CN107056665B - A kind of aromatic derivant synthetic method of sulphur perfluoroalkylation - Google Patents
A kind of aromatic derivant synthetic method of sulphur perfluoroalkylation Download PDFInfo
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- CN107056665B CN107056665B CN201611134408.3A CN201611134408A CN107056665B CN 107056665 B CN107056665 B CN 107056665B CN 201611134408 A CN201611134408 A CN 201611134408A CN 107056665 B CN107056665 B CN 107056665B
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Abstract
The invention discloses a kind of synthetic methods of the aromatic derivant of shown sulphur perfluoroalkylation, be using aromatic compound sum perfluoroalkyl sulfinic acid sodium as raw material, in the presence of reducing agent diethyl phosphite and lewis acid, excessive 1,2- dichloroethanes is under conditions of solvent, under 95~110 DEG C of reaction temperature, sufficiently react.After reaction, reaction solution is through isolating and purifying to obtain the aromatic derivant of sulphur perfluoroalkylation.The method of the present invention process conditions are reasonable, safety easy to operate；It is economical and practical without metal catalytic, it is environmental-friendly；Using Lewis acid activation aromatic compound c h bond, the application of sulphur perfluoroalkylation is reached.
Description
Technical field
The present invention designs organic synthesis field, and in particular to synthesizes sulphur perfluoroalkyl aromatic series by perfluoroalkyl sulfinic acid sodium
The method of compound.
Technical background
Sulphur perfluoroalkyl is a kind of critically important structure in organic synthesis field, since this kind of group has strong electrophilic
The characteristics such as property, lipophilicity and stable C-F key, can significantly change the acidity, dipole moment, pole of sulfur-bearing all-fluoroalkyl compound
Property, lipophilicity and its metabolism and chemical stability, long perfluoroalkyl chain not only facilitate stable matrix compound, moreover it is possible to changeization
The amphipathic of object is closed, therefore the compound containing sulphur perfluoroalkyl is widely applied in fields such as medicine, pesticide and materials.
Explore the hot spot that the method that sulphur perfluoroalkyl segments introduce is always synthesis field.Existing synthetic method is mainly at present.
Such as:
(Pooput C, Dolbier W R, the Medebielle M.Nucleophilic of document 1
Perfluoroalkylation of Aldehydes,Ketones,Imines,Disulfides,and Diselenides.
[J] .Journal of Organic Chemistry, 2006,71 (9): 3564-8.) using mercaptan and perfluoroalkyl iodides conduct
The method of Material synthesis sulphur perfluoroalkylation product be it is most common, due to do not have to consider the problems of sulphur source, sulphur perfluoroalkyl
Formation is then easier to realize, but its limitation is that raw material substrate must have the presence of-SH, upper in the presence of compared with the day of one's doom in application
System.Its reaction equation such as following formula:
(Pooput C, Dolbier W R, the Medebielle M.Nucleophilic of document 2
Perfluoroalkylation of Aldehydes,Ketones,Imines,Disulfides,and Diselenides.
[J] .Journal of Organic Chemistry, 2006,71 (9): 3564-8.) use disulfide for substrate Material synthesis
The thinking of sulphur perfluoroalkylation product is that disulfide itself contains sulphur atom, and perfluoroalkyl source can use carboxylic acids, iodo
Object etc., but there are still limitations in expansion.Its reaction equation such as following formula:
(Nguyen T, Rubinstein M, the Wakselman C.ChemInform Abstract:Reaction of document 3
of Perfluoroalkyl Carbanions with Thiocyanates.Synthesis of Fluorinated
Sulfides and Sulfenyl Chlorides [J] .J.org.chem, 1981,46 (9): 1938-1940.) document is total
It has tied using perfluoroalkyl Grignard Reagent and thiocyanogen compound as Material synthesis sulphur perfluoroalkyl product, nucleopilic reagent is perfluor alkane
Ji Yuan, sulphur source is then on raw material substrate.Its reaction equation such as following formula:
Above method substantially covers the existing synthetic method of sulphur perfluoroalkylation and newest research, uses sulfur-bearing bottom
Object is more direct as the method for Material synthesis sulphur perfluoroalkyl, efficiently, but needs to prepare corresponding mercaptan, disulfide in advance
Or thiocyanogen etc., additional cost is increased, the limitation on expanding is existed simultaneously.It is efficient to seek one kind, it is easily, economical
The method of synthesis sulphur perfluoroalkyl has critically important realistic meaning.
Summary of the invention
The purpose of the present invention is to provide a kind of rational technology, it is convenient for generation, low-cost via perfluoroalkyl Asia sulphur
Sour sodium, using diethyl phosphite as reducing agent, in lewis acid (FeCl3) the lower synthesis sulphur perfluoroalkyl aromatic compound of catalysis
Method.
Realize the technical scheme is that
A kind of aromatic derivant synthetic method of sulphur perfluoroalkylation, the method are as follows: with such as formula III aromatic compound
Object and Formula II perfluoroalkyl sulfinic acid sodium are raw material, at reducing agent diethyl phosphite ((EtO)2P (O) H) and lewis acid
(FeCl3) in the presence of, under conditions of excessive 1,2- dichloroethanes is solvent, under 95~110 DEG C of reaction temperature, sufficiently
Reaction.After reaction, reaction solution is through isolating and purifying to obtain the aromatic derivant of Formulas I sulphur perfluoroalkylation:
In Formulas I or formula III, R is selected from one of following: methoxyl group, bromine, hydroxyl.
Reaction equation are as follows:
The molar ratio of Formula II perfluoroalkyl sulfinic acid sodium and formula III aromatic compound raw material dosage of the present invention is 1:
1.5~1:2.5.
Diethyl phosphite dosage of the present invention is 1.1.5~2 times of formula III aromatic compound feed molar amount.
Lewis acid FeCl of the present invention3Dosage is 1~2 times of formula III aromatic compound feed molar amount, preferably
It is 1.3~1.5 times.
Solvent 1,2- dichloroethanes dosage of the present invention is the 20~80 of formula III aromatic compound feed molar amount
Times, preferably 40~60 times.
Reaction temperature of the present invention is 95~110 DEG C, preferably 100~105 DEG C.
Reaction time of the present invention is 12~36h, preferably 18~for 24 hours.
The reaction solution is through isolation and purification method are as follows: after reaction, is first filtered to reaction solution, is washed with ethyl acetate
It washs three times, after the reaction solution after filter is spin-dried for Rotary Evaporators, column chromatography sample is made with a small amount of silica gel.Crude product is via column layer
Analysis (eluant, eluent is ethyl acetate and petroleum ether mixed liquor, and the two volume ratio is 1:40) is isolated described as shown in formula (I)
Sulphur perfluoroalkylation aromatic derivant.
Compared with prior art, the present invention its remarkable advantage is:
(1) process conditions advantages of simple, yield is higher, can be easily separated purifying.
(2) the perfluoroalkyl sulfinic acid sodium used can facilitate acquisition with save the cost.
(3) there is good selectivity on aromatic ring.
Detailed description of the invention
Fig. 1 is 4- methoxyl group sulphur perfluorinated butane base benzene1H NMR figure；
Fig. 2 is 4- methoxyl group sulphur perfluorinated butane base benzene19F NMR figure；
Fig. 3 is 4- methoxyl group sulphur perfluorinated butane base benzene13C NMR figure；
Fig. 4 is 4- bromine sulphur perfluorinated butane base benzene1H NMR figure；
Fig. 5 is 4- bromine sulphur perfluorinated butane base benzene19F NMR figure；
Fig. 6 is 4- bromine sulphur perfluorinated butane base benzene13C NMR figure；
Fig. 7 is 4- hydroxyl sulphur perflexane base benzene1H NMR figure；
Fig. 8 is 4- hydroxyl sulphur perflexane base benzene19F NMR figure；
Fig. 9 is 4- hydroxyl sulphur perflexane base benzene13C NMR figure；
Figure 10 is 4- hydroxyl sulphur perfluorooctane base benzene1H NMR figure；
Figure 11 is 4- hydroxyl sulphur perfluorooctane base benzene19F NMR figure；
Figure 12 is 4- hydroxyl sulphur perfluorooctane base benzene13C NMR figure.
Specific embodiment
For a better understanding of the present invention, technical solution of the present invention is illustrated below by specific embodiment.
Embodiment 1
2.16g (0.02mol) methyl phenyl ethers anisole, 5.12ml (0.04mol) phosphorous acid diethyl are added in 50mL vacuum reaction pipe
Ester, 4.86g (0.03mol) FeCl3, 12g (0.04mol) perfluorinated butane sulfinic acid sodium and 15ml 1,2- dichloroethanes, 110
It is stirred to react for 24 hours at DEG C.After reaction, first reaction solution is filtered, is washed three times with ethyl acetate, by the reaction after filter
After liquid is spin-dried for Rotary Evaporators, column chromatography sample is made with a small amount of silica gel.Via column chromatography, (eluant, eluent is ethyl acetate to crude product
With petroleum ether mixed liquor, the two volume ratio is the isolated 4- methoxyl group sulphur perfluorinated butane base benzene 4.36g of 1:40), and yield is
61%.
4- methoxyl group sulphur perfluorinated butane base benzene1H NMR figure is shown in Fig. 1,4- methoxyl group sulphur perfluorinated butane base benzene19F NMR figure is shown in
Fig. 2,4- methoxyl group sulphur perfluorinated butane base benzene13C NMR figure is shown in Fig. 3.
1H NMR(500MHz,CDCl3)δ7.60-7.36(m,2H),6.92-6.77(m,2H),3.75(s,3H)；
13C NMR(126MHz,CDCl3)δ162.13(s),139.20(s),115.05(s),113.07(s),55.45
(s)；
19F NMR(470MHz,CDCl3) δ -81.03--81.10 (m, 3F), -88.06--88.12 (t, J=12.6,
2F), -120.22--120.29 (m, 2F), -125.60--125.64 (t, J=8.4,2F)
Embodiment 2
In 50mL vacuum reaction pipe be added 3.12g (0.02mol) bromobenzene, 5.12ml (0.04mol) diethyl phosphite,
4.86g(0.03mol)FeCl3, 12g (0.04mol) perfluorinated butane sulfinic acid sodium and 15ml 1,2- dichloroethanes, at 110 DEG C
It is stirred to react for 24 hours.After reaction, first reaction solution is filtered, is washed three times with ethyl acetate, the reaction solution after filter is used
After Rotary Evaporators are spin-dried for, column chromatography sample is made with a small amount of silica gel.Via column chromatography, (eluant, eluent is ethyl acetate and stone to crude product
Oily ether mixed liquor, the two volume ratio are the isolated 4- bromine sulphur perfluorinated butane base benzene 4.38g of 1:40), yield 54%.
4- bromine sulphur perfluorinated butane base benzene1H NMR figure is shown in Fig. 4,4- bromine sulphur perfluorinated butane base benzene19F NMR figure is shown in Fig. 5,4- bromine
Sulphur perfluorinated butane base benzene13C NMR figure is shown in Fig. 6.
1H NMR (500MHz, CDCl3) δ 7.57 (d, J=8.3Hz, 2H), 7.51 (d, J=8.2Hz, 2H)；
13C NMR(126MHz,CDCl3)δ138.84(s),132.87(s),126.50(s),121.84(s)；
19F NMR (470MHz, CDCl3) δ -78.57--83.59 (m, 3F), -87.06 (td, J=11.2,9.5,4.9Hz,
2F),-115.18--122.26(m,2F),-122.26--130.02(m,2F).
Embodiment 3
In 50mL vacuum reaction pipe be added 1.88g (0.02mol) phenol, 5.12ml (0.04mol) diethyl phosphite,
4.86g(0.03mol)FeCl3, 16g (0.04mol) perflexane sulfinic acid sodium and 15ml 1,2- dichloroethanes, at 110 DEG C
It is stirred to react for 24 hours.After reaction, first reaction solution is filtered, is washed three times with ethyl acetate, the reaction solution after filter is used
After Rotary Evaporators are spin-dried for, column chromatography sample is made with a small amount of silica gel.Via column chromatography, (eluant, eluent is ethyl acetate and stone to crude product
Oily ether mixed liquor, the two volume ratio are the isolated 4- hydroxyl sulphur perflexane base benzene 4.26g of 1:40), yield 48%.
4- hydroxyl sulphur perflexane base benzene1H NMR figure is shown in Fig. 7,4- hydroxyl sulphur perflexane base benzene19F NMR figure is shown in Fig. 8,
4- hydroxyl sulphur perflexane base benzene13C NMR figure is shown in Fig. 9.
1H NMR(500MHz,CDCl3)δ7.52-7.41(m,2H),6.88-6.74(m,2H),5.17(s,1H)；
13C NMR(126MHz,CDCl3)δ158.34(s),139.55(s),116.62(s),113.49(s)；
19F NMR (470MHz, CDCl3) δ -80.80 (t, J=10.1Hz, 3F), -87.81 (t, J=13.3Hz, 2F), -
119.30 (ddd, J=18.6,9.3,3.7Hz, 2F), -120.75--122.04 (m, 2F), -122.82 (ddt, J=16.6,
11.7,5.9Hz, 2F), -126.17 (td, J=14.9,6.8Hz, 2F)
Embodiment 4
In 50mL vacuum reaction pipe be added 1.88g (0.02mol) phenol, 5.12ml (0.04mol) diethyl phosphite,
4.86g(0.03mol)FeCl3, 20g (0.04mol) perfluorooctane sulfinic acid sodium and 15ml 1,2- dichloroethanes, at 110 DEG C
It is stirred to react for 24 hours.After reaction, first reaction solution is filtered, is washed three times with ethyl acetate, the reaction solution after filter is used
After Rotary Evaporators are spin-dried for, column chromatography sample is made with a small amount of silica gel.Via column chromatography, (eluant, eluent is ethyl acetate and stone to crude product
Oily ether mixed liquor, the two volume ratio are the isolated 4- hydroxyl sulphur perfluorooctane base benzene 4.98g of 1:40), yield 46%.
4- hydroxyl sulphur perfluorooctane base benzene1H NMR figure is shown in Figure 10,4- hydroxyl sulphur perfluorooctane base benzene19F NMR figure is shown in figure
11,4- hydroxyl sulphur perfluorooctane base benzene13C NMR figure is shown in Figure 12.
1H NMR(500MHz,CDCl3)δ7.56-7.38(m,2H),6.87-6.67(m,2H),5.34(s,1H)；
13C NMR(126MHz,CDCl3)δ157.27(s),138.39(s),115.49(s),112.26(s)；
19F NMR (470MHz, CDCl3) δ -80.71 (t, J=9.9Hz, 3F), -87.78 (t, J=14.0Hz, 2F), -
119.21 (q, J=13.2,11.9Hz, 2F), -120.34--121.41 (m, 2F), -121.41--122.22 (m, 4F), -
122.70 (d, J=19.1Hz, 2F), -126.11 (td, J=14.5,6.7Hz, 2F).
Claims (1)
1. a kind of aromatic derivant synthetic method of sulphur perfluoroalkylation, which is characterized in that this method are as follows: with aromatic compound
III
With perfluoroalkyl sulfinic acid sodium
NaSO2RF
(II)
For raw material, in reducing agent diethyl phosphite and FeCl3In the presence of, in the condition that excessive 1,2- dichloroethanes is solvent
Under, under 95~110 DEG C of reaction temperature, sufficiently after reaction, reaction solution is through isolating and purifying to obtain the fragrance of sulphur perfluoroalkylation
Race's derivative I
Wherein, R is selected from one of following: methoxyl group, bromine, hydroxyl, methyl, the perfluoroalkyl sulfinic acid sodium and aromatic compound
The molar ratio of raw material II I dosage is 1:5~1:2.5, and the diethyl phosphite dosage is I moles of aromatic compound raw material II
1.1.5~2 times of amount, the FeCl3Dosage is 1~2 times of aromatic compound raw material II I mole, the solvent 1,
2- dichloroethanes dosage is 20~80 times of aromatic compound raw material II I mole；The reaction temperature is 95~110 DEG C；
Reaction time is 12~36h, and the reaction solution is through isolation and purification method are as follows: after reaction, is first filtered, uses to reaction solution
Ethyl acetate washs three times, and after the reaction solution after filter is spin-dried for Rotary Evaporators, column chromatography sample is made with a small amount of silica gel, thick to produce
Object obtains the sulphur perfluoroalkylation aromatic derivant via column chromatography for separation.
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Citations (1)
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| CN103739451A (en) * | 2014-01-21 | 2014-04-23 | 南京理工大学 | Method for introducing fluorocarbon into aromatic compounds |
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| CN103739451A (en) * | 2014-01-21 | 2014-04-23 | 南京理工大学 | Method for introducing fluorocarbon into aromatic compounds |
Non-Patent Citations (3)
| Title |
|---|
| Direct Phosphorus-Induced Fluoroalkylthiolation with Fluoroalkylsulfonyl Chlorides;Lvqi Jiang 等;《Adv. Synth. Catal.》;20161109;第358卷;第3700-3705页 * |
| Direct Trifluoromethylthiolation and Perfluoroalkylthiolation of C(sp2)-H Bonds with CF3SO2Na and RfSO2Na;Lvqi Jiang 等;《Angew. Chem. Int. Ed.》;20151016;第54卷;第14965-14969页 * |
| 基于亚磺酸盐的含氟甲硫基化反应研究;易文斌;《中国化学会第十四届全国氟化学会议论文集》;20161120;第o-29页 * |
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Application publication date: 20170818 Assignee: Nanjing beta bioscience Co.,Ltd. Assignor: NANJING University OF SCIENCE AND TECHNOLOGY Contract record no.: X2023980030530 Denomination of invention: A Synthetic Method of Aromatic Derivative with Sulfur Perfluoroalkylation Granted publication date: 20190809 License type: Common License Record date: 20230111 |
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