CN116162057A - Preparation method of 5-sulfonyl-1, 4 dihydropyridine compound - Google Patents

Preparation method of 5-sulfonyl-1, 4 dihydropyridine compound Download PDF

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CN116162057A
CN116162057A CN202310085456.1A CN202310085456A CN116162057A CN 116162057 A CN116162057 A CN 116162057A CN 202310085456 A CN202310085456 A CN 202310085456A CN 116162057 A CN116162057 A CN 116162057A
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sulfonyl
prop
dimethylamino
dihydropyridines
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周书光
李搏天
杨启帆
崔淏南
吕前
雷骐尔
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Northwestern Polytechnical University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms

Abstract

The invention discloses a preparation method of a 5-sulfonyl-1, 4-dihydropyridine compound, which comprises the following steps: the enaminones and the binaphthols with the structures shown in the formulas (II) and (III) are used as raw materials, react for 12-24 hours in an organic solvent at the temperature of 90-120 ℃ under the action of an oxidant to obtain a reaction product, and then the obtained reaction product is purified to obtain the 5-sulfonyl-1, 4 dihydropyridines shown in the formula (I). The preparation method has the characteristics of low cost, mild reaction conditions, simplicity in operation, few reaction byproducts, environment friendliness and high yield of the obtained target product, and therefore, the preparation method has a wide application prospect.

Description

Preparation method of 5-sulfonyl-1, 4 dihydropyridine compound
Technical Field
The invention belongs to the technical field of synthesis of organic compounds, and particularly relates to a preparation method of 5-sulfonyl-1, 4-dihydropyridine compounds.
Background
Polysubstituted dihydropyridine rings (backbones) have specificity and remarkable medicinal value and thus have wide application in many bioactive molecules and drugs. Some examples include the most popular drugs such as Adalat' and Norvasc as calcium channel blockers for the treatment of hypertension, biktarvy and Tivicay as HIV-1 integrase inhibitors for the treatment of Human Immunodeficiency Virus (HIV) infection. In addition, polysubstituted Dihydropyridines (DHPs) are also widely used as efficient photoredox and alkylation reactions in organic synthesis. Therefore, development of simple and efficient synthetic methods for preparing multi-functional substituted dihydropyridine rings (backbones) has attracted considerable attention.
Many methods for synthesizing dihydropyridines have been reported. Among them, the Hantzsch reaction is most attractive because it is a multicomponent one-pot reaction and the ability to act as a solvent in water. However, this process also has disadvantages such as long reaction times, severe reaction conditions (in reflux of acetic acid or alcohol), low to medium yields of product, and limited substrate range (only suitable for symmetrical dihydropyridine synthesis).
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims to provide a preparation method of 5-sulfonyl-1, 4 dihydropyridine compounds, which has the characteristics of mild reaction conditions, simple operation, atom economy, environmental friendliness and high yield.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
in a first aspect, the present invention provides 5-sulfonyl-1, 4 dihydropyridines of the formula (I):
Figure BDA0004068758930000021
wherein R is selected from Ph, CH 3 -Ph、F-Ph、Cl-Ph、Br-Ph、OCH 3 Any one of R 1 Selected from CH 3 Any one of Bn and Ph, R 2 Selected from CH 3 Or CH 3 -Ph，R 3 Selected from H or CH 3 。
The second aspect of the present invention provides a method for preparing the above 5-sulfonyl-1, 4 dihydropyridines, comprising the steps of: the enaminones and the dienes with the structures shown in the following formulas (II) and (III) are used as raw materials, react for 12-24 hours in an organic solvent at the temperature of 90-120 ℃ under the action of an oxidant to obtain a reaction product, and then the obtained reaction product is purified to obtain the 5-sulfonyl-1, 4 dihydropyridines:
Figure BDA0004068758930000022
wherein R is selected from Ph, CH 3 -Ph、F-Ph、Cl-Ph、Br-Ph、OCH 3 Any one of R 1 Selected from CH 3 Any one of Bn and Ph, R 2 Selected from CH 3 Or CH 3 -Ph，R 3 Selected from H or CH 3 。
Preferably, the mol ratio of the oxidant, the enaminones and the diene compounds to the oxidant is 1.2-3.0: 1:1.2 to 2.0.
Preferably, the enaminones are selected from any one of (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one, (Z) -3- (dimethylamino) -1- (o-tolyl) prop-2-en-1-one, (Z) -3- (dimethylamino) -1- (2-fluorophenyl) propyl-2-en-1-one, (Z) -3- (dimethylamino) -1- (m-tolyl) prop-2-en-1-one, (Z) -3- (dimethylamino) -1- (3-fluorophenyl) propyl-2-en-1-one, (Z) -3- (dimethylamino) -1- (p-tolyl) prop-2-en-1-one, (Z) -1- (4-bromophenyl) -3- (dimethylamino) propyl-2-en-1-one, (Z) -4- (dimethylamino) butyl-3-en-2-one, and (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one.
Preferably, the oxidant is any one of cupric salt, silver salt, potassium persulfate, ammonium persulfate, potassium monopersulfate peroxide, sodium percarbonate and active manganese dioxide; wherein the silver salt is silver acetate, silver carbonate or silver trifluoroacetate.
Preferably, the organic solvent is one or more than two of ethylene glycol dimethyl ether, acetonitrile, dichloromethane, dichloroethane, chloroform, chlorobenzene and 1, 4-dioxane.
Preferably, the diene compound is selected from the group consisting of N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide, 4-methyl-N-phenyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide, N-benzyl-4-methyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide, N-methyl-N- (prop-1, 2-dien-1-yl) methylsulfonamide.
Preferably, the reaction product is purified by thin layer chromatography using a developing solvent system of petroleum ether/ethyl acetate and the volume ratio of petroleum ether to ethyl acetate in the developing solvent system is 1:0.2-0.5.
Compared with the prior art, the invention has the following beneficial effects:
the invention takes enaminones and binaphthyl compounds as raw materials, and prepares the 5-sulfonyl-1, 4 dihydropyridines through one-step cyclization reaction in the presence of an oxidant. The preparation method has the advantages of mild reaction conditions, simple operation, few reaction byproducts, environment friendliness and high yield of the obtained target product. The invention takes the enaminones compound as one of the main raw materials, which is a raw material with simple synthesis and high conversion rate, and has wide substrate application range; in addition, the cost of the used diene compound and oxidant is low. The 5-sulfonyl-1, 4 dihydropyridine compounds have wide distribution in biologically and pharmaceutically active molecules, so the preparation method has wide application prospect.
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In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a synthetic route diagram for 5-sulfonyl-1, 4 dihydropyridines;
FIG. 2 is a nuclear magnetic resonance spectrum of the compound 3a prepared in example 1;
FIG. 3 is a carbon spectrum of compound 3a prepared in example 1.
Detailed Description
In the following description, for purposes of explanation and not limitation, specific details are set forth such as the particular system architecture, techniques, etc., in order to provide a thorough understanding of the embodiments of the present invention. It will be apparent, however, to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details.
Example 1
Referring to fig. 1, 5-sulfonyl-1, 4 dihydropyridines, specifically compound 3a, are prepared having the following structural formula:
Figure BDA0004068758930000051
the method comprises the following specific steps: to a 10mL Schlenk tube were successively added ethylene glycol dimethyl ether, (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one (0.20 mmol,0.035 g), N, 4-dimethyl-N- (propan-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), sodium percarbonate (0.3 mmol,0.047 g), and the reaction was stirred in a sealed environment at 100deg.C for 24 hours, after completion of the reaction by TLC monitoring, the purified product was isolated as a yellow solid by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, volume ratio of 1:0.5), i.e., compound 3a, yield 88%. The nuclear magnetic and carbon spectrum results are shown in fig. 2 and 3. 1 H NMR(400MHz,CDCl 3 )δ7.77(d,J＝7.6Hz,2H),7.47-7.42(m,3H),7.39(t,J＝7.7Hz,2H),7.33(d,J＝8.0Hz,2H),7.01(s,1H),6.57(s,1H),3.23(s,2H),3.09(s,3H),2.43(s,3H). 13 C NMR(101MHz,CDCl 3 )δ194.25,144.78,144.38,139.21,136.87,135.91,130.96,130.06,128.55,128.46,128.27,115.79,113.42,41.73,21.83,20.88.
Example 2
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3b, wherein the structural formula is shown as follows:
Figure BDA0004068758930000052
the method comprises the following specific steps: to 10mL Shi LaiEthylene glycol dimethyl ether, (Z) -3- (dimethylamino) -1- (o-tolyl) propanediol-2-en-1-one (0.20 mmol,0.038 g), N, 4-dimethyl-N- (propane-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g) and copper acetate (0.30 mmol,0.060 g) are sequentially added into a gram tube, stirring reaction is carried out for 20h in a sealed environment at 100 ℃, after TLC monitoring reaction is completed, a thin layer chromatography (a developing agent system is petroleum ether/ethyl acetate, the volume ratio of the developing agent system to the developing agent system is 1:0.5) is adopted to separate and purify a product, namely an orange solid compound 3b, and the yield is 85%. 1 H NMR(400MHz,CDCl 3 )δ7.81–7.76(m,1H),7.35(d,J＝8.5Hz,1H),7.31–7.27(m,1H),7.22–7.13(m,1H),7.07(s,1H),7.00(s,1H),6.35(s,1H),3.24(s,1H),3.05(s,1H),2.46–2.44(m,1H),2.21(s,1H). 13 C NMR(101MHz,CDCl 3 )δ195.94,145.10,144.45,139.09,136.75,135.87,135.79,130.99,130.10,129.48,128.33,127.37,125.40,116.25,114.65,41.71,21.88,20.42,19.57.
Example 3
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3c, wherein the structural formula is shown as follows:
Figure BDA0004068758930000061
the method comprises the following specific steps: to a 10mL Schlenk tube were successively added dichloroethane, (Z) -3- (dimethylamino) -1- (2-fluorophenyl) propyl-2-en-1-one (0.20 mmol,0.039 g), N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), potassium peroxomonosulfate (0.3 mmol,0.057 g), followed by stirring in a sealed environment at 90℃for 3h, after completion of the TLC monitoring reaction, the product was isolated and purified by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, both volumes 1:0.5) as an orange solid compound 3c, yield 85%. 1 H NMR(400MHz,CDCl 3 )δ7.77(d,J＝8.0Hz,2H),7.43-7.37(m,1H),7.34(d,J＝8.0Hz,1H),7.28-7.24(m,1H),7.17(dt,J＝7.5,0.9Hz,1H),7.07(dd,J＝13.2,4.7Hz,1H),7.00(s,1H),6.45(s,1H),3.23(s,2H),3.09(s,3H),2.44(s,3H). 13 C NMR(101MHz,CDCl 3 )δ189.96,159.1(d,J＝249.7Hz),145.45,144.50,136.68,135.62,131.87(d,J＝7.9Hz),130.08,129.93,128.27,124.48,116.51,116.31(d,J＝21.9Hz),114.23,41.81,21.85,20.51.
Example 4
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3d, wherein the structural formula is shown as follows:
Figure BDA0004068758930000071
the method comprises the following specific steps: dichloromethane, (Z) -3- (dimethylamino) -1- (m-tolyl) propanediol-2-en-1-one (0.20 mmol,0.038 g), N, 4-dimethyl-N- (propan-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g) and potassium peroxomonosulphate (0.4 mmol,0.076 g) were added sequentially to a 10mL Schlenk tube, the reaction was stirred at 100deg.C for 18h under sealed conditions, after completion of TLC monitoring, the product was isolated and purified by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, volume ratio of 1:0.5) as a yellow solid compound 3d, yield 79%. 1 H NMR(400MHz,CDCl 3 )δ7.78(d,J＝8.1Hz,2H),7.33(d,J＝8.1Hz,2H),7.29–7.23(m,3H),7.23–7.17(m,1H),7.02(s,1H),6.58(s,1H),3.23(s,2H),3.09(s,3H),2.43(s,3H),2.36(s,3H). 13 C NMR(101MHz,CDCl 3 )δ194.49,144.74,144.33,139.19,138.48,136.91,135.84,131.66,130.01,128.93,128.25,128.21,125.50,115.60,113.38,41.70,21.81,21.57,20.81.
Example 5
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3e, wherein the structural formula is shown as follows:
Figure BDA0004068758930000081
the method comprises the following specific steps: to a 10mL Schlenk tube were added sequentially ethylene glycol dimethyl ether, (Z) -3- (dimethylamino) -1- (3-fluorophenyl) propyl-2-en-1-one (0.20 mmol,0.039 g), N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), ammonium persulfate (0.3 mmol,0.0684 g), in MiqStirring and reacting for 12h at 120 ℃ in a sealed environment, and separating and purifying the product by adopting a thin layer chromatography (the developing solvent system is petroleum ether/ethyl acetate with the volume ratio of 1:0.2) after the TLC monitoring reaction is completed, wherein the product is orange solid compound 3e, and the yield is 71%. 1 H NMR(400MHz,CDCl 3 )δ7.76(d,J＝8.3Hz,2H),7.35(ddd,J＝14.0,8.7,4.3Hz,3H),7.21(dt,J＝7.5,1.1Hz,1H),7.17-7.10(m,2H),7.01(d,J＝0.8Hz,1H),6.57(d,J＝0.7Hz,1H),3.21(s,2H),3.11(s,3H),2.43(s,3H). 13 C NMR(101MHz,CDCl 3 )δ192.57(d,J＝2.1Hz),163.83,161.36,145.06,144.47,141.20(d,J＝6.4Hz),136.73,135.72,130.42,129.97,128.26,124.11(d,J＝3.1Hz),118.02,117.80,116.13,115.57,115.35,113.02,41.81,21.83,20.79.
Example 6
Preparing a 5-sulfonyl-1, 4-dihydropyridine compound, specifically a compound 3f, wherein the structural formula is shown as follows:
Figure BDA0004068758930000091
the method comprises the following specific steps: chloroform, (Z) -3- (dimethylamino) -1- (p-tolyl) prop-2-en-1-one (0.20 mmol,0.038 g), N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), ammonium persulfate (0.48 mmol,0.11 g) were sequentially added to a 10mL Schlenk tube, the reaction was stirred at 90℃for 24h under a sealed condition, after the completion of the TLC monitoring, the product was isolated and purified by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, volume ratio of 1:0.5) as orange solid compound 3f, yield 76%. 1 H NMR(400MHz,CDCl 3 )δ7.76(d,J＝8.2Hz,2H),7.34(dd,J＝12.5,8.1Hz,4H),7.18(d,J＝7.9Hz,2H),7.01(s,1H),6.58(s,1H),3.22(s,2H),3.08(s,3H),2.42(s,3H),2.37(s,3H). 13 CNMR(101MHz,CDCl 3 )δ194.92,144.26,141.02,137.09,135.82,129.96,128.10,115.03,114.02,41.63,24.75,21.78,20.37.
Example 7
Preparing 5-sulfonyl-1, 4 dihydropyridines, specifically 3g, which have the following structural formula:
Figure BDA0004068758930000101
the method comprises the following specific steps: acetonitrile, (Z) -1- (4-bromophenyl) -3- (dimethylamino) propyl-2-en-1-one (0.20 mmol,0.051 g), N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), ammonium persulfate (0.24 mmol,0.055 g) were sequentially added to a 10mL Schlenk tube, the reaction was stirred at 90℃for 20h in a sealed environment, after completion of TLC monitoring, the product was isolated and purified by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, volume ratio of 1:0.5), as an orange solid compound 3g, yield 71%. 1 H NMR(400MHz,CDCl 3 )δ7.76(d,J＝8.2Hz,2H),7.53(d,J＝8.3Hz,2H),7.32(t,J＝7.3Hz,4H),7.01(s,1H),6.54(s,1H),3.21(s,2H),3.11(s,3H),2.43(s,3H). 13 C NMR(101MHz,CDCl 3 )δ192.97,144.82,144.46,137.91,136.73,135.75,131.80,130.07,130.06,128.26,125.54,116.07,113.20,41.79,21.84,20.84.
Example 8
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3h, wherein the structural formula is shown as follows:
Figure BDA0004068758930000102
the method comprises the following specific steps: dichloromethane, (Z) -4- (dimethylamino) butyl-3-en-2-one (0.20 mmol,0.023 g), N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), ammonium persulfate (0.48 mmol,0.11 g) were sequentially added to a 10mL Schlenk tube, the reaction was stirred at 110℃for 15h in a sealed environment, after the completion of the TLC monitoring reaction, the product was isolated and purified by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, volume ratio of both 1:0.5), as an orange solid compound for 3h, yield 79%. 1 HNMR(400MHz,CDCl 3 )δ7.72(d,J＝8.0Hz,2H),7.29(d,J＝7.9Hz,2H),6.98(s,1H),6.79(s,1H),3.16(s,3H),3.02(s,2H),2.40(s,3H),2.15(s,3H). 13 CNMR(101MHz,CDCl 3 )δ194.91,144.29,140.93,137.08,135.88,130.00,128.17,115.20,114.13,41.66,24.79,21.82,20.44.
Example 9
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3i, which has the following structural formula:
Figure BDA0004068758930000111
the method comprises the following specific steps: to a 10mL Schlenk tube were successively added 1, 4-dioxane, (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one (0.20 mmol,0.035 g), N, 4-dimethyl-N- (propan-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), sodium percarbonate (0.3 mmol,0.047 g), and after completion of the TLC monitoring reaction, the product was isolated and purified by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, volume ratio of the two was 1:0.35) as an orange solid compound 3i, yield 73%. 1 H NMR(500MHz,CDCl 3 )δ7.80(d,J＝7.8Hz,2H),7.44(d,J＝7.6Hz,3H),7.37(t,J＝7.4Hz,2H),7.31(d,J＝7.8Hz,2H),7.16(s,1H),6.60(s,1H),3.85(q,J＝6.4Hz,1H),3.18(s,3H),2.42(s,3H),1.08(d,J＝6.4Hz,3H). 13 C NMR(126MHz,CDCl 3 )δ194.13,144.19,143.39,139.56,137.98,137.80,130.99,130.05,128.45,128.43,128.03,119.88,118.82,41.96,26.19,23.38,21.83.
Example 10
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3j, which has the following structural formula:
Figure BDA0004068758930000121
the method comprises the following specific steps: to a 10mL Schlenk tube was added dichloromethane, (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one (0.20 mmol,0.062 g), 4-methyl-N-phenyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.4 mmol,0.114 g), ammonium persulfate (0.6 mmol,0.137 g) in a sealed environment of 1The reaction was stirred at 20℃for 12h. After the TLC monitoring reaction is finished, a thin layer chromatography (the developing solvent system is petroleum ether/ethyl acetate, the volume ratio of the developing solvent system to the ethyl acetate is 1:0.35) is adopted to separate and purify the product, and the product is orange solid compound 3j, and the yield is 75%. 1 H NMR(400MHz,CDCl 3 )δ7.82(d,J＝8.3Hz,2H),7.51(dd,J＝6.7,1.5Hz,3H),7.48–7.45(m,1H),7.42–7.35(m,6H),7.29–7.24(m,1H),7.13–7.08(m,3H),3.37(s,2H),2.45(s,3H). 13 C NMR(101MHz,CDCl 3 )δ194.62,144.61,142.74,142.09,138.77,135.55,134.78,131.32,130.25,130.12,128.65,128.54,128.37,127.06,120.94,118.01,115.10,21.85,21.38.
Example 11
Preparing a 5-sulfonyl-1, 4 dihydropyridine compound, specifically a compound 3k, which has the following structural formula:
Figure BDA0004068758930000131
the method comprises the following specific steps: to a 10mL Schlenk tube were added successively 1, 4-dioxane, (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one (0.20 mmol,0.035 g), N-benzyl-4-methyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.090 g), and active manganese dioxide (0.4 mmol,0.0248 g), and the reaction was stirred in a sealed atmosphere at 100deg.C for 20 hours. After the TLC monitoring reaction is finished, a thin layer chromatography (the developing solvent system is petroleum ether/ethyl acetate, the volume ratio of the developing solvent system to the ethyl acetate is 1:0.2) is adopted to separate and purify the product, and the product is yellow solid compound 3k, and the yield is 82%. 1 H NMR(400MHz,CDCl 3 )δ7.47-7.43(m,3H),7.40-7.35(m,5H),7.19-7.17(m,2H),6.98(d,J＝1.2Hz,1H),6.75(t,J＝0.8Hz,1H),4.42(s,2H),3.55(s,2H),2.93(s,2H). 13 C NMR(101MHz,CDCl 3 )δ194.23,144.21,138.83,137.38,135.27,131.29,129.56,128.96,128.66,128.59,127.52,115.02,113.55,58.34,40.11,21.75.
The present invention is not limited to the above-described specific embodiments, and various modifications may be made by those skilled in the art without inventive effort from the above-described concepts, and are within the scope of the present invention.

Claims (8)

  1. The 5-sulfonyl-1, 4 dihydropyridines are characterized by having the following formula (I):
    Figure FDA0004068758920000011
    wherein R is selected from Ph, CH 3 -Ph、F-Ph、Cl-Ph、Br-Ph、OCH 3 Any one of R 1 Selected from CH 3 Any one of Bn and Ph, R 2 Selected from CH 3 Or CH 3 -Ph，R 3 Selected from H or CH 3 。
  2. 2. A process for the preparation of 5-sulfonyl-1, 4 dihydropyridines according to claim 1 comprising the steps of: the enaminones and the dienes with the structures shown in the following formulas (II) and (III) are used as raw materials, react for 12-24 hours in an organic solvent at the temperature of 90-120 ℃ under the action of an oxidant to obtain a reaction product, and then the obtained reaction product is purified to obtain the 5-sulfonyl-1, 4 dihydropyridines:
    Figure FDA0004068758920000012
    wherein R is selected from Ph, CH 3 -Ph、F-Ph、Cl-Ph、Br-Ph、OCH 3 Any one of R 1 Selected from CH 3 Any one of Bn and Ph, R 2 Selected from CH 3 Or CH 3 -Ph，R 3 Selected from H or CH 3 。
  3. 3. The method for preparing 5-sulfonyl-1, 4 dihydropyridines according to claim 2, wherein the molar ratio of the oxidizing agent, enaminones, dienes and oxidizing agent is 1.2-3.0: 1:1.2 to 2.0.
  4. 4. The process for the preparation of 5-sulfonyl-1, 4 dihydropyridines according to claim 2, wherein the enaminones are selected from the group consisting of (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one, (Z) -3- (dimethylamino) -1- (o-tolyl) prop-2-en-1-one, (Z) -3- (dimethylamino) -1- (2-fluorophenyl) prop-2-en-1-one, (Z) -3- (dimethylamino) -1- (m-tolyl) prop-2-en-1-one, (Z) -3- (dimethylamino) -1- (3-fluorophenyl) prop-2-en-1-one, (Z) -3- (dimethylamino) -1- (p-tolyl) prop-2-en-1-one, (Z) -1- (4-bromophenyl) -3- (dimethylamino) prop-2-en-1-one, (Z) -4- (dimethylamino) butyl-3-en-2-one, (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one.
  5. 5. The method for producing 5-sulfonyl-1, 4 dihydropyridines according to claim 2, wherein the oxidizing agent is any one of a cupric salt, silver salt, potassium persulfate, amine persulfate, potassium monopersulfate, sodium percarbonate, and active manganese dioxide.
  6. 6. The method for producing 5-sulfonyl-1, 4 dihydropyridines according to claim 2, wherein the organic solvent is one or a combination of two or more of ethylene glycol dimethyl ether, acetonitrile, dichloromethane, dichloroethane, chloroform, chlorobenzene, and 1, 4-dioxane.
  7. 7. The process for the preparation of 5-sulfonyl-1, 4 dihydropyridines according to claim 2, wherein the bisene is selected from the group consisting of N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide, 4-methyl-N-phenyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide, N-benzyl-4-methyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide, N-methyl-N- (prop-1, 2-dien-1-yl) methylsulfonamide.
  8. 8. The method for preparing 5-sulfonyl-1, 4 dihydropyridines according to claim 2, wherein the reaction product is purified by thin layer chromatography using a developing solvent system of petroleum ether/ethyl acetate and the volume ratio of petroleum ether to ethyl acetate in the developing solvent system is 1:0.2-0.5.
CN202310085456.1A 2023-02-06 2023-02-06 Preparation method of 5-sulfonyl-1, 4 dihydropyridine compound Pending CN116162057A (en)

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