CN108530410A - A method of dihydropyran ring is built by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide jointly - Google Patents
A method of dihydropyran ring is built by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide jointly Download PDFInfo
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- C07D309/18—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member containing only hydrogen and carbon atoms in addition to the ring hetero atom
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Abstract
The invention discloses a kind of methods building dihydropyran ring jointly by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide, this method is compound of benzaldehyde category with α-methylstyrene class compound in the dimethyl sulfoxide solution system containing persulfate by one pot reaction to get dihydropyran derivatives；This method provides carbonyl by compound of benzaldehyde category for the first time, α-methylstyrene class compound provides acrylic and dimethyl sulfoxide (DMSO) provides methyl and builds dihydropyran ring jointly, the synthetic method is realized by one kettle way, and reaction condition is mild, is not necessarily to extra catalyst, the good, high income of selectivity, is conducive to industrialized production.
Description
Technical field
The present invention relates to a kind of synthetic methods of dihydropyran derivatives, and in particular to one kind is by one kettle way by benzaldehyde
The method that class compound builds dihydropyran ring jointly with α-methylstyrene class compound and dimethyl sulfoxide (DMSO), in belonging to organic
Mesosome synthesizes field.
Background technology
Dihydropyran derivatives are a kind of important hexa-atomic Oxygenic heterocyclic compounds, and there is unique biology and drug to live
Property, if Zanamivir is a kind of drug of resisiting influenza virus, Benesudon can be used as antibiotic usage, be a kind of heavy again
The organic intermediate wanted can pass through water if 2- ethyoxyl -3,4- dihydropyran is relatively inexpensive synthesis of glutaraldehyde intermediate
Solution obtains glutaraldehyde.Therefore, dihydropyran derivatives cause the concern of numerous organic chemists and drug scholar, and in the past
Decades are studied most one of heterocyclic compounds.
Currently, there are many synthesis about dihydropyran to report, such as common Terminal Acetylenes hydrogen alkoxylate Cyclization；
Oxo-Diels-Alder reaction synthesis；Michael additions/cyclisation cascade reaction synthesis；Knoevenagel /oxo-Diels-
Alder cascade reactions synthesize.And most valuable method is using Diels-Alder reactions come synthesizing dihydro pyrans, it is such as classical
Reaction be using conjugated diene and aldehyde radical under Louis (Lewis) acid catalysis, pass through Diels-Alder reaction
Dihydropyran is obtained, as United States Patent (USP) (publication number US5162551) discloses benzaldehyde with conjugated diene in AlCl3Urge
Change lower synthesis 2- phenyl -5,6- dihydro -2H- pyrans.Chinese patent (CN101143860A) disclose conjugated diene with it is anhydrous
Formaldehyde synthesizes 5,6- dihydro-pyrans and its derivative under Louis acid catalysis effect by Diels-Alder reaction,
Since Diels-Alder reaction is required to use lewis acid as catalyst, and need to carry out at high temperature, and Louis
Acid can also cause olefinic polymerization simultaneously, cause side reaction more, it is difficult to control.Chinese patent (CN101481369A) discloses one
Kind, as catalyst, 4,6 substitutions 3, -4- dihydros-is efficiently synthesized by aldehyde radical substituted cyclopropane alkanes compound by N-heterocyclic carbine
The method of pyran-2-one derivative, the aldehyde radical substituted cyclopropane alkanes compound that this method uses are that one kind is difficult to the raw material obtained,
Cost is higher.
Invention content
For it is existing structure dihydropyran ring method existing for defect, the purpose of the invention is to provide one kind by
Compound of benzaldehyde category provides carbonyl, α-methylstyrene class compound provides acrylic and dimethyl sulfoxide (DMSO) provides methyl,
The method of common structure dihydropyran ring, the synthetic method are realized by one kettle way, and reaction condition is mild, is not necessarily to additional catalysis
Agent, the good, high income of selectivity, are conducive to industrialized production.
In order to achieve the above technical purposes, the present invention provides one kind by benzaldehyde, α-methylstyrene class compound and
The method that dimethyl sulfoxide builds dihydropyran ring jointly, this method are by compound of benzaldehyde category and α-methylstyrene class chemical combination
Object is in the dimethyl sulfoxide solution system containing persulfate by one pot reaction to get dihydropyran derivatives；
The compound of benzaldehyde category has 1 structure of formula：
The α-methylstyrene class compound has 2 structure of formula：
The dihydropyran derivatives have 3 structure of formula：
Wherein,
R1、R2And R3It is independently selected from hydrogen, halogenic substituent, alkyl, trifluoromethyl, nitro, cyano or alkoxy；
R4Selected from hydrogen, halogenic substituent or alkyl.
The range of choice of compound of benzaldehyde category is wider in technical scheme of the present invention, the selection of the substituent group on phenyl ring
The influence of the structure of dihydropyran ring is not obvious, R1、R2And R3The yield of dihydropyran is equal when selecting various common substituent groups
Be maintained at 60% or so, the substituent group number for including on phenyl ring be 1~3, substituent group be selected from halogenic substituent (fluorine, chlorine, bromine or
Iodine), alkyl (C1~C5Alkyl), trifluoromethyl, nitro, cyano or alkoxy (C1~C5Alkoxy) at least one of；It takes
The position of Dai Ji does not have particular/special requirement, can be ortho position, the meta or para position of aldehyde radical, but many experiments show that bromine substituent exists
Ideal dihydropyran derivatives yield can be obtained when aldehyde radical meta or para position, but bromine substituent does not have at aldehyde radical ortho position
Dihydropyran product is obtained, and other substituent groups in addition to bromine can obtain ideal yield at aldehyde radical ortho position, this is unexpected
's.Most preferred compound of benzaldehyde category includes benzaldehyde, 2,4,6- trimethylbenzaldehydes, 4- tolyl aldehydes, 3- methylbenzenes
Formaldehyde, 2- tolyl aldehydes, 4-methoxybenzaldehyde, 4- chlorobenzaldehydes, 3- chlorobenzaldehydes, 2- chlorobenzaldehydes, 4- fluorobenzene first
Aldehyde, 2- fluorobenzaldehydes, 4- bromobenzaldehydes, 3- bromobenzaldehydes, 4- cyanobenzaldehydes, 4- nitrobenzaldehydes, 3- nitrobenzaldehydes,
2- nitrobenzaldehydes or 4- trifluoromethylated benzaldehydes；
The range of choice of α-methylstyrene class compound is confined to selection phenyl or substitution in technical scheme of the present invention
Phenyl, phenyl can provide big conjugated system, can make the Alpha-Methyl on alkenyl that there is enough activity to participate in cyclisation.Phenyl takes
It cannot arbitrarily be replaced by other substituent groups for phenyl, such as heteroaromatic, alkyl replacement aryl cannot obtain target product.It takes
For base R4It is preferably selected from alkyl or halogen, R4When selected from halogenic substituent, the halogenic substituent is selected from fluorine, chlorine, bromine or iodine；
R4When selected from alkyl substituent, the alkyl substituent is selected from C1~C5Alkyl.The position of substituent group is preferably pair of alkenyl
Position.Substituted-phenyl also has selection to require substituent group, and substituent group can be weak electron donating group, such as alkyl, or weak drawing
Electron group, such as halogen.And strong electron donating group hales electron group, such as nitro such as amido, alkoxy, it is difficult to obtain ideal
Yield.Most preferred α-methylstyrene class compound include 2- (4- aminomethyl phenyls) propylene, 2- (4- chlorphenyls) propylene or
2- (4- fluorophenyls) propylene.
The molar ratio of preferred scheme, the potassium peroxydisulfate and compound of benzaldehyde category is 0.5~2:1, it is more preferably 0.8
~1.2:1.
The molar ratio of preferred scheme, compound of benzaldehyde category and α-methylstyrene class compound is 1:1~1.5.
Preferred scheme, a concentration of 0.1~0.5mol/L of the compound of benzaldehyde category in dimethyl sulfoxide solution system.Two
Methyl sulfoxide acts on of both primarily serving, and on the one hand plays the role of good solvent, is on the other hand used as reaction substrate, carries
For a methyl as a carbon atom in dihydropyran ring.
The condition of preferred scheme, the reaction is：Under protective atmosphere, at a temperature of 120~160 DEG C, reaction 18~
30h.More preferably condition is：In a nitrogen atmosphere, at a temperature of 135~145 DEG C, 22~26h is reacted.
The present invention with benzaldehyde and dimethyl sulfoxide and 2- phenylpropens build jointly dihydropyran ring come to reaction mechanism into
Row explanation.By consulting and refer to pertinent literature, a series of mechanism study experiment is devised, following reaction equation (1)~
(4) shown in.In order to prove whether the reaction passes through the reaction mechanism mechanism of reaction of free radical, reaction (1) is devised, under the conditions of standard reaction
The 2,6-di-tert-butyl p-cresol (BHT) of 2.0 equivalents (opposite benzaldehyde) is added, reacts 8h, it as a result still can be suitable by GC-MS
Profit detects the generation of dihydropyran derivatives target product, illustrates that reaction is not suppressed, reacts no experience one certainly
By the reaction mechanism mechanism of reaction of base.In order to prove that the reaction whether there is reaction intermediate, by benzaldehyde and dimethyl sulfoxide and 2- phenyl third
Alkene reacts 8 hours under the conditions of standard reaction, by being detected in GC-MS, in addition to detecting target product dihydropyran derivatives,
The presence of compound B is also detected that simultaneously.In order to prove whether compound B is intermediate in dihydropyran building process, if
Reaction (2) has been counted, 2- phenylpropens has been replaced by raw material of compound B, reacts, surprisingly find at the standard conditions, pass through GC-
MS successfully is detected dihydropyran derivatives.In order to further understand fully the source of compound B, reaction (3) is further devised, it will
2- phenylpropens are directly reacted at the standard conditions with dimethyl sulfoxide, by being found that depositing for compound B in GC-MS detections
, while having also obtained compound A.In order to obtain whether more accurately verification dimethyl sulfoxide participates in dihydropyran cyclisation, design
Reaction (4) is replaced conventional dimethyl sulfoxide (DMSO) using the deuterated dimethyl sulfoxide of isotope labelling and is at the standard conditions reacted, at
The presence of deuterium is detected to work(in dihydropyran product.Standard reaction condition：In N2Under, by benzaldehyde (0.5mmol), α-first
Base styrene (0.6mmol) and DMSO (2mL), 140 DEG C, reaction is for 24 hours.
It reacts (1)：
It reacts (2):
It reacts (3)：
It reacts (4)：
According to above-mentioned experiment, the present invention is proposed builds dihydro pyrrole jointly by benzaldehyde and dimethyl sulfoxide and 2- phenylpropens
It mutters the reasonable mechanism of ring：Shown in following reaction equation.First, using K2S2O8DMSO is activated, obtains that DMSO is made to be converted to diformazan
Base sulphur cation C, while 2- phenylpropens discharge Hydrogen Proton, are converted to 2- phenylpropen anion D, and C and D are easy to idol
Connection generates sulphur first ether compound A, and sulphur first ether compound A is in K2S2O8Under oxidation, removed by demethylation small
Molecule methyl mercaptan compound obtains compound B, and compound B occurs ODA with benzaldehyde and reacts, and finally obtains target product.
Compared with the prior art, the advantageous effects that technical scheme of the present invention is brought：
1) present invention is for the first time by compound of benzaldehyde category, α-methylstyrene class compound and dimethyl sulfoxide (DMSO) success structure
Dihydropyran derivatives are built, a kind of completely new synthesis thinking is provided for the structure of pyranoid ring.
2) without using catalyst, relatively existing this Ah of Deere in the building-up process of dihydropyran derivatives of the invention
Er De reacts, and avoids the use of louis catalyst, reduces the possibility of olefinic polymerization side reaction.
3) using compound of benzaldehyde category, α-methylstyrene class in dihydropyran derivatives building-up process of the invention
Object and dimethyl sulfoxide (DMSO) are closed as base stock, is all existing conventional industrial chemicals, it is of low cost, be conducive to industrial metaplasia
Production.
4) one pot reaction is used in dihydropyran derivatives building-up process of the invention, and reaction condition is mild, operation
Simply, meet demand of industrial production.
5) raw material availability is high in dihydropyran derivatives building-up process of the invention, and product yield is 60% or so.
6) wider to the accommodation of substrate raw material in dihydropyran derivatives building-up process of the invention, it can build more
The dihydropyran derivatives of kind substituent group, and substituting group position is selectively strong, obtains disubstituted 3, the 6- dihydropyran of 2,4-
Derivative.
Description of the drawings
【Fig. 1】For the mono-crystalline structures figure of compound 2- (4- nitrobenzophenones) -4- phenyl -3,6- dihydro -2H- pyrans.
Specific implementation mode
Following embodiment is intended to further illustrate the content of present invention, rather than limits the protection model of the claims in the present invention
It encloses.
Unless otherwise stated, all reactions carry out in Schlenk test tubes.
All reaction raw materials solvents are obtained from commercial source, and are used without further purification.
Product separation uses silica gel chromatographic column, silica gel (- 400 mesh of 300 mesh of granularity).
1H NMR (400MHz), 13C NMR (100MHz) and 19F NMR (376MHz) detections use Bruker ADVANCE
III spectrometers, with CDCl3For solvent, using TMS as internal standard, chemical shift is in terms of parts per million (ppm), with tetramethylsilane
0.0ppm is with reference to displacement.Multiplicity is explained using following abbreviation (or combinations thereof)：S=is unimodal, and d=is bimodal, and t=is triple
Peak, q=quartets, m=multiplets, br=broad peaks.The unit of coupling constant J is hertz (Hz).Chemical shift indicates with ppm,
With reference to deuterochloroform the center line of 77.0ppm triplets or with reference to deuterated DMSO 39.52ppm septets center line.
GC-MS is detected using GC-MS QP2010 equipment, and HRMS is measured using electron ionization (EI) method, mass-synchrometer
Type is TOF, and EI is detected using Esquire 3000plus instruments.
1. condition optimizing is tested:
For building dihydropyran ring jointly by benzaldehyde and dimethyl sulfoxide and 2- phenylpropens, to oxidant and its use
Multiple influence factors such as amount, reaction temperature, reaction dissolvent and additive are inquired into, to seek best reaction condition.
Specific reaction process：By benzaldehyde (0.5mmol), α-methylstyrene (0.6mmol), oxidant, additive
(0.5mmol) and DMSO (2mL), in N2Under atmosphere, reaction is for 24 hours.
Reaction route is as follows：
Table 1：The yield of target product dihydropyran derivatives under the conditions of differential responses
1) selection of additive
As seen from Table 1, the use of additive has a great impact to reaction, and many experiments show such as project 1 in table 1
~6 and 11, in benzaldehyde and dimethyl sulfoxide and 2- phenylpropens build the reaction process of dihydropyran ring, it has not been found that having
Conducive to reaction efficiency is improved, increase the benign additive of yield, such as DABCO, DBU, K2CO3、Cs2CO3Equal alkaline matters conduct
Additive cannot get target product dihydropyran substantially in use, apparent inhibition reaction, and add Et3N or NaOAc are only obtained
Obtain the lower target product dihydropyran of yield.
3) selection of oxidant
The present invention has attempted the several frequently seen oxidant in this field, such as project 11 and 15~19 in table 1, oxidant such as over cure
There is preferable reaction to imitate when being found only at potassium peroxydisulfate as oxidant for sour potassium, organic peroxide, inorganic hydrogen peroxide etc.
Fruit, as use tert-butyl hydroperoxide (TBHP), DTBP or hydrogen peroxide (H2O2) when being used as oxidant almost without obtaining target
Therefore product selects potassium peroxydisulfate as optimal oxidant.But ammonium persulfate is not appropriate for the oxygen as the method for the present invention
Agent, it may be possible to which ammonium ion causes adverse effect to reaction.
4) selection of oxidizer
After determining that potassium peroxydisulfate etc. is best oxidant, influence of the oxidant to reaction of different amounts is explored.Such as table 1
Middle project 11~14.When the dosage of oxidant is between 0.5~1 equivalent, with the increase of oxidant content, the conversion of raw material
The yield of rate and product also increases therewith.And when the dosage of oxidant is more than 1 equivalent, yield declines apparent.Therefore, 1 works as
The potassium peroxydisulfate of amount is the optimum amount of reaction.
5) selection of reaction temperature
Reaction temperature is to influence a key factor of chemical reaction process, and optimal reaction temperature, has studied in order to obtain
The yield of the reaction at different temperatures, such as project 7~11 in table 1.In less than 120 DEG C temperature, it substantially cannot get target production
Object, when temperature reaches 120 DEG C or more, reaction yield significantly improves, and increases the temperature to 140 DEG C, reaction yield reaches highest, and high
In 140 DEG C, reaction side reaction is apparent.Therefore, 140 DEG C of optimum temperatures for the reaction.
6) selection of reaction dissolvent
Since DMSO is to be used as reaction substrate and solvent simultaneously during synthesizing dihydro pyrans, being other solvents can not replace
It changes.DMSO may be used in the solvent of the present invention, while can also use the mixed solvent of DMSO and other solvents.
2, the range of choice of reaction substrate：
After the optimal synthesis condition of dihydropyran is determined, the substrate spectrum and applicability of reaction are probed into, it is real
Result is tested as shown in table 2 and table 3.Table 2 is different compound of benzaldehyde category and α-methylstyrene class compound and DMSO
Reaction result.Compound of benzaldehyde category as can be seen from Table 1 containing various substituent groups can be with α-methylstyrene class
It closes object and DMSO effectively synthesizes corresponding dihydropyran ring structure under the reaction condition of standard, and the yield of target product exists
60% or so.Also, many experiments show the benzaldehyde containing substituent group, and influence of the substituent group to reaction is not obvious, various
Substituted benzaldehyde smoothly can build dihydropyran with 2- phenylpropens and DMSO.Sole exception is 2- bromobenzaldehydes the bottom of as
Object can not build dihydropyran with 2- phenylpropens and DMSO, it may be possible to which the influence of bromine atom, mechanism remain unknown.
Table 3 is different α-methylstyrene class compounds and benzaldehyde and the reaction result of DMSO, the experimental results showed that, third
2 bit substituents must be the aryl for having big conjugated system on alkene, such as phenyl and substituted-phenyl, other heteroaromatics, alkyl etc.
Requirement is cannot be satisfied, the aryl of big conjugated system is conducive to improve the activity of Alpha-Methyl.And the selection of the substituent group on aryl
Cannot be to push away electronics or draw the stronger substituent group of electronic capability, such as nitro, alkoxy, and push away electronics and by what is required
If or draw electronic capability compared with substituent group, such as halogen, alkyl be satisfied by requirement.
(1) different compound of benzaldehyde category and α-methylstyrene class compound and the reaction equation of DMSO：
Reaction process:
Weigh potassium persulfate (K2S2O8) (135mg, 0.5mmol) be placed in the Shi Lunke reaction tubes of 25ml, then thereto
Dimethyl sulfoxide (DMSO, 2mL), compound of benzaldehyde category (0.5mmol) is added, 2- phenylpropens (71mg, 0.6mmol) are filled with
Nitrogen.At 140 DEG C, stir 24 hours.It after the completion of reaction, is cooled to room temperature, water (4mL), ethyl acetate is added to extract (3*5mL),
Anhydrous Na2SO4Dry, after solvent is fallen in vacuum distillation, silicagel column (200-300 mesh) separation obtains target product.
The different compound of benzaldehyde category of table 2. and 2- phenylpropens and DMSO reaction results
The structural characterization of part dihydropyran derivatives in table 2：
2,4-diphenyl-3,6-dihydro-2H-pyran:
1H NMR(400MHz,CDCl3) δ 7.44 (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) δ 7.41 (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) δ 7.41 (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) δ 7.42 (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=9.9
Hz, 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) δ 7.54 (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) δ 7.41 (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) δ 7.41 (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) δ 7.45 (s, 1H), 7.39 (d, J=7.2 Hz, 2H), 7.34 (d, J=6.9
Hz, 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) δ 7.65 (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) δ 7.40 (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) δ 7.51 (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) δ 160.79,158.35,139.94,134.43,128.99 (d, J=8.2
), Hz 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) δ 7.51 (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) δ 7.63 (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) δ 7.68 (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) δ 8.25 (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) δ 8.34 (s, 1H), 8.17 (d, J=8.2 Hz, 1H), 7.79 (d, J=7.6
Hz, 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) δ 7.94 (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-methylstyrene class compounds and benzaldehyde and DMSO：
Reaction process：
Weigh potassium persulfate (K2S2O8) (135mg, 0.5mmol) be placed in the Shi Lunke reaction tubes of 25ml, then thereto
Dimethyl sulfoxide (DMSO, 2ml), benzaldehyde (54mg, 0.5mmol) is added, propene compound (0.6mmol) is filled with nitrogen.
At 140 DEG C, stir 24 hours.It after the completion of reaction, is cooled to room temperature, adds water (4ml), ethyl acetate extracts (3*5ml), anhydrous
Na2SO4Dry, after solvent is fallen in vacuum distillation, silicagel column (200-300 mesh) separation obtains target product dihydropyrane compound.
The different propene compound of table 3. and benzaldehyde and the reaction result of DMSO
The structural characterization of part dihydropyran derivatives in table 3：
4-(4-methylphenyl)-2-phenyl-3,6-dihydro-2H-pyran：
1H NMR(400MHz,CDCl3) δ 7.46 (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) δ 7.44 (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) δ 7.44 (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 kind of method that dihydropyran ring is built by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide jointly,
It is characterized in that：Compound of benzaldehyde category is with α-methylstyrene class compound in the dimethyl sulfoxide solution system containing potassium peroxydisulfate
By one pot reaction to get dihydropyran derivatives；
The compound of benzaldehyde category has 1 structure of formula：
The α-methylstyrene class compound has 2 structure of formula：
The dihydropyran derivatives have 3 structure of formula：
Wherein,
R1、R2And R3It is independently selected from hydrogen, halogenic substituent, alkyl, trifluoromethyl, nitro, cyano or alkoxy；
R4Selected from hydrogen, halogenic substituent or alkyl.
2. one kind according to claim 1 is built jointly by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide
The method of dihydropyran ring, it is characterised in that：
In the compound of benzaldehyde category, R1、R2And R3When selected from halogenic substituent, the halogenic substituent is selected from fluorine, chlorine, bromine
Or iodine；R1、R2And R3When selected from alkyl substituent, the alkyl substituent is selected from C1~C5Alkyl；
In the α-methylstyrene class compound, R4When selected from halogenic substituent, the halogenic substituent be selected from fluorine, chlorine, bromine or
Iodine；R4When selected from alkyl substituent, the alkyl substituent is selected from C1~C5Alkyl.
3. one kind according to claim 2 is built jointly by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide
The method of dihydropyran ring, it is characterised in that：The compound of benzaldehyde category includes benzaldehyde, 2,4,6- trimethylbenzene first
Aldehyde, 4- tolyl aldehydes, 3- tolyl aldehydes, 2- tolyl aldehydes, 4-methoxybenzaldehyde, 4- chlorobenzaldehydes, 3- chlorobenzene first
Aldehyde, 2- chlorobenzaldehydes, 4- fluorobenzaldehydes, 2- fluorobenzaldehydes, 4- bromobenzaldehydes, 3- bromobenzaldehydes, 4- cyanobenzaldehydes, 4- nitros
Benzaldehyde, 3- nitrobenzaldehydes, 2- nitrobenzaldehydes or 4- trifluoromethylated benzaldehydes；
The α-methylstyrene class compound includes 2- (4- aminomethyl phenyls) propylene, 2- (4- chlorphenyls) propylene or 2- (4- fluorine
Phenyl) propylene.
4. one kind according to claim 1 is built jointly by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide
The method of dihydropyran ring, it is characterised in that：The molar ratio of the potassium peroxydisulfate and compound of benzaldehyde category is 0.5~2:1.
5. one kind according to claim 1 is built jointly by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide
The method of dihydropyran ring, it is characterised in that：The molar ratio of compound of benzaldehyde category and α-methylstyrene class compound is 1:1
~1.5.
6. one kind according to claim 1 is built jointly by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide
The method of dihydropyran ring, it is characterised in that：Compound of benzaldehyde category in dimethyl sulfoxide solution system a concentration of 0.1~
0.5mol/L。
7. according to claim 1~6 any one of them one kind by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide
The method of common structure dihydropyran ring, it is characterised in that：The condition of the reaction is：Under protective atmosphere, in 120~160
At a temperature of DEG C, 18~30h is reacted.
8. one kind according to claim 7 is built jointly by benzaldehyde, α-methylstyrene class compound and dimethyl sulfoxide
The method of dihydropyran ring, it is characterised in that：The condition of the reaction is：In a nitrogen atmosphere, at a temperature of 135~145 DEG C,
React 22~26h.
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| JPH1077278A (en) * | 1996-09-05 | 1998-03-24 | Kao Corp | Method for producing dihydropyran derivative |
| CN1114599C (en) * | 1996-10-03 | 2003-07-16 | 花王株式会社 | Process for preparing dihydropyrane compound |
| CN1626527B (en) * | 2003-08-29 | 2012-05-09 | 株式会社半导体能源研究所 | Pyran derivative, method for manufacturing the same, and light-emitting element containing the pyran derivative |
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| JPH1077278A (en) * | 1996-09-05 | 1998-03-24 | Kao Corp | Method for producing dihydropyran derivative |
| CN1114599C (en) * | 1996-10-03 | 2003-07-16 | 花王株式会社 | Process for preparing dihydropyrane compound |
| CN1626527B (en) * | 2003-08-29 | 2012-05-09 | 株式会社半导体能源研究所 | Pyran derivative, method for manufacturing the same, and light-emitting element containing the pyran derivative |
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