CN114181122A - 一种苄位硫醚类化合物及其制备方法 - Google Patents
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- LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- -1 nickel halide Chemical class 0.000 claims abstract description 58
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- 239000003446 ligand Substances 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 15
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- 239000011593 sulfur Substances 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 229910052759 nickel Inorganic materials 0.000 claims abstract description 6
- 230000001681 protective effect Effects 0.000 claims abstract description 5
- 230000009471 action Effects 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 239000011572 manganese Substances 0.000 claims description 8
- DYSFHJWHGFZZAO-UHFFFAOYSA-N COC(C(OCC1=CC(F)=CC=C1)=O)=O Chemical compound COC(C(OCC1=CC(F)=CC=C1)=O)=O DYSFHJWHGFZZAO-UHFFFAOYSA-N 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- YJTRBEIWPYGSOY-UHFFFAOYSA-N COC(C(OCC1=CC2=CC=CC=C2C=C1)=O)=O Chemical group COC(C(OCC1=CC2=CC=CC=C2C=C1)=O)=O YJTRBEIWPYGSOY-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical group [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- UIPIQDGJTBLKCZ-UHFFFAOYSA-N COC(C(OCC1=CC=CN=C1)=O)=O Chemical compound COC(C(OCC1=CC=CN=C1)=O)=O UIPIQDGJTBLKCZ-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 claims description 2
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 229910052748 manganese Inorganic materials 0.000 claims description 2
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 2
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical group [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 7
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- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 238000004896 high resolution mass spectrometry Methods 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 150000003568 thioethers Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- GWIKYPMLNBTJHR-UHFFFAOYSA-M thiosulfonate group Chemical group S(=S)(=O)[O-] GWIKYPMLNBTJHR-UHFFFAOYSA-M 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- ZYZXGWGQYNTGAU-UHFFFAOYSA-N dibenzyl oxalate Chemical compound C=1C=CC=CC=1COC(=O)C(=O)OCC1=CC=CC=C1 ZYZXGWGQYNTGAU-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
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- LWWLUZKWDUKRET-UHFFFAOYSA-N 1-fluoro-3-(phenylsulfanylmethyl)benzene Chemical compound FC1=CC=CC(CSC=2C=CC=CC=2)=C1 LWWLUZKWDUKRET-UHFFFAOYSA-N 0.000 description 1
- FAWFBIHSPIZYHU-UHFFFAOYSA-N 1-methoxy-4-(phenylsulfanylmethyl)benzene Chemical compound C1=CC(OC)=CC=C1CSC1=CC=CC=C1 FAWFBIHSPIZYHU-UHFFFAOYSA-N 0.000 description 1
- KZCSDJKWEYGAIX-UHFFFAOYSA-N 2,4-dihydroxy-3-methylbenzoic acid Chemical compound CC1=C(O)C=CC(C(O)=O)=C1O KZCSDJKWEYGAIX-UHFFFAOYSA-N 0.000 description 1
- HBTALKVRVONZGI-UHFFFAOYSA-N 2-(phenylsulfanylmethyl)naphthalene Chemical compound C=1C=C2C=CC=CC2=CC=1CSC1=CC=CC=C1 HBTALKVRVONZGI-UHFFFAOYSA-N 0.000 description 1
- QAQODOCQHFQGPZ-UHFFFAOYSA-N 3-(phenylsulfanylmethyl)pyridine Chemical compound C=1C=CN=CC=1CSC1=CC=CC=C1 QAQODOCQHFQGPZ-UHFFFAOYSA-N 0.000 description 1
- BBMFSGOFUHEVNP-UHFFFAOYSA-N 4-hydroxy-2-methylbenzoic acid Chemical compound CC1=CC(O)=CC=C1C(O)=O BBMFSGOFUHEVNP-UHFFFAOYSA-N 0.000 description 1
- HCJMNOSIAGSZBM-UHFFFAOYSA-N 6-methylsalicylic acid Chemical compound CC1=CC=CC(O)=C1C(O)=O HCJMNOSIAGSZBM-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229910006148 NiII Inorganic materials 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical compound C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000006464 oxidative addition reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- 150000003573 thiols Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- 238000001845 vibrational spectrum Methods 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
- C07B45/06—Formation or introduction of functional groups containing sulfur of mercapto or sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明涉及一种苄位硫醚类化合物及其制备方法,属于有机化合物技术领域。本发明所述制备方法包括以下步骤:保护气氛下,将草酸酯与硫源在催化剂、还原剂和配体作用下,在溶剂中发生反应,得到所述苄位硫醚类化合物。本发明所述的苄位硫醚类化合物的制备过程,以草酸酯与硫源为原料,原料简单易得,反应条件温和,环境友好,反应中使用卤化镍作为催化剂,得到的产率较高,该方法可适用于放大反应,为工业生产奠定了基础。
Description
技术领域
本发明涉及有机化合物技术领域,尤其涉及一种苄位硫醚类化合物及其制备方法。
背景技术
含硫有机化合物广泛存在于动植物的体内,是蛋白质、氨基酸、维生素等生物活性分子和天然产物的重要组成部分,对维持生物体代谢及生命活动起着重要作用。由于其特殊结构性质,在农药、医药、材料等领域都有着广泛的应用。硫醚作为含硫化合物中的重要组成部分,近年来,化学家也在不断开发制备多功能硫醚化合物的有效方法。
硫醚骨架广泛存在于天然产物和药物分子中,其中具有代表性的结构式如下所示:
传统的合成烷基硫化物的方法是在强碱条件下,在极性溶剂中,使用硫试剂与卤代烃进行亲核取代反应。例如1978年,Migita课题组首次报道了使用Ph(PPh3)4催化硫醇和芳基卤化物的交叉偶联反应,得到了相应的硫醚化合物。而目前合成硫醚的代表性工作,是2006年Hartwing课题组报道在Pd催化下,由芳基卤化物和三氟甲磺酸酯与硫醇偶联。
上述文献公开的制备方法中,需要使用过渡金属钯作为催化剂,成本昂贵,同时卤代烃的原料受限,硫醇具有强刺激性和毒性,并且反应需要强氧化剂、温度较高等苛刻的反应条件。因此,使用简便易得的原料、以简便温和的方法合成硫醚类化合物,对有机化学及药物化学的领域都具有重要意义。
发明内容
为解决上述技术问题,本发明提供了一种苄位硫醚类化合物及其制备方法。
本发明的第一个目的是提供一种苄位硫醚类化合物的制备方法,包括以下步骤:
保护气氛下,将式(I)结构的草酸酯与(II)结构的硫源在催化剂、还原剂和配体作用下,在溶剂中发生反应,得到所述式(III)所示的苄位硫醚类化合物;
R1、R2独立地选自芳基或者烷基;所述烷基为碳原子数为1-18的直链烷基、支链烷基或环烷基。
在本发明的一个实施例中,所述草酸酯为(萘-2-基甲基)草酸甲酯、(6-甲氧基萘-2-基)甲基草酸甲酯、(萘-1-基甲基)草酸甲酯、(喹啉-6-基甲基)草酸甲酯、(喹啉-7-基甲基)草酸甲酯、甲基(喹啉-8-基甲基)草酸甲酯、(6-((环丙烷羰基)氧基)萘-2-基)甲基草酸甲酯、(6-((环丁烷羰基)氧基)萘-2-基)甲基草酸甲酯、((6-(新戊酰氧基)萘-2-基)甲基)草酸甲酯、4-甲氧基苄基草酸甲酯、3-氟苄基草酸甲酯、(吡啶-3-基甲基)草酸甲酯、(噻吩-2-基甲基)草酸甲酯和3,4-二甲氧基苄基草酸甲酯中的一种或多种。
进一步地,所述草酸酯为(萘-2-基甲基)草酸甲酯、(6-甲氧基萘-2-基)甲基草酸甲酯、(萘-1-基甲基)草酸甲酯、甲基(喹啉-8-基甲基)草酸甲酯、(6-((环丙烷羰基)氧基)萘-2-基)甲基草酸甲酯、(6-((环丁烷羰基)氧基)萘-2-基)甲基草酸甲酯、4-甲氧基苄基草酸甲酯、3-氟苄基草酸甲酯、(吡啶-3-基甲基)草酸甲酯、(噻吩-2-基甲基)草酸甲酯。根据所述草酸酯所连的取代基的不同,所制备的苄位硫醚也有区别。本申请所述硫源与催化剂配体的加成,并随后与草酸酯形成的苄基自由基反应,是该反应的关键。
在本发明的一个实施例中,所述催化剂为卤化镍。进一步地,所述卤化镍为溴化镍和/或氯化镍。
在本发明的一个实施例中,所述还原剂为锰和/或锌。
在本发明的一个实施例中,所述配体为1,10-菲咯啉或其衍生物。
在本发明的一个实施例中,所述溶剂为二甲亚砜、N,N,-二甲基甲酰胺和N,N-二甲基乙酰胺中的一种或多种。
进一步地,所述溶剂为二甲亚砜。
在本发明的一个实施例中,草酸酯、硫源和还原剂的摩尔比为1-2:1-2:1-5;所述催化剂和配体的用量均为草酸酯摩尔量的0.1-20%或硫源摩尔量的0.1-20%。进一步地,所述草酸酯与硫源的摩尔比为1:1.2。
在本发明的一个实施例中,所述反应是40-80℃反应20-24h。
进一步地,当草酸酯苄位相连为萘环时所述反应的温度为40℃,当草酸酯苄位相连为苯环时所述反应的温度为80℃。
在本发明的一个实施例中,所述保护气氛的气体为氩气。
在本发明的一个实施例中,反应结束后则减压除去溶剂,并以乙酸乙酯、石油醚为淋洗剂柱层析,得到纯化后的苄位硫醚。
本发明的第二个目的是提供一种所述方法制备得到的苄位硫醚类化合物,结构如式(III)所示:
R2为芳基或者烷基;所述烷基为碳原子数为1-18的直链烷基、支链烷基或环烷基。
本发明的原理是:本发明以草酸酯与硫源为原料,在反应过程中,锰粉或者锌粉对NiII的原位还原提供Ni0(L)2。Ni0(L)2和硫源的氧化加成提供RS-NiII(L)2,并与苄基自由基反应形成NiIII(L)2中间体。通过还原消除生成目标硫化物并形成NiI(L)2物种,随后其与草酸酯反应以再生苄基自由基并提供中间体,随后进一步被还原使Ni0(L)2再生,其中L是配体。
本发明的技术方案相比现有技术具有以下优点:
本发明所述的苄位硫醚类化合物的制备过程,以草酸酯与硫源为原料,原料简单易得,反应条件温和,环境友好,反应中使用卤化镍作为催化剂,得到的产率较高,该方法可适用于放大反应,为工业生产奠定了基础。
具体实施方式
下面结合具体实施例对本发明作进一步说明,以使本领域的技术人员可以更好地理解本发明并能予以实施,但所举实施例不作为对本发明的限定。
实施例1
一种苄位硫醚类化合物(萘-2-基甲基)(苯基)硫醚及其制备方法,具体步骤如下:
在手套箱中,在配备磁力搅拌棒的烘箱干燥螺旋盖8mL小瓶中装入(萘-2-基甲基)草酸甲酯(0.2mmol)、硫代磺酸酯(0.24mmol)通过注射器加入NiBr2(5.0mol%)、配体1,10-菲咯啉(10mol%)、Mn(1.5equiv.)、DMSO(1mL),并将混合物在40℃下搅拌24h。24h后,将粗反应混合物用乙酸乙酯(20mL)稀释并用水(20mL×3)洗涤。有机层用Na2SO4干燥,过滤并浓缩。残余物通过快速色谱纯化,得到产物产率为69%。
对本实施例制备的化合物进行检测,检测结果如下所示:
红外光谱(neat,ν,cm-1):2953,2921,2852,1730,1477,1438,1270,1089,1022,776,686,453,470;
核磁共振氢谱(400MHz,CDCl3)δ7.78(dd,J=9.1,6.9Hz,2H),7.75–7.70(m,1H),7.68–7.64(m,1H),7.47–7.43(m,2H),7.43–7.41(m,1H),7.34–7.31(m,1H),7.30(d,J=1.1Hz,1H),7.24(d,J=5.8Hz,1H),7.21(d,J=6.0Hz,1H),7.19–7.13(m,1H),4.26(s,2H);
核磁共振碳谱(101MHz,CDCl3)δ136.22,134.90,133.30,132.58,130.04,128.86,128.30,127.70,127.65,127.41,126.98,126.45,126.14,125.82,39.45;
高分辨率质谱(ESI):m/z calcd for:250.0816,found 250.0817。
实施例2
一种苄位硫醚类化合物((6-甲氧基萘-2-基)甲基)(苯基)硫醚及其制备方法,具体步骤如下:
在手套箱中,在配备磁力搅拌棒的烘箱干燥螺旋盖8mL小瓶中装入(6-甲氧基萘-2-基)甲基草酸甲酯(0.2mmol)、硫代磺酸酯(0.24mmol)通过注射器加入NiBr2(5.0mol%)、配体1,10-菲咯啉(10mol%)、Mn(1.5equiv.)、DMSO(1mL),并将混合物在40℃下搅拌24h。24h后,将粗反应混合物用乙酸乙酯(20mL)稀释并用水(20mL×3)洗涤。有机层用Na2SO4干燥,过滤并浓缩。残余物通过快速色谱纯化,得到产物产率为67%。
对本实施例制备的化合物进行检测,检测结果如下所示:
红外光谱(neat,ν,cm-1):2920,2850,2361,1599,1435,1261,1163,1024,856,814,732,685,480;
核磁共振氢谱(400MHz,CDCl3)δ7.66(d,J=8.5Hz,1H),7.62(d,J=8.8Hz,1H),7.60–7.57(m,1H),7.41(dd,J=8.4,1.8Hz,1H),7.34–7.27(m,2H),7.25–7.18(m,2H),7.18–7.14(m,1H),7.14–7.06(m,2H),4.22(s,2H),3.88(s,3H);
核磁共振碳谱(101MHz,CDCl3)δ157.71,136.46,133.76,132.52,129.98,129.23,128.88,128.81,127.56,127.33,127.18,126.40,118.96,105.75,55.33,39.37;
高分辨率质谱(ESI):m/z calcd for:280.0922,found 280.0925.。
实施例3
一种苄位硫醚类化合物8-((苯硫基)甲基)喹啉及其制备方法,具体步骤如下:
在手套箱中,在配备磁力搅拌棒的烘箱干燥螺旋盖8mL小瓶中装入甲基(喹啉-8-基甲基)草酸甲酯(0.2mmol)、硫代磺酸酯(0.24mmol)通过注射器加入NiBr2(5.0mol%)、配体1,10-菲咯啉(10mol%)、Mn(1.5equiv.)、DMSO(1mL),并将混合物在40℃下搅拌24h。24h后,将粗反应混合物用乙酸乙酯(20mL)稀释并用水(20mL×3)洗涤。有机层用Na2SO4干燥,过滤并浓缩。残余物通过快速色谱纯化,得到产物产率为63%。
对本实施例制备的化合物进行检测,检测结果如下所示:
红外光谱(neat,ν,cm-1):2921,2853,1725,1573,1472,1272,1071,793,728,688;
核磁共振氢谱(400MHz,CDCl3)δ9.00(dd,J=4.3,1.8Hz,1H),8.15(dd,J=8.2,1.8Hz,1H),7.74(dd,J=8.2,1.4Hz,1H),7.68(dd,J=7.1,1.4Hz,1H),7.49–7.44(m,1H),7.44–7.37(m,3H),7.27(dd,J=8.5,6.8Hz,2H),7.22–7.16(m,1H),4.90(s,2H);
核磁共振碳谱(101MHz,CDCl3)δ149.75,146.36,137.13,136.33,135.97,129.70,129.51,128.77,128.43,127.39,126.19,126.05,121.23,34.25;
高分辨率质谱(ESI):m/z calcd for:251.0769,found 251.0772。
实施例4
一种苄位硫醚类化合物(4-甲氧基苄基)(苯基)硫醚及其制备方法,具体步骤如下:
在手套箱中,在配备磁力搅拌棒的烘箱干燥螺旋盖8mL小瓶中装入4-甲氧基苄基草酸甲酯(0.2mmol)、硫代磺酸酯(0.24mmol)通过注射器加入NiBr2(5.0mol%)、配体1,10-菲咯啉(10mol%)、Mn(1.5equiv.)、DMSO(1mL),并将混合物在80℃下搅拌24h。24h后,将粗反应混合物用乙酸乙酯(20mL)稀释并用水(20mL×3)洗涤。有机层用Na2SO4干燥,过滤并浓缩。残余物通过快速色谱纯化,得到产物产率为54%。
对本实施例制备的化合物进行检测,检测结果如下所示:
红外光谱(neat,ν,cm-1):2920,1577,1504,1232,1029,824,734,688,472;
核磁共振氢谱(400MHz,CDCl3)δ7.37–7.32(m,2H),7.32–7.26(m,2H),7.27–7.18(m,3H),6.88–6.83(m,2H),4.11(s,2H),3.81(s,3H);
核磁共振碳谱(101MHz,CDCl3)δ158.75,136.55,129.95,129.75,129.36,128.83,126.26,113.90,55.28,38.44;
高分辨率质谱(ESI):m/z calcd for:230.0765,found 230.0771。
实施例5
一种苄位硫醚类化合物(3-氟苄基)(苯基)硫醚及其制备方法,具体步骤如下:
在手套箱中,在配备磁力搅拌棒的烘箱干燥螺旋盖8mL小瓶中装入3-氟苄基草酸甲酯(0.2mmol)、硫代磺酸酯(0.24mmol)通过注射器加入NiBr2(5.0mol%)、配体1,10-菲咯啉(10mol%)、Mn(1.5equiv.)、DMSO(1mL),并将混合物在80℃下搅拌24h。24h后,将粗反应混合物用乙酸乙酯(20mL)稀释并用水(20mL×3)洗涤。有机层用Na2SO4干燥,过滤并浓缩。残余物通过快速色谱纯化,得到产物产率为58%。
对本实施例制备的化合物进行检测,检测结果如下所示:
红外光谱(neat,ν,cm-1):2925,1615,1586,1480,1439,1255,1134,943,881,783,736,688,473;
核磁共振氢谱(400MHz,CDCl3)δ7.32–7.27(m,2H),7.27–7.20(m,3H),7.19–7.15(m,1H),7.05–6.96(m,2H),6.91(tdd,J=8.4,2.6,0.9Hz,1H),4.07(s,2H).;
核磁共振碳谱(101MHz,CDCl3)δ164.05,161.61,140.25,140.18,135.73,130.21,129.96,129.88,128.95,126.70,124.47,124.45,115.83,115.61,114.24,114.03,38.78;
高分辨率质谱(ESI):m/z calcd for:218.0565,found 218.0563。
实施例6
一种苄位硫醚类化合物3-((苯硫基)甲基)吡啶及其制备方法,具体步骤如下:
在手套箱中,在配备磁力搅拌棒的烘箱干燥螺旋盖8mL小瓶中装入(吡啶-3-基甲基)草酸甲酯(0.2mmol)、硫代磺酸酯(0.24mmol)通过注射器加入NiBr2(5.0mol%)、配体1,10-菲咯啉(10mol%)、Mn(1.5equiv.)、DMSO(1mL),并将混合物在80℃下搅拌24h。24h后,将粗反应混合物用乙酸乙酯(20mL)稀释并用水(20mL×3)洗涤。有机层用Na2SO4干燥,过滤并浓缩。残余物通过快速色谱纯化,得到产物产率为80%。
对本实施例制备的化合物进行检测,检测结果如下所示:
红外光谱(neat,ν,cm-1):2956,2926,1721,1577,1479,1438,1423,1266,1025,739,710,690,474;
核磁共振氢谱(400MHz,CDCl3)δ8.46(dd,J=5.0,1.8Hz,2H),7.58(dt,J=8.0,2.0Hz,1H),7.32–7.28(m,2H),7.28–7.23(m,2H),7.20(td,J=7.9,3.2Hz,2H),4.06(s,2H);
核磁共振碳谱(101MHz,CDCl3)δ149.89,148.45,136.24,134.93,133.48,130.74,129.02,127.04,123.36,36.50;
高分辨率质谱(ESI):m/z calcd for:201.0612,found 201.0616。
显然,上述实施例仅仅是为清楚地说明所作的举例,并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引申出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
2.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,所述草酸酯为(萘-2-基甲基)草酸甲酯、(6-甲氧基萘-2-基)甲基草酸甲酯、(萘-1-基甲基)草酸甲酯、(喹啉-6-基甲基)草酸甲酯、(喹啉-7-基甲基)草酸甲酯、甲基(喹啉-8-基甲基)草酸甲酯、(6-((环丙烷羰基)氧基)萘-2-基)甲基草酸甲酯、(6-((环丁烷羰基)氧基)萘-2-基)甲基草酸甲酯、((6-(新戊酰氧基)萘-2-基)甲基)草酸甲酯、4-甲氧基苄基草酸甲酯、3-氟苄基草酸甲酯、(吡啶-3-基甲基)草酸甲酯、(噻吩-2-基甲基)草酸甲酯和3,4-二甲氧基苄基草酸甲酯中的一种或多种。
3.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,所述催化剂为卤化镍;所述卤化镍为溴化镍和/或氯化镍。
4.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,所述还原剂为锰和/或锌。
5.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,所述配体为1,10-菲咯啉或其衍生物。
6.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,所述溶剂为二甲亚砜、N,N,-二甲基甲酰胺和N,N-二甲基乙酰胺中的一种或多种。
7.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,草酸酯、硫源和还原剂的摩尔比为1-2:1-2:1-5;所述催化剂和配体的用量均为草酸酯摩尔量的0.1-20%或硫源摩尔量的0.1-20%。
8.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,所述反应是40-80℃反应20-24h。
9.根据权利要求1所述的苄位硫醚类化合物的制备方法,其特征在于,所述保护气氛的气体为氩气。
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CN114933556A (zh) * | 2022-07-26 | 2022-08-23 | 苏州照固新材料科技有限公司 | 一种硫醚化合物的制备方法 |
CN115477600A (zh) * | 2022-09-15 | 2022-12-16 | 浙江理工大学 | 一种苄基硫醚化合物的制备方法 |
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CN114835615B (zh) * | 2022-05-26 | 2023-08-22 | 南京工业大学 | 一种有机硫化合物及其制备方法 |
CN114933556A (zh) * | 2022-07-26 | 2022-08-23 | 苏州照固新材料科技有限公司 | 一种硫醚化合物的制备方法 |
CN114933556B (zh) * | 2022-07-26 | 2022-12-02 | 苏州照固新材料科技有限公司 | 一种硫醚化合物的制备方法 |
CN115477600A (zh) * | 2022-09-15 | 2022-12-16 | 浙江理工大学 | 一种苄基硫醚化合物的制备方法 |
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