CN110256400B - Preparation method for synthesizing polysubstituted ring 1, 2-diketone by participation of sulfoxide in arylation - Google Patents
Preparation method for synthesizing polysubstituted ring 1, 2-diketone by participation of sulfoxide in arylation Download PDFInfo
- Publication number
- CN110256400B CN110256400B CN201910602120.1A CN201910602120A CN110256400B CN 110256400 B CN110256400 B CN 110256400B CN 201910602120 A CN201910602120 A CN 201910602120A CN 110256400 B CN110256400 B CN 110256400B
- Authority
- CN
- China
- Prior art keywords
- sulfoxide
- compound
- diketone
- temperature
- test tube
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000006254 arylation reaction Methods 0.000 title claims abstract description 10
- 150000003462 sulfoxides Chemical class 0.000 title claims abstract description 9
- 230000002194 synthesizing effect Effects 0.000 title claims description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims abstract description 24
- -1 sulfoxide compound Chemical class 0.000 claims abstract description 21
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000002390 rotary evaporation Methods 0.000 claims abstract description 5
- 238000000926 separation method Methods 0.000 claims abstract description 3
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 238000004440 column chromatography Methods 0.000 claims description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- JQPFYXFVUKHERX-UHFFFAOYSA-N 2-hydroxy-2-cyclohexen-1-one Natural products OC1=CCCCC1=O JQPFYXFVUKHERX-UHFFFAOYSA-N 0.000 claims 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 229910052751 metal Inorganic materials 0.000 abstract description 6
- 239000002184 metal Substances 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 14
- 238000001228 spectrum Methods 0.000 description 13
- OACYKCIZDVVNJL-UHFFFAOYSA-N 3-Methyl-1,2-cyclopentanedione Chemical compound CC1CCC(=O)C1=O OACYKCIZDVVNJL-UHFFFAOYSA-N 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 9
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000001837 2-hydroxy-3-methylcyclopent-2-en-1-one Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 238000010499 C–H functionalization reaction Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- JJHHIJFTHRNPIK-UHFFFAOYSA-N Diphenyl sulfoxide Chemical compound C=1C=CC=CC=1S(=O)C1=CC=CC=C1 JJHHIJFTHRNPIK-UHFFFAOYSA-N 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a preparation method of a sulfoxide participating in arylation synthesis of a polysubstituted cyclic 1, 2-diketone compound, which comprises the steps of adding the sulfoxide compound, the 1, 2-diketone compound and a solvent into a test tube, placing the test tube in a low-temperature reactor at the temperature of-10 ℃, adding trifluoroacetic anhydride when a reaction system is uniformly mixed and is cooled to-10 ℃, reacting for 4-4.5 hours at the temperature of-10 ℃, moving to the room temperature, carrying out rotary evaporation and concentration, and carrying out silica gel column chromatography separation to obtain a product. The invention enables the sulfoxide compound and the ring 1, 2-diketone compound to generate a C-C bond, the whole reaction does not need metal catalysis, and the method is particularly suitable for the synthesis of some medicaments in an organic solvent system, thereby fundamentally eliminating the problems of metal residue and the like, and has higher economic applicability, simple operation, high yield and purity of more than 98 percent. Mild condition and wide substrate range.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method for synthesizing polysubstituted ring 1, 2-diketone by participation of sulfoxide in arylation.
Background
For the method of synthesizing polysubstituted cyclic 1, 2-diketones, currently, the main synthesis method is: direct functionalization remains problematic due to the inertness of the cyclic 1, 2-diketone alpha-C-H bond and competition of O-arylation/alkylation. To obtain alpha-substituted cyclic 1, 2-diketones, indirect methods were developed. It is desirable to convert the cyclic 1, 2-diones to enol ethers or enamines to enhance sp under such conditions2alpha-C-H functionalization. Although effective, these stepwise methods generally require the use of expensive transition metals and high reactivityAnd (3) temperature.
Thus, under mild and metal-free conditions, it is very necessary to achieve direct regioselective C — H functionalization of the readily accessible parent cyclic 1, 2-dione in one step.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
The present invention has been made in view of the above and the problems of the conventional methods for preparing polysubstituted cyclic 1, 2-diketones.
Therefore, one of the purposes of the invention is to solve the defects of the existing method and provide a preparation method of a sulfoxide participating in arylation synthesis of polysubstituted cyclic 1, 2-diketone compounds.
In order to solve the technical problems, the invention provides the following technical scheme: a method for preparing a multi-substituted ring 1, 2-diketone compound by using sulfoxide to participate in arylation synthesis comprises the following steps,
adding a sulfoxide compound, a 1, 2-diketone compound and a solvent into a test tube, placing the test tube in a low-temperature reactor at minus 10 ℃, adding trifluoroacetic anhydride when a reaction system is uniformly mixed and cooled to minus 10 ℃, reacting for 4-4.5 hours at minus 10 ℃, then moving to the room temperature, carrying out rotary evaporation concentration, and carrying out silica gel column chromatography separation to obtain a product.
As a preferred embodiment of the preparation method of the polysubstituted cyclic 1, 2-diketone compound provided by the invention: the mol ratio of the sulfoxide compound to the 1, 2-diketone compound is 1: 1 to 2.
As a preferred embodiment of the preparation method of the polysubstituted cyclic 1, 2-diketone compound provided by the invention: the molar ratio of the trifluoroacetic anhydride to the sulfoxide compound is 1: 1 to 2.
As a preferred embodiment of the preparation method of the polysubstituted cyclic 1, 2-diketone compound provided by the invention: the solvent was added in an amount of 8ml per millimole of sulfoxide compound.
As a preferred embodiment of the preparation method of the polysubstituted cyclic 1, 2-diketone compound provided by the invention: the rotary evaporation is carried out at the rotating speed of 100-200 rpm, the temperature of 25-30 ℃, the vacuum of 0.08-0.12 Mpa and the treatment time of 3-5 min; the chromatography adopts 200-mesh column chromatography silica gel, and the developing agent is petroleum ether: and (3) ethyl acetate is 9-15: 1.
as a preferred embodiment of the preparation method of the polysubstituted cyclic 1, 2-diketone compound provided by the invention: the sulfoxide compound comprises one or more of phenyl, substituted phenyl and thienyl sulfoxide compounds.
As a preferred embodiment of the preparation method of the polysubstituted cyclic 1, 2-diketone compound provided by the invention: the 1, 2-diketone compound comprises one or more of pentacyclic 1, 2-diketone and hexacyclic 1, 2-diketone.
As a preferred embodiment of the preparation method of the polysubstituted cyclic 1, 2-diketone compound provided by the invention: the polysubstituted ring 1, 2-diketone compound comprises polysubstituted ring 1, 2-diketone compounds shown in formulas I and II,
in the formula Ar1,Ar2，Ar3，Ar4，Ar5，R2,R1Are independent groups, and have 1 to 12 carbon atoms, wherein n is 1 or 2.
The invention has the beneficial effects that:
(1) the preparation method for synthesizing the polysubstituted ring 1, 2-diketone compound by taking the sulfoxide into the arylation enables the sulfoxide compound and the ring 1, 2-diketone compound to generate a C-C bond.
(2) The whole reaction does not need metal catalysis, is particularly suitable for the synthesis of some medicines in an organic solvent system, fundamentally eliminates the problems of metal residue and the like, and has higher economic applicability.
(3) Simple operation, high yield and high purity of more than 98 percent.
(4) The method has the advantages of mild conditions, wide substrate range, applicability of simple substrates and capability of modifying complex natural products by the method.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:
FIG. 1 is a nuclear magnetic spectrum H of the compound of example 1.
FIG. 2 is a nuclear magnetic spectrum C of the compound of example 1.
FIG. 3 is a nuclear magnetic spectrum H of the compound of example 2.
FIG. 4 is a nuclear magnetic spectrum C of the compound of example 2.
FIG. 5 is a nuclear magnetic spectrum H of the compound of example 3.
FIG. 6 is a nuclear magnetic spectrum C of the compound of example 3.
FIG. 7 is a nuclear magnetic spectrum H of the compound of example 4.
FIG. 8 is a nuclear magnetic spectrum C of the compound of example 4.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with examples are described in detail below.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1:
to a 20mL test tube, phenylthiophene sulfoxide (21mg,0.1mmol), 3-methylcyclopentane-1, 2-dione (17.1mg,0.15mmol) and simultaneously 0.8mL of dichloroethane were sequentially added at room temperature, and the mixture was placed in a low-temperature reactor at-10 ℃ until the reaction system was mixed well and the reaction mixture was-10 ℃, trifluoroacetic anhydride (21mg,0.15mmol) was added, followed by reaction at-10 ℃ for 4 hours, and then the reaction mixture was warmed to room temperature (usually 25 ℃) and stirred at that temperature for 1 minute. After the reaction is finished, the reaction system in the test tube is transferred into a 10ml eggplant-shaped bottle without post-treatment operation, a Heidolph rotary evaporator is used, the rotating speed is 80-100rpm, the temperature is 38 ℃, the vacuum degree is 0.1Mpa, the reaction system is treated for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel, and the developing agent is petroleum ether: ethyl acetate ═ 9: 1, separating to obtain a target compound (29mg, the yield is 96%, the purity is 98% by HPLC analysis, and the product purity is very high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like).
1H NMR(600MHz,CDCl3)δ7.46(d,J＝5.6Hz,1H),7.23(dd,J＝10.9,4.6Hz,1H),7.19(d,J＝5.6Hz,1H),7.14(dd,J＝10.6,4.2Hz,1H),7.08–7.05(m,1H),6.33(t,J＝3.1Hz,1H),2.73(dd,J＝17.9,2.9Hz,1H),2.59(dd,J＝17.9,3.4Hz,1H),1.57(s,1H).
13C NMR(150MHz,CDCl3)δ205.80,150.35,149.75,138.33,130.18,128.88,128.39,126.61,125.96,125.74,125.51,47.32,41.23,26.11.
Example 2:
to a 20mL test tube, diphenylsulfoxide (20.6mg,0.1mmol), 3-methylcyclopentane-1, 2-dione (17.1mg,0.15mmol) and simultaneously 0.8mL of dichloroethane were sequentially added at room temperature, and the mixture was placed in a-10 ℃ low-temperature reactor, and the reaction system was mixed well and trifluoroacetic anhydride (21mg,0.15mmol) was added at-10 ℃ and then reacted at-10 ℃ for 4 hours, and then the reaction mixture was warmed to room temperature (usually 25 ℃) and stirred at that temperature for 1 minute. After the reaction is finished, the reaction system in the test tube is transferred into a 10ml eggplant-shaped bottle without post-treatment operation, a Heidolph rotary evaporator is used, the rotating speed is 80-100rpm, the temperature is 38 ℃, the vacuum degree is 0.1Mpa, the reaction system is treated for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel, and the developing agent is petroleum ether: ethyl acetate ═ 9: 1, separating to obtain a target compound (26.9mg, the yield is 91%, the purity is 98% by HPLC analysis, and the product purity is very high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like).
1H NMR(600MHz,CDCl3)δ7.54(dd,J＝8.0,1.2Hz,1H),7.39(dd,J＝7.7,1.4Hz,1H),7.35–7.31(m,1H),7.26–7.20(m,3H),7.18–7.13(m,1H),7.09(dt,J＝3.2,1.8Hz,2H),6.31(t,J＝3.1Hz,1H),5.61(s,1H),2.76(dd,J＝17.7,2.6Hz,1H),2.60(dd,J＝17.7,1H),1.61(s,3H).
13C NMR(150MHz,CDCl3)δ206.08,150.69,145.40,137.40,136.57,133.27,128.98,128.76,128.44,128.19,126.28,123.36,123.22,50.43,41.29,25.34.
Example 3:
to a 20mL test tube, 4-bromophenylthiophenesulfoxide (30mg,0.1mmol), 1.2-cyclohexanedione (17.1mg,0.15mmol) and simultaneously 0.8mL of dichloroethane were sequentially added at room temperature, and the mixture was placed in a low-temperature reactor at-10 ℃ until the reaction system was mixed well and the reaction mixture was-10 ℃, trifluoroacetic anhydride (21mg,0.15mmol) was added, followed by reaction at-10 ℃ for 4 hours, and then the reaction mixture was warmed to room temperature (usually 25 ℃) and stirred at that temperature for 1 minute. After the reaction is finished, the reaction system in the test tube is transferred into a 10ml eggplant-shaped bottle without post-treatment operation, a Heidolph rotary evaporator is used, the rotating speed is 80-100rpm, the temperature is 38 ℃, the vacuum degree is 0.1Mpa, the reaction system is treated for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel, and the developing agent is petroleum ether: ethyl acetate ═ 9: 1, separating to obtain a target compound (22.9mg, the yield is 60%, the purity is 98% by HPLC analysis, and the product purity is very high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like).
1H NMR(400MHz,CDCl3)δ7.49(d,J＝5.5Hz,1H),7.37–7.32(m,1H),7.22(d,J＝5.5Hz,1H),7.03–6.97(m,1H),6.39(s,1H),2.75(t,J＝5.9Hz,1H),2.60–2.52(m,1H),2.07–1.97(m,1H).
13C NMR(100MHz,CDCl3)δ195.12,144.06,143.77,137.66,132.02,130.03,129.62,128.52,127.69,125.20,119.86,36.05,29.45,22.94.
Example 4:
first, in the same procedure as in example 1, phenylthiophene sulfoxide (42mg,0.2mmol), 3-methylcyclopentane-1, 2-dione (34.2mg,0.3mmol) and simultaneously 1.6mL of dichloroethane were sequentially added to a 20mL test tube at room temperature, placed in a low-temperature reactor at-10 ℃ and the reaction system was mixed well and trifluoroacetic anhydride (42mg,0.3mmol) was added to the reaction mixture at-10 ℃ for 4 hours, and then the reaction mixture was warmed to room temperature (usually 25 ℃) and stirred at this temperature for 1 minute. After the reaction is finished, the reaction system in the test tube is transferred into a 25ml eggplant-shaped bottle without post-treatment operation, a Heidolph rotary evaporator is used, the rotating speed is 80-100rpm, the temperature is 38 ℃, the vacuum degree is 0.1Mpa, the reaction system is treated for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel, and the developing agent is petroleum ether: ethyl acetate ═ 9: 1, separating to obtain a target compound (58mg, the yield is 96%, the purity is 98% by HPLC analysis, and the product purity is very high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like).
The product (46.5mg,0.15mmol) of the previous step, phenylthiophene sulfoxide (21mg,0.1mmol) were taken, added sequentially to a 20mL test tube at room temperature while adding 0.8mL of dichloroethane, placed in a-10 ℃ low temperature reactor, and after the reaction system was mixed well and the reaction mass was-10 ℃, trifluoroacetic anhydride (21mg,0.15mmol) was added, reaction was carried out at-10 ℃ for 4h, and then the reaction mixture was allowed to warm to room temperature (usually 25 ℃) and stirred at this temperature for 1 minute. After the reaction is finished, the reaction system in the test tube is transferred into a 10ml eggplant-shaped bottle without post-treatment operation, a Heidolph rotary evaporator is used, the rotating speed is 80-100rpm, the temperature is 38 ℃, the vacuum degree is 0.1Mpa, the reaction system is treated for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel, and the developing agent is petroleum ether: ethyl acetate ═ 9: 1, separating to obtain a target compound (32.1mg, the yield is 65%, the purity is 98% by HPLC analysis, and the product purity is very high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like).
1H NMR(400MHz,CDCl3)δ7.86(d,J＝5.7Hz,1H),7.45(dd,J＝5.6,3.7Hz,2H),7.25–6.95(m,11H),6.52(s,1H),3.42(d,J＝17.3Hz,1H),3.25(d,J＝17.3Hz,1H),1.52(s,3H).
13C NMR(100MHz,CDCl3)δ205.24,149.94,145.87,138.91,138.53,138.11,131.56,130.55,130.30,130.11,129.46,129.19,128.77,128.62,127.06,126.66,126.29,125.91,125.44,46.52,43.61,26.23.
Example 5:
into a 20mL test tube, phenylthiophene sulfoxide (21mg,0.1mmol) and 3-methylcyclopentane-1, 2-dione (17.1mg,0.15mmol) were sequentially added at room temperature, dichloroethane of different concentrations in Table 1 was added, the mixture was placed in an 80 ℃ reactor, and after the reaction system was mixed uniformly and the reaction mixture was brought to 80 ℃, trifluoroacetic anhydride (21mg,0.15mmol) was added, the mixture was reacted at a low temperature of 80 ℃ for 4 hours. The effect of solvent concentration on yield is shown in Table 1
TABLE 1 Effect of different solvent concentrations on yield
| Serial number | Concentration (M as mol/L) | Yield (%) |
| 1 | 0.1 | 28 |
| 2 | 0.125 | 61 |
| 3 | 0.15 | 50 |
| 4 | 0.2 | 36 |
| 5 | 0.5 | 17 |
| 6 | 1 | 12 |
Example 6:
in a 20mL test tube, phenylthiophene sulfoxide (21mg,0.1mmol) and 3-methylcyclopentane-1, 2-dione (17.1mg,0.15mmol) were sequentially added at room temperature, 0.8mL of dichloroethane was added, the mixture was placed in a low-temperature reactor, and after the reaction system was mixed uniformly, trifluoroacetic anhydride (21mg,0.15mmol) was added, the mixture was reacted at different temperatures in Table 2 for 4 hours.
TABLE 2 Effect of different reaction temperatures on the yield
| Serial number | Temperature (T/. degree.C.) | Yield (%) |
| 1 | -30 | 77 |
| 2 | -10 | 96 |
| 3 | 30 | 67 |
The preparation method for synthesizing the polysubstituted ring 1, 2-diketone compound by taking the sulfoxide into the arylation enables the sulfoxide compound and the ring 1, 2-diketone compound to generate a C-C bond. The whole reaction does not need metal catalysis, is particularly suitable for the synthesis of some medicines in an organic solvent system, fundamentally eliminates the problems of metal residue and the like, and has higher economic applicability. Simple operation, high yield and high purity of more than 98 percent. The method has the advantages of mild conditions, wide substrate range, applicability of simple substrates and capability of modifying complex natural products by the method. The developed compound is a popular intermediate, and can be subsequently derived into basic skeletons of various natural products such as medicines and the like.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (5)
1. A preparation method for synthesizing polysubstituted ring 1, 2-diketone compounds by taking part in arylation of sulfoxide is characterized in that:
adding a sulfoxide compound, a 1, 2-diketone compound and a solvent into a test tube, placing the test tube in a low-temperature reactor at minus 10 ℃, adding trifluoroacetic anhydride when a reaction system is uniformly mixed and cooled to minus 10 ℃, reacting for 4-4.5 hours at minus 10 ℃, then moving to the room temperature, carrying out rotary evaporation concentration, and carrying out silica gel column chromatography separation to obtain a product;
the sulfoxide compound is selected from one of phenyl thiophene sulfoxide, diphenyl sulfoxide and 4-bromophenyl thiophene sulfoxide;
the 1, 2-diketone compound is selected from one of 3-methylcyclopentane-1, 2-diketone and 1, 2-cyclohexanedione.
2. The process for producing polysubstituted cyclic 1, 2-diones according to claim 1, characterized in that: the mol ratio of the sulfoxide compound to the 1, 2-diketone compound is 1: 1 to 2.
3. The process for producing polysubstituted cyclic 1, 2-diones according to claim 1, characterized in that: the molar ratio of the trifluoroacetic anhydride to the sulfoxide compound is 1: 1 to 2.
4. The process for producing polysubstituted cyclic 1, 2-diones according to claim 1, characterized in that: the solvent was added in an amount of 8ml per millimole of sulfoxide compound.
5. The process for producing polysubstituted cyclic 1, 2-diones according to claim 1, characterized in that: the rotary evaporation is carried out at the rotating speed of 100-200 rpm, the temperature of 25-30 ℃, the vacuum of 0.08-0.12 Mpa and the treatment time of 3-5 min; the chromatography adopts 200-mesh column chromatography silica gel, and the developing agent is petroleum ether: and (3) ethyl acetate is 9-15: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910602120.1A CN110256400B (en) | 2019-07-05 | 2019-07-05 | Preparation method for synthesizing polysubstituted ring 1, 2-diketone by participation of sulfoxide in arylation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910602120.1A CN110256400B (en) | 2019-07-05 | 2019-07-05 | Preparation method for synthesizing polysubstituted ring 1, 2-diketone by participation of sulfoxide in arylation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110256400A CN110256400A (en) | 2019-09-20 |
| CN110256400B true CN110256400B (en) | 2021-08-24 |
Family
ID=67924544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910602120.1A Expired - Fee Related CN110256400B (en) | 2019-07-05 | 2019-07-05 | Preparation method for synthesizing polysubstituted ring 1, 2-diketone by participation of sulfoxide in arylation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110256400B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0591763A1 (en) * | 1992-10-05 | 1994-04-13 | Haarmann & Reimer Gmbh | Use of thioalkanediones as flavouring agents |
| CN106748927A (en) * | 2016-12-07 | 2017-05-31 | 南京林业大学 | A kind of preparation method of thio-ether type compounds and products thereof |
| CN106946751A (en) * | 2017-03-03 | 2017-07-14 | 浙江师范大学 | A kind of method for preparing diaryl sulfide |
| CN107011223A (en) * | 2015-10-08 | 2017-08-04 | 钱小英 | The synthetic method of medicine intermediate sulfide compound |
-
2019
- 2019-07-05 CN CN201910602120.1A patent/CN110256400B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0591763A1 (en) * | 1992-10-05 | 1994-04-13 | Haarmann & Reimer Gmbh | Use of thioalkanediones as flavouring agents |
| CN107011223A (en) * | 2015-10-08 | 2017-08-04 | 钱小英 | The synthetic method of medicine intermediate sulfide compound |
| CN106748927A (en) * | 2016-12-07 | 2017-05-31 | 南京林业大学 | A kind of preparation method of thio-ether type compounds and products thereof |
| CN106946751A (en) * | 2017-03-03 | 2017-07-14 | 浙江师范大学 | A kind of method for preparing diaryl sulfide |
Non-Patent Citations (3)
| Title |
|---|
| "Photoreaction of Alicyclic Ketones";寺田幸正等;《药学杂志》;19761231;第96卷(第7期);第919-922页 * |
| "双吲哚硫醚衍生物的新合成方法";李晓棠等;《北京化工大学学报（自然科学版）》;20171231;第44卷(第3期);第8-12页 * |
| 活化亚砜介导的碳氢键官能团反应研究;胡罡;《中国博士学位论文全文数据库 工程科技I辑》;20190115;B13-34页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110256400A (en) | 2019-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108341760B (en) | Preparation method of water-phase thioether compound and product thereof | |
| CN110256400B (en) | Preparation method for synthesizing polysubstituted ring 1, 2-diketone by participation of sulfoxide in arylation | |
| CN108276260B (en) | Preparation method of novel fluoro cyclopentenone and product thereof | |
| CN109096067A (en) | A kind of method of the alpha-brominated cyclopentenone of synthesizing new | |
| CN105175365B (en) | A kind of method of the β benzyl butyrolactone efficiently synthesized with particular configuration | |
| CN110256314B (en) | Preparation method of beta-aryl ketone compound and product thereof | |
| CN115611726A (en) | Method for enabling nitroso to participate in ring opening of cyclic ketone compound | |
| CN115353457A (en) | Asymmetric carbonic ester and preparation method thereof | |
| CN115010753A (en) | Method for preparing phosphorylated gem-difluorodiene compound in aqueous phase | |
| CN113149835B (en) | Preparation method for rapidly generating alpha-ketoester by iodine-mediated oxidation of alpha-diazo ester | |
| CN110283040B (en) | Synthetic method of 3-methyl-D3-benzyl bromide | |
| CN109180592B (en) | Synthesis method of 7-chloro-2- (3-chlorophenyl) quinazoline | |
| Hsu et al. | A short synthesis of (±)-antroquinonol in an unusual scaffold of 4-hydroxy-2-cyclohexenone | |
| CN108976179B (en) | Preparation method for preparing deuterated compound by using deuterium source as deuterium source | |
| CN111499538A (en) | Preparation method of (2S,3R) -2-amidomethyl-3-hydroxybutyrate | |
| CN111499662A (en) | Isotretinoin C15-triphenylphosphine chloride and preparation method and application thereof | |
| CN108440242A (en) | A kind of synthetic method of high activity chirality alkynol (S, E) -1,9- diene -4,6- diine -3- octadecyl alcolols | |
| CN111100085A (en) | Preparation method of 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound | |
| CN103508999A (en) | Maxacalcitol synthesizing intermediate and preparation method and application thereof | |
| CN103159600A (en) | Chemical synthetic process of gingerols | |
| CN109096082B (en) | Method for synthesizing alpha-iodo-cyclopentenone compound | |
| CN116037152B (en) | Palladium copper-cuprous oxide core-shell nano-cage catalyst and preparation method and application thereof | |
| CN108822060B (en) | 3-aryl substituted oxetane and preparation method thereof | |
| CN115010656B (en) | Preparation method of 5-acetyl-2-bromopyridine | |
| CN115583902B (en) | Preparation method of alkynyl thioether compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210824 |