CN116162057B - Preparation method of 5-sulfonyl-1, 4 dihydropyridine compound - Google Patents
Preparation method of 5-sulfonyl-1, 4 dihydropyridine compoundInfo
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- CN116162057B CN116162057B CN202310085456.1A CN202310085456A CN116162057B CN 116162057 B CN116162057 B CN 116162057B CN 202310085456 A CN202310085456 A CN 202310085456A CN 116162057 B CN116162057 B CN 116162057B
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- 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
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Abstract
本发明公开了5‑磺酰基‑1,4二氢吡啶类化合物的制备方法，包括以下步骤：以结构如式(Ⅱ)和式(Ⅲ)所示的烯胺酮类化合物和联烯类化合物为原料，在氧化剂作用下，于有机溶剂中90～120℃下反应12～24h，得到反应产产物，然后将所得反应产物纯化，得到式(Ⅰ)所示的5‑磺酰基‑1,4二氢吡啶类化合物。本发明制备方法具有成本低廉、反应条件温和、操作简单、反应副产物少、绿色环保以及所得目标产物产率高的特点，因此，具有广阔的应用前景。
The present invention discloses a method for preparing a 5-sulfonyl-1,4-dihydropyridine compound, comprising the following steps: using an enaminone compound and an allene compound having structures such as those shown in formula (II) and formula (III) as raw materials, reacting in an organic solvent at 90 to 120° C. for 12 to 24 hours in the presence of an oxidant to obtain a reaction product, and then purifying the obtained reaction product to obtain a 5-sulfonyl-1,4-dihydropyridine compound shown in formula (I). The preparation method of the present invention has the characteristics of low cost, mild reaction conditions, simple operation, few reaction by-products, environmental protection, and high yield of the obtained target product, and therefore has broad application prospects.
Description
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 Dihydropyridines (DHPs) are widely used as efficient photooxidation reducing agents 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):
(I)
Wherein, R is selected from any one of Ph and CH 3-Ph、F-Ph、Cl-Ph、Br-Ph、OCH3, R 1 is selected from any one of CH 3, bn and Ph, R 2 is selected from CH 3 or CH 3-Ph,R3 is selected from H or CH 3.
The second aspect of the invention provides a preparation method of the 5-sulfonyl-1, 4 dihydropyridine compound, which comprises the following steps of taking enaminone compounds and diene compounds shown in the following structural formulas (II) and (III) as raw materials, reacting for 12-24 hours in an organic solvent at a temperature of 90-120 ℃ under the action of an oxidant to obtain a reaction product, and purifying the obtained reaction product to obtain the 5-sulfonyl-1, 4 dihydropyridine compound:
(II)(III)
Wherein, R is selected from any one of Ph and CH 3-Ph、F-Ph、Cl-Ph、Br-Ph、OCH3, R 1 is selected from any one of CH 3, bn and Ph, R 2 is selected from CH 3 or CH 3-Ph,R3 is selected from H or CH 3.
Preferably, the molar ratio of the oxidant to the enaminones to the bialkenes to the oxidant is 1.2-3.0:1:1.2-2.0.
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 in a volume ratio of petroleum ether to ethyl acetate of 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 enaminones as one of the main raw materials, is a raw material with simple synthesis and high conversion rate, has wide substrate application range, and has low cost of the used bialkenes and oxidant. The 5-sulfonyl-1, 4 dihydropyridine compounds have wide distribution in biologically and pharmaceutically active molecules, so the preparation method has wide application prospect.
Drawings
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:
(3a)
The preparation method comprises the specific steps of sequentially adding ethylene glycol dimethyl ether, (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one (0.20 mmol,0.035 g) and N, 4-dimethyl-N- (propan-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g) into a 10mL Schlenk tube, stirring to react for 24h in a sealed environment at 100 ℃ to monitor the reaction by TLC, and separating and purifying the product by adopting a thin layer chromatography (developing agent system is petroleum ether/ethyl acetate, the volume ratio of the developing agent system to the ethyl acetate is 1:0.5) to obtain a yellow solid substance, namely a compound 3a, wherein the yield is 88%. The nuclear magnetism and carbon spectrum results are shown in FIG. 2 and FIG. 3 .1H NMR (400 MHz, CDCl3)δ 7.77 (d,J= 7.6 Hz, 2H), 7.47-7.42 (m, 3H), 7.39 (t,J= 7.7 Hz, 2H), 7.33 (d,J= 8.0 Hz, 2H), 7.01 (s, 1H), 6.57 (s, 1H), 3.23 (s, 2H), 3.09 (s, 3H), 2.43 (s, 3H).13C NMR (101 MHz, CDCl3)δ 194.25, 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:
(3b)
The preparation method comprises the specific steps of sequentially adding ethylene glycol dimethyl ether, (Z) -3- (dimethylamino) -1- (o-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 copper acetate (0.30 mmol,0.060 g) into a 10mL Schlenk tube, stirring in a sealed environment at 100 ℃ for 20h, separating and purifying the product by adopting a thin layer chromatography (developing agent system is petroleum ether/ethyl acetate with the volume ratio of 1:0.5) after the TLC monitoring reaction is completed, wherein the product is an orange solid compound 3b, and the yield is high 85%.1H NMR (400 MHz, CDCl3)δ 7.81 – 7.76 (m, 1H), 7.35 (d,J= 8.5 Hz, 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).13C NMR (101 MHz, CDCl3)δ 195.94, 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:
(3c)
The preparation method comprises the specific steps of sequentially adding dichloroethane, (Z) -3- (dimethylamino) -1- (2-fluorophenyl) propyl-2-en-1-one (0.20 mmol,0.039 g) and N, 4-dimethyl-N- (propan-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g) into a 10mL Schlenk tube, stirring and reacting potassium peroxomonosulfate (0.3 mmol,0.057 g) in a sealed environment at 90 ℃ for 3h, separating and purifying the product by adopting a thin layer chromatography (developing solvent system is petroleum ether/ethyl acetate, the volumes of the developing solvent system and the developing solvent system are 1:0.5), wherein the product is an orange solid compound 3C, and the yield is high 85%.1H NMR (400 MHz, CDCl3)δ 7.77 (d,J= 8.0 Hz, 2H), 7.43-7.37 (m, 1H), 7.34 (d,J= 8.0 Hz, 1H), 7.28-7.24 (m, 1H), 7.17 (dt,J= 7.5, 0.9 Hz, 1H), 7.07 (dd,J= 13.2, 4.7 Hz, 1H), 7.00 (s, 1H), 6.45 (s, 1H), 3.23 (s, 2H), 3.09 (s, 3H), 2.44 (s, 3H).13C NMR (101 MHz, CDCl3)δ 189.96, 159.1(d,J= 249.7 Hz), 145.45, 144.50, 136.68, 135.62, 131.87 (d,J= 7.9 Hz), 130.08, 129.93, 128.27, 124.48, 116.51, 116.31 (d,J= 21.9 Hz), 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:
(3d)
The preparation method comprises the specific steps of sequentially adding dichloromethane, (Z) -3- (dimethylamino) -1- (m-tolyl) propanediol-2-en-1-one (0.20 mmol,0.038 g) and N, 4-dimethyl-N- (propan-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g) into a10 mL Schlenk tube, stirring and reacting for 18h under 100 ℃ in a sealed environment to monitor the reaction condition by TLC, separating and purifying the product by adopting a thin layer chromatography (developing agent system is petroleum ether/ethyl acetate, the volume ratio of the developing agent system to the petroleum ether/ethyl acetate is 1:0.5), wherein the product is yellow solid compound 3d, and the yield is high 79%.1H NMR (400 MHz, CDCl3)δ 7.78 (d,J= 8.1 Hz, 2H), 7.33 (d,J= 8.1 Hz, 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).13C NMR (101 MHz, CDCl3)δ 194.49, 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:
(3e)
the preparation method comprises the specific steps of sequentially adding 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) into a 10mL Schlenk's tube, stirring in a sealed environment at 120 ℃ for 12h, separating and purifying the product by adopting a thin layer chromatography (developing agent 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 an orange solid compound 3e, and the yield is high 71%.1H NMR (400 MHz, CDCl3)δ 7.76 (d,J= 8.3 Hz, 2H), 7.35 (ddd,J= 14.0, 8.7, 4.3 Hz, 3H), 7.21 (dt,J= 7.5, 1.1 Hz, 1H), 7.17-7.10 (m, 2H), 7.01 (d,J= 0.8 Hz, 1H), 6.57 (d,J= 0.7 Hz, 1H), 3.21 (s, 2H), 3.11 (s, 3H), 2.43 (s, 3H).13C NMR (101 MHz, CDCl3)δ 192.57 (d,J= 2.1 Hz), 163.83, 161.36, 145.06, 144.47, 141.20 (d,J= 6.4 Hz), 136.73, 135.72, 130.42,129.97 , 128.26, 124.11 (d,J= 3.1 Hz), 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:
(3f)
the preparation method comprises the specific steps of sequentially adding chloroform, (Z) -3- (dimethylamino) -1- (p-tolyl) propanediol-2-en-1-one (0.20 mmol,0.038 g) and N, 4-dimethyl-N- (propan-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g) into a10 mL Schlenk tube, stirring and reacting for 24h under the condition of 90 ℃ in a sealed environment with ammonium persulfate (0.48 mmol,0.11 g), separating and purifying the product by adopting a thin layer chromatography (developing agent system is petroleum ether/ethyl acetate, the volume ratio of the two is 1:0.5), wherein the product is orange solid compound 3f, and the yield is obtained after the TLC monitoring reaction is completed 76%.1H NMR (400 MHz, CDCl3)δ 7.76 (d,J= 8.2 Hz, 2H), 7.34 (dd,J= 12.5, 8.1 Hz, 4H), 7.18 (d,J= 7.9 Hz, 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).13C NMR (101 MHz, CDCl3)δ 194.92, 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:
(3g)
Acetonitrile, (Z) -1- (4-bromophenyl) -3- (dimethylamino) propyl-2-en-1-one (0.20 mmol,0.051 g), N, 4-dimethyl-N- (propane-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 ℃ in a sealed environment for 20h, after TLC monitoring was completed, the product was separated and purified by thin layer chromatography (developing solvent system petroleum ether/ethyl acetate, volume ratio of 1:0.5), and the product was 3g as orange solid compound, yield 71%.1H NMR (400 MHz, CDCl3)δ 7.76 (d,J= 8.2 Hz, 2H), 7.53 (d,J= 8.3 Hz, 2H), 7.32 (t,J= 7.3 Hz, 4H), 7.01 (s, 1H), 6.54 (s, 1H), 3.21 (s, 2H), 3.11 (s, 3H), 2.43 (s, 3H).13C NMR (101 MHz, CDCl3)δ 192.97, 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:
(3h)
The preparation method comprises the specific steps of sequentially adding methylene dichloride, (Z) -4- (dimethylamino) butyl-3-en-2-one (0.20 mmol,0.023 g), N, 4-dimethyl-N- (propane-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g), ammonium persulfate (0.48 mmol,0.11 g) into a 10mL Schlenk tube, stirring in a sealed environment at 110 ℃ for 15h, separating and purifying the product by adopting a thin layer chromatography (developing agent system is petroleum ether/ethyl acetate with the volume ratio of 1:0.5) after the TLC monitoring reaction is completed, wherein the product is an orange solid compound for 3h, and the yield is high 79%.1H NMR (400 MHz, CDCl3)δ 7.72 (d,J= 8.0 Hz, 2H), 7.29 (d,J= 7.9 Hz, 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).13CNMR (101 MHz, CDCl3)δ 194.91, 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:
(3i)
The preparation method comprises the following steps of sequentially adding 1, 4-dioxane, (Z) -3- (dimethylamino) -1-phenylpropyl-2-en-1-one (0.20 mmol,0.035 g), N, 4-dimethyl-N- (prop-1, 2-dien-1-yl) benzenesulfonamide (0.30 mmol,0.067 g) and sodium percarbonate (0.3 mmol,0.047 g) into a 10mL Schlenk tube, stirring in a sealed environment at 110 ℃ for 18h, separating and purifying the product by adopting a thin layer chromatography (developing agent system is petroleum ether/ethyl acetate with the volume ratio of 1:0.35) after the TLC monitoring reaction is completed, wherein the product is an orange solid compound 3i, the yield is 73%.1H NMR (500 MHz, CDCl3)δ 7.80 (d,J= 7.8 Hz, 2H), 7.44 (d,J= 7.6 Hz, 3H), 7.37 (t,J= 7.4 Hz, 2H), 7.31 (d,J= 7.8 Hz, 2H), 7.16 (s, 1H), 6.60 (s, 1H), 3.85 (q,J= 6.4 Hz, 1H), 3.18 (s, 3H), 2.42 (s, 3H), 1.08 (d,J= 6.4 Hz, 3H).13C NMR (126 MHz, CDCl3)δ 194.13, 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:
(3j)
To a10 mL Schlenk tube was added sequentially 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) and reacted under stirring in a sealed environment at 120℃for 12h. After TLC monitoring reaction, separating and purifying the product by thin layer chromatography (developing solvent system is petroleum ether/ethyl acetate, volume ratio of the two is 1:0.35), wherein the product is orange solid compound 3j, and the yield is high 75%.1H NMR (400 MHz, CDCl3)δ 7.82 (d,J= 8.3 Hz, 2H), 7.51 (dd,J= 6.7, 1.5 Hz, 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).13C NMR (101 MHz, CDCl3)δ 194.62, 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:
(3k)
To a10 mL Schlenk tube were added sequentially 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 reacted under stirring at 100℃for 20 hours in a sealed environment. After TLC monitoring reaction, separating and purifying the product by thin layer chromatography (developing solvent system is petroleum ether/ethyl acetate, volume ratio of the two is 1:0.2), wherein the product is yellow solid compound 3k, and the yield is high 82%.1H NMR (400 MHz, CDCl3)δ 7.47-7.43 (m, 3H), 7.40-7.35 (m, 5H), 7.19-7.17 (m, 2H), 6.98 (d,J= 1.2 Hz, 1H), 6.75 (t,J= 0.8 Hz, 1H), 4.42 (s, 2H), 3.55 (s, 2H), 2.93 (s, 2H).13C NMR (101 MHz, CDCl3)δ 194.23, 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 (5)
1. The preparation method of the 5-sulfonyl-1, 4 dihydropyridine compound is characterized by comprising the following steps of taking enaminone compound and diene compound shown in the following structural formulas (II) and (III) as raw materials, reacting for 12-24 hours in an organic solvent at a temperature of 90-120 ℃ under the action of an oxidant to obtain a reaction product, and purifying the obtained reaction product to obtain the 5-sulfonyl-1, 4 dihydropyridine compound shown in the following formula (I):
(I)
(II) (III)
Wherein, R is selected from any one of-Ph and CH 3-Ph-、F-Ph-、Cl-Ph-、Br-Ph-、-OCH3, R 1 is selected from any one of-CH 3, -Bn and-Ph, R 2 is selected from-CH 3 or CH 3-Ph-,R3 is selected from H or-CH 3;
The oxidant is any one of silver salt, potassium persulfate, ammonium persulfate, potassium monopersulfate peroxide, sodium percarbonate and active manganese dioxide;
the organic solvent is one or the combination of more than two of ethylene glycol dimethyl ether, acetonitrile, dichloromethane, dichloroethane, chloroform, chlorobenzene and 1, 4-dioxane.
2. The method for preparing 5-sulfonyl-1, 4 dihydropyridines according to claim 1, wherein the molar ratio of the oxidizing agent, the enaminones and the dienes is 1.2-3.0:1:1.2-2.0.
3. The process for the preparation of 5-sulfonyl-1, 4 dihydropyridines according to claim 1, 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.
4. The process for the preparation of 5-sulfonyl-1, 4 dihydropyridines according to claim 1, wherein the bisene 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.
5. The method for preparing 5-sulfonyl-1, 4 dihydropyridines according to claim 1, 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.
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| Shuguang Zhou等.Silver-mediated synthesis of 1,4-dihydropyridine sulfones via [4 + 2] cyclization of N-allenylsulfonamides and enaminones with a 1,3- sulfonyl shift.《Org. Chem. Front.》.2023,第11卷第100-105页. * |
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