medicines such as synthesizing chloramphenicol and syntomycin
The synthesis of material.
At present about ortho-nitroacetophenone and align nitro-acetophenone synthetic method there are mainly two types of:
A. nitro ethylbenzene oxidation method.This method is using nitro ethylbenzene as raw material, under the action of composite transition metal catalyst, uses
Tert-butyl hydroperoxide (such as Xu, Q.et al.Asian Journal of Chemistry, 2015,27 (10), 3555-
3558.) oxidation preparation ortho position or contraposition nitro-acetophenone are carried out.Composite transition metal catalyst used in this method, often
Multistep is needed to be prepared, cost is excessively high.
B. nitrobenzoyl chloride method.This method occurs chloride and generates nitrobenzoyl chloride using nitrobenzoic acid as raw material,
Then under the action of magnesium alkoxide, preparation ortho position or contraposition nitro-acetophenone are reacted with diethyl malonate.Inventor is to this method
It carried out that experiment is repeated several times, actual recovery is low far beyond reported in the literature.
Synthetic method about m-nitroacetophenone is mainly acetophenone nitrification process.This method is low using acetophenone as raw material
Under the conditions of temperature (generally -20 DEG C~-15 DEG C), nitrification is carried out using sulfuric acid/nitric acid mixed acid and prepares m-nitroacetophenone (such as
Blau,Lorena et al.European Journal of Medicinal Chemistry,2013,67,142-151.)。
Big excessive sulfuric acid, nitric acid are used in this method nitrifying process, while can generate ortho position and contraposition by-product, and it is tired to there is separation
Difficult, the problems such as product purity is low, serious three wastes.
Summary of the invention
The purpose of the present invention is to provide a kind of preparation methods of nitro-acetophenone, and raw material is simple, easy to operate, condition temperature
With, high income, pollute small.
The technical solution adopted by the present invention to solve the technical problems is:
A kind of preparation method of nitro-acetophenone, comprising the following steps:
1) using type I compound as raw material, the first atent solvent and catalyst is added, stirring is warming up to 55-65 DEG C, and chlorination is added dropwise
Agent is warming up to back flow reaction 2-3 hours, completes to acyl chloride reaction, is evaporated under reduced pressure out excessive chlorinating agent and atent solvent, obtains
II crude compound of formula, can be directly used for the next step;
2) inorganic salts, the second atent solvent, alkaline reagent are reacted with malonic acid di tert butyl carbonate or the addition of two tert-pentyl ester of malonic acid
It is sufficiently stirred in bottle, II crude compound of formula is added dropwise, is warming up to 55-65 DEG C of reaction 1-2 hours, completed to condensation reaction, hydrochloric acid
It is neutralized to pH=5-6, separates organic layer, is successively washed with saturated sodium bicarbonate, saturated common salt, anhydrous sodium sulfate is dry, decompression
It is concentrated to give III compound of formula;
3) water, organic acid is added, back flow reaction 2-3 hours in inorganic acid mixed solution in III compound of formula, it is complete to hydrolysis
At sodium hydroxide solution is adjusted to neutrality, and organic solvent extracts, and formula IV is concentrated under reduced pressure to obtain.
The present invention obtains target product using nitrobenzoic acid as raw material, by chloride, condensation, hydrolysis three-step reaction.Step
Rapid 1) the middle excessive chlorinating agent of addition, is conducive to the abundant conversion of nitrobenzoic acid.Addition atent solvent is conducive between reactant
Come into full contact with, accelerate reaction rate, shorten the reaction time;Meanwhile being conducive to steam excessive chlorinating agent after reaction, it can
It recycles.A small amount of catalyst, which is added, can obviously accelerate reaction rate, save the cost.
Inorganic salts are added in step 2) may advantageously facilitate the progress of reaction, if being generally difficult to react without inorganic salts.It is added
Alkaline reagent is conducive to leaving away for active hydrogen in two tert-pentyl ester of malonic acid di tert butyl carbonate or malonic acid;Meanwhile reaction can be absorbed
The hydrogen chloride generated in the process carries out condensation reaction complete.
Organic acid is added in step 3) and is conducive to sufficiently miscible between reactant, quickening reaction rate.Control inorganic acid
Additional amount is very crucial, if additional amount can mostly be such that yield reduces.
Technical foundation of the invention is embodied in inventor and finds in relevant chemical reaction research, such as the change of V structure of formula
Closing when object hydrolyzes in acid condition will appear two kinds of products.When R is the primary alkyls such as methyl, ethyl, propyl, the product of generation
Predominantly nitrobenzoic acid, and target product nitro-acetophenone is few;When R is tertiary alkyl, target product nitro-acetophenone exists
It is accounted in product leading.
Preferably, the type I compound is o-nitrobenzoic acid, m-Nitrobenzoic Acid or paranitrobenzoic acid.
Preferably, first atent solvent is one or both of toluene, benzene, dimethylbenzene;Second inertia
Solvent is ethyl acetate.
Preferably, the chlorinating agent is one or more of thionyl chloride, phosphorus trichloride, phosphorus pentachloride, triphosgene.
Preferably, the catalyst is n,N-Dimethylformamide, in triethylamine, n,N-Dimethylaniline, pyridine
It is one or more of.
Preferably, the inorganic salts are one or more of calcium chloride, calcium bromide, calcium iodide;The alkaline reagent
For triethylamine, diisopropyl ethyl amine, N, accelerine, pyridine, picoline, sodium carbonate, potassium carbonate, in calcium phosphate
It is one or more of.
Preferably, the type I compound and the molar ratio of chlorinating agent are 1:1~2.
Preferably, the molar ratio of the type I compound and two tert-pentyl ester of malonic acid di tert butyl carbonate or malonic acid be 1:1~
1.2。
Preferably, the dosage of the catalyst is the 4-6% of chlorinating agent quality;The dosage of the inorganic salts is the change of formula II
Close the 20-30% of object crude product quality;Mass ratio 1:1~2 of the alkaline reagent and chlorinating agent;The water, organic acid, inorganic acid
Volume ratio be 2~2.5:1:0.02~0.05.
The organic acid is selected from one or more of acetic acid, formic acid, propionic acid, methanesulfonic acid;The inorganic acid be selected from sulfuric acid,
One or more of hydrochloric acid, phosphoric acid, perchloric acid.
The beneficial effects of the present invention are: avoiding using expensive composite transition metal catalyst or the mixing of sulfuric acid/nitric acid
Acid etc., production safety coefficient is high, and the three wastes are few, yield height (75-85%), at low cost.In addition, the method for the present invention applicability is wide, adjacent,
Between or p-nitroacetophenone can all prepare.
Specific embodiment
Below by specific embodiment, technical scheme of the present invention will be further explained in detail.
In the present invention, if not refering in particular to, used raw material and equipment etc. are commercially available or commonly used in the art.
Method in following embodiments is unless otherwise instructed the conventional method of this field.
Embodiment 1
1) 16.7g (0.1mol) o-nitrobenzoic acid, 1ml DMF, 100ml toluene are added and are filled equipped with drying tube and tail gas absorption
In the reaction flask set, stirring is warming up to 60 DEG C, and 17.8g (0.15mol) thionyl chloride is added dropwise, and drop finishes, and is warming up to back flow reaction about
2-3h, device for absorbing tail gas are released without obvious bubble, are cooled to room temperature, and are evaporated under reduced pressure out excessive thionyl chloride and toluene, are obtained
Light yellow oil is directly used in the next step;
2) 21.6g (0.1mol) malonic acid di tert butyl carbonate, 5g anhydrous calcium chloride, 100ml ethyl acetate, 20ml triethylamine are added
In reaction flask, after being sufficiently stirred, light yellow oil is walked in instillation, is warming up to 60 DEG C of reactions about 1-2h, TLC detection reaction knot
Beam, cooling, hydrochloric acid tune pH=5-6 separates organic phase, successively twice with saturated sodium bicarbonate, saturated common salt washing, anhydrous slufuric acid
Sodium is dry, is concentrated to give yellow oil;
3) by upper step yellow oil, 100ml water, 40ml acetic acid, 2ml sulfuric acid, it is warming up to reflux about 2-3h, TLC detection reaction
Terminate, be cooled to room temperature, sodium hydroxide solution is adjusted to neutrality, and ethyl acetate extracts, and organic layer is washed twice with saturated common salt, nothing
Aqueous sodium persulfate is dry, and yellow oily liquid 13.3g, yield 80.5% is concentrated under reduced pressure to obtain.
Embodiment 2
1) 16.7g (0.1mol) paranitrobenzoic acid, 1ml DMF, 100ml toluene are added and are filled equipped with drying tube and tail gas absorption
In the reaction flask set, stirring is warming up to 60 DEG C, and 17.8g (0.15mol) thionyl chloride is added dropwise, and drop finishes, and is warming up to back flow reaction about
2-3h, device for absorbing tail gas are released without obvious bubble, are cooled to room temperature, and are evaporated under reduced pressure out excessive thionyl chloride and toluene, are obtained
Light yellow oil is directly used in the next step;
2) 21.6g (0.1mol) malonic acid di tert butyl carbonate, 5g anhydrous calcium chloride, 100ml ethyl acetate, 20ml triethylamine are added
In reaction flask, after being sufficiently stirred, light yellow oil is walked in instillation, is warming up to 60 DEG C of reactions about 1-2h, TLC detection reaction knot
Beam, cooling, hydrochloric acid tune pH=5-6 separates organic phase, successively twice with saturated sodium bicarbonate, saturated common salt washing, anhydrous slufuric acid
Sodium is dry, is concentrated to give yellow oil;
3) by upper step yellow oil, 100ml water, 40ml acetic acid, 2ml sulfuric acid, it is warming up to reflux about 2-3h, TLC detection reaction
Terminate, be cooled to room temperature, sodium hydroxide solution is adjusted to neutrality, and ethyl acetate extracts, and organic layer is washed twice with saturated common salt, nothing
Aqueous sodium persulfate is dry, and yellow oily liquid 13.6g, yield 82.3% is concentrated under reduced pressure to obtain.
Embodiment 3
1) 16.7g (0.1mol) m-Nitrobenzoic Acid, 1ml DMF, 100ml toluene are added and are filled equipped with drying tube and tail gas absorption
In the reaction flask set, stirring is warming up to 60 DEG C, and 17.8g (0.15mol) thionyl chloride is added dropwise, and drop finishes, and is warming up to back flow reaction about
2-3h, device for absorbing tail gas are released without obvious bubble, are cooled to room temperature, and are evaporated under reduced pressure out excessive thionyl chloride and toluene, are obtained
Light yellow oil is directly used in the next step;
2) 21.6g (0.1mol) malonic acid di tert butyl carbonate, 5g anhydrous calcium chloride, 100ml ethyl acetate, 20ml triethylamine are added
In reaction flask, after being sufficiently stirred, light yellow oil is walked in instillation, is warming up to 60 DEG C of reactions about 1-2h, TLC detection reaction knot
Beam, cooling, hydrochloric acid tune pH=5-6 separates organic phase, successively twice with saturated sodium bicarbonate, saturated common salt washing, anhydrous slufuric acid
Sodium is dry, is concentrated to give yellow oil;
3) by upper step yellow oil, 100ml water, 40ml acetic acid, 2ml sulfuric acid, it is warming up to reflux about 2-3h, TLC detection reaction
Terminate, be cooled to room temperature, sodium hydroxide solution is adjusted to neutrality, and ethyl acetate extracts, and organic layer is washed twice with saturated common salt, nothing
Aqueous sodium persulfate is dry, and yellow oily liquid 12.6g, yield 76.3% is concentrated under reduced pressure to obtain.
Practical range of the invention can adjust in following range:
1) using type I compound as raw material, the first atent solvent and catalyst is added, stirring is warming up to 55-65 DEG C, and chlorination is added dropwise
Agent is warming up to back flow reaction 2-3 hours, completes to acyl chloride reaction, is evaporated under reduced pressure out excessive chlorinating agent and atent solvent, obtains
II crude compound of formula, can be directly used for the next step;Type I compound is for o-nitrobenzoic acid, m-Nitrobenzoic Acid or to nitre
Yl benzoic acid.
2) inorganic salts, the second atent solvent, alkaline reagent and malonic acid di tert butyl carbonate or two tert-pentyl ester of malonic acid are added
It is sufficiently stirred in reaction flask, II crude compound of formula is added dropwise, is warming up to 55-65 DEG C of reaction 1-2 hours, completed to condensation reaction,
Hydrochloric acid is neutralized to pH=5-6, separates organic layer, is successively washed with saturated sodium bicarbonate, saturated common salt, and anhydrous sodium sulfate is dry,
III compound of formula is concentrated under reduced pressure to obtain.
3) water, organic acid is added, back flow reaction 2-3 hour in inorganic acid mixed solution in III compound of formula, wait hydrolyze instead
It should complete, sodium hydroxide solution is adjusted to neutrality, and organic solvent extracts, and formula IV is concentrated under reduced pressure to obtain.
Wherein, first atent solvent is one or both of toluene, benzene, dimethylbenzene;Second atent solvent
For ethyl acetate.The chlorinating agent is one or more of thionyl chloride, phosphorus trichloride, phosphorus pentachloride, triphosgene.It is described to urge
Agent is N,N-dimethylformamide, triethylamine, N, one or more of accelerine, pyridine.The inorganic salts are
One or more of calcium chloride, calcium bromide, calcium iodide;The alkaline reagent is triethylamine, diisopropyl ethyl amine, N, N- bis-
One or more of methylaniline, pyridine, picoline, sodium carbonate, potassium carbonate, calcium phosphate.The type I compound and chlorination
The molar ratio of agent is 1:1~2.The type I compound and the molar ratio of two tert-pentyl ester of malonic acid di tert butyl carbonate or malonic acid are 1:1
~1.2.The dosage of the catalyst is the 4-6% of chlorinating agent quality;The dosage of the inorganic salts is II crude compound matter of formula
The 20-30% of amount;Mass ratio 1:1~2 of the alkaline reagent and chlorinating agent;The water, organic acid, inorganic acid volume ratio be
2~2.5:1:0.02~0.05.The organic acid is selected from one or more of acetic acid, formic acid, propionic acid, methanesulfonic acid;The nothing
Machine acid is selected from one or more of sulfuric acid, hydrochloric acid, phosphoric acid, perchloric acid.
Above-mentioned embodiment is only a preferred solution of the present invention, not the present invention is made in any form
Limitation, there are also other variations and modifications on the premise of not exceeding the technical scheme recorded in the claims.
Claims (10)
1. a kind of preparation method of nitro-acetophenone, which comprises the following steps:
1) using type I compound as raw material, the first atent solvent and catalyst is added, stirring is warming up to 55-65 DEG C, and chlorination is added dropwise
Agent is warming up to back flow reaction 2-3 hours, completes to acyl chloride reaction, is evaporated under reduced pressure out excessive chlorinating agent and atent solvent, obtains
II crude compound of formula, can be directly used for the next step;
2) inorganic salts, the second atent solvent, alkaline reagent are reacted with malonic acid di tert butyl carbonate or the addition of two tert-pentyl ester of malonic acid
It is sufficiently stirred in bottle, II crude compound of formula is added dropwise, is warming up to 55-65 DEG C of reaction 1-2 hours, completed to condensation reaction, hydrochloric acid
It is neutralized to pH=5-6, separates organic layer, is successively washed with saturated sodium bicarbonate, saturated common salt, anhydrous sodium sulfate is dry, decompression
It is concentrated to give III compound of formula;
3) water, organic acid is added, back flow reaction 2-3 hours in inorganic acid mixed solution in III compound of formula, it is complete to hydrolysis
At sodium hydroxide solution is adjusted to neutrality, and organic solvent extracts, and formula IV is concentrated under reduced pressure to obtain.
2. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the type I compound is
O-nitrobenzoic acid, m-Nitrobenzoic Acid or paranitrobenzoic acid.
3. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: first atent solvent
For one or both of toluene, benzene, dimethylbenzene;Second atent solvent is ethyl acetate.
4. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the chlorinating agent is chlorination
One or more of sulfoxide, phosphorus trichloride, phosphorus pentachloride, triphosgene.
5. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the catalyst is N, N-
Dimethylformamide, triethylamine, N, one or more of accelerine, pyridine.
6. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the inorganic salts are chlorination
One or more of calcium, calcium bromide, calcium iodide;The alkaline reagent is triethylamine, diisopropyl ethyl amine, N, N- dimethyl
One or more of aniline, pyridine, picoline, sodium carbonate, potassium carbonate, calcium phosphate.
7. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the type I compound with
The molar ratio of chlorinating agent is 1:1~2.
8. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the type I compound with
The molar ratio of two tert-pentyl ester of malonic acid di tert butyl carbonate or malonic acid is 1:1~1.2.
9. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the dosage of the catalyst
For the 4-6% of chlorinating agent quality;The dosage of the inorganic salts is the 20-30% of II crude compound quality of formula;The alkalinity examination
Mass ratio 1:1~2 of agent and chlorinating agent;The water, organic acid, inorganic acid volume ratio be 2~2.5:1:0.02~0.05.
10. a kind of preparation method of nitro-acetophenone according to claim 1, it is characterised in that: the organic acid is selected from
One or more of acetic acid, formic acid, propionic acid, methanesulfonic acid;The inorganic acid in sulfuric acid, hydrochloric acid, phosphoric acid, perchloric acid one
Kind is several.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811133588.2A CN109232259B (en) | 2018-09-27 | 2018-09-27 | Preparation method of nitroacetophenone |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811133588.2A CN109232259B (en) | 2018-09-27 | 2018-09-27 | Preparation method of nitroacetophenone |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109232259A true CN109232259A (en) | 2019-01-18 |
CN109232259B CN109232259B (en) | 2021-05-28 |
Family
ID=65057204
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811133588.2A Active CN109232259B (en) | 2018-09-27 | 2018-09-27 | Preparation method of nitroacetophenone |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109232259B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109796397A (en) * | 2019-03-15 | 2019-05-24 | 浙江理工大学 | A kind of preparation method of 3- acetylpyridine |
CN111943854A (en) * | 2020-08-21 | 2020-11-17 | 阿里生物新材料(常州)有限公司 | Synthetic method of 3, 4-dichloro-2-nitrobenzoic acid |
CN117550981A (en) * | 2024-01-12 | 2024-02-13 | 成都工业学院 | Preparation method of 2-amino-5-fluoro acetophenone |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008054454A2 (en) * | 2006-02-10 | 2008-05-08 | Transtech Pharma, Inc. | Nitrogen-containing heterocycle derivatives, pharmaceutical compositions, and methods of use thereof as antiviral agents |
CN102753555A (en) * | 2010-02-11 | 2012-10-24 | 百时美施贵宝公司 | Macrocycles as factor XIA inhibitors |
WO2015049356A1 (en) * | 2013-10-02 | 2015-04-09 | Tolle Fabian | A method of identifying or producing an aptamer |
CN106488910A (en) * | 2013-10-10 | 2017-03-08 | 亚瑞克西斯制药公司 | Inhibitors of kras g12c |
-
2018
- 2018-09-27 CN CN201811133588.2A patent/CN109232259B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008054454A2 (en) * | 2006-02-10 | 2008-05-08 | Transtech Pharma, Inc. | Nitrogen-containing heterocycle derivatives, pharmaceutical compositions, and methods of use thereof as antiviral agents |
CN102753555A (en) * | 2010-02-11 | 2012-10-24 | 百时美施贵宝公司 | Macrocycles as factor XIA inhibitors |
WO2015049356A1 (en) * | 2013-10-02 | 2015-04-09 | Tolle Fabian | A method of identifying or producing an aptamer |
CN106488910A (en) * | 2013-10-10 | 2017-03-08 | 亚瑞克西斯制药公司 | Inhibitors of kras g12c |
Non-Patent Citations (1)
Title |
---|
HE, YANG等: "Expeditious synthesis of ivacaftor", 《HETEROCYCLES》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109796397A (en) * | 2019-03-15 | 2019-05-24 | 浙江理工大学 | A kind of preparation method of 3- acetylpyridine |
CN111943854A (en) * | 2020-08-21 | 2020-11-17 | 阿里生物新材料(常州)有限公司 | Synthetic method of 3, 4-dichloro-2-nitrobenzoic acid |
CN111943854B (en) * | 2020-08-21 | 2022-03-11 | 阿里生物新材料(常州)有限公司 | Synthetic method of 3, 4-dichloro-2-nitrobenzoic acid |
CN117550981A (en) * | 2024-01-12 | 2024-02-13 | 成都工业学院 | Preparation method of 2-amino-5-fluoro acetophenone |
CN117550981B (en) * | 2024-01-12 | 2024-03-15 | 成都工业学院 | Preparation method of 2-amino-5-fluoro acetophenone |
Also Published As
Publication number | Publication date |
---|---|
CN109232259B (en) | 2021-05-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109232259A (en) | A kind of preparation method of nitro-acetophenone | |
CN106748943B (en) | The method and device that a kind of continuous hydrolysis of the double grignard condensation products of vitamin A intermediate neutralizes | |
US20140256980A1 (en) | Process for manufacturing hmb and salts thereof | |
CN106278861B (en) | A method of preparing substituted phenylacetic acid | |
CN101863858A (en) | Synthetic method of bentazone | |
CN101870653B (en) | Synthesis method of 2 - methyl -3 - fluoride - 6 -nitrobenzoic acid | |
CN104016924A (en) | One-pot method for synthetizing enzalutamide | |
CN117229187B (en) | Synthesis method of thioimine ester compound | |
CN102285937B (en) | Method for synthesizing febuxostat | |
CN103319316B (en) | Green preparation method of dihydroxy dibutyl ether | |
CN104628577A (en) | Method for synthesizing bromhexine hydrochloride | |
CN106565531A (en) | Synthesis method for pharmaceutically acceptable salt of alkylhydrazine | |
CN109796397A (en) | A kind of preparation method of 3- acetylpyridine | |
CN106220474A (en) | A kind of new method preparing paracresol | |
CN106518758A (en) | Preparation method of Betrixaban intermediate N-(5-chloro-2-pyridyl)-2-(4-cyanobenzeneformamido)-5-metoxybenzamide | |
CN106279194A (en) | A kind of method utilizing microreactor to prepare sodium-glucose co-transport enzyme inhibitor intermediate | |
CN109503469A (en) | A kind of preparation method of 2- acetylpyridine | |
CN113329994B (en) | Method for continuously preparing 5-cyanodiol | |
CN103087033A (en) | Synthesis method of poly-substituted oxacycloheptatriene-3(2H) ketone compounds | |
CN106117060A (en) | A kind of purification process of 7 chlorine 2 oxoheptanoates | |
CN117756625B (en) | Preparation method of o-ethoxybenzoyl chloride | |
CN110407740A (en) | A kind of synthetic method of the bromo- 2- ethylpyridine of 3- | |
BRPI0608383B1 (en) | method for producing a nicotinic acid derivative or salt thereof | |
CN106083581B (en) | A kind of preparation method of the chloro- 2- of 7- (1- oxoethyl) cognac oil | |
CN104311456A (en) | Preparation method of guaiacol potassium sulfoacid |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |