CN113200812B - 1,3,5-三取代芳基化合物的合成方法 - Google Patents
1,3,5-三取代芳基化合物的合成方法 Download PDFInfo
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- -1 aryl compound Chemical class 0.000 title claims abstract description 36
- 238000001308 synthesis method Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 claims abstract description 22
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 125000001424 substituent group Chemical group 0.000 claims abstract description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 14
- 239000000654 additive Substances 0.000 claims description 14
- 230000000996 additive effect Effects 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- 230000002194 synthesizing effect Effects 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- 241000282326 Felis catus Species 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 3
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 20
- 230000015572 biosynthetic process Effects 0.000 abstract description 18
- 238000010189 synthetic method Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
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- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 10
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- 239000000243 solution Substances 0.000 description 10
- 238000000605 extraction Methods 0.000 description 7
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- 241001274216 Naso Species 0.000 description 6
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- 239000012141 concentrate Substances 0.000 description 6
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- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- RJNKCFNBMXDQRC-UHFFFAOYSA-N 1,3,5-tris(4-butylphenyl)benzene Chemical compound C(CCC)C1=CC=C(C=C1)C1=CC(=CC(=C1)C1=CC=C(C=C1)CCCC)C1=CC=C(C=C1)CCCC RJNKCFNBMXDQRC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- ZASXCTCNZKFDTP-UHFFFAOYSA-N 1-ethynyl-3-methoxybenzene Chemical group COC1=CC=CC(C#C)=C1 ZASXCTCNZKFDTP-UHFFFAOYSA-N 0.000 description 1
- CGHIBGNXEGJPQZ-UHFFFAOYSA-N 1-hexyne Chemical compound CCCCC#C CGHIBGNXEGJPQZ-UHFFFAOYSA-N 0.000 description 1
- KQDJTBPASNJQFQ-UHFFFAOYSA-N 2-iodophenol Chemical compound OC1=CC=CC=C1I KQDJTBPASNJQFQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 238000006006 cyclotrimerization reaction Methods 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2/00—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms
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- C07C2/42—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by addition between unsaturated hydrocarbons homo- or co-oligomerisation with ring formation, not being a Diels-Alder conversion
- C07C2/48—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by addition between unsaturated hydrocarbons homo- or co-oligomerisation with ring formation, not being a Diels-Alder conversion of only hydrocarbons containing a carbon-to-carbon triple bond
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- C07C17/278—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions of only halogenated hydrocarbons
- C07C17/281—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions of only halogenated hydrocarbons of only one compound
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- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C67/347—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
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Abstract
Description
技术领域
本发明属于有机合成领域,具体涉及一种1,3,5-三取代芳基化合物的合成方法。
背景技术
近年来通过氢键相互作用控制反应区域选择性的应用实例相继报道,我们希望将该策略引入末端炔烃的环化聚合反应中以解决长久以来存在的区域选择性问题。1,3,5-三取代的芳基化合物是一类重要的分子骨架,它广泛应用于材料科学和生物医药领域,而且某些天然产物的合成也经常用到分子内的炔烃环加成策略。目前,研究者们已经开发出了由末端炔烃出发构建1,2,4-三取代芳基化合物有效的方法,然而多数涉及计算方面的文章已经证明末端炔烃环化聚合时由于金属中间体插入炔烃面临的多种位点选择性以及后续转化的能垒问题而难以形成1,3,5-三取代芳基化合物。
尽管近二十年来有文献报道通过单一末端炔烃合成了1,3,5-三取代苯的衍生物,但是其往往区域选择性差或者极大地受到底物适用性和苛刻的反应条件的限制,因此双分子末端炔烃的高区域选择性环化聚合是一项更大的挑战。2001年江课题组报道了该类反应(如式(I)示出)。该反应体系以氯化钯为催化剂,加入当量的氯化亚铜做添加剂,在丁醇和苯的混合溶剂下实现了炔烃的环化三聚反应。2010年,王课题组同样报道了该类反应(如式(II)示出)。选用氯化铟作为催化剂,2-碘苯酚在该反应中做添加剂,在氯苯中回流即可实现末端炔烃的环化聚合反应。从上述两个反应中,我们可以发现,前者课题组所用的催化剂较为昂贵,当量的铜盐也使得反应后处理过程繁琐化。而后者课题组则需要使用毒性较强的溶剂和对空气敏感的氯化铟,并且他们的研究工作中均未实现不同分子间的区域选择性环化产物。以上两种方法的底物适用性和苛刻的反应体系极大地限制了这些方法的大规模应用。因此,发展更实用、更高效的合成1,3,5-三取代苯的方法仍然是很重要和迫切的。
发明内容
本发明的目的在于提供一种1,3,5-三取代芳基化合物的合成方法。
为实现上述目的,本发明采用的技术方案为:
一种1,3,5-三取代芳基化合物的合成方法,采用下式(I I I)进行;
其中,R,R1,R2为任何取代基,X为C-R3,其中R3为H或者其他任意取代基。
优选的R3为H。
催化剂为镍催化剂;添加剂为含硼试剂、或者锌试剂。
优选的催化剂为NiCl2(PPh3)2、NiCl2·DME、Ni(acac)2、NiCO3、NiCl2·6H2O或者NiNO3·6H2O;添加剂为B2(OH)4、B2cat2、Zn/B(OH)3或者Zn。
催化剂与添加剂的摩尔比为1-1.5:1-3。
催化剂与添加剂的摩尔比为1:3。
镍催化剂的用量为大于或等于0.01equiv原料,添加剂的用量为大于或等于0.03equiv原料。
溶剂为DCM,二甲基亚砜DMSO,MeCN,N,N-二甲基甲酰胺DMF,四氢呋喃THF中的一种。
R、R1以及R2可以相同,也可以不同。
化合物1与化合物2相同,且与化合物3不同;当其中化合物1或者2为丙炔酸乙酯时,化合物1:化合物3的摩尔比为3:2,当化合物1、化合物2以及化合物3均不是丙炔酸乙酯,化合物1与化合物3的投料的摩尔比为2:1。
具体包括下述步骤:加入催化剂以及添加剂于反应瓶内,惰性气体置换,然后加入溶剂,之后常温滴加炔烃原料后,将反应管进行加热;待反应完全后,旋蒸萃取,柱层析分离。加热温度为80-120℃。
与现有技术相比,本发明的有益效果是:
本发明实现了一种新的合成1,3,5-三取代的芳基化合物的方法。该方法对底物的适用范围广阔,区域选择性高,可以实现两分子的高区域选择性交叉聚合,极大地促进了1,3,5-三取代的芳基化合物的规模化生产和应用。
具体实施方式
为了使本技术领域的技术人员更好地理解本发明的技术方案,下面结合最佳实施例对本发明作进一步的详细说明。
实施例1:1,3,5-三取代苯化合物(2a)的合成:(MeCN作为溶剂用于三取代芳基化合物2a的合成)。
取磁子于25mL Schlenk瓶中,加入NiCl2·DME(22.0mg,0.1mmol,0.1equiv),B2(OH)4(26.9mg,0.3mmol,0.3equiv)于反应瓶内,在双排管上用氩气置换三次,然后加入MeCN(5.0mL),用微量注射器滴加苯乙炔(1a,110.0μL,1.0mmol,1.0equiv)后,将反应管移入油浴锅内于100℃下反应12小时。待反应完全后,将反应液转移至圆底烧瓶中,旋蒸除去乙腈溶剂,然后加入5mL水,用10mL乙酸乙酯萃取,水相用乙酸乙酯(5mL x 3)萃取三次,合并有机相,有机相分别用10mL水,饱和氯化钠水溶液(10mL x 2)洗涤,然后用无水NaSO4干燥,过滤,将过滤后的有机相旋蒸,旋蒸后的浓缩液转移至硅胶柱中,通过柱层析(PE)得到纯产物94.5mg(白色固体)。产率:93%。1H NMR(400MHz,CDCl3)δ7.83(s,3H),7.75(d,J=7.7Hz,6H),7.52(t,J=7.6Hz,6H),7.43(t,J=7.0Hz,3H).13C NMR(101MHz,CDCl3)δ142.5,141.3,129.0,127.7,127.5,125.3.
实施例2:1,3,5-三取代苯化合物(2a)的合成:(THF作为溶剂用于三取代芳基化合物2a的合成)。
取磁子于25mL Schlenk瓶中,加入NiCl2·DME(22.0mg,0.1mmol,0.1equiv),B2(OH)4(26.9mg,0.3mmol,0.3equiv)于反应瓶内,在双排管上用氩气置换三次,然后加入THF(5.0mL),用微量注射器滴加苯乙炔(1a,110.0μL,1.0mmol,1.0equiv)后,将反应管移入油浴锅内于80℃下反应12小时。待反应完全后,将反应液转移至圆底烧瓶中,旋蒸除去THF,然后加入5mL水,用10mL乙酸乙酯萃取,水相用乙酸乙酯(5mL x 3)萃取三次,合并有机相,有机相分别用10mL水,饱和氯化钠水溶液(10mL x 2)洗涤,然后用无水NaSO4干燥,过滤,将过滤后的有机相旋蒸,旋蒸后的浓缩液转移至硅胶柱中,通过柱层析(PE)得到混合产物70mg(白色固体),其中1,3,5-三取代苯:1,2,4-三取代苯的比例为3:2,产率:69%。
实施例3:1,3,5-三取代苯化合物(2a)的合成:(DMF作为溶剂用于三取代芳基化合物2a的合成)。
取磁子于25mL Schlenk瓶中,加入NiCl2·DME(22.0mg,0.1mmol,0.1equiv),B2(OH)4(26.9mg,0.3mmol,0.3equiv)于反应瓶内,在双排管上用氩气置换三次,然后加入DMF(5.0mL),用微量注射器滴加苯乙炔(1a,110.0μL,1.0mmol,1.0equiv)后,将反应管移入油浴锅内于80℃下反应12小时。待反应完全后,将反应液转移至圆底烧瓶中,然后加入5mL水,用10mL乙酸乙酯萃取,水相用乙酸乙酯(5mL x 3)萃取三次,合并有机相,有机相分别用10mL水,饱和氯化钠水溶液(10mL x 2)洗涤,然后用无水NaSO4干燥,过滤,将过滤后的有机相旋蒸,旋蒸后的浓缩液转移至硅胶柱中,通过柱层析(PE)得到混合产物38.7mg(白色固体),其中1,3,5-三取代苯:1,2,4-三取代苯的比例为4:1,产率:38%。
实施例4:1,3,5-三取代苯化合物(2a)的合成:(B2cat2作为添加剂用于三取代芳基化合物2a的合成)。
取磁子于25mL Schlenk瓶中,加入NiCl2·DME(22.0mg,0.1mmol,0.1equiv),B2(cat)2(71.34mg,0.3mmol,0.3equiv)于反应瓶内,在双排管上用氩气置换三次,然后加入THF(5.0mL),用微量注射器滴加苯乙炔(110.0μL,1.0mmol,1.0equiv)后,将反应管移入油浴锅内于80℃下反应12小时。待反应完全后,将反应液转移至圆底烧瓶中,旋蒸除去THF,然后加入5mL水,用10mL乙酸乙酯萃取,水相用乙酸乙酯(5mL x 3)萃取三次,合并有机相,有机相分别用10mL水,饱和氯化钠水溶液(10mL x 2)洗涤,然后用无水NaSO4干燥,过滤,将过滤后的有机相旋蒸,旋蒸后的浓缩液转移至硅胶柱中,通过柱层析(PE)得到混合产物30.6mg(白色固体),其中1,3,5-三取代苯:1,2,4-三取代苯的比例为7:1,产率:30%。
实施例5:3,5-二丁基-3'-甲氧基-1,1'-联苯化合物(3a)的合成
取磁子于25mL Schlenk瓶中,加入NiCl2·DME(33.0mg,0.15mmol,0.15equiv),B2(OH)4(40.4mg,0.45mmol,0.45equiv),间甲氧基苯乙炔(2',66.1mg,0.5mmol,0.5equiv)于反应瓶内,在双排管上用氩气置换三次,然后加入MeCN(7.0mL),用微量注射器滴加正己炔(1,115.0μL,1.0mmol,1.0equiv)后,将反应管移入油浴锅内于100℃下反应12小时。待反应完全后,将反应液转移至圆底烧瓶中,旋蒸除去乙腈溶剂,然后加入5mL水,用10mL乙酸乙酯萃取,水相用乙酸乙酯(5mL x 3)萃取三次,合并有机相,有机相分别用10mL水,饱和氯化钠水溶液(10mL x 2)洗涤,然后用无水NaSO4干燥,过滤,将过滤后的有机相旋蒸,旋蒸后的浓缩液转移至硅胶柱中,通过柱层析(PE/EA=30/1)得到纯产物119.3mg(无色油状物)。产率:80%。1H NMR(600MHz,CDCl3)δ7.35(t,J=7.9Hz,1H),7.22(d,J=1.6Hz,2H),7.21–7.16(m,1H),7.14–7.12(m,1H),7.01(s,1H),6.91–6.87(m,1H),3.88(s,3H),2.65(t,J=7.8Hz,4H),1.68-1.62(m,4H),1.43–1.36(m,4H),0.95(t,J=7.4Hz,6H).13C NMR(151MHz,CDCl3)δ160.0,143.4,141.1,129.7,128.0,124.9,120.0,113.2,112.5,55.5,35.9,33.9,22.6,14.1.HRMS(ESI)m/z:[M+H]+Calcd for C21H29O2 +297.2213;Found 297.2212.
实施例6:[1,1':3',1”-三苯基]-5'-羧酸乙酯(3e)的合成
取磁子于50mL Schlenk瓶中,加入NiCl2·DME(43.9mg,0.2mmol,0.2equiv),B2(OH)4(53.8mg,0.6mmol,0.6equiv)于反应瓶内,在双排管上用氩气置换三次,然后加入MeCN(10.0mL),用微量注射器滴加苯乙炔(1a,88.0μL,0.8mmol,0.8equiv)和丙炔酸乙酯(1',121.0μL,1.2mmol,1.2equiv)将反应管移入油浴锅内于100℃下反应12小时。待反应完全后,将反应液转移至圆底烧瓶中,旋蒸除去乙腈溶剂,然后加入5mL水,用10mL乙酸乙酯萃取,水相用乙酸乙酯(5mL x 3)萃取三次,合并有机相,有机相分别用10mL水,饱和氯化钠水溶液(10mL x 2)洗涤,然后用无水NaSO4干燥,过滤,将过滤后的有机相旋蒸,旋蒸后的浓缩液转移至硅胶柱中,通过柱层析(PE/EA=30/1)得到纯产物78.7mg(白色固体)。产率:65%。1H NMR(600MHz,CDCl3)δ8.27(d,J=1.8Hz,2H),7.99(t,J=1.8Hz,1H),7.80–7.62(m,4H),7.53–7.46(m,4H),7.46–7.34(m,2H),4.45(q,J=7.1Hz,2H),1.44(t,J=7.1Hz,3H).13CNMR(151MHz,CDCl3)δ166.7,142.2,140.4,131.7,130.4,129.1,128.0,127.4,127.2,61.3,14.5.
实施例7:1,3,5-三(4-正丁基苯基)苯(2b)化合物的合成
该反应步骤和实施例1中反应步骤相类似,通过柱层析(PE)得到纯产物142.1mg(无色油状物)。产率:90%。1H NMR(400MHz,CDCl3)δ7.90(s,3H),7.75(d,J=7.2Hz,6H),7.42(d,J=7.3Hz,6H),2.81(t,J=7.3Hz,6H),1.94–1.71(m,6H),1.55(q,J=7.0Hz,6H),1.11(t,J=7.0Hz,9H).13C NMR(101MHz,CDCl3)δ142.4,142.3,138.8,129.0,127.3,124.7,35.5,33.8,22.6,14.1.
实施例8:1,3,5-三(4-甲氧羰基苯基)苯化合物(2c)的合成
该反应步骤和实施例1中反应步骤相类似,通过柱层析(PE/EA=10:1)得到纯产物145.2mg(黄色油状物)。产率:91%。1H NMR(600MHz,CDCl3)δ8.16(d,J=8.4Hz,6H),7.85(s,3H),7.76(d,J=8.5Hz,6H),3.96(s,9H).13C NMR(151MHz,CDCl3)δ167.0,145.1,141.8,130.4,129.6,127.4,126.2,52.4.
实施例9:1,3,5-三己基苯化合物(2q)的合成
该反应步骤和实施例1中反应步骤相类似,通过柱层析(PE)得到纯产物86.4mg(无色油状物)。产率:70%。1H NMR(400MHz,CDCl3)δ6.73(s,3H),2.46(t,J=7.6Hz,6H),1.44–1.64(m,6H),1.06–1.43(m,18H),0.81(t,9H).13C NMR(101MHz,CDCl3)δ142.8,126.0,36.2,31.9,31.7,29.3,22.8,14.2.
实施例10:5'-丁基-4,4”-二甲氧基-1,1':3',1”-三联苯(3b)的合成
该反应步骤和实施例5中反应步骤相类似,通过柱层析(PE/EA=10/1)得到纯产物129.4mg(无色油状物)。产率:75%。1H NMR(400MHz,CDCl3)δ7.62–7.56(m,4H),7.54(t,J=1.7Hz,1H),7.32(d,J=1.6Hz,2H),7.05–6.96(m,4H),3.87(s,6H),2.72(t,J=7.8Hz,2H),1.91–1.61(m,2H),1.48–1.36(m,2H),0.96(t,J=7.3Hz,3H).13C NMR(101MHz,CDCl3)δ159.2,143.9,141.4,134.1,128.4,125.6,122.9,114.3,55.5,36.0,34.0,22.6,14.2.HRMS(ESI)m/z:[M+H]+Calcd for C24H27O2 +347.2011;Found 347.2013.
实施例11:4,4”-二溴-[1,1':3',1”-三苯基]-5'-羧酸乙酯化合物(3e)的合成
该反应步骤和实施例6中反应步骤相类似,通过柱层析(PE/EA=30/1)得到纯产物124.5mg(黄色固体)。产率:68%。1H NMR(400MHz,CDCl3)δ8.22(d,J=1.8Hz,2H),7.91–7.86(m,1H),7.61(d,J=8.5Hz,4H),7.53(d,J=8.5Hz,4H),4.44(q,J=7.2Hz,2H),1.44(t,J=7.1Hz,3H).13C NMR(101MHz,CDCl3)δ166.3,141.2,139.1,132.3,132.1,129.8,129.0,127.3,122.5,61.5,14.5.HRMS(ESI)m/z:[M+H]+Calcd for C21H17Br2O2 +458.9590;Found458.9595.
其他1,3,5-三取代芳基化合物的制备方法同实施例1,例5,例6类似,产物及其收率如表1示出。
表1
有多种实施产物可以看出本发明实现了一种新的合成1,3,5-三取代芳基化合物的方法。该方法对底物适用范围广,区域选择性好,收率高,且不需要额外添加配体和碱,极大地促进了1,3,5-三取代芳基化合物的规模化生产和应用。
1,3,5-三取代芳基化合物在不同条件下的收率及比例如表2所示。
表2
双分子环化聚合反应物投料比例的条件筛选如表3所示。
表3
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (7)
1.一种1,3,5-三取代芳基化合物的合成方法,其特征在于,采用下式(III)进行;
(III);
其中,R ,R1 ,R2为相同取代基时,R为烷基、苯基、硅烷基、噻吩基、烯基,苄基甲氧基或者取代的苯基;苯基的取代基为烷基、卤素、氨基、烷氧羰基、三氟甲基、或者苄氧基;
其中,R ,R1为相同取代基时,R2为与R ,R1不相同取代基时,R为烷基、苯基或者取代的苯基;苯基的取代基为甲氧基、烷基或者卤素;R2为硅烷基、烷基、烯基、或者烷氧羰基;
X为C-R3,其中R3为H;
催化剂为NiCl2·DME,所述的添加剂为B2(OH)4,所述的溶剂为CH3CN。
2.根据权利要求1所述的1,3,5-三取代芳基化合物的合成方法,其特征在于,所述的催化剂替换为NiCl2(PPh3)2、Ni(acac)2、或者NiCl2·6H2O。
3.根据权利要求1所述的1,3,5-三取代芳基化合物的合成方法,其特征在于,所述的添加剂替换为B2cat2、或者Zn。
4.根据权利要求1所述的1,3,5-三取代芳基化合物的合成方法,其特征在于,所述的溶剂替换为N,N-二甲基甲酰胺或者四氢呋喃。
5.根据权利要求1所述的1,3,5-三取代芳基化合物的合成方法,其特征在于,催化剂与添加剂的摩尔比为1-1.5:1-3。
6.根据权利要求1所述的1,3,5-三取代芳基化合物的合成方法,其特征在于,镍催化剂的用量为大于或等于0.01 equiv原料,添加剂的用量为大于或等于0.03 equiv原料。
7.根据权利要求1所述的1,3,5-三取代芳基化合物的合成方法,其特征在于,催化剂与添加剂的摩尔比为1:3。
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