CN104557464B - 一种叔醇类化合物及其制备方法 - Google Patents
一种叔醇类化合物及其制备方法 Download PDFInfo
- Publication number
- CN104557464B CN104557464B CN201310481955.9A CN201310481955A CN104557464B CN 104557464 B CN104557464 B CN 104557464B CN 201310481955 A CN201310481955 A CN 201310481955A CN 104557464 B CN104557464 B CN 104557464B
- Authority
- CN
- China
- Prior art keywords
- structural formula
- tertiary alcohols
- compound
- alkyl
- alcohols compound
- 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.)
- Active
Links
- -1 tertiary alcohols compound Chemical class 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000007818 Grignard reagent Substances 0.000 claims abstract description 20
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 239000000575 pesticide Substances 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 9
- 150000003509 tertiary alcohols Chemical class 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 238000005935 nucleophilic addition reaction Methods 0.000 abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 3
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000000654 additive Substances 0.000 description 8
- 230000000996 additive effect Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 230000005311 nuclear magnetism Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000003809 water extraction Methods 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methyl-2-butanol Substances CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 2
- QZLWQLNBMRHKHF-UHFFFAOYSA-N 4-(bromomethyl)-2h-triazole Chemical compound BrCC1=CNN=N1 QZLWQLNBMRHKHF-UHFFFAOYSA-N 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 238000005882 aldol condensation reaction Methods 0.000 description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 description 2
- AKGGYBADQZYZPD-UHFFFAOYSA-N benzylacetone Chemical compound CC(=O)CCC1=CC=CC=C1 AKGGYBADQZYZPD-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 1
- PXMNMQRDXWABCY-UHFFFAOYSA-N 1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol Chemical compound C1=NC=NN1CC(O)(C(C)(C)C)CCC1=CC=C(Cl)C=C1 PXMNMQRDXWABCY-UHFFFAOYSA-N 0.000 description 1
- ILQGIJDYSLHIOX-UHFFFAOYSA-N 1-(4-chlorophenyl)-4,4-dimethylpentan-3-one Chemical compound CC(C)(C)C(=O)CCC1=CC=C(Cl)C=C1 ILQGIJDYSLHIOX-UHFFFAOYSA-N 0.000 description 1
- CEFVCNWQCJCMHZ-UHFFFAOYSA-N 2-(bromomethyl)furan Chemical class BrCC1=CC=CO1 CEFVCNWQCJCMHZ-UHFFFAOYSA-N 0.000 description 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N 2-butanol Substances CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- UVMIAVWGKUGXKQ-UHFFFAOYSA-N 4,4-dimethyl-1-(4-methylphenyl)pentan-3-one Chemical compound CC1=CC=C(CCC(=O)C(C)(C)C)C=C1 UVMIAVWGKUGXKQ-UHFFFAOYSA-N 0.000 description 1
- 241000223600 Alternaria Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- 239000005839 Tebuconazole Substances 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920002120 photoresistant polymer Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
本发明提供了一种叔醇类化合物及其制备方法，由所述叔醇类化合物为结构式（Ⅰ）所示化合物或其农药医学上可接受的盐，由结构式（Ⅲ）所示的芳（杂）环苄位格氏试剂与结构式（Ⅱ）所示的苯基乙基酮进行亲核加成反应制得：
Description
技术领域
本发明涉及一种醇类化合物，尤其涉及一种叔醇类化合物及其制备方法。
背景技术
叔醇是羟基所在位置有三个取代基的没有α-H的醇。格氏试剂对酮类的亲核加成反应式制备叔醇类化合物最为重要、运用最广泛的方法之一。此方法不仅原料易得、操作简单，还可以增加反应物的碳链，因此可以用来制备各种叔醇。但是传统的格氏试剂对酮类的亲核加成反应存在的缺点是：在亲核加成反应过程中，通常伴随着底物本身的羟醛缩合副产物和还原产物的产生，导致主产物的收率大大降低。为了阻止这些副反应的发生，人们使用过量添加剂，尤其是无机金属盐类添加剂，例如Imamoto小组报道了使用过量的无水氯化铯作为添加剂来促进格氏试剂对酮高效加成的反应体系（Imamoto, T.; Sugiura, Y.;Takiyama, N. Tetrahedron Lett. 1984, 25, 4233-4236），又如Knochel小组报道了使用LnCl3·2LiCl很好地促进了格氏试剂对酮的加成，尤其是加入30mol%的LnCl3·2LiCl作为添加剂对此反应非常有效。然而，使用无水金属盐类作为添加剂，来活化羰基或者形成活性较高的过渡态中间体，达到降低副反应提高产率的目的，其存在着缺陷：1、添加剂价格昂贵，较易吸潮，要在手套箱中称量，不适合于工业化生产；2、用金属盐作为添加剂，后处理麻烦复杂，且后处理后产品中易残留金属离子，最终金属离子残留在农药对环境不友好，或残留在药品中降低药效且对人类健康有很大的影响。
叔醇类化合物在有机合成方法学、以及农药、医药等产品中具有广泛的应用价值。例如CN102976891A公开了一种不对称叔醇，具有单环或多环的非芳香族环或芳香族环，可用作感光性树脂等功能性高分子、或医药品等精密化学品等的原料。由于叔醇类化合物具有很高的应用价值，对各类相关农药及医药产品的开发都具有积极作用，因此，需要进一步开发更多的叔醇类化合物来满足研究和生产需求。
发明内容
本发明的目的在于克服上述不足，提供一种新型的叔醇类化合物，且该叔醇类化合物的制备方法简单、反应条件温和、产品纯度高、收率高，且对环境友好。
本发明的第一个方面是提供一种叔醇类化合物，其特征在于，所述叔醇类化合物为结构式（Ⅰ）所示化合物或其农药医学上可接受的盐：
（Ⅰ）
优选地，所述叔醇类化合物包括结构式（Ⅰ）所示化合物的光学异构体或其农药医学上可接受的盐、或者结构式（Ⅰ）所示化合物的顺反异构体或其农药医学上可接受的盐。
在本发明第一个方面所述的叔醇类化合物的一种优选实施例中，Ar为芳香基、取代芳香基中的一种。
其中，芳香基可以为不含杂原子，也可以含有一个或多个杂原子，所述杂原子可以为O、S、N、P、Si等，优选为O、S、N。
进一步优选地， Ar为不含有取代基或者含有一个或多个取代基的苯基、三氮唑基、吡啶基、萘基、噻唑基、嘧啶基、呋喃基、噻吩基、噁唑基、喹啉基中的一种。
更进一步优选地，Ar为苯基、三氮唑基、吡啶基、噻唑基、嘧啶基、四氢呋喃基、或其卤代物中的一种。
优选地，所述取代芳香基中的取代基为1-8个，更优选为1-6个，更优选为1-4个，更优选为1-3个，例如2个。
所述取代芳香基中的取代基选自卤素、腈基、硝基、羟基、甲氨基、二甲氨基、烷基、烷氧基或卤代烷基中的一种或多种。
烷基优选为C1-20烷基，更优选为C1-10烷基，更优选为C1-8烷基、更优选为C1-6烷基、更优选为C1-4烷基，例如甲基、乙基、丙基、异丙基、丁基、叔丁基等。
烷氧基优选为C1-20烷氧基，更优选为C1-10烷氧基，更优选为C1-8烷氧基、更优选为C1-6烷氧基、更优选为C1-4烷氧基，例如甲氧基、乙氧基、丙氧基、异丙氧基、丁氧基、叔丁氧基等。
卤代烷基优选为C1-20卤代烷基，更优选为C1-10卤代烷基，更优选为C1-8卤代烷基、更优选为C1-6卤代烷基、更优选为C1-4卤代烷基，例如卤代甲基、卤代乙基、卤代丙基、卤代异丙基、卤代丁基、卤代叔丁基等。
卤代烷基可以为部分卤代烷基（例如一元卤代、二元卤代或三元卤代等）或全卤代烷基。卤代基团可以为I、Br、Cl、F等。
在本发明第一个方面所述的叔醇类化合物的一种优选实施例中，R1为H、卤素（例如I、Br、Cl、F等）、腈基、硝基、羟基、甲氨基、二甲氨基、烷基、烷氧基或卤代烷基，更优选为卤素、烷氧基、烷基或硝基。
烷基优选为C1-20烷基，更优选为C1-10烷基，更优选为C1-8烷基、更优选为C1-6烷基、更优选为C1-4烷基，例如甲基、乙基、丙基、异丙基、丁基、叔丁基等。
烷氧基优选为C1-20烷氧基，更优选为C1-10烷氧基，更优选为C1-8烷氧基、更优选为C1-6烷氧基、更优选为C1-4烷氧基，例如甲氧基、乙氧基、丙氧基、异丙氧基、丁氧基、叔丁氧基等。
卤代烷基优选为C1-20卤代烷基，更优选为C1-10卤代烷基，更优选为C1-8卤代烷基、更优选为C1-6卤代烷基、更优选为C1-4卤代烷基，例如卤代甲基、卤代乙基、卤代丙基、卤代异丙基、卤代丁基、卤代叔丁基等。
卤代烷基可以为部分卤代烷基（例如一元卤代、二元卤代或三元卤代等）或全卤代烷基。卤代基团可以为I、Br、Cl、F等。
在本发明第一个方面所述的叔醇类化合物的一种优选实施例中，R2为C1-6烷基（更优选为C1-4烷基，例如甲基、乙基、丙基、异丙基、丁基、叔丁基等）、烯丙基、苄基、C1-4烷氧基-C1-4烷基（例如甲烷氧基甲基、乙烷氧基丙基、甲烷氧基叔丁基等）或Ar，更优选为C1-6烷基（更优选为C1-4烷基，例如甲基、乙基、丙基、异丙基、丁基、叔丁基等）或C1-4烷氧基-C1-4烷基（例如甲烷氧基甲基、乙烷氧基丙基、甲烷氧基叔丁基等）。
在一个特别优选的实施方式中，结构式（Ⅰ）所示叔醇类化合物中，Ar为三氮唑基，R1为卤素（例如I、Br、Cl、F等）或甲氧基，R2为叔丁基或甲基。
本发明的第二个方面是提供一种上述叔醇类化合物的制备方法，由结构式（Ⅱ）所示羰基化合物与结构式（Ⅲ）所示格氏试剂反应制得结构式（Ⅰ）所示叔醇类化合物，反应式如下：
（Ⅱ） （Ⅲ） （Ⅰ）
其中，结构式（Ⅲ）中的X为Cl或Br。
其中，结构式（Ⅱ）所示羰基化合物与结构式（Ⅲ）所示格氏试剂反应完成后，水解，萃取，浓缩萃取液即得结构式（Ⅰ）所示叔醇类化合物。
其中，结构式（Ⅲ）所示格氏试剂由结构式（Ⅳ）所示卤化物与镁反应制得：
（Ⅳ）。
结构式（Ⅳ）所示卤化物与镁反应使用的溶剂可以为四氢呋喃、乙醚、甲苯中的一种或者多种。
优选地，所述格氏试剂的浓度为0.1-10 mol/L，更优选为0.2-8 mol/L，更优选为0.5-6 mol/L，更优选为1-4 mol/L，更优选为1.5-3 mol/L。
优选地，结构式（Ⅱ）所示羰基化合物与结构式（Ⅲ）所示格氏试剂反应温度为0-70℃，更优选为10-60℃，更优选为15-50℃，更优选为20-40℃，更优选为25-35℃。
优选地，结构式（Ⅱ）所示羰基化合物与结构式（Ⅲ）所示格氏试剂反应时间为1-4h，更优选为1.5-3.5h，更优选为2-3h。
本发明上述各个方面以及各优选实施例可以不受限制的任意组合。
本发明采用芳（杂）环苄位格氏试剂（结构式（Ⅲ）所示）与苯基乙基酮（结构式（Ⅱ）所示）进行亲核加成反应，反应活性好，在室温下即可进行反应，反应完成时间，短羟醛缩合副产物和还原副产物大大减少，无需加入添加剂来促进亲核加成反应，反应产率高，而且易纯化，只需经过简单的萃取浓缩即可获得纯度为95%左右的叔醇类化合物，所得叔醇类化合物在有机合成方法学、以及农药、医药等产品中具有广泛的应用价值。
经生物活性测试，本发明所提供的叔醇类结构对小麦纹枯病以及苹果斑点落叶病的抑制活性较显著。
具体实施方式
下面参照具体的实施例对本发明作进一步地描述，以更好地理解本发明。
实施例1 2-甲基-1,4-二苯基-2-丁醇的合成
在25ml四氢呋喃中加入4-苯基-2-丁酮（2 mmol），再加入苄溴格氏试剂（2 mmol/ml，1 ml），搅拌2小时反应完成，加入醋酸水溶液，继续搅拌1小时，加入二氯甲烷和水萃取，合并有机相，干燥浓缩得到产品，收率82%，纯度97%，经红外和核磁鉴定为2-甲基-1,4-二苯基-2-丁醇。
实施例2 4-(4-氯苯基)-1-(呋喃-2-基) -2-甲基2-丁醇的合成
在25ml四氢呋喃中加入4-对氯苯基-2-丁酮（2 mmol），再加入溴甲基呋喃的格氏试剂（2 mmol/ml，1 ml），搅拌3小时反应完成，加入醋酸水溶液，继续搅拌1小时，加入二氯甲烷和水萃取，合并有机相，干燥浓缩得到产品，收率75%，纯度96%，经红外和核磁鉴定为4-(4-氯苯基)-1-(呋喃-2-基) -2-甲基2-丁醇。
实施例3 3-(2-甲氧基苯基)-1-苯基-1-(1H-吡咯-2-基)-1-丙醇的合成：
在25ml四氢呋喃中加入3-(2-甲氧基苯基)-1-苯基-1-丙酮（2 mmol），再加入溴甲基吡咯的格氏试剂（2 mmol/ml，1 ml），搅拌2小时反应完成，加入醋酸水溶液，继续搅拌1小时，加入二氯甲烷和水萃取，合并有机相，干燥浓缩得到产品，收率71%，纯度94%，经红外和核磁鉴定为3-(2-甲氧基苯基)-1-苯基-1-(1H-吡咯-2-基)-1-丙醇。
实施例4 4,4-二甲基-1-(对甲基苯基)-3-(1H-1,2,3-三唑-1-基)-3-戊醇的合成：
在25ml四氢呋喃中加入4,4-二甲基-1-(对甲基苯基)-3-戊酮（2.0 mmol），再加入溴甲基三唑的格氏试剂（2.0 mmol/ml，1.0 ml），搅拌2小时反应完成，加入醋酸水溶液，继续搅拌1小时，加入二氯甲烷和水萃取，合并有机相，干燥浓缩得到产品，收率74%，纯度95%，经红外和核磁鉴定为4,4-二甲基-1-(对甲基苯基)-3-(1H-1,2,3-三唑-1-基)-3-戊醇。
实施例5 上述格氏试剂与酮反应，合成叔醇类结构化合物的合成方法同样适用于戊唑醇的合成（3-((1H-1,2,4-三氮唑-1-基)甲基)-1-(4-氯苯基)-4,4-二甲基-3-戊醇）
在25ml四氢呋喃中加入1-(4-氯苯基)-4,4-二甲基-3-戊酮（2.0 mmol），再加入N-溴甲基三氮唑的格氏试剂（2.0 mmol/ml，1.0 ml），搅拌2小时反应完成，加入醋酸水溶液，继续搅拌1小时，加入二氯甲烷和水萃取，合并有机相，干燥浓缩得到产品，收率78%，纯度96%，经红外和核磁鉴定为3-((1H-1,2,4-三氮唑-1-基)甲基)-1-(4-氯苯基)-4,4-二甲基-3-戊醇。
按照与实施例1-5类似的方法制备如表1所述化合物，并经过红外和核磁鉴定确认结构。
（Ⅱ） （Ⅲ） （Ⅰ）
表1，化合物结构与生物活性一览表
表1中的R1项中的基团前的数字与结构式（Ⅰ） 中的位置标号对应，例如R1为2-Cl，对应的叔醇类化合物为：
。
以上对本发明的具体实施例进行了详细描述，但其只是作为范例，本发明并不限制于以上描述的具体实施例。对于本领域技术人员而言，任何对本发明进行的等同修改和替代也都在本发明的范畴之中。因此，在不脱离本发明的精神和范围下所作的均等变换和修改，都应涵盖在本发明的范围内。
Claims (6)
1.一种叔醇类化合物，其特征在于，所述叔醇类化合物为结构式(Ⅰ)所示化合物或其农药医学上可接受的盐：
其中，Ar基团为不含有取代基的呋喃基、吡咯基中的一种；
R1为H、卤素、C1-2烷基、甲氧基；
R2为C1-4烷基、苯基。
2.根据权利要求1所述的叔醇类化合物，其特征在于，所述叔醇类化合物包括结构式(Ⅰ)所示化合物的光学异构体或其农药医学上可接受的盐。
3.根据权利要求1或2所述的叔醇类化合物，其特征在于，所述叔醇类化合物包括结构式(Ⅰ)所示化合物的顺反异构体或其农药医学上可接受的盐。
4.一种权利要求1所述的叔醇类化合物的制备方法，其特征在于，由结构式(Ⅱ)所示羰基化合物与结构式(Ⅲ)所示格氏试剂反应、水解、萃取、浓缩制得结构式(Ⅰ)所示叔醇类化合物，反应式如下：
其中，结构式(Ⅲ)中的X为Cl或Br。
5.根据权利要求4所述的制备方法，其特征在于，所述格氏试剂的浓度为0.1-10mol/L。
6.根据权利要求4所述的制备方法，其特征在于，结构式(Ⅱ)所示羰基化合物与结构式(Ⅲ)所示格氏试剂反应温度为0-70℃。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310481955.9A CN104557464B (zh) | 2013-10-15 | 2013-10-15 | 一种叔醇类化合物及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310481955.9A CN104557464B (zh) | 2013-10-15 | 2013-10-15 | 一种叔醇类化合物及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104557464A CN104557464A (zh) | 2015-04-29 |
| CN104557464B true CN104557464B (zh) | 2019-05-07 |
Family
ID=53074649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310481955.9A Active CN104557464B (zh) | 2013-10-15 | 2013-10-15 | 一种叔醇类化合物及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104557464B (zh) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106117009A (zh) * | 2016-06-13 | 2016-11-16 | 湖北华世通生物医药科技有限公司 | 叔醇类化合物的制备方法 |
| CN106588791A (zh) * | 2016-11-01 | 2017-04-26 | 盐城辉煌化工有限公司 | 一种无溶剂合成杀菌剂戊唑醇的新工艺 |
| CN114409600A (zh) * | 2022-01-19 | 2022-04-29 | 武汉回盛生物科技股份有限公司 | 一种恩康唑的合成方法 |
| CN117924197B (zh) * | 2024-03-21 | 2024-06-07 | 山东百农思达生物科技有限公司 | 戊唑醇的高纯度合成方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870093A (en) * | 1980-05-16 | 1989-09-26 | Bayer Aktiengesellschaft | Antimicrobial agents and their use |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4174405A (en) * | 1974-02-25 | 1979-11-13 | Uniroyal, Inc. | Thiophenes useful in control of acarids |
| JP5870093B2 (ja) * | 2010-05-27 | 2016-02-24 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | 殺菌剤としてのヘテロ環式アルカノール誘導体 |
-
2013
- 2013-10-15 CN CN201310481955.9A patent/CN104557464B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870093A (en) * | 1980-05-16 | 1989-09-26 | Bayer Aktiengesellschaft | Antimicrobial agents and their use |
Non-Patent Citations (1)
| Title |
|---|
| Oxygen Versus Carbon Acidity in the Side-Chain Fragmentation of 2-, 3-, and 4-Arylalkanol Radical Cations in Aqueous Solution: TheInfluence of the Distance between the OH Group and the Aromatic Ring;Enrico Baciocchi等;《Journal of the American Chemical Society》;19990207;第121卷(第28期);参见6629页左栏倒数第2段 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104557464A (zh) | 2015-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104557464B (zh) | 一种叔醇类化合物及其制备方法 | |
| Nicolaou et al. | A novel regio‐and stereoselective synthesis of sulfamidates from 1, 2‐diols using burgess and related reagents: A facile entry into β‐amino alcohols | |
| TW204337B (zh) | ||
| CN106336383B (zh) | 一种三氮唑醇类衍生物及其制备方法和应用 | |
| Noreen et al. | Synthesis, density functional theory (DFT), urease inhibition and antimicrobial activities of 5-aryl thiophenes bearing sulphonylacetamide moieties | |
| Zhang et al. | A unique one-pot reaction via CC cleavage from aminomethylene benzimidazoles to access benzimidazolones with wide potentiality | |
| Fu et al. | Azo-incorporating increases inhibitory activity of succinate dehydrogenase | |
| Mogensen et al. | Homocoupling reactions of azoles and their applications in coordination chemistry | |
| Ding et al. | Synthesis, antimicrobial activity, and molecular docking of benzoic hydrazide or amide derivatives containing a 1, 2, 3‐triazole group as potential SDH inhibitors | |
| Jarrahpour et al. | Design, synthesis, activity evaluation and QSAR studies of novel antimalarial 1, 2, 3-triazolo-β-lactam derivatives | |
| CN102746282B (zh) | N-5-取代苯基-2-呋喃甲酰基类化合物及其制备方法与应用 | |
| Hussen et al. | Novel penicillin derivatives against selected multiple-drug resistant bacterial strains: design, synthesis, structural analysis, in silico and in vitro studies | |
| Yadav et al. | Piperazine-1, 2, 3-triazole scaffolds: Design, synthesis, anticancer and antimicrobial evaluation | |
| CN103201266A (zh) | 芳氧基二卤丙烯醚类化合物与应用 | |
| Kazemzadeh et al. | Isoindolin-1-ones fused to barbiturates: from design and molecular docking to synthesis and urease inhibitory evaluation | |
| Komatsuda et al. | Ring‐Opening Fluorination of Carbo/Heterocycles and Aromatics: Construction of Complex and Diverse Fluorine‐Containing Molecules | |
| Wang et al. | 4, 5-Dihydro-1, 2, 4-oxadiazole as a single nitrogen transfer reagent: Synthesis of functionalized isoxazoles assisted by Sc (OTf) 3 or Au (I)/Sc (OTf) 3 synergistic catalysis | |
| Chai et al. | Design, synthesis, antifungal activity, and action mechanism of pyrazole-4-carboxamide derivatives containing oxime ether active fragment as succinate dehydrogenase inhibitors | |
| Chander et al. | Novel benzenesulfonamide bearing 1, 2, 4-triazoles as potent anti-microbial and anti-oxidant agents | |
| CN106188011B (zh) | 基于芳基吡唑骨架的四元环状β-内酰胺衍生物的超声合成与应用 | |
| CN102030710A (zh) | 杀菌剂唑菌酯14c标记化合物的合成方法 | |
| Li et al. | Domino Cyclization/Trifluoromethylation of 2‐Alknylphenols for the Synthesis of 3‐(Trifluoromethyl) benzofurans and Evaluation of their Antibacterial and Antifungal Activities | |
| CN109384722A (zh) | N-取代酰胺类化合物及其制备方法和应用和一种杀菌剂 | |
| CN102807563B (zh) | 伏立康唑及其中间体的制备方法 | |
| Xu et al. | Synthesis and biological activity of silicon-containing Ethylsulfonylpyridine insecticides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: Songjiang District Jing Dong Zhen Dong Zhou road 201619 Shanghai City No. 51 Co-patentee after: As Dong Zhongyi Chemical Co., Ltd. Patentee after: Shanghai biochemical products Limited by Share Ltd Address before: Songjiang District Jing Dong Zhen Dong Zhou road 201619 Shanghai City No. 51 Co-patentee before: As Dong Zhongyi Chemical Co., Ltd. Patentee before: Shengnong Biological-Chemical Products Co., Ltd., Shanghai |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200103 Address after: Yimatu town yimatu village, Fumeng County, Fuxin City, Liaoning Province (Fluorine Industry Development Zone) Patentee after: Liaoning Zhonghui Biotechnology Co., Ltd Address before: Songjiang District Jing Dong Zhen Dong Zhou road 201619 Shanghai City No. 51 Co-patentee before: As Dong Zhongyi Chemical Co., Ltd. Patentee before: Shanghai biochemical products Limited by Share Ltd |