CN110204465B - 光催化合成高烯丙基胺类化合物的方法 - Google Patents
光催化合成高烯丙基胺类化合物的方法 Download PDFInfo
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- -1 homoallylamine compound Chemical class 0.000 title claims abstract description 31
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- 230000015572 biosynthetic process Effects 0.000 claims abstract description 18
- 238000005286 illumination Methods 0.000 claims abstract description 13
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
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- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- YVJPMMYYRNHJAU-UHFFFAOYSA-N chembl1206021 Chemical group C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)[N+]([O-])=O)=C1 YVJPMMYYRNHJAU-UHFFFAOYSA-N 0.000 claims description 9
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- 229910052736 halogen Inorganic materials 0.000 claims description 6
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- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
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- 239000003960 organic solvent Substances 0.000 claims description 4
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
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- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
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- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 8
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- IICCLYANAQEHCI-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 IICCLYANAQEHCI-UHFFFAOYSA-N 0.000 description 1
- SSULGNXFUGLULI-UHFFFAOYSA-N 4-chloro-3-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC(S(Cl)(=O)=O)=CC=C1Cl SSULGNXFUGLULI-UHFFFAOYSA-N 0.000 description 1
- 229930188224 Cryptophycin Natural products 0.000 description 1
- ZPLVYYNMRMBNGE-UHFFFAOYSA-N Eponemycin Natural products CC(C)CCCCC(=O)NC(CO)C(=O)NC(CC(C)=C)C(=O)C1(CO)CO1 ZPLVYYNMRMBNGE-UHFFFAOYSA-N 0.000 description 1
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- 125000000304 alkynyl group Chemical group 0.000 description 1
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- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
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- 108010006226 cryptophycin Proteins 0.000 description 1
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 description 1
- PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 description 1
- PFWWSGFPICCWGU-UHFFFAOYSA-N cyclopropanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CC1 PFWWSGFPICCWGU-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
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- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- ZPLVYYNMRMBNGE-TWOQFEAHSA-N eponemycin Chemical compound CC(C)CCCCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)=C)C(=O)[C@@]1(CO)CO1 ZPLVYYNMRMBNGE-TWOQFEAHSA-N 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- ZHLNJOPWJGYFKU-UHFFFAOYSA-N n-but-3-enyl-n,4-dimethylbenzenesulfonamide Chemical compound C=CCCN(C)S(=O)(=O)C1=CC=C(C)C=C1 ZHLNJOPWJGYFKU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000005245 nitryl group Chemical group [N+](=O)([O-])* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical compound C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 1
- 229930187593 rose bengal Natural products 0.000 description 1
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- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
-
- 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
- C07D215/16—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
本发明提供了一种光催化合成高烯丙胺类化合物的方法，该方法是以N‑取代基4‑羟基哌啶化合物为原料，在光照和光敏剂催化下与磺酰氯反应，得到高烯丙基胺类化合物。本发明利用茜素黄R钠盐为光敏剂，家用LED白光灯为光源即可完成反应，具有合成成本低，效率高；合成过程操作简洁，反应条件温和，产率高的优点。
Description
技术领域
本发明涉及一种高烯丙基胺类化合物的合成方法，尤其涉及一种光催化合成高烯丙基胺类化合物的方法，属于化学合成技术领域。
背景技术
高烯丙基胺类化合物广泛存在于天然产物中，且高烯丙基胺类化合物还是非常重要的有机合成中间体被广泛的应用于氨基酸、各种杂环化合物、医药产品和天然产物[Chem. Rev. 2013, 113, 5595. ]的合成当中[Chem. Commun.2000, 18, 1771]。特别高烯丙基胺类的一些化合物本身具有药物活性如有抗癌活性的Cryptophycin 337[Tetrahedron. 2000, 56, 3339]、抑制黑色素瘤B 16的Eponemycin [Synthesis. 1994,3, 300], 且高烯丙基胺类化合物易于修饰转换为其他基团的化合物，所以近年也是药物化学领域研究的闪光点。已有高烯丙基胺类衍生药物用于临床，如广谱抗生素万古胺[Angew.Chem. Int. Ed. 1998, 37, 1871]。常用的高烯丙基胺的制取方法是亲核性的烯丙基试剂对C=N双键进行加成，而已报道出高烯丙胺类化合物的合成方法非常多，主要包括：(1)有机金属试剂参与的高烯丙基胺的合成如烯丙基Mg试剂对亚胺进行加成反应[J. Am. Chem. Soc. 1984, 106, 5031]；(2)烯丙基硅试剂对亚胺的加成反应[J. Am. Chem. Soc. 2002, 124, 7920]；(3)其他高烯丙基胺的制备方法如醛催化烯丙基化合物的α-氨基阴离子等价物的胺化反应[Org. Lett.2014, 16 , 720]。本发明的高烯丙胺类化合物的合成方法，其高烯丙胺化合物结构如下式所示：
该化合物中含有一个C-C双键，其可以为化合物链中双键或末端双键。R为烷基、取代烷基、芳香基、取代芳香基中的任何一种或几种。芳基可以是苯，以及被各种卤素、烷基、烷氧基、硝基和其他芳基等基团取代的苯、联苯、萘等芳香族化合物基团，芳香环上的取代位置可以是对位、邻位或间位，也可以为单取代或多取代。
R1可以为烷基、芳基，R2可以为氢、烷基、芳基、苄基、硝基、卤素、酯基中的任何一种或几种。
发明内容
本发明的目的是提供一种光催化合成高烯丙胺类化合物的方法。
本发明高烯丙基胺类化合物的合成方法，是以磺酰氯与N-取代基的4-羟基哌啶化合物为原料，在光照和光敏剂催化下，于无水有机溶剂中和氮气保护下，室温反应24~48小时，再经柱层析分离纯化而得。
合成原理：通过N-取代的4-羟基哌啶与磺酰氯在光照下的反应合成了高烯丙基胺类化合物。其合成式如下：
其中磺酰氯为脂肪族磺酰氯，苯系芳香族磺酰氯。式中，R为烷基、取代烷基、芳香基、取代芳香基中的任何一种或几种；其中R所述的烷基为C1-C20，如甲基、乙基、丙基、异丙基、正丁基、仲丁基、叔丁基等；取代芳香基为卤素、硝基、烷氧基、苄氧基、乙烯基、炔基或烷基所取代的基团，在芳香环上的位置为对位、邻位或间位，可以为单取代或多取代。
R1为烷基、芳基，R2可以为氢、烷基、芳基、苄基、硝基、卤素、酯基中的任何一种或几种。
磺酰氯与N-取代基的4-羟基哌啶化合物以1:1.2的摩尔比配比。
光照光源为可见光。光催化剂采用茜素黄R、曙红Y、溶剂红、孟加拉玫瑰红，光催化剂用量为磺酰氯摩尔量的5~10%。
有机溶剂采用乙腈、甲苯、二氯乙烷、1,4-二氧六环、N,N-二甲基甲酰胺、四氢呋喃、二甲亚砜等溶剂或混合溶剂。
本发明制备的产物经波谱表征，确证了所合成的化合物即为目标化合物。
本发明合成方法相对现有技术具有以下优点：
1、采用廉价易得的光敏剂作为催化剂在光照条件下完成反应，成本低，效率高；
2、合成过程操作简洁，不使用过渡金属催化符合经济环保，反应条件温和，合成产率高；
3、开发了一种不使用强亲核性有机金属试剂参与反应的高烯丙基胺类化合物的合成方法。
具体实施方式
下面通过具体实施例对本发明的化合物的合成做进一步的说明。
实施例1：N-(丁-3-烯-1-基)-N,4-二甲基苯磺酰胺的合成
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取1-甲基哌啶-4-醇（138mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈，用注射器打入反应管，搅拌20分钟后将对甲基苯磺酰氯（19mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品179mg，产率75%。
光谱数据：1H NMR (600 MHz, CDCl3) δ (ppm):7.66 (d, J = 8.1 Hz, 2H),7.30 (d, J = 8.1 Hz, 2H), 5.75 (d, J = 6.8 Hz, 1H), 5.17 – 5.00 (m, 2H), 3.06(t, J = 7.4 Hz, 2H), 2.72 (s, 3H), 2.42 (s, 2H), 2.28 (q, J = 7.1 Hz, 2H).13CNMR (151 MHz, CDCl3) δ (ppm):143.3 , 134.7 , 134.6 , 129.6 , 127.4 , 117.1 ,49.6 , 34.8 , 32.3 , 21.5。
实施例2：N-(丁-3-烯-1-基)-4-氯-N-甲基-3-(三氟甲基)苯磺酰胺的合成
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取1-甲基哌啶-4-醇（138mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈并用注射器打入反应管，搅拌20分钟后将对氯间三氟甲基苯磺酰氯（279mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品252mg，产率77%。
光谱数据：1H NMR (600 MHz, CDCl3) δ (ppm):8.08 (d, J = 1.9 Hz, 1H),7.89 (dd, J = 8.4, 2.0 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 5.81 – 5.65 (m,1H), 5.14 – 5.01 (m, 2H), 3.14 (t, J = 7.3 Hz, 2H), 2.79 (s, 2H), 2.32 (q, J= 7.0 Hz, 2H).13C NMR (151 MHz, CDCl3) δ (ppm):137.5 , 137.0 , 134.0 , 132.4 ,131.4 , 129.5 (q, J = 32.4 Hz), 126.5 (q, J = 5.4 Hz), 122.0 (q, J = 274.0Hz), 117.6 , 49.6 , 34.64 , 32.3。
实施例3：N-(丁-3-烯-1-基)-N-甲基环丙烷磺酰胺的合成
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取1-甲基哌啶-4-醇（138mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈用注射器打入反应管，搅拌20分钟后将环丙基磺酰氯（140mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品121mg，产率64%。
光谱数据：1H NMR (600 MHz, CDCl3) δ (ppm):5.83 – 5.69 (m, 1H), 5.17 –5.01 (m, 2H), 3.32 – 3.19 (m, 4H), 2.89 (s, 5H), 2.35 (q, J = 7.0 Hz, 4H),2.32 – 2.18 (m, 1H), 1.18 – 1.14 (m, 5H), 0.97 – 0.93 (m, 5H).13C NMR (151MHz, CDCl3) δ (ppm):134.6 , 117.1 , 49.6 , 34.8 , 32.6 , 27.1 , 4.5。
实施例4：N-(丁-3-烯-1-基)-N-乙基萘-2-磺酰胺的合成
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取1-乙基哌啶-4-醇（154mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈用注射器打入反应管，搅拌20分钟后将2-萘磺酰氯（227mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品232mg，产率80%。
光谱数据：1H NMR (600 MHz, CDCl3) δ (ppm):8.39 (s, 1H), 7.95 (t, J =8.7 Hz, 2H), 7.90 (d, J = 7.8 Hz,2H), 7.79 (dd, J = 8.6, 1.8 Hz, 1H), 7.66 –7.57 (m,2H), 5.74 (ddt, J = 17.0, 10.2, 6.8 Hz, 1H), 5.06 (dq, J = 17.2, 1.6Hz, 1H), 5.03 (dq, J = 10.2, 1.4 Hz, 1H), 3.33 – 3.29 (m, 2H), 3.29 – 3.25(m, 2H), 2.33 (q, J = 7.2 Hz,2H), 1.13 (t, J = 7.1 Hz, 3H).13C NMR (151 MHz,CDCl3) δ (ppm):137.2 , 134.7 , 132.2 , 129.3 , 129.1 , 128.6 , 128.2 , 127.8, 127.4 , 122.5 , 117.1 , 46.9 , 42.8 , 33.7 , 14.0。
实施例5：N-(丁-3-烯-1-基)-N-丙基苯磺酰胺的合成
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取1-丙基哌啶-4-醇（172mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈用注射器打入反应管，搅拌20分钟后将苯磺酰氯（176mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品195mg，产率77%。
光谱数据：1H NMR (600 MHz, CDCl3) δ (ppm):7.82 (d, J = 7.0 Hz, 2H),7.56 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 5.71 (ddt, J = 17.1,10.2, 6.8 Hz, 1H), 5.08 – 4.99 (m, 2H), 3.22 – 3.16 (m, 2H), 3.14 – 3.08 (m,2H), 2.29 (q, J = 7.2 Hz, 2H), 1.60 – 1.52 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H).13C NMR (600 MHz, CDCl3) δ (ppm):140.1 , 134.6 , 132.3 , 129.0 , 127.0 ,117.0 , 50.0 , 47.6 , 33.3, 21.9 , 11.1。
实施例6：N-(丁-3-烯-1-基)-N-喹啉-8-磺酰胺
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取1-丙基哌啶-4-醇（172mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈用注射器打入反应管，搅拌20分钟后将对8-喹啉磺酰氯（228mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品253mg，产率83%。
光谱数据：1H NMR (600 MHz, CDCl3) δ (ppm):9.05 (dd, J = 4.2, 1.8 Hz,1H), 8.50 (dd, J = 7.3, 1.4 Hz, 1H), 8.22 (dd, J = 8.3, 1.8 Hz, 1H), 8.00(dd, J = 8.2, 1.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.50 (dd, J = 8.3, 4.2Hz, 1H), 5.67 (ddt, J = 17.0, 10.2, 6.8 Hz, 1H), 4.96 (dq, J = 17.2, 1.6 Hz,1H), 4.91 (ddt, J = 10.2, 2.0, 1.2 Hz, 1H), 3.56 – 3.50 (m, 2H), 3.43 – 3.37(m, 2H), 2.26 (q, J = 7.3 Hz, 2H), 1.51 (h, J = 7.4 Hz,2H), 0.81 (t, J = 7.4Hz, 3H).13C NMR(151 MHz, CDCl3) δ (ppm):150.9 , 144.1 , 138.7 , 136.3 , 135.2, 133.0 , 132.6 , 128.9 , 125.4 , 121.8 , 116.5 , 50.2 , 47.8 , 33.6 , 22.0,11.1。
实施例7：(Z)-N-甲基-N-(戊-3-烯-1-基)噻吩-2-磺酰胺
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取1,3-二甲基哌啶-4-醇（154mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈用注射器打入反应管，搅拌20分钟后将噻吩-2-磺酰氯（182mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品191mg，产率78%。
光谱数据：1H NMR (600 MHz, CDCl3) δ (ppm): 7.58 (dd, J = 5.0, 1.3 Hz,1H), 7.54 (dd, J = 3.7, 1.4 Hz, 1H), 7.12 (dd, J = 5.0, 3.7 Hz, 1H), 5.56 –5.47 (m, 1H), 5.41 – 5.32 (m, 1H), 3.08 – 3.03 (m, 2H), 2.78 (s, 3H), 2.25(q, J = 7.2 Hz, 2H), 1.65 (dq, J = 6.4, 1.3 Hz, 3H).13C NMR (151 MHz, CDCl3) δ(ppm):131.7 , 131.4 , 127.9 , 127.4 , 126.8 , 50.33 , 34.9 , 31.2 , 18.0。
实施例8：（Z）-4-甲基-N-(戊-3-烯-1-基)-N-苯乙基苯磺酰胺的合成
在干燥的10ml反应管中加入氢化钙20mg作为干燥剂，通入氮气为反应体系创造无氧环境，取3-甲基-1-(2-苯乙基)哌啶-4-醇（263mg，1.2mmol），茜素黄R（5mol%）溶于1.5ml乙腈用注射器打入反应管，搅拌20分钟后将对甲基苯磺酰氯（191mg，1.0mmol）溶于1.5ml乙腈用注射器打入反应体系，在常温30w LED灯照射下反应24h，撤去光照，用饱和NH4Cl溶液（20ml）淬灭，并用乙酸乙酯（20ml×3次）萃取，保留有机相，用饱和NaCl水溶液洗一次。减压蒸去溶剂，快速柱层析分离得到产品271mg，产率79%。
光谱数据：1H NMR (600MHz，CDCl3) δ (ppm):7.70 (d, J = 8.3 Hz, 2H), 7.33(d, J = 8.0 Hz, 2H), 3.87 (dd, J = 12.1, 5.4 Hz, 1H), 2.83 (td, J = 12.2, 3.1Hz, 1H), 2.49 – 2.45 (m, 1H), 2.44 (s, 3H), 2.42 – 2.38 (m, 1H), 2.12 – 2.05(m, 2H), 1.97 – 1.89 (m, 2H), 1.39 (dt, J = 32.2, 13.3 Hz, 2H), 1.21 – 1.13(m, 1H).13C NMR (151 MHz, CDCl3) δ (ppm):143.0 , 138.5 , 137.1 , 129.6 , 128.7, 128.5 , 127.7 , 127.1 , 127.1 , 126.5 , 49.8 , 48.4 , 35.7 , 32.0 , 21.4 ,17.9。
Claims (6)
1.光催化合成高烯丙基胺类化合物的方法，是以磺酰氯与N-取代基的4-羟基哌啶化合物为原料，在光照和光敏剂催化下，在无水有机溶剂中和氮气保护条件下反应，再经柱层析分离纯化而得；
磺酰氯的结构式如下：
R为芳基、取代芳基；芳基为苯、联苯、萘，取代芳基为被卤素、烷基、烷氧基、硝基取代的苯、联苯、萘；
N-取代的4-羟基哌啶化合物的结构式如下：
所得高烯丙胺化合物结构式如下：
R1为烷基、芳基，R2为氢、烷基、芳基、苄基、硝基、卤素；
所述光敏剂为茜素黄R。
2.如权利要求1所述光催化合成高烯丙基胺类化合物的方法，其特征在于：磺酰氯与N-取代基的4-羟基哌啶化合物以1:1.2的摩尔比配比。
3.如权利要求1所述光催化合成高烯丙基胺类化合物的方法，其特征在于：所述有机溶剂为乙腈、甲苯、二氯乙烷、1,4-二氧六环、N,N-二甲基甲酰胺、四氢呋喃、二甲亚砜中的至少一种。
4.如权利要求1所述光催化合成高烯丙基胺类化合物的方法，其特征在于：光催化剂用量为磺酰氯摩尔量的5~10%。
5.如权利要求1所述光催化合成高烯丙基胺类化合物的方法，其特征在于：光照光源为可见光。
6.如权利要求1所述光催化合成高烯丙基胺类化合物的方法，其特征在于：所述反应是在室温24~48小时进行。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107954906A (zh) * | 2017-11-24 | 2018-04-24 | 西北师范大学 | 一种芳基磺酰叔胺类化合物的合成方法 |
| CN108440345A (zh) * | 2018-04-08 | 2018-08-24 | 西北师范大学 | 一种磺酰胺类化合物的制备方法 |
| CN108822002A (zh) * | 2018-06-21 | 2018-11-16 | 中南大学 | 一种超声辅助合成n-芳基磺酰胺的方法 |
-
2019
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107954906A (zh) * | 2017-11-24 | 2018-04-24 | 西北师范大学 | 一种芳基磺酰叔胺类化合物的合成方法 |
| CN108440345A (zh) * | 2018-04-08 | 2018-08-24 | 西北师范大学 | 一种磺酰胺类化合物的制备方法 |
| CN108822002A (zh) * | 2018-06-21 | 2018-11-16 | 中南大学 | 一种超声辅助合成n-芳基磺酰胺的方法 |
Non-Patent Citations (5)
| Title |
|---|
| Aminative Umpolung of Aldehydes to α‑Amino Anion Equivalents for Pd-Catalyzed Allylation: An Efficient Synthesis of Homoallylic Amines;Lei Ding等;《Org. Lett.》;20140117;第16卷(第3期);720-723页 * |
| Charge-Transfer Complex Promoted Regiospecific C-N Bond Cleavage of Vicinal Tertiary Diamines;Ying Fu等;《Adv. Synth. Catal.》;20180716;第360卷(第18期);3502-3506页 * |
| Strained Silacycles in Organic Synthesis: A New Reagent for the Enantioselective Allylation of Aldehydes;James W. A. Kinnaird等;《J. AM. CHEM. SOC.》;20020617;第124卷(第27期);7920-7921页 * |
| Very High 1,2-Asymmetric Induction in the Reaction of Allyl-9-BBN with Certain Imines. Evidence for a Stereoelectronic Effect To Enhance the Cram Selectivity;Yoshinori Yamamoto等;《Journal of the American Chemical Society》;19840831;第106卷(第17期);5031-5033页 * |
| 高烯丙基胺类化合物合成新方法的研究;丁磊;《中国优秀硕士学位论文 工程科技Ｉ辑》;20150215(第02期);全文 * |
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Effective date of registration: 20220118 Address after: Room 415, 4th floor, No.2 office building, sangyuan Road, Licheng District, Jinan City, Shandong Province Patentee after: Zhongxin konong (Shandong) Ecological Agriculture Co.,Ltd. Address before: 730070 No. 967 Anning East Road, Anning District, Gansu, Lanzhou Patentee before: Northwest Normal University |
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Denomination of invention: Photocatalytic synthesis of high allyl group amine compounds Effective date of registration: 20230426 Granted publication date: 20210511 Pledgee: Ji'nan rural commercial bank Limited by Share Ltd. high tech branch Pledgor: Zhongxin konong (Shandong) Ecological Agriculture Co.,Ltd. Registration number: Y2023980039258 |
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Address after: Room 304, Building 4, South District, Agricultural Academy of Sciences, No. 28 Sangyuan Road, Quanfu Street, Licheng District, Jinan City, Shandong Province, 250000 Patentee after: Shandong Zhongxin Kenong Life Technology Co.,Ltd. Address before: Room 415, 4th floor, No.2 office building, sangyuan Road, Licheng District, Jinan City, Shandong Province Patentee before: Zhongxin konong (Shandong) Ecological Agriculture Co.,Ltd. |