CN114605263A - A kind of synthetic method of phenyl allyl ether compound - Google Patents

Abstract

。The invention discloses a method for synthesizing phenyl allyl ether compounds, belonging to the field of organic synthesis. The method comprises the following steps: adding phenolic compounds, GMDVs, catalysts and solvents to the reactor in sequence under an inert gas atmosphere, stirring at a certain temperature until the reaction is completed, concentrating the solvent to obtain a crude product, and separating the phenyl groups by column chromatography. Allyl ether compounds. The synthesis method of the invention has the advantages of high yield, good atom economy, wide substrate application, mild reaction conditions, convenient post-processing and the like. Its reaction equation is as follows:

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Description

A kind of synthetic method of phenyl allyl ether compound

technical field

The invention discloses a method for synthesizing a phenylallyl ether compound, which belongs to the technical field of organic synthesis.

Background technique

Phenyl allyl ether compounds are very important intermediates in organic synthesis, which can synthesize a series of biologically active molecules or natural products (Chem. Rev., 2003, 103, 2921.). In addition, phenylallyl ethers are reagents for many important reactions, such as the Claisen rearrangement.

The synthetic method of the reported phenyl allyl ether compounds is mainly the nucleophilic substitution reaction of phenolic compound and allyl halide under the effect of strong base, or the allyl precursor under the catalysis of transition metal ( Such as allyl alcohol, allyl ester, etc.) involved in the allylation reaction. At present, the synthetic method of phenyl allyl ether is still relatively limited, which greatly limits its application in organic synthesis. Therefore, it is very important to develop an efficient method for synthesizing phenylallyl ethers.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a novel method for efficiently synthesizing phenyl allyl ether compounds in order to overcome the relatively limited problem of the synthesis method of the existing phenyl allyl ether compounds.

In order to achieve the above object, the present invention provides an efficient method for synthesizing phenyl allyl ether compounds by using GMDVs as an allylation reagent. Described phenyl allyl ether compound has the structure shown in formula I:

Wherein, Ar is selected from any one of phenyl, naphthyl and estrone;

R ¹ is selected from any one of saturated alkyl, alkoxy, halogen, nitro, trifluoromethyl, formyl and acetamido, and is located at the ortho, meta or para position of the hydroxyl group.

Under inert gas atmosphere, add phenolic compound, GMDVs, catalyst and solvent successively to the reactor, stir at a certain temperature until the reaction is completed; its chemical process is shown in reaction formula II:

The catalyst is selected from any one of tetrakistriphenylphosphine palladium (Pd(PPh ₃ ) ₄ ), palladium acetate and tris(dibenzylideneacetone)dipalladium (Pd ₂ (dba) ₃ ).

The solvent is selected from any one of dichloromethane, 1,2-dichloroethane, tetrahydrofuran, ethyl acetate, acetonitrile, and 1,4-dioxane.

The molar ratio of the phenolic compound, the GMDVs and the catalyst is 1.0:(1.0-2.0):(0.01-0.1).

The reaction time is 1-24h.

The reaction temperature is -30-60°C.

After the reaction, column chromatography was performed with a mixed solvent of petroleum ether and ethyl acetate.

The beneficial effects of the present invention are as follows: the synthetic method of the phenylallyl ether compound provided by the present invention is scientific and reasonable, and compared with the traditional method, it has the following significant advantages:

(1) Using GMDVs as allylation reagent, the reaction yield is high and the atom economy is good;

(2) The conditions are mild, the operation is simple, the substrate is suitable for a wide range, and the product is easy to separate, which is suitable for diversified large-scale production.

Description of drawings

Fig. 1 is the NMR spectrum of compound (3a) prepared in Example 1;

Figure 2 is the NMR spectrum of compound (3b) prepared in Example 2;

Figure 3 is the NMR spectrum of compound (3c) prepared in Example 3;

Figure 4 is the NMR spectrum of compound (3d) prepared in Example 4;

FIG. 5 is the NMR spectrum of compound (3e) prepared in Example 5. FIG.

Detailed ways

The method of the present invention will be described herein through specific embodiments, but the present invention is not limited to this. Any modification, equivalent replacement and improvement within the scope of the technical concept of the present invention shall be included in the scope of the present invention. within the scope of protection.

Example 1:

The reaction equation is as follows:

Compound 1a (5 mmol), GMDVs (7.5 mmol), and Pd(PPh ₃ ) ₄ (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, and 50 ml of anhydrous tetrahydrofuran was added, followed by degassing, and the reaction was carried out at 0 degrees Celsius for 16 Hour. After the reaction was completed, the reaction system was concentrated to obtain a crude product, which was subjected to column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain pure 3a. The yield of 3a was 92%.

The NMR data of 3a are as follows:

¹ H NMR (500 MHz, CDCl ₃ ) δ 7.36-7.29 (m, 6H), 7.27 (td, J=8.5, 4.0 Hz, 1H), 6.73 (d, J=8.5 Hz, 2H), 5.14 (s, 1H),5.02(s,1H),4.42-4.32(m,2H),3.88(dd,J=8.5,6.5Hz,1H),3.63(s,3H),2.94(dd,J=14.5,9.0Hz ,1H),2.58(dd,J＝15.0,6.5Hz,1H)ppm.

¹³ C NMR (125MHz, CDCl ₃ ) δ 173.73, 157.61, 141.52, 138.40, 132.17, 128.70, 127.85, 127.48, 116.52, 114.71, 113.02, 71.03, 52.06, 50.03, 36.56 ppm.

Example 2

The reaction equation is as follows:

Compound 1b (5 mmol), GMDVs (7.5 mmol), and Pd ₂ (dba) ₃ (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, and 50 ml of anhydrous tetrahydrofuran was added, followed by degassing, and the reaction was carried out at 0 degrees Celsius for 16 Hour. After the reaction was completed, the reaction system was concentrated to obtain a crude product, which was subjected to column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain pure 3b. The yield of 3b was 90%.

The NMR data of 3b are as follows:

¹ H NMR (500MHz, CDCl ₃ ) δ 7.36-7.28 (m, 4H), 7.27-7.22 (m, 1H), 6.94-6.82 (m, 3H), 6.79 (d, J=8.0Hz, 1H), 5.15(s, 1H), 4.99(s, 1H), 4.57-4.39(m, 2H), 4.03-3.91(m, 1H), 3.86(d, J=10.5Hz, 3H), 3.63(s, 3H) ,2.95(dd,J＝15.0,9.0Hz,1H),2.62(dd,J＝14.5,6.5Hz,1H)ppm.

¹³ C NMR (125MHz, CDCl ₃ ) δ173.89, 149.55, 148.03, 141.71, 138.57, 128.59, 127.92, 127.33, 121.32, 120.67, 114.44, 113.86, 111.80, 71.93, 55.79, 51.90 ppm

Example 3

The reaction equation is as follows:

Compound 1c (5 mmol), GMDVs (7.5 mmol), and Pd(PPh ₃ ) ₄ (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, and 50 mL of anhydrous dichloromethane was added, and then degassed at 0 degrees Celsius. The reaction was carried out for 16 hours. After the reaction was completed, the reaction system was concentrated to obtain a crude product, which was subjected to column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain pure 3c. The yield of 3c was 83%.

The NMR data of 3c are as follows:

¹ H NMR (500MHz, CDCl ₃ ) δ 7.38-7.29(m, 5H), 7.28-7.24(m, 1H), 7.20(d, J=7.5Hz, 1H), 7.10(s, 1H), 7.02( dd,J＝8.5,2.0Hz,1H),5.18(s,1H),5.05(s,1H),4.48-4.38(m,2H),3.89(dd,J＝9.0,7.0Hz,1H),3.64 (s, 3H), 2.96 (dd, J=15.0, 9.0Hz, 1H), 2.61 (dd, J=15.0, 6.5Hz, 1H) ppm.

¹³ C NMR (125MHz, CDCl ₃ )δ173.74,158.64,141.37,138.41,131.90,131.65,131.39,129.91,128.72,127.84,127.51,122.83,118.17,117.56(dd,J=11.6Hz) , J=7.4, 3.7Hz), 71.10, 52.07, 50.10, 36.61ppm.

Example 4

The reaction equation is as follows:

Compound 1d (5 mmol), GMDVs (7.5 mmol), and Pd(PPh ₃ ) ₄ (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, and 50 mL of anhydrous tetrahydrofuran was added, followed by degassing, and the reaction was carried out at room temperature for 16 hours . After the reaction was completed, the reaction system was concentrated to obtain a crude product, which was subjected to column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain pure 3d. The yield of 3d was 85%.

The 3d NMR data are as follows:

¹ H NMR (500MHz, CDCl ₃ ) δ 7.78-7.66 (m, 3H), 7.42 (t, J=7.0Hz, 1H), 7.37-7.29 (m, 5H), 7.28-7.20 (m, 1H), 7.15(dd,J=9.0,2.5Hz,1H),7.08(d,J=2.0Hz,1H),5.22(s,1H),5.05(s,1H),4.57-4.47(m,2H),3.94 (dd,J=9.0,6.5Hz,1H),3.63(s,3H),3.01(dd,J=15.0,9.0Hz,1H),2.66(dd,J=15.0,6.5Hz,1H)ppm.

¹³ C NMR(125MHz,CDCl ₃ )δ173.81,156.46,141.79,138.52,134.43,129.35,129.00,128.68,127.87,127.59,127.43,126.72,126.31,123.64,118.87,114.65,107.04,70.84,52.03,50.05,36.80 ppm.

Example 5

The reaction equation is as follows:

Compound 1e (5 mmol), GMDVs (7.5 mmol), and Pd(PPh ₃ ) ₄ (0.25 mmol) were successively added to the reactor under an inert gas atmosphere, and 50 ml of anhydrous tetrahydrofuran was added, and then degassed, and reacted at 0 degrees Celsius for 24 Hour. After the reaction was completed, the reaction system was concentrated to obtain a crude product, which was subjected to column chromatography with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain pure 3e. The yield of 3e was 76%.

The NMR data of 3e are as follows:

¹ H NMR (500MHz, CDCl ₃ ) δ 7.35-7.29 (m, 4H), 7.28-7.23 (m, 1H), 7.17 (d, J=8.5Hz, 1H), 6.68 (dd, J=8.5, 2.5 Hz, 1H), 6.62(s, 1H), 5.15(s, 1H), 4.99(s, 1H), 4.43-4.35(m, 2H), 3.90(dd, J=9.0, 7.0Hz, 1H), 3.64 (s,3H),2.95(dd,J=15.0,9.0Hz,1H),2.88(dd,J=10.0,6.5Hz,2H),2.60(dd,J=15.0,6.5Hz,1H),2.50( dd, J=19.0, 9.0Hz, 1H), 2.43-2.31(m, 1H), 2.24(m, 1H), 2.18-2.08(m, 1H), 2.08-1.97(m, 2H), 1.95(dd, J=9.5,2.5Hz,1H),1.65-1.56(m,2H),1.55-1.46(m,3H),1.46-1.40(m,1H),0.90(s,3H)ppm.

¹³ C NMR(125MHz,CDCl ₃ )δ173.76,156.57,142.01,138.50,137.64,132.18,128.61,127.83,127.35,126.21,114.70,114.29,112.21,70.72,53.38,51.98,50.33,49.91,47.92,43.91,38.27 ,36.71,35.79,31.51,29.57,26.47,25.83,21.51,13.78ppm.

It can be seen from the above examples that according to the method for synthesizing phenylallyl ether compounds using GMDVs according to the present invention, diversified products can be efficiently obtained under mild conditions.

Claims (7)

1. a synthetic method of phenyl allyl ether compound, described phenyl allyl ether compound has the structure shown in formula I:

Wherein, Ar is selected from one of phenyl, naphthyl and estrone group; R ¹ is selected from any one of saturated alkyl, alkoxy, halogen, nitro, trifluoromethyl, formyl, and acetamide, and is located at the ortho, meta or para position of the hydroxyl group; The method comprises: adding phenolic compound, GMDVs, catalyst and solvent into the reactor in sequence under an inert gas atmosphere, and stirring at a certain temperature until the reaction is completed; the chemical process is shown in reaction formula II:

2. The preparation method according to claim 1, wherein the catalyst is selected from tetrakistriphenylphosphine palladium (Pd(PPh ₃ ) ₄ ), palladium acetate, tris(dibenzylideneacetone)dipalladium (Pd ₂ (dba) ₃ ). 3. The preparation method according to claim 1, wherein the solvent is selected from the group consisting of dichloromethane, 1,2-dichloroethane, tetrahydrofuran, ethyl acetate, acetonitrile, and 1,4-dioxane. any kind. 4. The preparation method according to claim 1, wherein the molar ratio of the phenolic compound, the GMDVs and the catalyst is 1.0:(1.0-2.0):(0.01-0.1). 5. The preparation method according to claim 1, wherein the reaction time is 1-24h. 6. The preparation method according to claim 1, wherein the reaction temperature is -30-60°C. 7. The preparation method according to claim 1, wherein column chromatography separation is carried out with a mixed solvent of petroleum ether and ethyl acetate.

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