CN117069677B - Preparation method of 2, 3-dihydro-5, 6-diaryl oxathiane - Google Patents
Preparation method of 2, 3-dihydro-5, 6-diaryl oxathiane Download PDFInfo
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Abstract
本发明公开了一种2,3‑二氢‑5,6‑二芳基氧硫杂环己二烯的制备方法，包括以下步骤：(1)将1‑芳基乙酮与氧化剂在氢溴酸以及溶剂的存在下进行氧化反应，得到1‑芳基‑2,2‑二羟基乙酮；(2)在保护气氛下，将1‑芳基‑2,2‑二羟基乙酮与苯胺衍生物在甲苯中进行取代反应，得到二芳基乙醇酮；(3)在保护气氛下，将二芳基乙醇酮与巯基乙醇在水溶性酸以及溶剂的存在下进行环化反应，得到所述2,3‑二氢‑5,6‑二芳基氧硫杂环己二烯。上述制备方法底物适用范围广，可用于合成不同分子结构的化合物，且上述合成方法的反应温和、副反应少，产物后处理简便且产率高，得到的产物纯度高，有利于该类化合物的工业化生产和应用。
The invention discloses a method for preparing 2,3-dihydro-5,6-diaryloxythiacyclohexine, comprising the following steps: (1) 1-aryl ethyl ketone and an oxidant are subjected to oxidation reaction in the presence of hydrobromic acid and a solvent to obtain 1-aryl-2,2-dihydroxy ethyl ketone; (2) 1-aryl-2,2-dihydroxy ethyl ketone and an aniline derivative are subjected to substitution reaction in toluene under a protective atmosphere to obtain diaryl ethanol ketone; (3) diaryl ethanol ketone and mercaptoethanol are subjected to cyclization reaction in the presence of a water-soluble acid and a solvent under a protective atmosphere to obtain the 2,3-dihydro-5,6-diaryloxythiacyclohexine. The above-mentioned preparation method substrate has a wide scope of application, can be used to synthesize compounds of different molecular structures, and the above-mentioned synthesis method has a mild reaction, few side reactions, simple product post-processing and high yield, and the obtained product has high purity, which is conducive to the industrial production and application of such compounds.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of 2, 3-dihydro-5, 6-diaryl oxathiane diene.
Background
2, 3-Dihydro-5, 6-diaryl-1, 4-oxathiolane is a compound with a unique structure, and an endocyclic double bond of the compound can react with an oxidant or oxygen under the condition of illumination and the like, so that the compound is widely interested in the fields related to optical technology such as light absorbing agents, luminescent agents, photochemical buffering agents and the like, and is valued to (WO 01/44811A2;Angew.Chem.Int.Ed.2022,61,e202211767;Angew.Chem.Int.Ed.2022,61,e202201630;CN 112500434A;CN 115947711 A)., the synthesis report of the compound is less, and the synthesis mainly comprises the following steps of oxidizing aryl ethanone into 1-aryl-2, 2-dihydroxyethanone, preparing diaryl ethanone from the 1-aryl-2, 2-dihydroxyethanone, and finally reacting the diaryl ethanone with mercaptoethanol to obtain a final target product, but the present preparation method has the defect of low synthesis efficiency in the second step and the third step.
The second step is to react 1-aryl-2, 2-dihydroxyethanone with a formazan reagent prepared from arylamine compounds, which is supposed to be because the activity of the formazan reagent is high, and benzoin compounds contain active structures, and the formazan reagent can react with the active structures, so that the yield of the target product prepared by the method is low, namely only 50 percent (WO 0144811 A2), and the 1-aryl-2, 2-dihydroxyethanone compounds and arylamine compounds can undergo Friedel-crafts reaction to synthesize the diaryl ethanone, for example, the prior art (Singh, S.; ullman, E.Syn Comm,2003, 34:451) reports that the reaction is carried out in solvent benzene, but the yield of the product obtained by reacting for 3 days at room temperature is only 57 percent, and the reaction rate is improved, but a great deal of byproducts are required to be produced, for example, the yield of the product obtained by 37 percent is high, and the byproduct is obtained by the reaction at the same time of 37 percent of the product is obtained by the Friedel-crafts reaction at 80 degrees.
The third step is to react diaryl ethanone with mercaptoethanol to obtain the final target product, wherein the process needs a catalyst, and in the prior art (WO 01/44811A2;Angew.Chem.Int.Ed.2022,61,e202211767;Angew.Chem.Int.Ed.2022,61,e202201630;CN 112500434A;CN 115947711A), trimethylchlorosilane is used as the catalyst to promote the ring forming reaction, and the reaction system has the following problems that on one hand, the usage amount of trimethylchlorosilane (TMSCl) is more than equivalent, and trimethylchlorosilane can react with hydroxyl in diaryl ethanone to generate byproducts, so that the difficulty of post-treatment is increased, the yield of the target product is reduced, the yield reported in the prior art is greatly in the range of 50% -60%, only a few of the products reach 60% -65%, and in addition, trimethylchlorosilane is used as the catalyst, and the post-treatment of the reaction product needs more water, so that the system containing the product is easy to emulsify and difficult to separate, and the post-treatment is complex and is not suitable for industrial production.
Based on this, in order to improve the synthesis efficiency and reduce the cost of 2, 3-dihydro-5, 6-diaryloxylthio hexadiene, a preparation method that is simple in post-treatment and can effectively improve the yield is needed, so as to be suitable for industrial production and promote the practical application thereof.
Disclosure of Invention
The invention provides a preparation method of 2, 3-dihydro-5, 6-diaryl oxathiolene, which is mainly characterized in that the second step and the third step of synthesizing the 2, 3-dihydro-5, 6-diaryl oxathiolene in the prior art are improved, the synthesis yield of a target compound is effectively improved, the post-treatment of a product is simple, and the preparation method is suitable for industrial production.
In order to solve the technical problems, the invention provides the following technical scheme:
The invention provides a preparation method of 2, 3-dihydro-5, 6-diaryl oxathiane, which is characterized by comprising the following steps:
(1) Carrying out oxidation reaction on 1-aryl-ethanone shown in a formula (I) and an oxidant in the presence of hydrobromic acid and a solvent to obtain 1-aryl-2, 2-dihydroxyethanone shown in a formula (II);
(2) Carrying out substitution reaction on the 1-aryl-2, 2-dihydroxyethanone shown in the formula (II) and the aniline derivative shown in the formula (III) prepared in the step (1) in toluene under a protective atmosphere to obtain diaryl ethanone shown in the formula (IV);
(3) In a protective atmosphere, cyclizing the diaryl ethanone shown in the formula (IV) prepared in the step (2) with mercaptoethanol in the presence of water-soluble acid and a solvent to obtain 2, 3-dihydro-5, 6-diaryl oxathiolene shown in the formula (V);
The structures of the above formulas (I) to (V) are as follows:
Wherein R 1 is selected from one of hydrogen, halogen, acyl, cyano, nitro, amino, hydroxy, sulfonyl, sulfonic acid, C1-C22 alkyl, C2-C22 alkynyl, C2-C22 ester, C1-C22 alkoxy, C1-C24 haloalkyl, C6-C22 aryl, C1-C17 heteroaryl containing O, N or S;
R 2 and R 3 are each independently selected from one of hydrogen, C1-C22 alkyl, C1-C22 acyl, C6-C22 aryl, C1-C17 heteroaryl containing O, N or S.
In the present invention, unless otherwise indicated, terms used have the ordinary meanings known to those skilled in the art.
The term "halogen" refers to all halogens, i.e., fluorine, chlorine, bromine or iodine; the term "acyl" refers to the group-COR; the term "cyano" refers to the group-CN; the term "nitro" refers to the group-NO 2, the term "hydroxy" refers to the group-OH, the term "amine" refers to the group-NHR 2 or NR 2R3, the term "sulfonyl" refers to the group-SO 3R2, the term "sulfonate" refers to the group-SO 3 H, the term "ester" refers to the group-COOR, where R may be alkyl.
The term "alkane" refers to cycloalkanes, straight chain alkanes and branched alkanes having the indicated number of carbon atoms, and the C1-C22 alkane groups of the present invention refer to those having 1-22 numbers of carbon atoms, and the alkyl groups of the present invention include, but are not limited to, methyl, ethyl, propyl, n-butyl, n-hexyl, cyclohexyl, n-tetradecyl, and the like. Alkyl groups also include substituted alkyl groups. Substituted alkyl means that the alkyl is substituted in one or more positions, in particular 1 to 2 substituents, and may be substituted in any position.
The term "alkynyl" refers to a carbon chain containing at least one carbon-carbon triple bond, which may be straight or branched, or a combination thereof, and the C1-C22 alkynyl of the present invention refers to alkynyl groups having 1-22 carbon atoms, including but not limited to ethynyl.
The term "alkoxy" refers to cycloalkanes, straight chain alkanes and branched alkanes having the indicated number of carbon atoms, in certain embodiments having 1 to 3 oxygen atoms, for example, 1 oxygen atom.
The term "haloalkyl" refers to straight, branched or cyclic saturated aliphatic halogenated hydrocarbon groups, and C1-C24 haloalkyl of the present invention refers to those having from 1 to 22 carbon atoms, wherein haloalkyl includes monohaloalkyl and polyhaloalkyl.
The term "aryl" refers to aromatic groups having a single ring, multiple rings or multiple condensed rings, having 6 to 22 carbon atoms, and having 1 to 4 rings, especially monocyclic and bicyclic groups. In certain specific embodiments, the aryl group has from 6 to 14 carbon atoms. Aryl includes simple aryl and substituted aryl, such as unsubstituted aryl groups including phenyl, naphthyl, and biphenyl. Substituted aryl means that one or more hydrogens in the aryl group are substituted, especially 1-3 substituents, in any position, and the substituents on the substituted aryl group are halogen, alkyl, acyl, sulfonate, sulfonyl, hydroxy, cyano, amine, or any combination of the foregoing.
The term "heteroaryl" refers to a monocyclic, polycyclic or polycyclic fused ring radical containing 1 to 4 heteroatoms, and C1-C17O, N or S-containing heteroaryl according to the invention refers to a radical having 1 to 17 carbon atoms, where the heteroatoms are O, N or S. Heteroaryl includes unsubstituted heteroaryl and substituted heteroaryl, the substituents on the substituted heteroaryl being halogen, alkyl, acyl, sulfonate, sulfonyl, hydroxy, cyano, amine, or any combination of the foregoing.
Here, in the present invention, the selection groups in the listed definitions of the respective substituents may be combined with each other to form a new substituent conforming to the bond formation rule.
Further, the 2, 3-dihydro-5, 6-diaryloxylthio hexadiene may be selected from one of the structures shown in the following V-1~V-18:
Further, in the step (1), the oxidant is preferably dimethyl sulfoxide, the solvent is preferably dimethyl sulfoxide, and specifically, the molar ratio of the 1-aryl ethanone shown in the formula (I) to the dimethyl sulfoxide to hydrobromic acid is preferably 1:4-12:0.2-1.5, such as 1:6:6.
Further, in the step (1), the reaction temperature of the oxidation reaction is preferably 60 to 110 ℃, more preferably 90 ℃, and the reaction time is preferably 2 to 10 hours, more preferably 3 to 6 hours.
In some preferred embodiments of the invention, the step (1) further comprises a post-treatment process, specifically, after the oxidation reaction is finished, adding alkali into the system for neutralization, adding water and stirring until solid is separated out, filtering, and washing with petroleum ether to obtain the 1-aryl-2, 2-dihydroxyethanone shown in the formula (II).
Further, in the step (2), the molar ratio of the 1-aryl-2, 2-dihydroxyethanone represented by the formula (II) to the aniline derivative represented by the formula (III) is preferably 1:0.8 to 2, for example, 1:1.
Further, in the step (2), the temperature of the substitution reaction is preferably 40 to 70 ℃, more preferably 45 to 65 ℃, for example 60 ℃, and the reaction time is preferably 8 to 24 hours.
In some preferred embodiments of the present invention, the step (2) further includes a post-treatment process, specifically, column chromatography separation and purification are performed after the substitution reaction is completed, and elution is performed by using a petroleum ether/ethyl acetate mixed solvent with a volume ratio of 2-10:1, so as to obtain the diaryl ethanone represented by the formula (IV).
In the process of preparing diaryl ethanone from the second step of 1-aryl-2, 2-dihydroxyethanone and aniline derivatives, the invention unexpectedly discovers that when the solvent in the reaction system is toluene, the yield of diaryl ethanone in the reaction product can be effectively improved by controlling the reaction temperature, and the amount of byproducts is reduced, so that the present product is convenient for post-treatment separation.
Further, in the step (3), the water-soluble acid is selected from one or more of hydrochloric acid, sulfuric acid, sodium bisulfate, potassium bisulfate, acetic acid, trifluoroacetic acid, methanesulfonic acid, and trifluoromethanesulfonic acid, and more preferably is trifluoromethanesulfonic acid.
Further, in step (3), the solvent is preferably toluene or 1, 4-dioxane.
Further, in the step (3), the temperature of the cyclization reaction is preferably 90 to 130 ℃, more preferably 110 ℃, and the reaction time is preferably 2 to 24 hours.
In some preferred embodiments of the present invention, the step (3) further includes a post-treatment process, specifically, after the cyclization reaction is completed, sequentially performing alkali neutralization, water washing, drying, vacuum solvent removal and column chromatography separation and purification, and eluting with a petroleum ether/ethyl acetate mixed solvent with a volume ratio of 50-150:1 during column chromatography to obtain the target product 2, 3-dihydro-5, 6-diaryl oxathiolene.
In the process of preparing the target product 2, 3-dihydro-5, 6-diaryl oxathiolane by cyclizing reaction of diaryl ethanone and mercaptoethanol in the third step, the invention uses water-soluble acid as a catalyst, thereby effectively improving the yield of the target product, facilitating post-treatment and enabling the product to obtain the product with the purity of more than 99 percent after simple post-treatment.
Compared with the prior art, the invention has the beneficial effects that:
The invention optimizes the method for preparing 2, 3-dihydro-5, 6-diaryl oxathiolane in the prior art, mainly optimizes the second step for preparing diaryl ethanone and the third step for cyclization reaction, and specifically discovers that the method can effectively improve the yield of target products and reduce the content of byproducts in the products by regulating and controlling the solvent and the temperature of a second step reaction system, for example, toluene is used as the solvent of the second step reaction system, the product with the yield of diaryl ethanone being 75% and the yield of byproducts being less than 1% can be obtained after the reaction is carried out for 12 hours at 60 ℃, and in addition, the method discovers that when water-soluble acid is used for replacing trimethylchlorosilane in the prior art, the reaction efficiency of the third step for cyclization reaction can be effectively improved, the yield of the target products is high, the target products can be easily separated and purified, and the product with the purity being more than 99% can be obtained after the separation by simple column chromatography. The invention improves the synthesis method of the 2, 3-dihydro-5, 6-diaryl oxathiolane, and the improved preparation process has the advantages of mild reaction condition, easy regulation and control, short production period, high yield and the like, and is suitable for the industrial production of the 2, 3-dihydro-5, 6-diaryl oxathiolane.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of the product V-1 prepared in example 1;
FIG. 2 is an HPLC plot of the product V-1 prepared in example 1;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of the product V-2 prepared in example 2;
FIG. 4 is an HPLC plot of product V-2 prepared in example 2.
Detailed Description
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 to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items. The term "comprising" or "comprises" as used herein means that it may include or comprise other components in addition to the components described. The term "comprising" or "comprising" as used herein may also be replaced by "being" or "consisting of" closed.
The present invention will be further described with reference to specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the present invention and practice it.
Example 1
The embodiment provides a preparation method of 2, 3-dihydro-5, 6-diaryl oxathiolane shown in a formula V-1, which comprises the following specific processes:
(1) Accurately weighing acetophenone (60 g,500 mmol) and 250mL DMSO in a 500mL three-port reaction bottle, installing a reflux condenser and a constant pressure dropping funnel, placing the reaction bottle in an 80 ℃ oil bath, stirring at the temperature, slowly dropping hydrobromic acid (30 mL,40% aq), after the continuous stirring for 1 hour, turning off the heating, naturally cooling the reaction bottle, returning the oil bath temperature to room temperature, adding sodium hydroxide aqueous solution to neutralize the reaction bottle to be neutral, cooling the reaction system to 5 ℃, stirring until solid is separated out, filtering, washing a filter cake with Petroleum Ether (PE) to obtain solid, and drying to obtain 65.4g of 2, 2-dihydroxyacetophenone with the yield of 86%, wherein the product is a light yellow solid (the higher the purity is, the lighter the color is). The 2, 2-dihydroxyacetophenone and its derivatives used in the subsequent examples were all obtained by this method.
(2) Transferring 60.8g (400 mmol) of the 2, 2-dihydroxyacetophenone prepared in the step (1) into a reaction bottle, adding raw material N, N-dimethylaniline (48.5 g,400 mmol), adding 400mL of toluene as a reaction solvent, reacting in an oil bath at 60 ℃ under the protection of inert gas, turning off the heat after reacting for 12 hours, naturally cooling, concentrating to obtain a crude product, and directly separating by column chromatography (ethyl acetate: petroleum ether=1:5, rf is approximately equal to 0.4) to obtain 76.6gThe yield thereof was found to be 75%.
(3) 76.6G (300 mmol) of the product obtained in step (2)Transferring to a reaction bottle, adding mercaptoethanol (30.5 g,390 mmol), adding 300mL of toluene solvent as solvent, adding trifluoromethanesulfonic acid (4.5 g,30 mmol) as catalyst, reacting at 110 ℃ under the protection of inert gas, turning off the heat after reacting for 12 hours, naturally cooling, adding sodium hydroxide solution to neutralize to neutrality, washing with water, drying, concentrating to obtain crude product, and directly performing column chromatography separation (ethyl acetate: petroleum ether=1:100, rf is approximately equal to 0.6) to obtain 81.2g of compound IV1, wherein the yield is 91% and the product is light yellow solid. And (3) carrying out nuclear magnetism and high performance liquid chromatography characterization on the product, wherein the characterization result is as follows:
1H NMR(400MHz,CCl3D)δ7.26-7.22(m,2H),7.19-7.13(m,5H),6.60(d,J＝8Hz,2H),4.53(t,J＝4Hz,2H),3.25(t,J＝4Hz,2H),2.95(s,6H);
The purity was 99.94%.
In addition, for the above step (2), the influence of the kind of solvent and the reaction temperature on the reaction product was studied in this example, and the specific examples are shown in the following table 1:
TABLE 1
| Group of | Solvent(s) | Reaction temperature | Reaction time | IV yield (%) | IVA yield (%) |
| 1 | Toluene (toluene) | 40°C | 24 Hours | 62% | <1% |
| 2 | Toluene (toluene) | 50°C | For 12 hours | 69% | <1% |
| 3 | Toluene (toluene) | 60°C | For 12 hours | 75% | <1% |
| 4 | Toluene (toluene) | 65°C | For 12 hours | 82% | 2% |
| 5 | Toluene (toluene) | 70°C | For 6 hours | 79% | 5% |
| 6 | Chlorobenzene (Chlorobenzene) | 65°C | For 12 hours | 65% | 2% |
| 7 | Benzotrifluoride (TFA) | 65°C | For 12 hours | 59% | 1% |
| 8 | Xylene (P) | 65°C | For 12 hours | 67% | 3% |
| 9 | DMSO | 65°C | For 12 hours | 31% | <1% |
| 10 | DMF | 65°C | For 12 hours | 23% | <1% |
| 11 | 1, 4-Dioxahexacyclic ring | 65°C | For 12 hours | 52% | 12% |
| 12 | Tetrahydrofuran (THF) | 65°C | For 12 hours | 47% | 15% |
| 13 | 1, 2-Dichloroethane | 65°C | For 12 hours | 45% | <1% |
| 14 | Ethanol | 65°C | For 12 hours | <5% | <1% |
IV in the table isIVA is
As can be seen from table 1, when the reaction system solvent was toluene, compound IV was obtained in a high yield within 12 hours, and in this reaction system, the reaction rate was increased with an increase in the reaction temperature, but the reaction temperature was not excessively high, and when the reaction temperature was >60 ℃, the yield of by-product IVA was significantly increased.
Example 2
The embodiment provides a preparation method of 2, 3-dihydro-5, 6-diaryl oxathiolane shown in a formula V-2, which comprises the following specific processes:
(1) Consistent with step (1) of example 1;
(2) Transferring 60.8g (400 mmol) of the 2, 2-dihydroxyacetophenone prepared in the step (1) into a reaction bottle, and adding (194.2 G,400 mmol) and 400mL of toluene are added as reaction solvent, the reaction is carried out under the protection of inert gas and placed in an oil bath at 60 ℃ for reaction, after the reaction is carried out for 12 hours, the heating is turned off, the natural cooling is carried out, the crude product is obtained after concentration, and column chromatography separation is directly carried out (ethyl acetate: petroleum ether=1:5, rf is approximately equal to 0.5), thus 190.8g is obtainedThe yield thereof was found to be 77%.
(3) 185.9G (300 mmol) of the product obtained in step (2) are reactedTransferring to a reaction bottle, adding mercaptoethanol (30.5 g,390 mmol), adding 300mL of toluene solvent for dissolution, adding trifluoromethanesulfonic acid (4.5 g,30 mmol) as a catalyst, reacting at 110 ℃ under the protection of inert gas, turning off the heat after reacting for 12 hours, naturally cooling, adding sodium hydroxide solution for neutralization to neutrality, washing with water, drying, concentrating to obtain a crude product, and directly performing column chromatography separation (ethyl acetate: petroleum ether=1:150, rf is approximately equal to 0.5) to obtain 174.6gThe yield is 88%, the product is light yellow oily matter, and the product is subjected to nuclear magnetism and high performance liquid chromatography characterization, wherein the characterization result is as follows:
1H NMR(400MHz,CCl3D)δ7.21-7.19(m,2H),7.14-7.08(m,3H),7.02(d,J＝8Hz,2H),6.43(d,J＝8Hz,2H),4.48(t,J＝4Hz,2H),3.22-3.15(m,6H),1.55-1.47(m,4H),1.32-1.22(m,44H),0.88(t,J＝8Hz,6H);
the purity is 99.796%.
Example 3
The embodiment provides a preparation method of 2, 3-dihydro-5, 6-diaryl oxathiolane shown in a formula V-3, which comprises the following specific processes:
(1) Consistent with step (1) of example 1;
(2) Transferring 60.8g (400 mmol) of the 2, 2-dihydroxyacetophenone prepared in the step (1) into a reaction bottle, adding triphenylamine (98.1 g,400 mmol), adding 400mL of toluene as a reaction solvent, reacting under the protection of inert gas and in an oil bath at 60 ℃, turning off the heat after reacting for 12 hours, naturally cooling, concentrating to obtain a crude product, and directly separating by column chromatography (ethyl acetate: petroleum ether=1:5, rf approximately equal to 0.45) to obtain 119.9g The yield thereof was found to be 79%.
(3) 113.8G (300 mmol) of the product obtained in step (2) are reacted withTransferring to a reaction bottle, adding mercaptoethanol (30.5 g,390 mmol), adding 300mL of toluene solvent for dissolution, adding trifluoromethanesulfonic acid (4.5 g,30 mmol) as a catalyst, reacting at 110 ℃ under the protection of inert gas, turning off the heat after reacting for 12 hours, naturally cooling, adding sodium hydroxide solution for neutralization to neutrality, washing with water, drying, concentrating to obtain a crude product, and directly performing column chromatography separation (ethyl acetate: petroleum ether=1:120, rf is approximately equal to 0.5) to obtain 106.2gThe yield is 84%, the product is a pale yellow solid, and the product is subjected to nuclear magnetic characterization, wherein the characterization result is as follows:
1H NMR(400MHz,CCl3D)δ7.27-7.12(m,9H),7.11-6.95(m,8H),6.88(d,J＝8Hz,2H),4.53(t,J＝4Hz,2H),3.25(t,J＝4Hz,2H).
Example 4
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-4 by substituting 4-bromoacetophenone for acetophenone of example 2 to give the desired compound V-4 in 82% yield in the second step and 83% in the third step. The product is light yellow oily matter, and the nuclear magnetic characterization data are as follows ：1H NMR(400MHz,CCl3D)δ7.52(d,J＝8Hz,2H),7.23(d,J＝8Hz,2H),7.03(d,J＝8Hz,2H),6.45(d,J＝8Hz,2H),4.50(t,J＝4Hz,2H),3.24-3.16(m,6H),1.56-1.48(m,4H),1.34-1.23(m,44H),0.88(t,J＝8Hz,6H).
Example 5
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-5 by substituting 4-nitroacetophenone for acetophenone from example 2 to give the desired compound V-5 in a yield of 70% in the second step and 79% in the third step. The product is yellow solid, and the nuclear magnetism characterization data is as follows ：1HNMR(400MHz,CCl3D)δ8.12(d,J＝8Hz,2H),7.56(d,J＝8Hz,2H),7.10(d,J＝8Hz,2H),6.51(d,J＝8Hz,2H),4.56(t,J＝4Hz,2H),3.29-3.20(m,6H),1.57-1.47(m,4H),1.36-1.24(m,44H),0.89(t,J＝8Hz,6H).
Example 6
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-6 by substituting 4-phenylacetophenone for acetophenone of example 2 to give the desired compound V-6 in 83% yield in the second step and 85% yield in the third step. The product is light yellow solid, and the nuclear magnetic characterization data is as follows ：1H NMR(400MHz,CCl3D)δ7.72-7.49(m,9H),7.23(d,J＝8Hz,2H),7.01(d,J＝8Hz,2H),6.40(d,J＝8Hz,2H),4.52(t,J＝4Hz,2H),3.22-3.14(m,6H),1.56-1.45(m,4H),1.33-1.22(m,44H),0.87(t,J＝8Hz,6H).
Example 7
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-7, which is carried out in the same manner as in example 2, using 4- (1-isoquinolinyl) acetophenone instead of acetophenone of example 2, to give the desired compound V-7 in a second step in 71% yield and in a third step in 77% yield. The product is yellow solid, and the nuclear magnetism characterization data is as follows ：1H NMR(400MHz,CCl3D)δ8.39(d,J＝8Hz,1H),8.11(d,J＝8Hz,2H),7.65-7.50(m,7H),7.06(d,J＝8Hz,2H),6.41(d,J＝8Hz,2H),4.50(t,J＝4Hz,2H),3.21-3.13(m,6H),1.55-1.44(m,4H),1.32-1.21(m,44H),0.89(t,J＝8Hz,6H).
Example 8
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-8, which is carried out in the same manner as in example 2, using 4- (2-1, 10-phenanthroline) -acetophenone instead of acetophenone of example 2 to give the desired compound V-8 in a yield of 69% in the second step and 76% in the third step. The product is yellow solid, and the nuclear magnetism characterization data is as follows ：1H NMR(400MHz,CCl3D)δ8.75-9.69(m,3H),8.23-8.10(m,3H),7.71-7.52(m,4H),7.07(d,J＝8Hz,2H),6.46(d,J＝8Hz,2H),4.52(t,J＝4Hz,2H),3.24-3.14(m,6H),1.56-1.46(m,4H),1.36-1.24(m,44H),0.88(t,J＝8Hz,6H).
Example 9
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-9 by substituting 4- (6-phenanthridinyl) acetophenone for acetophenone from example 2 to give the desired compound V-9 in 69% yield in the second step and 73% in the third step. The product is yellow solid, and the nuclear magnetism characterization data is as follows ：1H NMR(400MHz,CCl3D)δ8.19-8.10(m,3H),7.81-7.65(m,9H),7.22(d,J＝8Hz,2H),7.04(d,J＝8Hz,2H),6.42(d,J＝8Hz,2H),4.50(t,J＝4Hz,2H),3.23-3.15(m,6H),1.54-1.45(m,4H),1.34-1.22(m,44H),0.88(t,J＝8Hz,6H).
Example 10
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-10 by substituting 4-bromoacetophenone for acetophenone from example 3 to give the desired compound V-10 in a second step in 76% yield and in a third step in 80% yield. The product is light yellow solid, and the nuclear magnetic characterization data is as follows ：1H NMR(400MHz,CCl3D)δ7.56(d,J＝8Hz,2H),7.32-7.12(m,6H),7.10-6.95(m,8H),6.89(d,J＝8Hz,2H),4.55(t,J＝4Hz,2H),3.26(t,J＝4Hz,2H).
Example 11
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-11, which is carried out in the same manner as in example 3, substituting 4-fluoroacetophenone for acetophenone of example 3 to obtain the desired compound V-11 in a yield of 70% in the second step and 82% in the third step. The product is light yellow solid, and the nuclear magnetic characterization data is as follows ：1HNMR(400MHz,CCl3D)δ7.53(d,J＝8Hz,2H),7.30-7.12(m,6H),7.11-6.95(m,8H),6.88(d,J＝8Hz,2H),4.54(t,J＝4Hz,2H),3.26(t,J＝4Hz,2H).
Example 12
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-12 by substituting 4-cyanoacetophenone for acetophenone of example 3 to give the desired compound V-12 in a yield of 72% in the second step and 81% in the third step. The product is light yellow solid, and the nuclear magnetic characterization data is as follows ：1H NMR(400MHz,CCl3D)δ7.83(d,J＝8Hz,2H),7.35-7.16(m,6H),7.12-6.97(m,8H),6.91(d,J＝8Hz,2H),4.55(t,J＝4Hz,2H),3.25(t,J＝4Hz,2H).
Example 13
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-13, which is carried out in the same manner as in example 3, substituting 4-trifluoromethyl acetophenone for acetophenone of example 3 to obtain the target compound V-13 with 82% yield in the second step and 86% yield in the third step. The product is light yellow solid, and the nuclear magnetic characterization data is as follows ：1HNMR(400MHz,CCl3D)δ7.31-7.17(m,8H),7.13-6.97(m,8H),6.89(d,J＝8Hz,2H),4.56(t,J＝4Hz,2H),3.26(t,J＝4Hz,2H).
Example 14
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-14, which is carried out in the same manner as in example 3, substituting 4-ethynylacetophenone for acetophenone of example 3 to obtain the desired compound V-14 in a yield of 56% in the second step and 70% in the third step. The product is yellow solid, and the nuclear magnetism characterization data is as follows ：1H NMR(400MHz,CCl3D)δ7.33-7.14(m,8H),7.12-6.97(m,8H),6.89(d,J＝8Hz,2H),4.52(t,J＝4Hz,2H),3.24(t,J＝4Hz,2H),3.01(s,1H).
Example 15
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-15, which is carried out in the same manner as in example 3, substituting methyl 4-acetylbenzoate for acetophenone of example 3 to obtain the desired compound V-15, the yield in the second step being 82%, and the yield in the third step being 75%. The product is yellow solid, and the nuclear magnetism characterization data is as follows ：1HNMR(400MHz,CCl3D)δ7.69-7.57(m,4H),7.31-7.16(m,6H),7.12-6.94(m,6H),6.89(d,J＝8Hz,2H),4.52(t,J＝4Hz,2H),3.86(s,1H),3.24(t,J＝4Hz,2H).
Example 16
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-16 by substituting 4-acetylbiphenyl for acetophenone of example 3 to give the desired compound V-16 in a yield of 84% in the second step and 82% in the third step. The product is yellow solid, and the nuclear magnetism characterization data is as follows ：1HNMR(400MHz,CCl3D)δ7.61-7.45(m,5H),7.27-7.14(m,8H),7.12-6.95(m,8H),6.89(d,J＝8Hz,2H),4.55(t,J＝4Hz,2H),3.24(t,J＝4Hz,2H).
Example 17
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-17, which is carried out in the same manner as in example 3, substituting 4- (4-pyridyl) acetophenone for acetophenone of example 3 to obtain the target compound V-17 in 68% yield in the second step and 77% in the third step. The product is light yellow solid, and the nuclear magnetic characterization data is as follows ：1H NMR(400MHz,CCl3D)δ8.65(d,J＝8Hz,2H),7.61-7.52(m,6H),7.23-7.14(m,4H),7.12-6.97(m,8H),6.89(d,J＝8Hz,2H),4.54(t,J＝4Hz,2H),3.25(t,J＝4Hz,2H).
Example 18
This example provides a process for the preparation of 2, 3-dihydro-5, 6-diaryloxylthio-hexadiene of formula V-18, which is similar to example 3, wherein 4-quinolinylacetophenone is substituted for acetophenone of example 3 to give the desired compound V-18 in a second step in 71% yield and in a third step in 78% yield. The product is light yellow solid, and the nuclear magnetic characterization data is as follows ：1H NMR(400MHz,CCl3D)δ8.69(s,1H),7.75-7.61(m,4H),7.29-7.15(m,9H),7.13-6.96(m,8H),6.89(d,J＝8Hz,2H),4.54(t,J＝4Hz,2H),3.25(t,J＝4Hz,2H).
The above-described embodiments are merely preferred embodiments for fully explaining the present invention, and the scope of the present invention is not limited thereto. Equivalent substitutions and modifications will occur to those skilled in the art based on the present invention, and are intended to be within the scope of the present invention. The protection scope of the invention is subject to the claims.
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