CN108530410B - Method for constructing dihydropyran ring by benzaldehyde, α -methyl styrene compound and dimethyl sulfoxide - Google Patents
Method for constructing dihydropyran ring by benzaldehyde, α -methyl styrene compound and dimethyl sulfoxide Download PDFInfo
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Abstract
The invention discloses a method for jointly constructing a dihydropyran ring by benzaldehyde, α -methyl styrene compounds and dimethyl sulfoxide, which is characterized in that the benzaldehyde compounds and α -methyl styrene compounds are subjected to one-pot reaction in a dimethyl sulfoxide solution system containing persulfate to obtain dihydropyran derivatives, the method is used for jointly constructing the dihydropyran ring by providing carbonyl with the benzaldehyde compounds, providing propenyl with the α -methyl styrene compounds and providing methyl with the dimethyl sulfoxide for the first time, and the synthesis method is realized by a one-pot method.
Description
Technical Field
The invention relates to a method for synthesizing a dihydropyran derivative, in particular to a method for constructing a dihydropyran ring by a benzaldehyde compound, an α -methyl styrene compound and dimethyl sulfoxide through a one-pot method, and belongs to the field of synthesis of organic intermediates.
Background
The dihydropyran derivatives are important hexatomic oxygen-containing heterocyclic compounds and have unique biological and pharmaceutical activities, for example, Zanamivir is a medicament for resisting influenza viruses, Benesusun can be used as an antibiotic, and the Benesudon is an important organic intermediate, for example, 2-ethoxy-3, 4-dihydropyran is a relatively cheap intermediate for synthesizing glutaraldehyde, and glutaraldehyde can be obtained by hydrolysis. Therefore, dihydropyran derivatives have attracted attention from numerous organic chemists and pharmacologists, and are one of the most studied heterocyclic compounds over the past several decades.
At present, a plurality of reports about the synthesis of dihydropyrane are available, such as common alkyne-hydrogen oxyalkylation cyclization synthesis; oxo-Diels-Alder reaction; michael addition/cyclization tandem reaction synthesis; Knoevenagel/oxo-Diels-Alder series reaction. The most valuable method is to synthesize dihydropyran by Diels-Alder reaction, for example, the classical reaction is to obtain dihydropyran by Diels-Alder reaction of conjugated diolefine and aldehyde group under Lewis acid catalysis, for example, U.S. Pat. No. 5,5162551 discloses benzaldehyde and conjugated diolefine in AlCl32-benzene synthesis under catalysis ofA radical-5, 6-dihydro-2H-pyran. Chinese patent (CN101143860A) discloses that 5, 6-dihydro-pyran and its derivatives are synthesized by diels-alder reaction of conjugated diene and anhydrous formaldehyde under the catalysis of lewis acid, since diels-alder reaction all needs lewis acid as catalyst and needs to be carried out at high temperature, and lewis acid can also initiate olefin polymerization, resulting in many side reactions and difficult control. Chinese patent (CN101481369A) discloses a method for efficiently synthesizing 4, 6-substituted 3, -4-dihydro-pyran-2-one derivatives from aldehyde-substituted cyclopropane compounds by using azacyclo-carbene as a catalyst, wherein the aldehyde-substituted cyclopropane compounds adopted in the method are raw materials which are difficult to obtain and have higher cost.
Disclosure of Invention
Aiming at the defects of the existing method for constructing the dihydropyran ring, the invention aims to provide a method for constructing the dihydropyran ring together by providing carbonyl by a benzaldehyde compound, providing propenyl by an α -methyl styrene compound and providing methyl by dimethyl sulfoxide.
In order to realize the technical purpose, the invention provides a method for constructing a dihydropyran ring by benzaldehyde, α -methyl styrene compounds and dimethyl sulfoxide, wherein the method comprises the steps of carrying out one-pot reaction on benzaldehyde compounds and α -methyl styrene compounds in a dimethyl sulfoxide solution system containing persulfate to obtain dihydropyran derivatives;
the benzaldehyde compound has a structure shown in a formula 1:
the α -methyl styrene compound has the structure of formula 2:
the dihydropyran derivative has the structure of formula 3:
wherein the content of the first and second substances,
R1、R2and R3Independently selected from hydrogen, halogen substituents, alkyl, trifluoromethyl, nitro, cyano or alkoxy;
R4selected from hydrogen, halogen substituents or alkyl groups.
In the technical scheme of the invention, the benzaldehyde compound has wide selection range, the selection of substituent groups on a benzene ring has no obvious influence on the construction of a dihydropyran ring, and R is1、R2And R3The yield of the dihydropyrane is kept about 60% when various common substituent groups are selected, the number of the substituent groups contained on the benzene ring is 1-3, and the substituent groups are selected from halogen substituent groups (fluorine, chlorine, bromine or iodine) and alkyl groups (C)1～C5Alkyl), trifluoromethyl, nitro, cyano or alkoxy (C)1～C5Alkoxy group of (a); the position of the substituent is not particularly required and can be ortho-position, meta-position or para-position of the aldehyde group, but a large number of experiments show that the ideal yield of the dihydropyran derivative can be obtained when the bromine substituent is meta-position or para-position of the aldehyde group, but the dihydropyran product can not be obtained when the bromine substituent is ortho-position of the aldehyde group, and the ideal yield can be obtained when other substituents except bromine are ortho-position of the aldehyde group, which is unexpected. Most preferred benzaldehyde compounds include benzaldehyde, 2,4, 6-trimethylbenzaldehyde, 4-methylbenzaldehyde, 3-methylbenzaldehyde, 2-methylbenzaldehyde, 4-methoxybenzaldehyde, 4-chlorobenzaldehyde, 3-chlorobenzaldehyde, 2-chlorobenzaldehyde, 4-fluorobenzaldehyde, 2-fluorobenzaldehyde, 4-bromobenzaldehyde, 3-bromobenzaldehyde, 4-cyanobenzaldehyde, 4-nitrobenzaldehyde, 3-nitrobenzaldehyde, 2-nitrobenzaldehyde or 4-trifluoromethylbenzaldehyde;
in the technical scheme of the invention, the selection range of the α -methyl styrene compound is limited to selecting phenyl or substituted phenyl, the phenyl can provide a large conjugated system and can enable alkene to be in a conjugated stateThe α -methyl group on the radical has enough activity to participate in the cyclization, the phenyl or substituted phenyl can not be replaced by other substituent groups at will, such as aromatic heterocyclic ring, alkyl and the like, for replacing aryl, and the target product can not be obtained4Preferably selected from alkyl or halogen, R4When selected from halogen substituents, the halogen substituents are selected from fluorine, chlorine, bromine or iodine; r4When selected from alkyl substituents, said alkyl substituents are selected from C1～C5The substituent is preferably positioned para to the alkenyl group, the substituent may be optionally substituted with a weakly electron donating group such as alkyl or a weakly electron donating group such as halogen, while a strongly electron donating group such as amino, alkoxy or a strongly electron donating group such as nitro is difficult to achieve in the desired yield, the most preferred α -methylstyrene compounds include 2- (4-methylphenyl) propene, 2- (4-chlorophenyl) propene or 2- (4-fluorophenyl) propene.
In a preferred embodiment, the molar ratio of the potassium persulfate to the benzaldehyde compound is 0.5-2: 1, and more preferably 0.8-1.2: 1.
Preferably, the molar ratio of the benzaldehyde compound to the α -methyl styrene compound is 1: 1-1.5.
In a preferable scheme, the concentration of the benzaldehyde compound in a dimethyl sulfoxide solution system is 0.1-0.5 mol/L. Dimethyl sulfoxide serves mainly as a benign solvent on the one hand and as a reaction substrate on the other hand, providing a methyl group as a carbon atom in the dihydropyran ring.
In a preferred embodiment, the reaction conditions are as follows: and reacting for 18-30 h at the temperature of 120-160 ℃ in a protective atmosphere. More preferred conditions are: reacting for 22-26 h at 135-145 ℃ in a nitrogen atmosphere.
The invention explains the reaction mechanism by constructing a dihydropyran ring by using benzaldehyde, dimethyl sulfoxide and 2-phenyl propylene together. After reviewing and referring to relevant documents, a series of mechanism research experiments were designed, as shown in the following reaction equations (1) to (4). To verify whether the reaction proceeds through the reaction history of the free radical, reaction (1) was designed, under the standard2.0 equivalent (relative to benzaldehyde) of 2, 6-di-tert-butyl-p-cresol (BHT) is added under the reaction condition and reacted for 8 hours, and as a result, the generation of the target product of the dihydropyran derivative can still be successfully detected by GC-MS, which indicates that the reaction is not inhibited and does not undergo a free radical reaction process. To verify the presence of the reaction intermediate in the reaction, benzaldehyde was reacted with dimethylsulfoxide and 2-phenylpropylene under standard reaction conditions for 8 hours, and the presence of compound B was detected in addition to the desired dihydropyran derivative by GC-MS detection. To verify whether compound B is an intermediate in the construction of dihydropyrane, reaction (2) was designed to replace 2-phenylpropylene with compound B as starting material, and under standard conditions, it was surprisingly found that dihydropyrane derivatives were successfully detected by GC-MS. To further clarify the source of compound B, reaction (3) was further designed to react 2-phenylpropylene with dimethylsulfoxide directly under standard conditions, and the presence of compound B was detected by GC-MS, while compound A was obtained. In order to obtain a more accurate verification of whether dimethyl sulfoxide is involved in the cyclization of dihydropyrane, reaction (4) is designed, and isotopically labeled deuterated dimethyl sulfoxide is adopted to replace the conventional dimethyl sulfoxide to react under standard conditions, so that the existence of deuterium in the dihydropyrane product is successfully detected. Standard reaction conditions: in N2Next, benzaldehyde (0.5mmol), α -methylstyrene (0.6mmol) and DMSO (2mL) were reacted at 140 ℃ for 24 hours.
Reaction (1):
reaction (2):
reaction (3):
reaction (4):
according to the above experiment, the present invention proposes a reasonable mechanism for constructing a dihydropyran ring from benzaldehyde, dimethylsulfoxide and 2-phenylpropylene: the following reaction equation. First, adopt K2S2O8Activating DMSO to obtain DMSO converted into dimethyl sulfide positive ion C, simultaneously, 2-phenylpropylene releases hydrogen proton and converts into 2-phenylpropylene negative ion D, C and D are easily coupled to generate thiomethyl compound A, and the thiomethyl compound A is at K2S2O8Under the oxidation action, removing the micromolecule methyl mercaptan compound through a demethylation reaction to obtain a compound B, and carrying out ODA reaction on the compound B and benzaldehyde to finally obtain a target product.
Compared with the prior art, the technical scheme of the invention has the beneficial technical effects that:
1) the invention successfully constructs the dihydropyran derivative by the benzaldehyde compound, the α -methyl styrene compound and the dimethyl sulfoxide for the first time, and provides a brand new synthetic thought for the construction of a pyran ring.
2) The dihydropyran derivative does not need to use a catalyst in the synthesis process, and compared with the existing Diels-Alder reaction, the dihydropyran derivative avoids the use of a Lewis catalyst and reduces the possibility of side reaction of olefin polymerization.
3) In the synthetic process of the dihydropyran derivative, benzaldehyde compounds, α -methyl styrene compounds and dimethyl sulfoxide are used as basic raw materials, and the raw materials are conventional chemical raw materials, so that the cost is low, and the synthetic method is favorable for industrial production.
4) The dihydropyran derivative disclosed by the invention adopts a one-pot reaction in the synthetic process, and is mild in reaction condition, simple to operate and capable of meeting the requirements of industrial production.
5) The dihydropyran derivative has high utilization rate of raw materials in the synthesis process, and the product yield is about 60 percent.
6) The application range of the dihydropyran derivative to substrate raw materials in the synthetic process is wider, the dihydropyran derivative with various substituent groups can be constructed, the position selectivity of the substituent groups is strong, and the 2, 4-disubstituted 3, 6-dihydropyran derivative is obtained.
Drawings
FIG. 1 is a single crystal structure diagram of the compound 2- (4-nitrophenyl) -4-phenyl-3, 6-dihydro-2H-pyran.
Detailed Description
The following examples are intended to further illustrate the present disclosure, but not to limit the scope of the claims.
All reactions were performed in Schlenk tubes unless otherwise noted.
All reaction starting solvents were obtained from commercial sources and used without further purification.
The product is separated by silica gel chromatographic column and silica gel (granularity is 300-400 meshes).
1H NMR (400MHz), 13C NMR (100MHz) and 19F NMR (376MHz) measurements were performed using a Bruker ADVANCEEIII spectrometer with CDCl3As solvent, TMS as internal standard, chemical shifts in parts per million (ppm) and reference shifts of 0.0ppm tetramethylsilane. The following abbreviations (or combinations thereof) are used to explain the multiplicity: s is singlet, d is doublet, t is triplet, q is quartet, m is multiplet, br is broad. Coupling constant J is in Hertz (Hz). Chemical shifts are expressed in ppm, with the center line for the triplet state referenced to deuterated chloroform at 77.0ppm or the center line for the heptad state referenced to deuterated DMSO at 39.52 ppm.
The GC-MS adopts a GC-MS QP2010 device for detection, the HRMS adopts an Electron Ionization (EI) method for measurement, the type of the mass analyzer is TOF, and the EI is detected by an Esquire 3000plus instrument.
1. Condition optimization experiment:
the construction of a dihydropyran ring from benzaldehyde together with dimethyl sulfoxide and 2-phenylpropylene is exemplified, and various influencing factors such as an oxidant and an amount thereof, a reaction temperature, a reaction solvent and an additive are discussed to find an optimum reaction condition.
Concretely, the reverseThe reaction process comprises reacting benzaldehyde (0.5mmol), α -methylstyrene (0.6mmol), an oxidizing agent, an additive (0.5mmol) and DMSO (2mL) in N2And reacting for 24 hours under the atmosphere.
The reaction route is as follows:
table 1: yield of dihydropyran derivatives as target products under different reaction conditions
1) Selection of additives
As shown in Table 1, the use of the additive has a great influence on the reaction, and a large number of experiments show that, as shown in items 1-6 and 11 in Table 1, no benign additive which is beneficial to improving the reaction efficiency and increasing the yield, such as DABCO, DBU, K and the like, has been found in the reaction process of constructing the dihydropyran ring by benzaldehyde, dimethyl sulfoxide and 2-phenylpropylene2CO3、Cs2CO3When alkaline substances are used as additives, the reaction is obviously inhibited, the target product dihydropyrane is basically not obtained, and Et is added3N or NaOAc only yield the lower yield of the desired product dihydropyran.
3) Selection of oxidizing agent
The invention tries a plurality of common oxidants in the field, such as items 11 and 15-19 in table 1, and oxidants such as potassium persulfate, organic peroxide, inorganic hydrogen peroxide and the like are found to have good reaction effect only when the potassium persulfate is used as the oxidant, and when tert-butyl hydroperoxide (TBHP), DTBP or hydrogen peroxide (H) is used2O2) As the oxidizing agent, almost no target product was obtained, and therefore, potassium persulfate was selected as the most preferable oxidizing agent. Ammonium persulfate is not suitable as an oxidizing agent for the process of the present invention, however, and may be ammonium ionAdversely affecting the reaction.
4) Selection of the quantity of oxidant
After determining potassium persulfate and the like as the optimal oxidizing agent, the influence of different amounts of the oxidizing agent on the reaction was explored. As shown in items 11-14 of Table 1. When the amount of the oxidant is 0.5-1 equivalent, the conversion rate of the raw materials and the yield of the product are increased with the increase of the amount of the oxidant. And when the amount of the oxidizing agent is more than 1 equivalent, the yield is remarkably decreased. Therefore, 1 equivalent of potassium persulfate is the optimum amount for the reaction.
5) Selection of reaction temperature
The reaction temperature is an important factor affecting the chemical reaction process, and in order to obtain the optimum reaction temperature, the yield of the reaction at different temperatures was investigated, as in items 7 to 11 in Table 1. The target product can not be obtained basically at the temperature of less than 120 ℃, the reaction yield is obviously improved when the temperature reaches above 120 ℃, the reaction yield reaches the highest when the temperature is raised to 140 ℃, and the reaction side reaction is obvious when the temperature is higher than 140 ℃. Thus, 140 ℃ is the optimum temperature for the reaction.
6) Selection of reaction solvent
Since DMSO is used as a reaction substrate and a solvent in the process of synthesizing dihydropyran, the DMSO is not replaceable by other solvents. The solvent of the invention can adopt DMSO, and can also adopt a mixed solvent of DMSO and other solvents.
2. Selection range of reaction substrates:
after the optimal synthesis conditions of the dihydropyrane are determined, the substrate range and the applicability of the reaction are researched, and the experimental results are shown in tables 2 and 3, wherein table 2 is the reaction results of different benzaldehyde compounds, α -methyl styrene compounds and DMSO, table 1 shows that the benzaldehyde compounds containing various substituents can effectively synthesize corresponding dihydropyrane ring structures with α -methyl styrene compounds and DMSO under standard reaction conditions, the yield of target products is about 60 percent, a large number of experiments show that the substituent influence of the substituent on the reaction is not obvious, various substituted benzaldehydes can successfully construct the dihydropyrane with 2-phenylpropene and DMSO, and the only exception is that the 2-bromobenzaldehyde as a substrate cannot construct the dihydropyrane with the 2-phenylpropene and the DMSO, possibly the influence of bromine atoms is not yet understood.
Table 3 shows the reaction results of different α -methylstyrene compounds with benzaldehyde and DMSO, and experimental results show that the substituent at the 2-position of propylene must be an aryl group with a large conjugated system, such as phenyl and substituted phenyl, other aromatic heterocycles, alkyl and the like cannot meet the requirements, the aryl group with the large conjugated system is favorable for improving the activity of α -methyl, and the substituent on the aryl group is selected according to the requirements and cannot be a substituent group with stronger electron pushing or pulling capacity, such as nitro, alkoxy and the like, while the substituent group with the stronger electron pushing or pulling capacity, such as halogen, alkyl and the like, can meet the requirements.
(1) The reaction equation of different benzaldehyde compounds with α -methyl styrene compounds and DMSO:
the reaction process is as follows:
weighing potassium peroxodisulfate (K)2S2O8) (135mg,0.5mmol) was placed in a 25mL Schlenk reaction tube, and dimethyl sulfoxide (DMSO, 2mL), a benzaldehyde compound (0.5mmol), 2-phenylpropylene (71mg, 0.6mmol) and charged with nitrogen. Stirring was carried out at 140 ℃ for 24 hours. After completion of the reaction, it was cooled to room temperature, water (4mL) was added, and extraction was performed with ethyl acetate (3 × 5mL) and anhydrous Na2SO4Drying, distilling off the solvent under reduced pressure, and separating by a silica gel column (200-300 meshes) to obtain the target product.
TABLE 2 reaction results of different benzaldehyde compounds with 2-phenylpropylene and DMSO
Structural characterization of some dihydropyran derivatives in table 2:
2,4-diphenyl-3,6-dihydro-2H-pyran:
1H NMR(400MHz,CDCl3)δ7.44(s,2H),7.41(s,3H),7.37(s,1H),7.34(d,J＝4.1Hz,3H), 7.27(d,J＝12.0Hz,1H),6.22(s,1H),4.72–4.64(m,1H),4.64–4.49(m,2H),2.71(q,J＝17.1 Hz,2H).
13C NMR(101MHz,CDCl3)δ142.39,140.04,134.41,128.54,128.51,127.71,127.42,126.00, 124.80,122.25,76.02,66.89,34.94。
2-mesityl-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400MHz,CDCl3)δ7.41(d,J＝7.4Hz,2H),7.32(t,J＝7.4Hz,2H),7.23(dd,J＝16.5, 9.4Hz,1H),6.85(s,2H),6.26(s,1H),5.01(d,J＝10.9Hz,1H),4.49(q,J＝17.1Hz,2H),2.98–2.86(m,1H),2.46(s,1H),2.41(s,6H),2.25(s,3H).
13C NMR(101 MHz,CDCl3)δ139.94,136.85,136.17,134.74,134.30,130.11,128.54,127.42, 124.68,122.62,73.86,66.82,31.26,20.87,20.83。
4-phenyl-2-(p-tolyl)-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.41(d,J＝7.3 Hz,2H),7.33(d,J＝6.8 Hz,4H),7.28–7.24(m, 1H),7.20(d,J＝7.4 Hz,2H),6.21(s,1H),4.64(d,J＝9.7 Hz,1H),4.60–4.48(m,2H),2.76– 2.62(m,2H),2.36(s,3H).
13C NMR(101 MHz,CDCl3)δ140.10,139.42,137.36,134.46,129.19,128.49,127.38,125.97, 124.79,122.28,75.88,66.85,34.90,21.21。
4-phenyl-2-(m-tolyl)-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.42(d,J＝7.2 Hz,2H),7.34(t,J＝7.3 Hz,3H),7.28(s,2H),7.23 (d,J＝7.6 Hz,1H),7.13(d,J＝7.3 Hz,1H),6.21(s,1H),4.64(d,J＝9.9Hz,1H),4.53(d,J＝ 21.7 Hz,2H),2.68(dd,J＝23.0,12.9 Hz,2H),2.38(s,3H).
13C NMR(101 MHz,CDCl3)δ142.33,140.08,138.22,134.48,128.50,128.45,128.42,127.40, 126.66,124.81,123.09,122.23,76.10,66.92,34.97,21.54。
4-phenyl-2-(o-tolyl)-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.54(d,J＝7.4 Hz,1H),7.42(d,J＝7.2 Hz,2H),7.34(t,J＝7.3 Hz,2H),7.30–7.24(m,2H),7.19(t,J＝9.3 Hz,2H),6.23(s,1H),4.85(d,J＝9.9 Hz,1H),4.63 –4.48(m,2H),2.75–2.60(m,2H),2.38(s,3H).
13C NMR(101 MHz,CDCl3)δ140.40,140.08,134.72,134.62,130.36,128.52,127.49,127.41, 126.44,125.62,124.77,122.25,72.96,66.93,33.56,19.26。
2-(4-methoxyphenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.41(d,J＝7.5 Hz,2H),7.35(dd,J＝16.2,7.8 Hz,4H),7.29– 7.24(m,1H),6.92(d,J＝7.6 Hz,2H),6.20(s,1H),4.62(d,J＝9.7 Hz,1H),4.53(s,2H),3.81(s, 3H),2.76–2.59(m,2H).
13C NMR(101 MHz,CDCl3)δ159.17,140.11,134.58,134.47,128.50,127.39,127.37,124.81, 122.29,113.91,75.63,66.87,55.35,34.81。
2-(4-chlorophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.41(d,J＝7.5 Hz,2H),7.39–7.32(m,6H),7.29(d,J＝6.7 Hz, 1H),6.21(s,1H),4.66(t,J＝6.3 Hz,1H),4.63–4.47(m,2H),2.65(s,2H).
13C NMR(101 MHz,CDCl3)δ140.94,139.90,134.20,133.31,128.64,128.53,127.49,127.35, 124.79,122.20,75.23,66.80,34.89。
2-(3-chlorophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.45(s,1H),7.39(d,J＝7.2 Hz,2H),7.34(d,J＝6.9Hz,2H), 7.31–7.26(m,4H),6.19(s,1H),4.63(t,J＝6.7 Hz,1H),4.53(q,J＝17.3 Hz,2H),2.65(s,2H).13C NMR(101 MHz,CDCl3)δ144.49,139.87,134.43,134.15,129.79,128.54,127.75,127.51, 126.19,124.80,124.05,122.16,75.24,66.82,34.86。
2-(2-chlorophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.65(d,J＝7.2 Hz,1H),7.41(d,J＝7.0 Hz,2H),7.37–7.32(m, 4H),7.24(dd,J＝10.0,5.8 Hz,2H),6.22(s,1H),5.04(d,J＝10.4 Hz,1H),4.67–4.51(m,2H), 2.85(d,J＝16.5 Hz,1H),2.55–2.46(m,1H).
13C NMR(101 MHz,CDCl3)δ140.23,139.92,134.46,131.63,129.29,128.59,128.51,127.46, 127.37,127.13,124.83,121.99,72.82,66.97,33.45。
2-(4-fluorophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.40(d,J＝6.3 Hz,4H),7.33(t,J＝7.2 Hz,2H),7.29–7.23(m, 1H),7.06(t,J＝8.1 Hz,2H),6.20(s,1H),4.69–4.60(m,1H),4.59–4.46(m,2H),2.71–2.58 (m,2H).
13C NMR(101 MHz,CDCl3)δ163.50,161.06,139.96,138.25,134.29,128.52,128.02–127.25 (m),124.80,122.22,115.33(d,J＝21.3 Hz),75.33,66.86,34.97。
2-(2-fluorophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.51(t,J＝7.2 Hz,1H),7.33(d,J＝7.1 Hz,2H),7.26(d,J＝6.8 Hz,2H),7.21–7.16(m,2H),7.11(t,J＝7.3 Hz,1H),6.97(t,J＝9.1 Hz,1H),6.13(s,1H),4.91 (d,J＝10.0 Hz,1H),4.55–4.35(m,2H),2.62(dd,J＝28.1,13.3 Hz,2H).
13C NMR(101 MHz,CDCl3)δ160.79,158.35,139.94,134.43,128.99(d,J＝8.2Hz),128.52, 127.47,127.24(d,J＝4.3 Hz),124.85,124.51(d,J＝3.4 Hz),122.03,115.24(d,J＝21.6 Hz), 69.90(d,J＝2.5 Hz),66.91,33.96。
2-(4-bromophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.51(d,J＝7.6 Hz,2H),7.41(d,J＝7.6 Hz,2H),7.34(dd,J＝12.5,7.0 Hz,4H),7.28(d,J＝7.0 Hz,1H),6.21(s,1H),4.64(t,J＝6.7 Hz,1H),4.59–4.44(m, 2H),2.66(s,2H).
13C NMR(101 MHz,CDCl3)δ141.47,139.90,134.18,131.58,128.52,127.67,127.49,124.78, 122.19,121.42,75.25,66.78,34.85。
2-(3-bromophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.63(s,1H),7.46–7.40(m,3H),7.36(t,J＝7.9 Hz,3H),7.30– 7.26(m,2H),6.22(s,1H),4.65(t,J＝6.7 Hz,1H),4.56(q,J＝17.3 Hz,2H),2.67(d,J＝1.8 Hz, 2H).
13C NMR(101 MHz,CDCl3)δ144.75,139.86,134.15,130.68,130.07,129.09,128.53,127.50, 124.79,124.51,122.66,122.15,75.18,66.82,34.88。
4-(4-phenyl-3,6-dihydro-2H-pyran-2-yl)benzonitrile：
1H NMR(400 MHz,CDCl3)δ7.68(d,J＝7.7 Hz,2H),7.56(d,J＝7.7 Hz,2H),7.40(d,J＝7.7 Hz,2H),7.35(t,J＝7.2 Hz,2H),7.29(d,J＝6.7 Hz,1H),6.22(s,1H),4.73(d,J＝9.5 Hz,1H), 4.56(q,J＝17.3 Hz,2H),2.65(t,J＝11.4 Hz,2H).
13C NMR(101 MHz,CDCl3)δ147.77,139.69,133.95,132.36,128.56,127.62,126.50,124.77, 122.14,118.89,111.35,75.06,66.75,34.82。
2-(4-nitrophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ8.25(d,J＝7.7 Hz,2H),7.62(d,J＝7.8 Hz,2H),7.40(d,J＝7.7 Hz,2H),7.35(t,J＝7.3 Hz,2H),7.29(d,J＝6.7 Hz,1H),6.23(s,1H),4.79(d,J＝9.7 Hz,1H), 4.58(q,J＝17.3 Hz,2H),2.77–2.56(m,2H).
13C NMR(101 MHz,CDCl3)δ149.78,147.35,139.66,133.91,128.58,127.64,126.56,124.78, 123.76,122.15,74.89,66.76,34.89。
2-(3-nitrophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ8.34(s,1H),8.17(d,J＝8.2 Hz,1H),7.79(d,J＝7.6Hz,1H), 7.56(t,J＝8.0 Hz,1H),7.41(d,J＝7.6 Hz,2H),7.36(t,J＝7.3 Hz,2H),7.29(d,J＝6.7 Hz,1H), 6.23(s,1H),4.78(d,J＝9.9 Hz,1H),4.59(q,J＝17.4 Hz,2H),2.77–2.62(m,2H).
13C NMR(101 MHz,CDCl3)δ148.41,144.63,139.70,133.92,131.96,129.44,128.57,127.62, 124.81,122.57,122.17,121.03,74.72,66.82,34.82。
2-(2-nitrophenyl)-4-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.94(d,J＝8.2 Hz,1H),7.89(d,J＝7.8 Hz,1H),7.68(t,J＝7.6 Hz,1H),7.46(d,J＝7.8 Hz,1H),7.41(d,J＝7.5 Hz,2H),7.34(t,J＝7.2 Hz,2H),7.28(d,J＝ 6.7 Hz,1H),6.20(s,1H),5.22(d,J＝10.2 Hz,1H),4.54(q,J＝17.5 Hz,2H),2.97(d,J＝16.4 Hz,1H),2.66–2.54(m,1H).
13C NMR(101MHz,CDCl3)δ147.83,139.83,137.86,134.46,133.63,128.50,128.25,128.15, 127.52,124.92,124.19,121.85,71.75,66.98,34.35。
4-phenyl-2-(4-(trifluoromethyl)phenyl)-3,6-dihydro-2H-pyran：
1H),4.65–4.50(m,2H),2.69(t,J＝13.9Hz,2H).
13C NMR(101MHz,CDCl3)δ146.43,139.82,134.10,128.55,127.55,126.16,125.47,125.43, 124.78,122.20,75.26,66.79,34.94。
(2) reaction equation of different α -methyl styrene compounds with benzaldehyde and DMSO:
the reaction process is as follows:
weighing potassium peroxodisulfate (K)2S2O8) (135mg,0.5mmol) was placed in a 25ml Schlenk reaction tube, and dimethyl sulfoxide (DMSO, 2ml), benzaldehyde (54mg, 0.5mmol), and a propylene compound (0.6mmol) were added thereto, followed by nitrogen gas injection. Stirring was carried out at 140 ℃ for 24 hours. After completion of the reaction, it was cooled to room temperature, water (4ml) was added, and extraction was performed with ethyl acetate (3 x 5ml) and anhydrous Na2SO4Drying, distilling off the solvent under reduced pressure, and separating by a silica gel column (200-300 meshes) to obtain the target product dihydropyran compound.
TABLE 3 reaction results of different propylene compounds with benzaldehyde and DMSO
Structural characterization of some dihydropyran derivatives in table 3:
4-(4-methylphenyl)-2-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400MHz,CDCl3)δ7.46(d,J＝7.3Hz,2H),7.40(t,J＝7.3Hz,2H),7.33(d,J＝7.5 Hz,3H),7.17(d,J＝7.6Hz,2H),6.19(s,1H),4.73–4.65(m,1H),4.62–4.49(m,2H),2.76– 2.63(m,2H),2.36(s,3H).
13C NMR(101MHz,CDCl3)δ142.49,137.22,137.16,134.22,129.18,128.51,127.66,126.01, 124.66,121.36,76.04,66.88,34.97,21.12。
4-(4-chlorophenyl)-2-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.44(d,J＝7.4 Hz,2H),7.39(t,J＝7.3 Hz,2H),7.32(q,J＝7.9 Hz,5H),6.21(s,1H),4.66(d,J＝9.5 Hz,1H),4.63–4.46(m,2H),2.74–2.58(m,2H).
13C NMR(101 MHz,CDCl3)δ142.2,138.46,133.43,133.12,128.61,128.54,127.76,126.06, 125.95,122.81,75.92,66.79,34.86。
4-(4-fluorophenyl)-2-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400 MHz,CDCl3)δ7.44(d,J＝7.2 Hz,2H),7.39(t,J＝7.3 Hz,2H),7.32(q,J＝7.9 Hz,5H),6.21(s,1H),4.66(d,J＝9.6 Hz,1H),4.60–4.49(m,2H),2.75–2.59(m,2H).
13C NMR(101 MHz,CDCl3)δ142.21,138.46,133.43,133.12,128.61,128.55,127.76,126.06, 125.95,122.81,75.92,66.79,34.86。
Claims (8)
1. a method for constructing a dihydropyran ring by benzaldehyde, α -methyl styrene compound and dimethyl sulfoxide is characterized in that the benzaldehyde compound and α -methyl styrene compound react in a dimethyl sulfoxide solution system containing potassium persulfate in one pot to obtain a dihydropyran derivative;
the benzaldehyde compound has a structure shown in a formula 1:
the α -methyl styrene compound has the structure of formula 2:
the dihydropyran derivative has the structure of formula 3:
wherein the content of the first and second substances,
R1、R2and R3Independently selected from hydrogen, halogen substituents, C1～C5Alkyl, trifluoromethyl, nitro, cyano or C1～C5Alkoxy group of (a);
R4selected from hydrogen, halogen substituents or C1～C5Alkyl group of (1).
2. The method for constructing the dihydropyran ring by jointly using benzaldehyde, α -methyl styrene compound and dimethyl sulfoxide according to claim 1, wherein:
in the benzaldehyde compound, R1、R2And R3When selected from halogen substituents, the halogen substituents are selected from fluorine, chlorine, bromine or iodine;
in the α -methylstyrene compound, R is4When selected from halogen substituents, the halogen substituents are selected from fluorine, chlorine, bromine or iodine.
3. The method for co-constructing dihydropyran ring from benzaldehyde, α -methyl styrene compound and dimethyl sulfoxide according to claim 2, wherein the benzaldehyde compound comprises benzaldehyde, 2,4, 6-trimethyl benzaldehyde, 4-methyl benzaldehyde, 3-methyl benzaldehyde, 2-methyl benzaldehyde, 4-methoxy benzaldehyde, 4-chloro benzaldehyde, 3-chloro benzaldehyde, 2-chloro benzaldehyde, 4-fluoro benzaldehyde, 2-fluoro benzaldehyde, 4-bromo benzaldehyde, 3-bromo benzaldehyde, 4-cyano benzaldehyde, 4-nitro benzaldehyde, 3-nitro benzaldehyde, 2-nitro benzaldehyde or 4-trifluoromethyl benzaldehyde;
the α -methyl styrene compound comprises 2- (4-methyl phenyl) propylene, 2- (4-chlorphenyl) propylene or 2- (4-fluorophenyl) propylene.
4. The method for constructing the dihydropyran ring by using the benzaldehyde, the α -methylstyrene compound and the dimethyl sulfoxide as claimed in claim 1, wherein the molar ratio of the potassium persulfate to the benzaldehyde compound is 0.5-2: 1.
5. The method for constructing the dihydropyran ring by using the benzaldehyde, the α -methylstyrene compound and the dimethyl sulfoxide as claimed in claim 1, wherein the molar ratio of the benzaldehyde compound to the α -methylstyrene compound is 1: 1-1.5.
6. The method for constructing the dihydropyran ring by the benzaldehyde, the α -methylstyrene compound and the dimethyl sulfoxide as claimed in claim 1, wherein the concentration of the benzaldehyde compound in the dimethyl sulfoxide solution system is 0.1-0.5 mol/L.
7. The method for constructing the dihydropyran ring by using the benzaldehyde, the α -methylstyrene compound and the dimethyl sulfoxide as claimed in any one of claims 1 to 6, wherein the reaction condition is that the reaction is carried out at 120-160 ℃ for 18-30 h under a protective atmosphere.
8. The method for constructing the dihydropyran ring by the benzaldehyde, the α -methylstyrene compound and the dimethyl sulfoxide according to claim 7, wherein the reaction is carried out under the condition of nitrogen atmosphere at 135-145 ℃ for 22-26 h.
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