Synthesis method of a 1,4-diaryl-1,3-diene compound

Abstract

The present invention relates to a method for synthesizing 1,4-diaryl-1,3-diene compounds. Specifically, it is prepared by a one-pot method from iodoarene and aryl diene under the condition of nickel catalysis. The present invention starts from simple and readily available raw materials and catalysts, and a series of 1,4-diaryl-1,3-diene compounds are obtained through Heck reaction.

Description

Technical Field

[0001] The invention relates to a method for synthesizing a 1,4-diaryl-1,3-diene compound. Background Art

[0002] As a large branch of olefins, 1,3-diene compounds are widely present in nature due to their unique structure, such as 1,3-butadiene, isoprene, etc. It is one of the important raw materials for the preparation of functional materials such as polymer materials, photosensitive materials, and bionic materials. Therefore, achieving its functionalization is the most direct means to obtain high value-added and high-functional products. However, due to its multiple and similar reaction sites, the realization of 1,3-diene compounds often requires overcoming difficulties such as reaction activity, chemical selectivity, regioselectivity, and cis-trans selectivity. With the continuous growth in the number and variety of substituted 1,3-diene compounds in recent years, the application fields have been continuously broadened, and the low-cost and high-selectivity synthesis of substituted 1,3-diene compounds has also become a major direction that needs to be developed and broken through.

[0003] Compared with the previous synthesis method of substituted 1,3-diene compounds, the present invention does not require an equivalent amount of organophosphorus reagent, but uses cheap metal nickel catalysis to achieve a highly regioselective Heck reaction to construct 1,4-diaryl-1,3-diene compounds.

[0004] In summary, this paper describes an inexpensive, metal-catalyzed, highly regioselective Heck reaction to prepare 1,4-diaryl-1,3-diene compounds. Summary of the invention

[0005] The object of the present invention is to provide a method for synthesizing 1,4-diaryl-1,3-diene compounds.

[0006]

[0007] Reaction equation 1: Synthesis of 1,4-diaryl-1,3-diene compounds

[0008] The specific operation steps are as follows (reaction equation 1):

[0009] The reaction is carried out in a reactor. First, a catalyst, a ligand, an additive, an iodinated aromatic hydrocarbon 1, and an aromatic diene 2 are added to a solvent, and the mixture is stirred and heated to 70-90° C. The reaction time is 18-24 hours. After the reaction is completed, a 1,4-diaryl-1,3-diene compound 3 is separated and obtained.

[0010] The molar ratio of the iodinated aromatic hydrocarbon 1 to the aromatic diene 2 is 1.5-3.0:1.0, preferably 1.5-2.0:1.0.

[0011] The catalyst is one or more of nickel chloride, nickel bromide, nickel iodide, nickel acetylacetonate, preferably nickel chloride; the amount of the catalyst is 2-15 mol%, preferably 5-10 mol%, based on the amount of aryl diene 2.

[0012] The ligand is one or more of 1,2-bis(diphenylphosphino)ethane, 1,1'-bis(diphenylphosphino)ferrocene, 1,3-bis(diphenylphosphino)propane, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; the amount of the ligand is 5 mol%-15 mol%, preferably 8-12 mol%, based on the amount of aryl diene 2.

[0013] The additive is composed of an organic amine compound and an inorganic salt.

[0014] The organic amine is one or more of diisopropylethylamine, dicyclohexylmethylamine, cyclohexyldiethylamine; the inorganic salt is one or more of sodium chloride, magnesium chloride, potassium chloride, lithium chloride; the preferred combination is triethylamine and sodium chloride;

[0015] The amount of the organic amine is 100-200 mol%, preferably 150-200 mol%, based on the amount of aryl diene 2; the amount of the inorganic salt is 100-300 mol%, preferably 200-300 mol%, based on the amount of aryl diene 2.

[0016] The reducing agent is one or more of zinc powder, indium powder, manganese powder, methyldiethoxysilane, preferably manganese powder; the amount of the reducing agent is 50 mol%-200 mol%, preferably 50-100 mol%, based on the amount of aryl diene 2.

[0017] The solvent is one or more of 1,2-dichloroethane, dichloromethane, chloroform, acetone, N,N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, chlorobenzene, benzotrifluoride, 1,2-dichlorobenzene, tetrahydrofuran, water, preferably acetonitrile; the amount of the solvent is 0.1-2.0 mL, preferably 0.3-0.8 mL, per 0.2 mmol of aryl diene 2.

[0018] The present invention has the following advantages:

[0019] First, the reaction has high regioselectivity and stereoselectivity, and the reaction of iodoarene with aryl diene substrates gives terminal-substituted 1,4-diaryl-1,3-diene compounds, which is beneficial to the further conversion and derivation of material products. Second, the raw material iodoarene required for the reaction is commercially available, with a rich variety and low price. Finally, the catalyst used in this reaction system is a simple divalent nickel salt, which is cheaper than the reported palladium-based catalysts. Specific Embodiments

[0020] To better understand the present invention, it is illustrated by the following examples. The reaction raw materials and results of Examples 1-12 are shown in Table 1.

[0021] Table 1 Reaction results of different iodoarenes and 1,3-dienes

[0022]

[0023]

[0024]

[0025]

[0026] As can be seen from Table 1: The present invention has medium to good results (yield: 52-92%) for various substituents. When there is an electron-donating group at the para position of aryl iodobenzene (such as 1b, 1c or 1h), by changing the catalyst (such as in Example 2, changing the catalyst to nickel bromide), the solvent (such as in Example 3, changing acetonitrile to a mixed solvent of acetonitrile / tetrahydrofuran), and the temperature (such as in Example 8, raising the reaction temperature from 80 °C to 90 °C), the yield can be maintained. When there is an electron-withdrawing group at the para position of aryl iodobenzene (such as 1d, 1e or 1f), the yield can be maintained by adjusting the additive (such as in Example 5, changing sodium chloride to potassium chloride) and the ligand (such as in Example 6, changing the ligand to 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene). The present invention is also not sensitive to the steric hindrance of aryl dienes (such as 2d, 2e or 2f), and the yield can be maintained above 78%.

[0027] Example 1

[0028] The reaction was carried out in a reactor. First, nickel chloride (0.02 mmol), 1,2-bis(diphenylphosphino)ethane (0.02 mmol), triethylamine (0.4 mmol), sodium chloride (0.6 mmol), manganese powder (0.2 mmol), iodoarene 1 (0.4 mmol), and aryl diene 2 (0.2 mmol) were added to acetonitrile (0.5 mL). The mixture was stirred and heated to 80 °C for 18.0 hours. After the reaction was completed, the 1,4-diaryl-1,3-diene compound 3a was obtained by column chromatography separation with a yield of 92%. The compound was identified by IR, NMR (proton NMR and carbon NMR), and high-resolution mass spectrometry. The 1,4-diaryl-1,3-diene compound 3a is a kind of fluorescent whitening agent and is widely used in plastic products. (References: [1] Garcia, R.S.; Silva, A.T.S.; Losada, P.P.Determination of diphenylbutadiene by liquid chromatography-UV-fluorescence in foodstuffs.J.Chromatogr.A 2004, 1056, 99.)

[0029] The detection data are as follows:

[0030] 3a: White solid, 46.4 mg, 92% yield, R f = 0.5 (PE), 1 H NMR (400 MHz, Chloroform-d) δ 7.43 (d, J = 7.6 Hz, 4H), 7.32 (t, J = 7.6 Hz, 4H), 7.22 (t, J = 7.2 Hz, 2H), 7.02 - 6.88 (m, 2H), 6.77 - 6.56 (m, 2H); 13 C NMR (100 MHz, Chloroform-d) δ 137.49, 132.95, 129.38, 128.79, 127.69, 126.52. HRMS calculated for C 16 H 14 [M] + 206.1090, found 206.1097.

[0031] Example 2:

[0032] The operation process and conditions were the same as those in Example 1. The difference from Example 1 was that, except for the differences described in Table 1, the catalyst was nickel bromide (the dosage was 10 mol% of the amount of aryl diene 2), and the yield of the product 3b was 81%. The compound was identified by IR, NMR (proton NMR and carbon NMR), and high-resolution mass spectrometry.

[0033] Example 3:

[0034] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences described in Table 1, the solvent is acetonitrile / tetrahydrofuran (volume ratio 5:1), the yield of product 3c is 87%, and the structure of the compound is identified by infrared, nuclear magnetic resonance (hydrogen spectrum and carbon spectrum), and high-resolution mass spectrometry.

[0035] Example 4:

[0036] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences described in Table 1, the reaction temperature is 70 °C, the yield of product 3d is 83%, and the structure of the compound is identified by infrared, nuclear magnetic resonance (hydrogen spectrum and carbon spectrum), and high-resolution mass spectrometry.

[0037] Example 5:

[0038] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences described in Table 1, the additive replaces sodium chloride with potassium chloride (the dosage is 300 mol% of the amount of aryl diene 2), the yield of product 3e is 90%, and the structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0039] Example 6:

[0040] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences described in Table 1, the ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (the dosage is 10 mol% of the amount of aryl diene 2), the yield of product 3f is 63%, and the structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0041] Example 7:

[0042] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences described in Table 1, the reducing agent is zinc powder (the dosage is 100 mol% of the amount of aryl diene 2), the yield of product 3g is 77%, and the structure of the compound is identified by infrared, nuclear magnetic resonance (hydrogen spectrum and carbon spectrum), and high-resolution mass spectrometry.

[0043] Example 8:

[0044] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences described in Table 1, the catalyst is nickel chloride (the dosage is 5 mol% of the amount of aryl diene 2), the yield of product 3h is 74%, and the structure of the compound is identified by infrared, nuclear magnetic resonance (hydrogen spectrum and carbon spectrum), and high-resolution mass spectrometry.

[0045] Example 9:

[0046] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences stated in Table 1, the catalyst is pre-coordinated 1,2-bis(diphenylphosphino)ethane nickel chloride (the dosage is 10 mol% of the amount of aryl diene 2), the yield of product 3i is 52%, and the structure of the compound is identified by infrared spectroscopy, nuclear magnetic resonance (proton NMR and carbon NMR), and high-resolution mass spectrometry.

[0047] Example 10:

[0048] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences stated in Table 1, the reaction temperature is 90 °C, the yield of product 3j is 81%, and the structure of the compound is identified by infrared spectroscopy, nuclear magnetic resonance (proton NMR and carbon NMR), and high-resolution mass spectrometry.

[0049] Example 11:

[0050] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences stated in Table 1, the reaction time is 24 h, the yield of product 3k is 81%, and the compound is analyzed by infrared spectroscopy, nuclear magnetic resonance (proton NMR and carbon NMR), and high-resolution mass spectrometry.

[0051] Example 12:

[0052] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences stated in Table 1, sodium chloride is not added, the yield of product 3l is 78%, and the structure of the compound is identified by nuclear magnetic resonance (proton NMR and carbon NMR) and high-resolution mass spectrometry.

[0053] Comparative Example 1:

[0054] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences stated in Table 1, the additive is changed from triethylamine to N,N-dimethylaniline (the dosage is 200 mol% of the amount of aryl diene 2), and no formation of product 3a is observed.

[0055] Comparative Example 2:

[0056] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that, except for the differences stated in Table 1, the ligand is changed from 1,2-bis(diphenylphosphino)ethane to triphenylphosphine (the dosage is 20 mol% of the amount of aryl diene 2), and no formation of product 3b is observed.

Claims

1. A method for preparing 1,4-diaryl-1,3-diene compounds, characterized in that: using the iodoarene 1 and aryl diene 2 shown in the following formula as raw materials to generate 1,4-diaryl-1,3-diene compound 3, and the reaction formula is as follows: Wherein Ar 1 is phenyl, p-methylphenyl, p-tert-butylphenyl, p-methoxyphenyl, p-chlorophenyl, p-fluorophenyl, p-bromophenyl or naphthyl; Ar 2 is phenyl, p-methylphenyl, m-methylphenyl, o-methylphenyl, p-tert-butylphenyl or naphthyl; The catalyst is one or more of nickel chloride, nickel bromide, nickel iodide, nickel acetylacetonate; the ligand is one or more of 1,2-bis(diphenylphosphino)ethane, 1,1'-bis(diphenylphosphino)ferrocene, 1,3-bis(diphenylphosphino)propane, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; the reducing agent is one or more of zinc powder, indium powder, manganese powder, methyldiethoxysilane, and the additive is composed of an organic amine compound and an inorganic salt, The organic amine is one or more of diisopropylethylamine, dicyclohexylmethylamine, cyclohexyldiethylamine; the inorganic salt is one or more of sodium chloride, magnesium chloride, potassium chloride, lithium chloride; The solvent is one or more of 1,2-dichloroethane, dichloromethane, chloroform, acetone, N,N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, chlorobenzene, trifluorotoluene, 1,2-dichlorobenzene, tetrahydrofuran, water.

2. The method for preparing 1,4-diaryl-1,3-diene compounds according to claim 1, characterized in that: The specific operation steps are as follows: Carry out the reaction in a reactor. First, add the catalyst, ligand, additive, iodoarene 1, and aryl diene 2 into the solvent, stir and heat to 70-90 °C, and the reaction time is 18-24 hours; after the reaction is completed, separate to obtain 1,4-diaryl-1,3-diene compound 3.

3. The method according to claim 1 or 2, characterized in that: The molar ratio of the iodoarene 1 to the aryl diene 2 is 1.5-3.0:1.

0.

4. The method according to claim 1 or 2, characterized in that: The catalyst is nickel chloride; the dosage of the catalyst is 2-15 mol% of the dosage of the aryl diene 2.

5. The method according to claim 1 or 2, characterized in that: The dosage of the ligand is 5-15 mol% of the dosage of the aryl diene 2.

6. The method according to claim 1 or 2, characterized in that: The reducing agent is manganese powder; the dosage of the reducing agent is 50-200 mol% of the dosage of the aryl diene 2.

7. The method according to claim 1 or 2, characterized in that: The dosage of the organic amine is 100-200 mol% of the dosage of the aryl diene 2; the dosage of the inorganic salt is 100-300 mol% of the dosage of the aryl diene 2.

8. The method according to claim 7, characterized in that: The dosage of the organic amine is 150-200 mol% of the dosage of the aryl diene 2; the dosage of the inorganic salt is 200-300 mol% of the dosage of the aryl diene 2.

9. The method according to claim 2, characterized in that: The solvent is acetonitrile; the dosage of the solvent is 0.1-2.0 mL of solvent per 0.2 mmol of aryl diene 2.

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