CN110015981A - A kind of synthetic method of (2-iodo-2-aryl) ethyl aryl ether derivatives - Google Patents

Abstract

The invention discloses a method for synthesizing (2-iodo-2-aryl) ethyl aryl ether derivatives, belonging to the technical field of organic synthesis intermediates. The method of the invention specifically comprises the following steps: 1) adding a reaction tube to a reaction tube Add styrene derivatives, diaryl disulfide, N-iodosuccinimide, 1,2-dichloroethane, tighten the stopper of the reaction tube, and conduct the reaction under magnetic stirring at 80°C for 1 hour; 2) After the reaction, ethyl acetate extraction was performed, the organic phases were combined, and most of the solvent was removed by distillation under reduced pressure to obtain a crude product, and the crude product was carried out with petroleum ether and ethyl acetate having a volume ratio of 5:1 to 30:1 as eluents. Column chromatography separation and purification to obtain the target product. The invention has wide application in many fields such as medicine, pesticide, chemical industry, organic synthesis, etc. In addition, the invention has simple operation, mild reaction conditions, low cost and high yield, and has good application prospects.

Description

A kind of synthetic method of (2-iodo-2-aryl) ethyl aryl ether derivatives

technical field

The invention belongs to the field of organic synthesis intermediates, and relates to the use of cuprous iodide to catalyze the three-component reaction of styrene derivatives, diaryl disulfides and N-iodosuccinimide to obtain (2-iodo- Methods for the synthesis of 2-aryl)ethylaryl ethers.

Background technique

Organothioether compounds are important organic synthesis intermediates, which can be widely used in chemical industry, materials, pesticides and other fields. In recent years, the synthesis methods of such compounds have attracted much attention. We envisaged the introduction of an iodine atom into the alkyl chain of the thioether compound at the same time as the construction of the molecule. Because this alkyl iodide undergoes further nucleophilic substitution reactions with various nucleophiles, it can also participate in transition metal-catalyzed coupling reactions, so that various functionalized thioether compounds can be obtained. Recently, the use of thiophenol or diphenyl disulfide to participate in the free radical oxidative coupling reaction of alkenes is a new method to construct carbon-sulfur bonds. However, under the condition of free radical oxidation, the benzyl radical intermediate obtained by the addition of sulfur radical to styrene derivatives is easily oxidized to obtain β-hydroxyl sulfide, β-carbonyl sulfide, β-hydroxyl sulfones, β-carbonyl sulfones and other compounds. Using this radical oxidation strategy, it is difficult to obtain β-iodothioether compounds. Therefore, it is of great significance to explore a green, transition metal-catalyzed coupling reaction for the synthesis of (2-iodo-2-aryl)ethylaryl ether derivatives.

SUMMARY OF THE INVENTION

The present invention is devoted to finding a green, transition metal-catalyzed three-component reaction of styrene derivatives, diaryl disulfides, and N-iodosuccinimide, under relatively mild conditions, (2-iodo-2-aryl) ethyl aryl ether derivatives were synthesized efficiently with good yields.

For realizing the purpose of the present invention, adopt the following scheme to realize: a kind of synthetic method of (2-iodo-2-aryl) ethyl aryl ether derivatives,

The reaction equation is:

Wherein: R ¹ =NO ₂ , F, Cl, Br, Alkyl; R ² =NO ₂ , F, Cl, Br, Alkyl.

Specifically include the following steps:

1) Add styrene derivatives, diaryl disulfide, N-iodosuccinimide, 1,2-dichloroethane to the reaction tube, tighten the stopper of the reaction tube, and stir the reaction at 80°C with magnetic force 1 hour;

2) after the reaction finishes, extract with ethyl acetate, combine the organic phases, remove most of the solvent by distillation under reduced pressure to obtain a crude product, and use petroleum ether and ethyl acetate as eluents to separate and purify the crude product by column chromatography to obtain the target product .

As a preference: the molar ratio of styrene derivative, diaryl disulfide and N-iodosuccinimide is 4:2:1.

As a preference: the volume ratio of petroleum ether and ethyl acetate is 5:1 to 30:1.

Compared with existing synthetic method, the beneficial effects of the present invention are:

1) The present invention utilizes styrene derivatives, diaryl disulfides, N-iodosuccinimide as raw materials, and utilizes cuprous iodide to catalyze and synthesize a series of (2-iodo-2-aryl) Ethyl aryl ether derivatives with considerable benefits;

2) The compound of the present invention contains the skeleton of sulfide and alkyl iodide, can be used as an intermediate in organic synthesis, has the advantages of good group tolerance, wide substrate expansion range, etc., and can be widely used in fields such as pesticides and medicines. The synthesis of new drugs provides effective fragments;

3) The present invention adopts cuprous iodide to catalyze the synthesis of (2-iodo-2-aryl) ethyl aryl ether derivatives, which improves the product yield and shortens the reaction time.

Description of drawings

Fig. 1 is the nuclear magnetic resonance spectrum of the ¹ H-NMR of (2-iodo-2-phenyl) ethyl p-tolyl ether prepared in Example 1;

Fig. 2 is the nuclear magnetic resonance spectrum of ¹ H-NMR of (2-iodo-2-(4'-nitrophenyl)) ethyl p-toluene ether prepared in Example 2;

Fig. 3 is the nuclear magnetic resonance spectrum of ¹ H-NMR of (2-iodo-2-(4'-fluorophenyl)) ethyl p-tolyl ether prepared in Example 3;

Fig. 4 is the nuclear magnetic resonance spectrum of ¹ H-NMR of (2-iodo-2-(4'-chlorophenyl)) ethyl p-toluene ether prepared in Example 4;

5 is the nuclear magnetic resonance spectrum of ¹ H-NMR of (2-iodo-2-(4′-bromophenyl))ethyl p-tolyl ether prepared in Example 5. FIG.

Detailed ways

The present invention utilizes the three-component reaction of styrene derivative, diaryl disulfide and N-iodosuccinimide, styrene derivative, diaryl disulfide and N-iodosuccinyl The molar ratio of imine is 4:2:1, which realizes the bifunctionalization of styrene derivatives and efficiently synthesizes (2-iodo-2-aryl) ethyl aryl ether derivatives. In the reaction equation, NIS is N-iodosuccinimide.

Example 1: Synthesis of (2-iodo-2-phenyl) ethyl p-toluene ether

Into a 25 mL reaction tube were added styrene (0.4 mmol, 41.6 mg), N-iodosuccinimide (0.1 mmol, 22.5 mg), p-methyl diphenyl disulfide (0.2 mmol, 49.2 mg), iodine Cuprous (0.4eq, 7.6mg), o-phenanthroline (0.4eq, 7.9mg), 1,2-dichloroethane (2mL), magnetically stirred at 80°C for 1 hour; after the reaction was over, add acetic acid Ethyl ester extraction, combined organic phases, evaporated most of the solvent under reduced pressure to obtain a crude product, and used petroleum ether: ethyl acetate (20:1) as eluent to carry out column chromatography separation and purification on the crude product to obtain the target product. It was a pale yellow solid with a yield of 68%.

Its nuclear magnetic data are as follows:

¹ H NMR (300MHz, CDCl ₃ )δ=7.34～7.25(m, 4H), 7.21～7.18(d, J=8.1Hz, 1H), 7.12～7.06(m, 4H), 4.23～4.18(dd, J ＝4.8Hz, J＝10.2Hz, 1H), 3.51～3.45 (dd, J＝5.1Hz, J＝13.5Hz, 1H), 3.36～3.28 (dd, J＝10.2Hz, J＝13.2Hz, 1H), 2.34(s, 3H).

Example 2: Synthesis of (2-iodo-2-(4'-nitrophenyl))ethyl p-tolyl ether

Into a 25 mL reaction tube were added 4-nitrostyrene (0.4 mmol, 59.6 mg), N-iodosuccinimide (0.1 mmol, 22.5 mg), p-methyl diphenyl disulfide (0.2 mmol, 49.2 mg) mg), cuprous iodide (0.4eq, 7.6mg), o-phenanthroline (0.4eq, 7.9mg), 1,2-dichloroethane (2mL), magnetically stirred at 80°C for 1 hour; the reaction was completed Then, extract with ethyl acetate, combine the organic phases, evaporate most of the solvent under reduced pressure to obtain the crude product, use petroleum ether:ethyl acetate (10:1) as the eluent to separate the crude product by column chromatography, purify, The obtained target product was a brownish-yellow solid with a yield of 70%.

Its nuclear magnetic data are as follows:

¹ H NMR (300 MHz, CDCl ₃ ) δ=7.42 (d, J=8.1 Hz, 2H), 7.19 (d, J=8.1 Hz, 2H), 7.11～7.05 (m, 4H), 4.18～4.13 (dd, J＝4.8Hz, J＝10.5Hz, 1H), 3.50～3.44 (dd, J＝4.5Hz, J＝13.5Hz, 1H), 3.30～3.22 (dd, J＝10.2Hz, J＝13.5Hz, 1H) , 2.36(s, 3H).

Example 3: Synthesis of (2-iodo-2-(4'-fluorophenyl))ethyl p-tolyl ether

Into a 25 mL reaction tube were added 4-fluorostyrene (0.4 mmol, 48.8 mg), N-iodosuccinimide (0.1 mmol, 22.5 mg), p-methyl diphenyl disulfide (0.2 mmol, 49.2 mg) ), cuprous iodide (0.4eq, 7.6mg), o-phenanthroline (0.4eq, 7.9mg), 1,2-dichloroethane (2mL), magnetic stirring at 80°C for 1 hour; after the reaction is over , extracted with ethyl acetate, combined the organic phases, evaporated most of the solvent under reduced pressure to obtain the crude product, and used petroleum ether: ethyl acetate (10:1) as the eluent to separate the crude product by column chromatography, purify, and obtain The target product was a pale yellow solid with a yield of 70%.

Its nuclear magnetic data are as follows:

¹ H NMR (300MHz, CDCl ₃ )δ=7.27～7.18(m,3H),7.16～7.07(m,4H),7.05～6.94(m,1H),4.20～4.15(dd,J=4.5Hz,J ＝10.2Hz,1H),3.49～3.43(dd,J＝4.8Hz,J＝13.5Hz,1H),3.29～3.21(dd,J＝10.2Hz,J＝13.5Hz,1H),2.33(s,3H) ).

Example 4: Synthesis of (2-iodo-2-(4'-chlorophenyl))ethyl p-tolyl ether

Into a 25 mL reaction tube were added 4-chlorostyrene (0.4 mmol, 55.2 mg), N-iodosuccinimide (0.1 mmol, 22.5 mg), p-methyl diphenyl disulfide (0.2 mmol, 49.2 mg) ), cuprous iodide (0.4eq, 7.6mg), o-phenanthroline (0.4eq, 7.9mg), 1,2-dichloroethane (2mL), magnetic stirring at 80°C for 1 hour; after the reaction is over , extracted with ethyl acetate, combined the organic phases, evaporated most of the solvent under reduced pressure to obtain the crude product, and used petroleum ether: ethyl acetate (10:1) as the eluent to separate the crude product by column chromatography, purify, and obtain The target product was a pale yellow solid with a yield of 63%.

Its nuclear magnetic data are as follows:

¹ H NMR (300MHz, CDCl ₃ ) δ=7.24 (d, J=8.4Hz, 2H), 7.17～7.09 (m, 2H), 7.06～7.02 (m, 4H), 4.17～4.12 (dd, J=4.5 Hz,J＝10.2Hz,1H),3.48～3.42(dd,J＝4.5Hz,J＝13.5Hz,1H),3.27～3.19(dd,J＝10.5Hz,J＝13.5Hz,1H),2.33( s, 3H).

Example 5: Synthesis of (2-iodo-2-(4'-bromophenyl))ethyl p-tolyl ether

Into a 25 mL reaction tube were added 4-bromostyrene (0.4 mmol, 72.8 mg), N-iodosuccinimide (0.1 mmol, 22.5 mg), p-methyl diphenyl disulfide (0.2 mmol, 49.2 mg) ), cuprous iodide (0.4eq, 7.6mg), o-phenanthroline (0.4eq, 7.9mg), 1,2-dichloroethane (2mL), magnetic stirring at 80°C for 1 hour; after the reaction is over , extracted with ethyl acetate, combined the organic phases, evaporated most of the solvent under reduced pressure to obtain the crude product, and used petroleum ether: ethyl acetate (10:1) as the eluent to separate the crude product by column chromatography, purify, and obtain The target product was a pale yellow solid with a yield of 53%.

Its nuclear magnetic data are as follows:

¹ H NMR (300 MHz, CDCl ₃ ) δ=7.39 (d, J=8.4 Hz, 2H), 7.16 (d, J=8.1 Hz, 2H), 7.08～7.02 (m, 4H), 4.15～4.10 (dd, J＝4.5Hz, J＝10.2Hz, 1H), 3.47～3.41 (dd, J＝4.8Hz, J＝13.8Hz, 1H), 3.27～3.19 (dd, J＝10.2Hz, J＝13.2Hz, 1H) , 2.33(s, 3H).

Compared with existing synthetic method, the beneficial effects of the present invention are:

1) The present invention utilizes styrene derivatives, diaryl disulfides, N-iodosuccinimide as raw materials, and utilizes cuprous iodide to catalyze and synthesize a series of (2-iodo-2-aryl) Ethyl aryl ether derivatives with considerable benefits.

2) The compound of the present invention contains the skeleton of sulfide and alkyl iodide, can be used as an intermediate in organic synthesis, has the advantages of good group tolerance, wide substrate expansion range, etc., and can be widely used in fields such as pesticides and medicines. The synthesis of novel drugs provides effective fragments.

3) The present invention adopts cuprous iodide to catalyze the synthesis of (2-iodo-2-aryl) ethyl aryl ether derivatives, which improves the product yield and shortens the reaction time.

The invention has wide application in many fields such as medicine, pesticide, chemical industry, organic synthesis, etc. In addition, the invention has simple operation, mild reaction conditions, low cost and high yield, and has good application prospects.

The above-mentioned embodiments are only preferred implementations, and all the methods of the present invention or conventional equivalent replacements, modifications, etc., all belong to the protection scope of the present invention.

Claims (3)

1. a synthetic method of (2-iodo-2-aryl) ethyl aryl ether derivatives, main synthetic steps: 1) Add styrene derivatives, diaryl disulfide, N-iodosuccinimide, 1,2-dichloroethane to the reaction tube, tighten the stopper of the reaction tube, and stir the reaction at 80°C with magnetic force 1 hour; 2) after the reaction finishes, extract with ethyl acetate, combine the organic phases, remove most of the solvent by distillation under reduced pressure to obtain a crude product, and use the mixture of petroleum ether and ethyl acetate as eluent to carry out column chromatography separation and purification to the crude product, get the target product; The equation for the reaction is: Wherein: R ¹ =NO ₂ , F, Cl, Br, Alkyl; R ² =NO ₂ , F, Cl, Br, Alkyl. 2. the synthetic method of a kind of (2-iodo-2-aryl) ethyl aryl ether derivatives according to claim 1, is characterized in that: styrene derivative, diaryl disulfide and N - The molar ratio of iodosuccinimide is: 4:2:1. 3. the synthetic method of a kind of (2-iodo-2-aryl) ethyl aryl ether derivatives according to claim 1 and 2, is characterized in that: the volume ratio of sherwood oil and ethyl acetate is 5 :1～30:1.