CN1020727C - 3-(4-氯苯基)-3-(3，4-二甲氧基苯基)丙烯酸酰吗啉的制备方法 - Google Patents
3-(4-氯苯基)-3-(3，4-二甲氧基苯基)丙烯酸酰吗啉的制备方法 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 title 2
- VGCXOXISUUVBAX-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)prop-2-enoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C(=CC(O)=O)C1=CC=C(Cl)C=C1 VGCXOXISUUVBAX-UHFFFAOYSA-N 0.000 title 1
- 125000002252 acyl group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 13
- 239000012442 inert solvent Substances 0.000 claims abstract description 5
- 239000011541 reaction mixture Substances 0.000 claims abstract description 3
- MLLIIHAKTPXMFF-UHFFFAOYSA-N (4-chlorophenyl)-(3,4-dimethoxyphenyl)methanone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)C1=CC=C(Cl)C=C1 MLLIIHAKTPXMFF-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000010438 heat treatment Methods 0.000 claims abstract 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 8
- -1 N-acetyl morphine Chemical compound 0.000 claims description 8
- XLPJNCYCZORXHG-UHFFFAOYSA-N 1-morpholin-4-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCOCC1 XLPJNCYCZORXHG-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 229960005181 morphine Drugs 0.000 claims description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Natural products O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims 1
- KYWXRBNOYGGPIZ-UHFFFAOYSA-N 1-morpholin-4-ylethanone Chemical compound CC(=O)N1CCOCC1 KYWXRBNOYGGPIZ-UHFFFAOYSA-N 0.000 abstract 1
- CAOVWAHHHSZHHG-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-3-hydroxy-1-morpholin-4-ylpropan-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C(O)(C=1C=CC(Cl)=CC=1)CC(=O)N1CCOCC1 CAOVWAHHHSZHHG-UHFFFAOYSA-N 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- QNBTYORWCCMPQP-UHFFFAOYSA-N dimethomorph Chemical compound C1=C(OC)C(OC)=CC=C1C(C=1C=CC(Cl)=CC=1)=CC(=O)N1CCOCC1 QNBTYORWCCMPQP-UHFFFAOYSA-N 0.000 abstract 1
- 238000002955 isolation Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- WWMFRKPUQJRNBY-UHFFFAOYSA-N (2,3-dimethoxyphenyl)-phenylmethanone Chemical compound COC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1OC WWMFRKPUQJRNBY-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000233622 Phytophthora infestans Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 125000000304 alkynyl group Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241001281803 Plasmopara viticola Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- NAGQWRDADOSUPH-UHFFFAOYSA-N [ClH](CCCCCCCCCCCCCCC)N1CCOCC1 Chemical compound [ClH](CCCCCCCCCCCCCCC)N1CCOCC1 NAGQWRDADOSUPH-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- QKQSRIKBWKJGHW-UHFFFAOYSA-N morpholine;prop-2-enoic acid Chemical compound OC(=O)C=C.C1COCCN1 QKQSRIKBWKJGHW-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
一种制备3-(4-氯苯基)-3-(3，4-二甲氧基苯基)丙烯酰吗啉的方法，其中包括在强碱存在下，于室温至反应混合物回流的温度下，使4-氯-3′，4′-二甲氧基二苯酮与N-乙酰吗啉缩合并将作为中间体生成的3-(4-氯苯基)-3-(3，4-二甲氧基苯基)-3-羟基丙酰吗啉脱水，其特征在于，该中间体化合物不经分离在惰性溶剂中加热而脱水。本发明上述方法制成的化合物具有杀菌活性。
Description
本发明涉及通式如下的3，3-二芳基丙烯酸酰胺的新的制备方法，
式中
A代表
B代表
Q代表
其中R1代表C1-4烷基，C1-4烷氧基，氨基，单或双（C1-4烷基）氨基，C3-4烯基，C3-4炔基，C3-4烯氧基，C3-4炔氧基或C3-6环烷基;
R2代表C1-4烷基或C1-4烷氧基或卤素;
R3代表氢或卤素;
R4代表氢或卤素或者C1-4烷基或C1-4烷氧基;
R5代表氢，可任意取代有1个或多个C1-4烷基、C1-4烷氧基、卤素、苯基或苯氧基的苯基，可任意取代有1个或多个囟素的C1-12烷基，C3-7环烷基，C2-6烯基或C2-6炔基（该烯基或炔基还可取代有苯基或萘基或C5-8环烯基）;
-x-y-代表单键或-O-，-S（O）p-（其中p是0，1或2），-N＝N-，-CHR10-O-，-O-CHR10-，-CHR10-S（O）p，-S（O）p-CHR10-，-CnH2n-（其中n是1至10的一个整数），-HC＝CH-或-C≡C-;
R6代表C1-4烷基，C3-7，苄基，C3-4烯基或C3-4炔基;
R7代表C1-4烷基;
R8代表氢或C1-4烷基或C1-4烷氧基;和
R9和R10各自代表氢或C1-4烷基;
通式Ⅰ的化合物具有杀菌活性，对于植物真菌，特别是葡萄生单轴霉（plasmopara viticola）和致病疫霉（phytophthora infestans）的防治尤其有用。在这一方面，特别好的通式Ⅰ化合物是A代表3，4-二甲氧基苯基，3-乙氧基-4-甲氧基苯基，3-氯-4-甲氧基苯基，3-溴-4-甲氧基苯基，3-甲基-4-甲氧基苯基，3-乙基-4-甲氧基苯基，3-丙基-4-甲氧基苯基，3，4-二甲基苯基，3-氨基-4-甲氧基苯基，3，5-二氯-4-氨基苯基或3-甲氧基-4-甲基苯基的那些化合物，其中A为3，4-二甲氧基苯基的化合物尤其好。Q最好为吗啉代。特别好的通式Ⅰ化合物是3-（4-氯苯基）-3-（3，4-二甲氧基苯基）丙烯酸酰吗啉。
通式Ⅰ化合物分别是以EP0120 321AI和EP0219 756AI公布的欧洲专利的主题（申请号分别为84102012.6及86113835.2），但这些文件仅仅叙述了制备这些化合物的已有方法。而我们已经意外地发现通式Ⅰ化合物可以通过二苯酮与相应的乙酰胺反应（已知方法的改进），如果需要，接着脱水来制备。
因此，本发明提供了制备上述的通式Ⅰ化合物的方法，其特征是，通式为（Ⅱ）的化合物与通式为（Ⅲ）的化合物缩合，
ZCH2-CO-Q （Ⅲ）
式中A和B的定义如上，Z代表氢或卤素，特别是氯或溴，Q的定义如上;如果形成通式为
（Ⅳ）的中间体化合物，
(Ⅳ）
式中A、B和Q的定义如上，将此中间体化合物进一步脱水。上述方法可用如下反应式表示：
在此反应式中，A、B、Q和Z的定义如上。如反应式所示，取决于反应条件和所用试剂，上述反应可以一步直接得到通式（Ⅰ）的最终产物或通过式（Ⅳ）的中间体两步完成。在后一种情形下，中间体经脱水得到通式（Ⅰ）的最经产物。
当Z代表氢时，该缩合反应可以在强碱存下进行。适宜的强碱包括碱性氢氧化物，碱性碳酸盐，叔丁醇钾和叔丁基锂。取决于所用的碱和反应进行的温度，通式（Ⅰ）的化合物有时经脱除水直接形成而不需要单独的脱水步骤（参见W.Chodkiewicz等，Bull.Soc.Chim.France，1959，1586-9）。
当Z代表卤素特别是溴时，该缩合反应适于在锌的存在下进行[参见N.L.Drake等J.Am.Chem.Soc.，70，677（1948）]。在此情形下，该反应通常需要分离通式（Ⅳ）的中间体，再单独进行脱水步骤
该反应可以在惰性溶剂如甲苯、苯、乙醚、二异丙醚、二甘醇二甲醚、四氢呋喃、二甲基甲酰胺、丙酮或二氯化乙烯的存在下进行。另一方法，也可以用一种过量的反应剂作溶剂。根据这些反应剂的反应活性，该缩合反应可以于从室温至反应混合物的回流温度之间任何温度进行。
如果生成通式（Ⅳ）的中间体化合物，脱水作用可在惰性溶剂中加热该化合物而开始，所说的惰性溶剂例如甲苯、苯等，可在任选的一种酸例如甲苯磺酸、硫酸、磷酸和盐酸存在下进行反应。另一方面，脱水作用可通过与适宜的酸例如上面所列举的酸反应而容易地完成。许多酸例如冰醋酸原则上可以用作溶剂。一些酸，例如甲酸同时具有酸和溶剂作用。
通式为（Ⅱ）和（Ⅲ）的化合物或者是已知化合物或者可通过已知方法由已知化合物制备。
本发明的方法通过下面的实施例进一步说明。
实施例1
3-（4-氯苯基）-3-（3，4-二甲氧基苯基）丙烯酸酰吗啉的制备
将6.92g（25mmol）4-氯-3′，4′-二甲氧基二苯酮，12.9g（100mmol）N-乙酰吗啉和11.2g（170mmol）粉碎的氢氧化钾（85%）充分混合并于室温下放置30分钟，并偶尔搅拌，然后，将所得粘性物加到激烈搅拌的100ml水和50ml甲苯的混合物中。干燥甲苯相并经装有50g硅胶的柱子分离，以95∶5，90∶10和80∶20的甲苯-丙酮混合物各150ml作洗脱剂。Rf值为0.37（甲苯/丙酮7∶3）的流分经旋转蒸发器蒸发，然后，用少量二异丙醚研制，得到0.8g标题化合物。
Rf值为0.52的流分经蒸发，得到3.4g（理论值的33.5%）3-（4-氯苯基）-3，4-二甲氧基苯基）-3-羟基丙酰吗啉，m.p.150℃。在脱水步骤中，通过温热将该物质溶解于10ml冰醋酸中，加0.1ml浓硫酸，然后，回流此混合物5分钟。冷却至50℃之后，在搅拌下将此混合物加入100ml水中。最初分出的油状物进一步搅拌而固化。抽滤该物质，水洗并干燥。薄层色谱（TLC）表明最终产物基本上是纯的。
产量：2.9g（理论值的30%）
总产量：3.7g（理论值的38%），TLC纯。
实施例2
3-（4-氯苯基）-3-（3，4-二甲氧基苯基）丙烯酸酰吗啉的制备
将13.84g（50mmol）4-氯-3′，4′-二甲氧基二苯酮，7.75g（60mmol）N-乙酰吗啉，7.29g（65mmol）叔丁醇钾和75ml无水甲苯混合并在氮气保护下于80℃搅拌2小时。冷却该溶液，用100ml水提取，干燥并在旋转蒸发器中蒸发，所得11.5g粘性油状物与50ml异丙醚一起在搅拌下加热。冷却并摩擦析出结晶。抽滤出结晶，以少量二异丙醚洗涤并干燥。
产量：9.25g（理论值的48%）
m.p.122-148°
TLC纯，Rf值为0.38（甲苯/丙酮7∶3）。
实施例3
3-（4-氯苯基）-3-（3，4-二甲氧基苯基），丙烯酸酰吗啉的制备
5.53g（20mml）4-氯-3′，4′-二甲氧基二苯酮，3.23g（25mmol）N-乙酰吗啉，3.29g（50mmol）粉碎的氢氧化钾（85%）和30ml无水四氢呋喃在氮气保护和回流下搅拌5小时。冷却后，将所得液态糊状物加到充分搅拌的100ml水和50ml甲苯的混合物中。干燥甲苯相并经装有50g硅胶的柱子分离，以95∶5，90∶10和80∶20的甲苯-丙酮混合物各100ml洗脱。含Rf值为0.38（甲苯/丙酮7∶3）物质的流分在旋转蒸发器中蒸发。所得油状物与少量二异丙醚一起研制而固化。
m.p.122-145℃
产量：3.25g（理论值的42%）
实施例4
3-（4-氯苯基）-3-（3，4-二甲氧基苯基）丙烯酸酰吗啉的制备
将20.9g（76mmol）4-氯-3′，4′-二甲氧基二苯酮，32.7g（200mmol）氯乙酰吗啉，50ml甲苯和50ml苯一起混合成溶液。在回流和快速搅拌下，将10%此溶液加到16.3g（250mmol）新活化的锌（30筛目）和少许碘晶体中。然后，滴加入其余的溶液并回流所得混合物4小时。冷却此混合物，加150ml二氯化乙烯并滤出固体。将滤液加到200ml10∶1冰和浓硫酸的混合物中并振荡，分出有机相，以50ml水洗，然后以30ml2N氢氧化钠溶液洗，再以50ml水洗，最后以30ml饱和氯化钠溶液洗。而后，以硫酸镁干燥有机相并蒸发。残余物以30ml二异丙醚处理并急冷，抽滤出产物并以少量二异丙醚洗涤。
产量：22.0g（理论值的74.3%）
纯度：＞95%
NMR：与产物结构一致。
Claims (3)
1、一种制备3-(4-氯苯基)-3-(3，4-二甲氧基苯基)丙烯酰吗啉的方法，其中包括在强碱存在下，于室温至反应混合物回流的温度下，使4-氯-3′，4′-二甲氧基二苯酮与N-乙酰吗啉缩合并将作为中间体生成的3-(4-氯苯基)-3-(3，4-二甲氧基苯基)-3-羟基丙酰吗啉脱水，其特征在于，该中间体化合物不经分离在惰性溶剂中加热而脱水。
2、权利要求1的方法，其中的强碱选自碱性氢氧化物和叔丁醇钾。
3、权利要求1或2的方法，其中的反应溶剂选自甲苯、二异丙醚和四氢呋喃。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19873719488 DE3719488A1 (de) | 1987-06-11 | 1987-06-11 | Verfahren zur herstellung von 3,3-diarylacrylsaeureamiden |
| DEP3719488.7 | 1987-06-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1038810A CN1038810A (zh) | 1990-01-17 |
| CN1020727C true CN1020727C (zh) | 1993-05-19 |
Family
ID=6329491
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN88103469A Expired - Lifetime CN1020727C (zh) | 1987-06-11 | 1988-06-09 | 3-(4-氯苯基)-3-(3，4-二甲氧基苯基)丙烯酸酰吗啉的制备方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4933449A (zh) |
| EP (1) | EP0294907B1 (zh) |
| JP (1) | JPH0822840B2 (zh) |
| KR (1) | KR960012210B1 (zh) |
| CN (1) | CN1020727C (zh) |
| AT (1) | ATE106397T1 (zh) |
| BR (1) | BR8802830A (zh) |
| DE (2) | DE3719488A1 (zh) |
| ES (1) | ES2053707T3 (zh) |
| HK (1) | HK1000109A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1296362C (zh) * | 2003-12-23 | 2007-01-24 | 李泽方 | 烯酰吗啉的制备方法 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3805235A1 (de) * | 1988-02-19 | 1989-08-31 | Shell Int Research | Verfahren zur herstellung von 3,3-diarylacrylsaeureamiden |
| DE3817711A1 (de) * | 1988-05-25 | 1989-11-30 | Shell Int Research | Verfahren zur herstellung von 3,3-diphenylacrylsaeureamiden |
| DE3903247A1 (de) * | 1989-02-03 | 1990-08-09 | Shell Int Research | Fungizid wirkende zusammensetzung, verfahren zu ihrer herstellung und ihre verwendung, insbesondere zur heilenden behandlung von an pilzerkrankungen leidenden pflanzen |
| IL106122A (en) * | 1992-07-10 | 1997-04-15 | Shell Int Research | Preparation of 3, 3-diaryl acrylic acid amides |
| CN100516055C (zh) * | 2006-04-28 | 2009-07-22 | 江苏常隆化工有限公司 | 3-(4-氯苯基)-3-(3,4-二烷氧基苯基)丙烯酰吗啉的制备方法 |
| CN103992294B (zh) * | 2014-05-29 | 2016-06-08 | 常州大学 | 一种丙烯酰胺类活性稀释剂的合成方法 |
| CN104130214A (zh) * | 2014-07-22 | 2014-11-05 | 江苏长青农化股份有限公司 | 烯酰吗啉原药的制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3306996A1 (de) * | 1983-02-28 | 1984-08-30 | Celamerck Gmbh & Co Kg, 6507 Ingelheim | Acrylsaeuremorpholide, ihre herstellung und verwendung |
| CS244440B2 (en) * | 1983-02-28 | 1986-07-17 | Celamerck Gmbh & Co Kg | Method of acrylic acids' new amides production |
| ES2061432T3 (es) * | 1985-10-09 | 1994-12-16 | Shell Int Research | Nuevas amidas de acido acrilico. |
| DE3536029A1 (de) * | 1985-10-09 | 1987-04-09 | Celamerck Gmbh & Co Kg | Neue acrylsaeureamide |
| DE3541718A1 (de) * | 1985-11-26 | 1987-05-27 | Celamerck Gmbh & Co Kg | Neue acrylsaeuremorpholide |
-
1987
- 1987-06-11 DE DE19873719488 patent/DE3719488A1/de not_active Withdrawn
-
1988
- 1988-06-01 US US07/200,856 patent/US4933449A/en not_active Expired - Lifetime
- 1988-06-08 KR KR1019880006863A patent/KR960012210B1/ko not_active IP Right Cessation
- 1988-06-09 CN CN88103469A patent/CN1020727C/zh not_active Expired - Lifetime
- 1988-06-09 EP EP88201191A patent/EP0294907B1/en not_active Expired - Lifetime
- 1988-06-09 ES ES88201191T patent/ES2053707T3/es not_active Expired - Lifetime
- 1988-06-09 JP JP63140675A patent/JPH0822840B2/ja not_active Expired - Lifetime
- 1988-06-09 AT AT88201191T patent/ATE106397T1/de not_active IP Right Cessation
- 1988-06-09 BR BR8802830A patent/BR8802830A/pt not_active IP Right Cessation
- 1988-06-09 DE DE3889772T patent/DE3889772T2/de not_active Expired - Lifetime
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1997
- 1997-07-18 HK HK97101579A patent/HK1000109A1/xx not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1296362C (zh) * | 2003-12-23 | 2007-01-24 | 李泽方 | 烯酰吗啉的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0294907B1 (en) | 1994-06-01 |
| JPS6425750A (en) | 1989-01-27 |
| CN1038810A (zh) | 1990-01-17 |
| BR8802830A (pt) | 1989-01-03 |
| EP0294907A1 (en) | 1988-12-14 |
| US4933449A (en) | 1990-06-12 |
| KR890000453A (ko) | 1989-03-14 |
| JPH0822840B2 (ja) | 1996-03-06 |
| ATE106397T1 (de) | 1994-06-15 |
| DE3889772D1 (de) | 1994-07-07 |
| DE3889772T2 (de) | 1994-09-08 |
| DE3719488A1 (de) | 1988-12-29 |
| KR960012210B1 (ko) | 1996-09-16 |
| HK1000109A1 (en) | 1997-11-28 |
| ES2053707T3 (es) | 1994-08-01 |
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