CN108610317B

CN108610317B - Synthetic method of 3, 6-dihydropyran derivative

Info

Publication number: CN108610317B
Application number: CN201810614491.7A
Authority: CN
Inventors: 郭灿城; 李慧; 郭欣
Original assignee: Yuanjiang Hualong Catalyst Technology Co ltd
Current assignee: Xinjiang Puhesu New Environmental Protection Materials Co ltd
Priority date: 2018-06-14
Filing date: 2018-06-14
Publication date: 2020-06-05
Anticipated expiration: 2038-06-14
Also published as: CN108610317A

Abstract

The invention discloses a synthesis method of a 3, 6-dihydropyran derivative, which comprises the steps of carrying out one-pot reaction on aryl aldehyde and 2-aryl propylene in a dimethyl sulfoxide solution system containing potassium persulfate to obtain the dihydropyran derivative; the method is characterized in that the aryl aldehyde provides carbonyl, the 2-aryl propylene provides propenyl and the dimethyl sulfoxide provides methyl to jointly construct the 3, 6-dihydropyran ring for the first time, the synthesis method is realized by a one-pot method, the reaction condition is mild, no additional catalyst is needed, the selectivity is good, the yield is high, and the method is favorable for industrial production.

Description

Synthetic method of 3, 6-dihydropyran derivative

Technical Field

The invention relates to a synthetic method of a dihydropyran derivative, in particular to a method for jointly constructing 3, 6-dihydropyran by aryl aldehyde, 2-aryl propylene 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 reactionSynthesizing; 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 AlCl₃The 2-phenyl-5, 6-dihydro-2H-pyran is synthesized under the catalysis of the catalyst. 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 3, 6-dihydropyran ring together by providing carbonyl by aryl aldehyde, providing propenyl by 2-aryl propylene and providing methyl by dimethyl sulfoxide.

In order to realize the technical purpose, the invention provides a synthesis method of a 3, 6-dihydropyran derivative, which comprises the steps of carrying out one-pot reaction on aryl aldehyde and 2-aryl propylene in a dimethyl sulfoxide solution system containing potassium persulfate to obtain the 3, 6-dihydropyran derivative;

the aryl aldehyde has the structure of formula 1:

the 2-arylpropene has the structure of formula 2:

the dihydropyran derivative has the structure of formula 3:

wherein,

ar is aryl;

r is halogen substituent, alkyl or hydrogen.

According to the technical scheme, the aryl aldehyde is wide in selection range, the influence of the selection of the Ar substituent group on the construction of the dihydropyran is not obvious, and the yield of the dihydropyran is kept about 60% when the Ar selects various common substituent groups. Ar is preferably phenyl, substituted phenyl or naphthyl. When Ar is selected from substituted phenyl, the number of the substituent groups contained in the substituted phenyl is 1-3, and the substituent groups are selected from at least one of halogen substituent groups, alkyl groups, trifluoromethyl groups, nitro groups, cyano groups or alkoxy groups; 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.

The selection range of the 2-aryl propylene in the technical scheme of the invention is limited to the selection of the aryl substituent group, and the aryl substituent group provides a large conjugated system, so that the methyl on the alkenyl group has enough activity to participate in cyclization. The aryl substituent can not be replaced by other substituent groups at will, and the target product can not be obtained by replacing aryl with aromatic heterocycle, alkyl and the like. Ar may be phenyl or substituted phenyl. When R is optionally substituted phenyl, the substituent is preferably positioned para to the alkenyl group, and may be a weak electron-withdrawing group such as alkyl (C)₁～C₅Alkyl group of) may also beA weakly electron-withdrawing group such as halogen (fluorine, chlorine, bromine or iodine). However, it is difficult to obtain an ideal yield from a strongly electron-withdrawing group such as an amino group and an alkoxy group, and a strongly electron-withdrawing group such as a nitro group.

In a preferred embodiment, the molar ratio of the persulfate to the aryl aldehyde is 0.5-2: 1, and more preferably 0.8-1.2: 1.

In a preferred embodiment, the molar ratio of the aryl aldehyde to the 2-aryl propylene is 1:1 to 1.5.

In a preferable scheme, the concentration of the aryl 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 20-28 h at 130-150 ℃ 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). In order to prove whether the reaction goes through the reaction course of free radicals, the reaction (1) is designed, 2.0 equivalent (relative to benzaldehyde) of 2, 6-ditertbutyl-p-cresol (BHT) is added under standard reaction conditions, the reaction is carried out for 8 hours, and 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 the reaction does not go through the reaction course of one free radical. 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. In order to verify whether compound B is an intermediate in the construction of dihydropyrane, reaction (2) was devised, starting from compound B instead of 2-phenylpropylene, and reacting 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 3, 6-dihydropyran derivative by the aryl aldehyde, the 2-aryl propylene and the dimethyl sulfoxide for the first time, and provides a brand new synthetic thought for the construction of the pyran ring.

2) The 3, 6-dihydropyran derivative does not need to use a catalyst in the synthesis process, and compared with the existing Diels-Alder reaction, the use of a Lewis catalyst is avoided, and the possibility of side reaction of olefin polymerization is reduced.

3) In the synthetic process of the dihydropyran derivative, aryl aldehyde, 2-aryl propylene 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 industrial production is facilitated.

4) The 3, 6-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 3, 6-dihydropyran derivative has high utilization rate of raw materials in the synthesis process, and the product yield is about 60 percent.

6) The 3, 6-dihydropyran derivative has wide application range to substrate raw materials in the synthesis process, can construct 3, 6-dihydropyran derivatives with various substituent groups, has strong position selectivity of the substituent groups, and obtains the 2, 4-disubstituted 3, 6-dihydropyran derivative.

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.

The specific reaction process is that benzaldehyde (0.5mmol), α -methyl styrene (0.6mmol), oxidant, additive (0.5mmol) and DMSO (2mL) are added 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 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 and K, has been found in the reaction process of constructing the 3, 6-dihydropyran ring by benzaldehyde, dimethyl sulfoxide and 2-phenylpropylene₂CO₃、Cs₂CO₃When the alkaline substance is used as an additive, the reaction is obviously inhibited, the target product 3, 6-dihydropyran derivative can not be basically obtained, and Et is added₃N or NaOAc only obtain the target product 3, 6-dihydropyran derivative with lower yield.

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) Since the target product is hardly obtained as an oxidizing agent, potassium persulfate is selected as the most preferable oxidizing agent.

4) Selection of the quantity of oxidant

After determining potassium persulfate as the optimal oxidant, the effect of varying amounts of oxidant 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 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

DMSO is not replaceable by other solvents because DMSO is used as a reaction substrate and a solvent simultaneously in the process of synthesizing the 3, 6-dihydropyran derivative. 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 3, 6-dihydropyran are determined, the substrate range and the applicability of the reaction are researched, and the experimental results are shown in tables 2 and 3. Table 2 shows the results of the reaction of different aryl aldehydes with 2-phenylpropene and DMSO. As can be seen from Table 1, the aryl aldehydes can be effectively synthesized with 2-phenylpropene and DMSO under standard reaction conditions to obtain the corresponding 3, 6-dihydropyran ring structure, and the yield of the target product is about 60%. Moreover, a large number of experiments show that the substituted group of benzaldehyde containing the substituted group has no obvious influence on the reaction, and various substituted benzaldehydes can successfully construct dihydropyrane with 2-phenylpropylene and DMSO. The only exception is that 2-bromobenzaldehyde as a substrate together with 2-phenylpropene and DMSO cannot construct dihydropyrane, probably due to the influence of bromine atoms, and the mechanism is unknown.

Table 3 shows the reaction results of different 2-aryl propylene, benzaldehyde and DMSO, and experimental results show that the substituent at the 2-position of propylene must be aryl with a large conjugated system, such as phenyl or substituted phenyl, other aromatic heterocyclic rings, alkyl and the like cannot meet the requirements, the aryl of the large conjugated system is favorable for improving the activity of α -methyl, and the substituent on the benzene ring is also required to be a substituent group which cannot be used for pushing electrons or pulling electrons with stronger capability, such as nitro, alkoxy and the like, while the substituent group with the higher electron pushing or pulling capability, such as halogen, alkyl and the like, can meet the requirements.

(1) Reaction equations for different aryl aldehydes with 2-phenylpropene and DMSO:

the reaction process is as follows:

weighing potassium peroxodisulfate (K)₂S₂O₈) (135mg,0.5mmol) was placed in a 25mL Schlenk reaction tube, to which was added dimethylsulfoxide (DMSO, 2mL), arylaldehyde (0.5mmol), 2-phenylpropylene (71mg, 0.6mmol), and nitrogen gas was introduced. 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 arylaldehydes 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(101MHz,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(400MHz,CDCl₃)δ7.41(d,J＝7.3Hz,2H),7.33(d,J＝6.8Hz,4H),7.28–7.24(m, 1H),7.20(d,J＝7.4Hz,2H),6.21(s,1H),4.64(d,J＝9.7Hz,1H),4.60–4.48(m,2H),2.76– 2.62(m,2H),2.36(s,3H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.42(d,J＝7.2Hz,2H),7.34(t,J＝7.3Hz,3H),7.28(s,2H),7.23 (d,J＝7.6Hz,1H),7.13(d,J＝7.3Hz,1H),6.21(s,1H),4.64(d,J＝9.9Hz,1H),4.53(d,J＝ 21.7Hz,2H),2.68(dd,J＝23.0,12.9Hz,2H),2.38(s,3H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.54(d,J＝7.4Hz,1H),7.42(d,J＝7.2Hz,2H),7.34(t,J＝7.3 Hz,2H),7.30–7.24(m,2H),7.19(t,J＝9.3Hz,2H),6.23(s,1H),4.85(d,J＝9.9Hz,1H),4.63 –4.48(m,2H),2.75–2.60(m,2H),2.38(s,3H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.41(d,J＝7.5Hz,2H),7.35(dd,J＝16.2,7.8Hz,4H),7.29–7.24(m,1H),6.92(d,J＝7.6Hz,2H),6.20(s,1H),4.62(d,J＝9.7Hz,1H),4.53(s,2H),3.81(s, 3H),2.76–2.59(m,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.41(d,J＝7.5Hz,2H),7.39–7.32(m,6H),7.29(d,J＝6.7Hz, 1H),6.21(s,1H),4.66(t,J＝6.3Hz,1H),4.63–4.47(m,2H),2.65(s,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.45(s,1H),7.39(d,J＝7.2Hz,2H),7.34(d,J＝6.9Hz,2H), 7.31–7.26(m,4H),6.19(s,1H),4.63(t,J＝6.7Hz,1H),4.53(q,J＝17.3Hz,2H),2.65(s,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.65(d,J＝7.2Hz,1H),7.41(d,J＝7.0Hz,2H),7.37–7.32(m, 4H),7.24(dd,J＝10.0,5.8Hz,2H),6.22(s,1H),5.04(d,J＝10.4Hz,1H),4.67–4.51(m,2H), 2.85(d,J＝16.5Hz,1H),2.55–2.46(m,1H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.40(d,J＝6.3Hz,4H),7.33(t,J＝7.2Hz,2H),7.29–7.23(m, 1H),7.06(t,J＝8.1Hz,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(101MHz,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＝21.3Hz),75.33,66.86,34.97。

2-(2-fluorophenyl)-4-phenyl-3,6-dihydro-2H-pyran：

¹H NMR(400MHz,CDCl₃)δ7.51(t,J＝7.2Hz,1H),7.33(d,J＝7.1Hz,2H),7.26(d,J＝6.8 Hz,2H),7.21–7.16(m,2H),7.11(t,J＝7.3Hz,1H),6.97(t,J＝9.1Hz,1H),6.13(s,1H),4.91 (d,J＝10.0Hz,1H),4.55–4.35(m,2H),2.62(dd,J＝28.1,13.3Hz,2H).

¹³C NMR(101MHz,CDCl₃)δ160.79,158.35,139.94,134.43,128.99(d,J＝8.2Hz),128.52, 127.47,127.24(d,J＝4.3Hz),124.85,124.51(d,J＝3.4Hz),122.03,115.24(d,J＝21.6Hz), 69.90(d,J＝2.5Hz),66.91,33.96。

2-(4-bromophenyl)-4-phenyl-3,6-dihydro-2H-pyran：

¹H NMR(400MHz,CDCl₃)δ7.51(d,J＝7.6Hz,2H),7.41(d,J＝7.6Hz,2H),7.34(dd,J＝ 12.5,7.0Hz,4H),7.28(d,J＝7.0Hz,1H),6.21(s,1H),4.64(t,J＝6.7Hz,1H),4.59–4.44(m, 2H),2.66(s,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.63(s,1H),7.46–7.40(m,3H),7.36(t,J＝7.9Hz,3H),7.30– 7.26(m,2H),6.22(s,1H),4.65(t,J＝6.7Hz,1H),4.56(q,J＝17.3Hz,2H),2.67(d,J＝1.8Hz, 2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.68(d,J＝7.7Hz,2H),7.56(d,J＝7.7Hz,2H),7.40(d,J＝7.7 Hz,2H),7.35(t,J＝7.2Hz,2H),7.29(d,J＝6.7Hz,1H),6.22(s,1H),4.73(d,J＝9.5Hz,1H), 4.56(q,J＝17.3Hz,2H),2.65(t,J＝11.4Hz,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ8.25(d,J＝7.7Hz,2H),7.62(d,J＝7.8Hz,2H),7.40(d,J＝7.7 Hz,2H),7.35(t,J＝7.3Hz,2H),7.29(d,J＝6.7Hz,1H),6.23(s,1H),4.79(d,J＝9.7Hz,1H), 4.58(q,J＝17.3Hz,2H),2.77–2.56(m,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ8.34(s,1H),8.17(d,J＝8.2Hz,1H),7.79(d,J＝7.6Hz,1H), 7.56(t,J＝8.0Hz,1H),7.41(d,J＝7.6Hz,2H),7.36(t,J＝7.3Hz,2H),7.29(d,J＝6.7Hz,1H), 6.23(s,1H),4.78(d,J＝9.9Hz,1H),4.59(q,J＝17.4Hz,2H),2.77–2.62(m,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.94(d,J＝8.2Hz,1H),7.89(d,J＝7.8Hz,1H),7.68(t,J＝7.6 Hz,1H),7.46(d,J＝7.8Hz,1H),7.41(d,J＝7.5Hz,2H),7.34(t,J＝7.2Hz,2H),7.28(d,J＝ 6.7Hz,1H),6.20(s,1H),5.22(d,J＝10.2Hz,1H),4.54(q,J＝17.5Hz,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-(naphthalen-1-yl)-4-phenyl-3,6-dihydro-2H-pyran：

Colourless oil,HRMS(APCI):286.1355

¹H NMR(400MHz,CDCl₃)δ8.13(d,J＝7.6Hz,1H),7.89(d,J＝7.2Hz,1H),7.82(d,J＝8.0 Hz,1H),7.72(d,J＝7.0Hz,1H),7.53–7.47(m,3H),7.43(d,J＝7.4Hz,2H),7.34(t,J＝7.3Hz, 2H),7.25(d,J＝8.8Hz,1H),6.29(s,1H),5.46–5.33(m,1H),4.65(s,2H),2.97–2.81(m,2H).

¹³C NMR(101MHz,CDCl₃)δ140.01,137.96,134.62,133.86,130.55,128.95,128.53,128.20, 127.45,126.09,125.63,125.55,124.81,123.48,123.35,122.24,73.46,66.93,34.20.

(2) reaction equations of different propylene 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(400MHz,CDCl₃)δ7.44(d,J＝7.4Hz,2H),7.39(t,J＝7.3Hz,2H),7.32(q,J＝7.9 Hz,5H),6.21(s,1H),4.66(d,J＝9.5Hz,1H),4.63–4.46(m,2H),2.74–2.58(m,2H).

¹³C NMR(101MHz,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(400MHz,CDCl₃)δ7.44(d,J＝7.2Hz,2H),7.39(t,J＝7.3Hz,2H),7.32(q,J＝7.9 Hz,5H),6.21(s,1H),4.66(d,J＝9.6Hz,1H),4.60–4.49(m,2H),2.75–2.59(m,2H).

¹³C NMR(101MHz,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

1. a method for synthesizing 3, 6-dihydropyran derivatives is characterized in that: aryl aldehyde and 2-aryl propylene react in a dimethyl sulfoxide solution system containing potassium persulfate in one pot to obtain a 3, 6-dihydropyran derivative;

the aryl aldehyde has the structure of formula 1:

the 2-arylpropene has the structure of formula 2:

the dihydropyran derivative has the structure of formula 3:

wherein,

ar is phenyl, substituted phenyl or naphthyl; the number of the substituent groups contained in the substituted phenyl is 1-3, and the substituent groups are selected from at least one of halogen substituent groups, alkyl groups, trifluoromethyl groups, nitro groups, cyano groups or alkoxy groups; the halogen substituent is not a bromine substituent;

r is selected from fluorine, chlorine, bromine, iodine or C₁～C₅Alkyl groups of (a);

the reaction conditions are as follows: and reacting for 20-28 h at 130-150 ℃ in a protective atmosphere.

2. The method for synthesizing a 3, 6-dihydropyran derivative according to claim 1, characterized in that: the molar ratio of the potassium persulfate to the aryl aldehyde is 0.5-2: 1.

3. The method for synthesizing a 3, 6-dihydropyran derivative according to claim 1, characterized in that: the molar ratio of the aryl aldehyde to the 2-aryl propylene is 1: 1-1.5.

4. The method for synthesizing a 3, 6-dihydropyran derivative according to claim 1, characterized in that: the concentration of the aryl aldehyde in the dimethyl sulfoxide solution system is 0.1-0.5 mol/L.

5. The method for synthesizing a 3, 6-dihydropyran derivative according to claim 1, characterized in that: the reaction conditions are as follows: reacting for 22-26 h at 135-145 ℃ in a nitrogen atmosphere.