CN117736126A - Synthesis method of perfluoroalkyl-benzene sulfurized alkane - Google Patents
Synthesis method of perfluoroalkyl-benzene sulfurized alkane Download PDFInfo
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- CN117736126A CN117736126A CN202311655711.8A CN202311655711A CN117736126A CN 117736126 A CN117736126 A CN 117736126A CN 202311655711 A CN202311655711 A CN 202311655711A CN 117736126 A CN117736126 A CN 117736126A
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- 150000001335 aliphatic alkanes Chemical class 0.000 title claims abstract description 29
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000001308 synthesis method Methods 0.000 title abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 36
- -1 perfluoroalkyl iodide Chemical compound 0.000 claims abstract description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- 239000002904 solvent Substances 0.000 claims abstract description 28
- 150000001336 alkenes Chemical class 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 21
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000000047 product Substances 0.000 claims abstract description 20
- 239000000654 additive Substances 0.000 claims abstract description 18
- 230000000996 additive effect Effects 0.000 claims abstract description 18
- 125000005228 aryl sulfonate group Chemical group 0.000 claims abstract description 18
- 239000012043 crude product Substances 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 12
- 238000005406 washing Methods 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000004440 column chromatography Methods 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 238000005286 illumination Methods 0.000 claims abstract description 9
- 239000012299 nitrogen atmosphere Substances 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 16
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 14
- 229940077388 benzenesulfonate Drugs 0.000 claims description 9
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical compound CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 claims description 8
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- LDLDYFCCDKENPD-UHFFFAOYSA-N ethenylcyclohexane Chemical group C=CC1CCCCC1 LDLDYFCCDKENPD-UHFFFAOYSA-N 0.000 claims description 4
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims 9
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 239000002994 raw material Substances 0.000 abstract description 2
- 229910052731 fluorine Inorganic materials 0.000 description 10
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 8
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- PGRFXXCKHGIFSV-UHFFFAOYSA-N 1,1,1,2,2,3,3,4,4-nonafluoro-4-iodobutane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)I PGRFXXCKHGIFSV-UHFFFAOYSA-N 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 4
- 239000001294 propane Substances 0.000 description 4
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- XTGYEAXBNRVNQU-UHFFFAOYSA-N 1,1,1,2,2,3,3-heptafluoro-3-iodopropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)I XTGYEAXBNRVNQU-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000012834 electrophilic reactant Substances 0.000 description 1
- HGWXXIZVRRTDKT-UHFFFAOYSA-N ethyl 2,2-difluoro-2-iodoacetate Chemical compound CCOC(=O)C(F)(F)I HGWXXIZVRRTDKT-UHFFFAOYSA-N 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229940002661 lipitor Drugs 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 150000004812 organic fluorine compounds Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 238000007539 photo-oxidation reaction Methods 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 229940035613 prozac Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- OQVHGJGFGGDKAF-UHFFFAOYSA-N sulfosulfonylbenzene Chemical compound OS(=O)(=O)S(=O)(=O)C1=CC=CC=C1 OQVHGJGFGGDKAF-UHFFFAOYSA-N 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000004149 thio group Chemical group *S* 0.000 description 1
- GWIKYPMLNBTJHR-UHFFFAOYSA-M thiosulfonate group Chemical group S(=S)(=O)[O-] GWIKYPMLNBTJHR-UHFFFAOYSA-M 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses a synthesis method of perfluoroalkyl-benzene sulfurized alkane, which relates to the technical field of organic synthesis; the method comprises the following steps: s1, taking olefin, perfluoroalkyl iodide, arylsulfonate, an additive and a dimethyl sulfoxide solvent, placing the olefin, perfluoroalkyl iodide, arylsulfonate, the additive and the dimethyl sulfoxide solvent in a reaction container, and mixing; s2, continuously stirring and reacting for 4-8 hours at room temperature under the nitrogen atmosphere and under illumination; s3, after the reaction is finished, washing with water, extracting with ethyl acetate, drying, concentrating under reduced pressure to remove a solvent, and separating a crude product through column chromatography to obtain a perfluoroalkyl-phenylsulfurized alkane product; the synthesis method provided by the application has the advantages of simplicity, high efficiency, low cost and easy acquisition of raw materials, simplicity and convenience in operation, wide application range and environment friendliness.
Description
Technical Field
The application relates to the technical field of organic synthesis, in particular to a synthesis method of perfluoroalkyl-benzene sulfurized alkane.
Background
Because the fluorine atom has the characteristics of small atomic radius and large electronegativity, the fluorine atom has stronger bond energy and chemical stability with a C-F bond formed by the carbon atom. Fluorine or fluorine-containing groups are introduced into the organic molecules to alter the dipole moment, lipophilicity, chemical stability, and other physicochemical properties of the parent compound, such as: increased metabolic stability, increased lipid solubility, enhanced cell membrane penetration, and altered intramolecular or intermolecular forces, among others. The characteristics lead the fluorine-containing organic compound to be widely applied in the fields of materials, medicines, pesticides and the like. It has been reported that over 20% of the drugs and 30% of the agrochemicals contain at least one fluoride source, and that popular fluorinated drugs include the antidepressants fluoxetine (Prozac), the cholesterol lowering drugs atorvastatin (Lipitor) and the antimicrobial ciprofloxacin (Ciprobay). Despite the importance of fluorine-containing organic molecules, natural fluorine-containing organic compounds are very few. In recent years, how to introduce fluorine atoms and build new C-F bonds has become a great research hotspot, and research on fluorination such as monofluorination, polyfluorination, fluoroalkylation, trifluoromethoxy and the like has reached a new height. Despite the increasing number of new methods reported, the development of more efficient, green, and compact synthetic methodologies for selectively introducing fluorine atoms or fluorine-containing groups into organic molecules still holds great challenges and opportunities, and is one of the important directions of current organofluorine chemistry research. In addition, C-S bonds are also widely present in natural products, medicines, pesticides, functional materials, and it is clear that if perfluoroalkyl and thio groups are simultaneously introduced into organic molecules, their potential for use in pharmaceutical, agrochemical and material chemistry will be further broadened.
Dilman developed a photooxidation reduction/copper catalyzed olefin and fluorinationThe free radical difunctional of halide and thiolate anions involves classical redox neutral processes, with electrophiles and nucleophiles introduced sequentially into the c—c double bond. In contrast to redox neutral strategies, the reduction or oxidative bifunctionalization of olefins by two different nucleophiles or electrophiles is relatively limited. In this case, song et al reported a copper/B 2 pin 2 The system catalyzes the reaction of aryl alkene with two electrophilic reactants (BrCF 2 CO 2 Et and thiosulfonate). At the same time, song also describes photoinduced Ir catalyzed terminal olefins with CF 3 SO 2 Na and benzenesulfonate quench the cyclic thiotrifluoromethylation reaction by reduction. Although useful, the above methods all require the use of metal catalysts and limit their further use in the pharmaceutical industry due to stringent metal catalyst residue standards. Therefore, the development of a simpler, more environment-friendly and metal-free olefin perfluoroalkyl-sulfuration method is continued, and the method has very important significance. [ reference: muller K, faeh C, diederich F.science,2007,317,1881; purser S, moore P R, swallow S, et al chemical Society Reviews,2008,37,320; preshlock S, tredwell M, gouverneur v.chemical Reviews,2016,116,719; wang J, sanchez-Rosello M, del Pozo C, et al chemical Reviews,2014,114,2432; beguage J P, bonnet-Delpon D.journal of Fluorine Chemistry,2006,127,992; kirk l. Journal of Fluorine Chemistry,2006,127,1013; wong D T, bymaster F P, engleman E A.Life Science,1995,57,411; roth, B.D. In Progress in Medicinal Chemistry, vol.40, eds.: king FD, oxford AW, elsevier, amsterdam,2002, pp.1-22; dragica K, malik m.current Topics in Medicinal Chemistry,2003,3,249; xu X H, matsuzaki K, shibata N.chemical Reviews,2015,115,731; ni C, hu M, hu j.chemical Reviews,2015,115,765; kostromit V S, levin V, dilman ad.the Journal of Organic Chemistry,2023,88,6252; kong W, yu C, an H, song q.organic Letters,2018,20,4975; kong W, an H, song Q.chemical Communications,2017,53,8968]。
Disclosure of Invention
The present application aims to provide a synthesis method of perfluoroalkyl-benzene sulfurized alkane, so as to solve at least one technical problem described above.
In order to solve the technical problems, the application provides a synthesis method of perfluoroalkyl-benzene sulfurized alkane, which comprises the following steps:
s1, taking olefin, perfluoroalkyl iodide, arylsulfonate, an additive and a dimethyl sulfoxide solvent, placing the olefin, perfluoroalkyl iodide, arylsulfonate, the additive and the dimethyl sulfoxide solvent in a reaction container, and mixing;
s2, continuously stirring and reacting for 4-8 hours at room temperature under the nitrogen atmosphere and under illumination;
s3, after the reaction is finished, washing with water, extracting with ethyl acetate, drying, concentrating under reduced pressure to remove the solvent, and separating the crude product by column chromatography to obtain the perfluoroalkyl-benzene sulfurized alkane product.
Preferably, the perfluoroalkyl-benzene sulfurized alkane product has the following structural formula:
in the structural formula of the perfluoroalkyl-phenylsulfurized alkane product, R is one of benzyl, 1-amyl, cyclohexyl and pyrrolidone groups; ar is one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 2-naphthyl and 2-thienyl; r is R f Is C 3 F 7 、C 4 F 9 、C 5 F 11 、C 6 F 13 、C 8 F 17 、CF 2 CO 2 Et.
Preferably, the olefin is selected from one of styrene, 1-octene, cyclohexyl ethylene and N-vinyl pyrrolidone.
Preferably, the perfluoroalkyl iodide is selected from C 3 F 7 I、C 4 F 9 I、C 5 F 11 I、C 6 F 13 I、C 8 F 17 I、ICF 2 CO 2 Et.
Preferably, the arylsulfonate is selected from one of S-benzenesulfonate, S- (p-tolyl) 4-methylsulfenesulfonate, S- (p-methoxyphenyl) 4-methoxybenzenesulfonate, S- (p-tert-butylphenyl) 4-tert-butylbenzenesulfonate, S- (p-methoxyphenyl) 4-methoxybenzenesulfonate, S- (naphthalene-2-yl) naphthalene-2-sulfosulfonate, and S- (thiophene-2-yl) thiophene-2-sulfosulfonate.
Preferably, the additive is selected from one of triethylamine, N, N-diisopropylethylamine, N, N, N ', N' -tetramethyl ethylenediamine and triethylene diamine.
Preferably, in step S2, the illumination light selected under the illumination condition includes one of blue light, white light and sunlight of 450-460 nm.
Preferably, the mol ratio of the olefin, the perfluoroalkyl iodide, the arylsulfonate and the additive is 1:1-2:1-3:1-2.
Preferably, the concentration of the reaction system of the olefin, the perfluoroalkyl iodide, the arylsulfonate and the additive is 1-2M.
Compared with the prior art, the beneficial effect of this application lies in: the application provides a method for preparing perfluoroalkyl-benzene sulfurized alkane by metal-free catalytic olefin, perfluoroalkyl iodide and arylsulfonate in a high-selectivity and rapid difunctional way, which at least comprises the following beneficial effects:
(1) The raw materials are cheap and easy to obtain, and the reaction system is simple and mild; the technical scheme provided by the application only needs to use the commercial tertiary amine which is easy to store, stable in property, low in cost and easy to obtain as an additive, and does not need additional photocatalyst or metal.
(2) The reaction operation is simple and convenient, the substrate range is wide, and the environment is protected; the reaction can be completed by utilizing sunlight, and the method is clean and environment-friendly.
(3) A lengthy reaction process is not required; perfluoroalkyl radical R generated by activating perfluoroalkyl iodides under visible light induction using electron donor-acceptor (EDA) strategy f Then generates a new alkyl radical A by free radical addition with olefin, then generates an intermediate B by reduction, and finally generates nucleophilic substitution reaction with arylsulfonate to obtain the target product of perfluorAnd (3) a glycosylated-benzene sulfurized alkane (TM).
(4) The regiochemical selectivity is good; the yield of the target product is higher, and the isomer yield is less.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive faculty for a person skilled in the art.
FIG. 1 is a schematic representation of the reaction scheme for preparing perfluoroalkyl-benzene sulfurized alkanes according to one embodiment of the present application.
Detailed Description
The invention will be further illustrated by the following examples. These examples are only intended to illustrate the invention but not to limit it in any way. All parameters and descriptions in the examples are based on mass unless otherwise indicated. The test methods for which specific conditions are not specified in the examples are generally conducted under conventional conditions or under conditions recommended by the manufacturer.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention.
For a further understanding of the invention, features and efficacy of this application, the following examples are set forth:
the application provides a synthesis method of perfluoroalkyl-benzene sulfurized alkane, which comprises the following steps:
s1, taking olefin, perfluoroalkyl iodide, arylsulfonate, an additive and a dimethyl sulfoxide solvent, placing the olefin, perfluoroalkyl iodide, arylsulfonate, the additive and the dimethyl sulfoxide solvent in a reaction container, and mixing;
s2, continuously stirring and reacting for 4-8 hours at room temperature under the nitrogen atmosphere and under illumination;
s3, after the reaction is finished, washing with water, extracting with ethyl acetate, drying, concentrating under reduced pressure to remove the solvent, and separating the crude product by column chromatography to obtain the perfluoroalkyl-benzene sulfurized alkane product.
In one embodiment, the perfluoroalkyl-phenylsulfurized alkane product has the following structural formula:
wherein, in the structural formula of the perfluoroalkyl-benzene sulfurized alkane product, R is one of benzyl, 1-amyl, cyclohexyl and pyrrolidone group; ar is one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 2-naphthyl and 2-thienyl; r is R f Is C 3 F 7 、C 4 F 9 、C 5 F 11 、C 6 F 13 、C 8 F 17 、CF 2 CO 2 Et.
In one embodiment, the olefin is selected from one of styrene, 1-octene, cyclohexylethylene, N-vinylpyrrolidone.
In one embodiment, the perfluoroalkyl iodide is selected from C 3 F 7 I、C 4 F 9 I、C 5 F 11 I、C 6 F 13 I、C 8 F 17 I、ICF 2 CO 2 Et.
In one embodiment, the arylsulfonate is selected from one of S-benzenesulfonate, S- (p-tolyl) 4-methylsulfenesulfonate, S- (p-methoxyphenyl) 4-methoxybenzenesulfonate, S- (p-tert-butylphenyl) 4-tert-butylbenzenesulfonate, S- (p-methoxyphenyl) 4-methoxybenzenesulfonate, S- (naphthalene-2-yl) naphthalene-2-sulfonate, and S- (thiophen-2-yl) thiophene-2-sulfonate.
In one embodiment, the additive is selected from one of triethylamine, N, N-diisopropylethylamine, N, N, N ', N' -tetramethyl ethylenediamine, and triethylene diamine.
In one embodiment, in step S2, the illumination light selected under the illumination condition includes one of blue light, white light, and sunlight of 450-460 nm.
In one embodiment, the mol ratio of olefin, perfluoroalkyl iodide, arylsulfonate and additive is 1:1-2:1-3:1-2.
In one embodiment, the concentration of the reaction system of the olefin, the perfluoroalkyl iodide, the arylsulfonate and the additive is 1-2M.
Example 1
Synthesis of 3-phenyl-2-phenylthio-1-perfluoropropyl propane.
Adding 0.2mmol of styrene, 0.3mmol of perfluoroiodopropane, 0.4mmol of S-benzenesulfonyl sulfonate and 0.4mmol of triethylamine into a reactor, adding 1mL of dimethyl sulfoxide solvent, continuously stirring under the condition of room temperature and sunlight irradiation for reaction for 6 hours, washing with water after the reaction is finished, extracting with ethyl acetate, drying, distilling under reduced pressure, concentrating to remove the solvent, and separating the crude product by column chromatography to obtain the target product with 60 percent of yield. 1 H NMR(400MHz,CDCl 3 ):δ7.29–7.27(m,2H),7.23–7.19(m,5H),7.16–7.12(m,3H),3.60–3.53(m,1H),3.05–3.00(m,1H),2.81–2.76(m,1H),2.34–2.23(m,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ137.6,133.27,133.23,129.3,129.1,128.4,128.0,126.9,122.2–119.2(m),44.7,41.4(d,J＝2.7Hz),33.01(d,J＝18.7Hz).
Example 2
Synthesis of 3-phenyl-2-phenylthio-1-perfluorobutyl propane.
Adding 0.2mmol of styrene, 0.3mmol of perfluoroiodobutane, 0.4mmol of S-benzenesulfonate and 0.4mmol of N, N-diisopropylethylamine into a reactor, adding 1mL of dimethyl sulfoxide solvent, continuously stirring and reacting for 5h at room temperature under the irradiation of 450-460 nm of blue light in a nitrogen atmosphere, washing with water after the reaction is finished, extracting with ethyl acetate, drying, distilling under reduced pressure and concentrating to remove the solvent, and separating the crude product by column chromatography to obtain the target product with 64% yield. 1 H NMR(400MHz,CDCl 3 ):δ7.36(d,J＝7.5Hz,2H),7.33–7.24(m,6H),7.21(d,J＝7.8Hz,2H),3.74–3.67(m,1H),3.11(dd,J＝14.4,5.8Hz,1H),2.94(dd,J＝14.4,7.8Hz,1H),2.43–2.32(m,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ137.6,133.4,132.6,129.3,129.1,128.4,127.7,126.9,42.7,41.0,34.8(t,J＝21.0Hz), 13 C-NMR for CF 2 CF 2 CF 2 CF 3 could not be assigned.
Example 3
Synthesis of 2-phenylthio-1-perfluorobutyloctane.
0.2mmol of 1-octene, 0.3mmol of perfluoroiodobutane, 0.4mmol of S-benzenesulfonate and 0.4mmol of N, N-diisopropylethylamine are added into a reactor, then 1mL of dimethyl sulfoxide solvent is added, the reaction is continuously stirred for 5 hours at room temperature under the irradiation of white light in the nitrogen atmosphere, water is used for washing after the reaction is finished, ethyl acetate is used for extraction, drying and reduced pressure distillation is carried out to remove the solvent, and the crude product is separated by column chromatography to obtain the target product with 60 percent of yield. 1 H NMR(400MHz,CDCl 3 ):δ7.41(d,J＝7.5Hz,2H),7.34–7.27(m,3H),3.49–3.43(m,1H),2.51–2.21(m,2H),1.85–1.76(m,1H),1.67–1.59(m,2H),1.53–1.50(m,1H),1.34–1.29(m,6H),0.89(t,J＝6.4Hz,3H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ133.6,132.6,129.1,127.6,41.5(d,J＝1.3Hz),35.8(t,J＝20.8Hz),34.5(d,J＝2.2Hz),31.6,28.9,26.3,22.5,14.0, 13 C-NMR for CF 2 CF 2 CF 2 CF 3 could not be assigned.
Example 4
Synthesis of 2-cyclohexyl-2-phenylthio-1-perfluorobutylethane.
Adding 0.2mmol of cyclohexyl ethylene, 0.3mmol of perfluoroiodobutane, 0.4mmol of S-benzenesulfonate and 0.4mmol of N, N-diisopropylethylamine into a reactor, then adding 1mL of dimethyl sulfoxide solvent, continuously stirring and reacting for 6 hours at room temperature under the irradiation of 450-460 nm of blue light in a nitrogen atmosphere, washing with water after the reaction is finished, extracting with ethyl acetate, drying, distilling under reduced pressure, concentrating to remove the solvent, and separating the crude product by column chromatography to obtain the target product with 65% yield. 1 H NMR(400MHz,CDCl 3 ):δ7.44(d,J＝7.5Hz,2H),7.35–7.27(m,3H),3.46–3.42(m,1H),2.60–2.29(m,2H),1.84–1.70(m,6H),1.51–1.42(m,1H),1.31–1.18(m,4H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ135.1,131.9,129.1,127.2,48.2,41.8,33.40(t,J＝21.0Hz),30.4,28.3,26.34,26.30,26.2, 13 C-NMR for CF 2 CF 2 CF 2 CF 3 could not be assigned.
Example 5
Synthesis of 2-pyrrolidone-2-phenylthio-1-perfluorobutylethane
Adding 0.2mmol of N-vinyl pyrrolidone, 0.3mmol of perfluoroiodobutane, 0.4mmol of S-benzenesulfonate and 0.4mmol of N, N-diisopropylethylamine into a reactor, adding 1mL of dimethyl sulfoxide solvent, continuously stirring under the irradiation of blue light at room temperature and 450-460 nm for reaction for 6 hours in a nitrogen atmosphere, washing with water after the reaction is finished, extracting with ethyl acetate, drying, distilling under reduced pressure to concentrate and remove the solvent, and separating the crude product by column chromatography to obtain the target product with 66% yield. 1 H NMR(400MHz,CDCl 3 ):δ7.44–7.42(m,2H),7.29–7.27(m,3H),6.12–6.09(m,1H),3.56–3.50(m,1H),3.28–3.22(m,1H),2.72–2.46(m,2H),2.27–2.19(m,1H),2.07–1.99(m,1H),1.94–1.87(m,1H),1.82–173(m,1H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ174.6,133.3,130.8,129.0,128.5,52.5(d,J＝3.5Hz),41.6,32.3(t,J＝21.4Hz),30.7,17.7, 13 C-NMR for CF 2 CF 2 CF 2 CF 3 could not be assigned.
Example 6
Synthesis of 2-pyrrolidone-2-p-toluenesulfonyl-1-perfluorobutylethane.
Adding 0.2mmol of N-vinyl pyrrolidone, 0.3mmol of perfluoroiodobutane, 0.5mmol of S- (p-tolyl) 4-methylbenzenesulfonate and 0.4mmol of N, N-diisopropylethylamine into a reactor, adding 1mL of dimethyl sulfoxide solvent, continuously stirring under the irradiation of blue light of 450-460 nm at room temperature under the atmosphere of nitrogen for reaction for 6h, washing with water after the reaction is finished, extracting with ethyl acetate, drying, concentrating under reduced pressure to remove the solvent, and obtaining a crude product, wherein the crude product is subjected to column colorSpectrum separation to obtain the target product with 61% yield. 1 H NMR(400MHz,CDCl 3 ):δ7.34(d,J＝7.6Hz,2H),7.11(d,J＝7.6Hz,2H),6.06–6.03(m,1H),3.59–3.54(m,1H),3.29–3.23(m,1H),2.71–2.46(m,2H),2.31(s,3H),2.29–2.21(m,1H),2.10–2.02(m,1H),1.98–1.81(m,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ174.6,139.0,133.8,129.9,127.1,52.8(d,J＝3.6Hz),41.6,32.2(t,J＝21.2Hz),30.8,21.1,17.8, 13 C-NMR for CF 2 CF 2 CF 2 CF 3 could not be assigned.
Example 7
Synthesis of 3-phenyl-2- (thiophene-2-thio) -1-perfluorobutyl propane.
0.2mmol of styrene, 0.3mmol of perfluoroiodobutane, 0.4mmol of S- (thiophen-2-yl) thiophene-2-sulfosulfonate and 0.4mmol of triethylamine are added into a reactor, then 1mL of dimethyl sulfoxide solvent is added, the reaction is continuously stirred for 6 hours under the condition of room temperature and sunlight irradiation, water is used for washing after the reaction is finished, ethyl acetate is used for extraction, drying and reduced pressure distillation is carried out to remove the solvent, and the crude product is separated by column chromatography to obtain the target product with 40 percent of yield. 1 H NMR(400MHz,CDCl 3 ):δ7.50(d,J＝5.3Hz,1H),7.41–7.37(m,2H),7.33(d,J＝7.2Hz,1H),7.29–7.27(m,2H),7.21–7.20(m,1H),7.10–7.07(m,1H),3.54–3.47(m,1H),3.11–3.00(m,2H),2.58–2.28(m,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ137.6,136.5,131.2,130.2,129.3,128.5,127.8,126.9,44.6,40.9,34.4(t,J＝20.9Hz), 13 C-NMR for CF 2 CF 2 CF 2 CF 3 could not be assigned.
Example 8
Synthesis of 3-phenyl-2-phenylsulfanyl-1-difluoroacetic acid ethyl ester propane.
Adding 0.2mmol of styrene, 0.3mmol of ethyl difluoroiodoacetate, 0.4mmol of S-benzenesulfonate and 0.4mmol of triethylamine into a reactor, adding 1mL of dimethyl sulfoxide solvent, continuously stirring under the condition of room temperature and sunlight for reaction for 6 hours in a nitrogen atmosphere, washing with water after the reaction is finished, extracting with ethyl acetate,drying, distilling under reduced pressure, concentrating to remove solvent, and separating the crude product by column chromatography to obtain the target product with 55% yield. 1 H NMR(400MHz,CDCl 3 ):δ7.45–7.42(m,2H),7.37–7.27(m,6H),7.22–7.20(m,2H),4.32(q,J＝7.2Hz,2H),3.59–3.52(m,1H),3.05–2.94(m,2H),2.49–2.39(m,2H),1.34(t,J＝7.2Hz,3H). 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ164.05(t,J＝32.5Hz),137.9,133.8,132.8,129.4,129.2,128.5,127.8,126.9,115.52(dd,J＝252.3,249.9Hz),63.1,44.1(d,J＝2.9Hz),41.8,38.5(t,J＝23.6Hz),13.9.
It should be noted that, without conflict, the embodiments and features of the embodiments in the present application may be combined with each other.
The foregoing description is only of the preferred embodiments of the present application and is not intended to limit the present application in any way, and any simple modification, equivalent variations and modification made to the above embodiments according to the technical principles of the present application are within the scope of the technical solutions of the present application.
Claims (9)
1. A method for synthesizing perfluoroalkyl-benzene sulfurized alkane is characterized by comprising the following steps: the method comprises the following steps:
s1, taking olefin, perfluoroalkyl iodide, arylsulfonate, an additive and a dimethyl sulfoxide solvent, placing the olefin, perfluoroalkyl iodide, arylsulfonate, the additive and the dimethyl sulfoxide solvent in a reaction container, and mixing;
s2, continuously stirring and reacting for 4-8 hours at room temperature under the nitrogen atmosphere and under illumination;
s3, after the reaction is finished, washing with water, extracting with ethyl acetate, drying, concentrating under reduced pressure to remove the solvent, and separating the crude product by column chromatography to obtain the perfluoroalkyl-benzene sulfurized alkane product.
2. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: the perfluoroalkyl-benzene sulfurized alkane product has the following structural formula:
in the structural formula of the perfluoroalkyl-phenylsulfurized alkane product, R is one of benzyl, 1-amyl, cyclohexyl and pyrrolidone groups; ar is one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 2-naphthyl and 2-thienyl; r is R f Is C 3 F 7 、C 4 F 9 、C 5 F 11 、C 6 F 13 、C 8 F 17 、CF 2 CO 2 Et.
3. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: the olefin is selected from one of styrene, 1-octene, cyclohexyl ethylene and N-vinyl pyrrolidone.
4. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: the perfluoroalkyl iodide is selected from C 3 F 7 I、C 4 F 9 I、C 5 F 11 I、C 6 F 13 I、C 8 F 17 I、ICF 2 CO 2 Et.
5. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: the arylsulfonate is selected from one of S-benzenesulfonate, S- (p-tolyl) 4-methylbenzenesulfonate, S- (p-methoxyphenyl) 4-methoxybenzenesulfonate, S- (p-tert-butylphenyl) 4-tert-butylphenylsulfonate, S- (p-methoxyphenyl) 4-methoxybenzenesulfonate, S- (naphthalene-2-yl) naphthalene-2-sulfosulfonate and S- (thiophene-2-yl) thiophene-2-sulfosulfonate.
6. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: the additive is selected from one of triethylamine, N, N-diisopropylethylamine, N, N, N ', N' -tetramethyl ethylenediamine and triethylene diamine.
7. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: in step S2, the irradiation light selected under the illumination condition comprises one of blue light, white light and sunlight with the wavelength of 450-460 nm.
8. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: the mol ratio of the alkene, the perfluoroalkyl iodide, the arylsulfonyl sulfonate and the additive is 1:1-2:1-3:1-2.
9. The method for synthesizing a perfluoroalkyl-phenylsulfurized alkane according to claim 1, wherein: the concentration of the reaction system of the olefin, the perfluoroalkyl iodide, the arylsulfonate and the additive is 1-2M.
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