CN114149373A - 4-aryl substituted 2,4, 6-triene suberate and synthesis method thereof - Google Patents

4-aryl substituted 2,4, 6-triene suberate and synthesis method thereof Download PDF

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CN114149373A
CN114149373A CN202111512432.7A CN202111512432A CN114149373A CN 114149373 A CN114149373 A CN 114149373A CN 202111512432 A CN202111512432 A CN 202111512432A CN 114149373 A CN114149373 A CN 114149373A
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triene
pyrazine
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styryl
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张坚
钟国富
沈聪
钟良军
贺瑞
丁丽媛
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Hangzhou Normal University
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    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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

The invention discloses 4-aryl substituted 2,4, 6-triene suberate and a synthesis method thereof. Placing N- (2-styryl) pyrazine-2-amide derivatives, acrylate compounds, palladium salt catalysts, acids and oxidants in an organic solvent, heating and reacting for a period of time at a certain temperature in a certain gas atmosphere, and after the reaction is finished, carrying out post-treatment on reaction liquid to obtain a compound shown in a formula (I) corresponding to a reactant; the method has simple operation, adopts simple transition metal salt as a catalyst under relatively mild conditions, can react in an air environment, and has high reaction yield which reaches 81 percent at most. The method for synthesizing the 4-aryl substituted 2,4, 6-triene suberate compound by adopting the N, N-bidentate coupling reaction of the guide group has the advantages of simple and efficient operation, no need of inert gas protection and stronger practicability.

Description

4-aryl substituted 2,4, 6-triene suberate and synthesis method thereof
Technical Field
The invention belongs to the technical field of organic chemical synthesis, relates to a 4-aryl substituted 2,4, 6-triene suberate compound and a synthesis method thereof, and particularly relates to a synthesis method for realizing alpha-and beta-site double hydrocarbon olefination reaction of styrene by a one-pot method from simple styrene and electron-deficient olefin.
Background
Polyenes are important building blocks for many natural products and pharmaceuticals, and such structures also have important applications in the field of organic synthesis. The styrene is easily available and widely applied, and the conversion of the styrene is a direction of attention of chemists for a long time.
Figure BDA0003399709500000011
The site of the styrene hydrocarbon functionalization reaction is multiple, and the selective hydrocarbon functionalization reaction has considerable challenges. The alkenyl hydrocarbon functionalization of the monosubstituted styrene with a guiding group on a benzene ring is carried out at a single beta position, and the activation and functionalization of a carbon-hydrogen bond at the alpha position and the alpha and beta positions by a one-pot method are not reported all the time; on the other hand, for mono-substituted olefins, the one-pot method for the same-carbon and adjacent-carbon hydrocarbon olefination reaction to obtain conjugated trienes has not been reported (chem. Soc. Rev.,2021,50, 3263-containing material 3314). The invention provides a method for preparing (E, E, E) -conjugated triene by using simple o-amino methyl substituted styrene as a raw material and realizing alpha and beta site diene alkylation reaction of the styrene under the catalysis of transition metal, wherein the Z/E selectivity is excellent. The method uses 8-aminopyrazinamide as an N, N-bidentate guide group and an acrylate compound as an alkenylation reagent, efficiently realizes one-pot double-hydrocarbon alkenylation reaction of styrene alkenyl alpha and beta, and obtains a 4-aryl substituted 2,4, 6-triene suberate product in one step.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide 4-aryl substituted 2,4, 6-triene suberate.
To achieve the above objects, the 4-aryl substituted 2,4, 6-triene suberate compound of the present invention has the following chemical formula (I):
Figure BDA0003399709500000021
in the formula (I), R1Is hydrogen, a C1-C3 alkyl, alkoxy, or halohydrocarbon group; r2Is an ester group.
Preferably, R in formula (I)1When it is hydrogen or trifluoromethyl, R2Is a butyl ester group, an ethyl ester group or a tert-butyl ester group.
Preferably, R in formula (I)1When it is hydrogen, R2Is tert-butyl ester group.
Preferably, the 4-aryl-substituted 2,4, 6-triene suberate compound is (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene dibutyl ester, (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene di-tert-butyl ester, (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene dimethyl ester, (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene diphenyl ester, (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene dibenzyl ester, (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene diethyl ester, (2E,4Z,6E) -4- (2-methyl-6- (pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene di-tert-butyl ester, (2E,4Z,6E) -4- (3-methyl-2- (pyrazine-2-carboxamide) methyl) phenyl) octa-2, di-tert-butyl-4, 6-triene, (2E,4Z,6E) -4- (4-methoxy-2- (pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene di-tert-butyl ester, (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) -5-trifluoromethylphenyl) octa-2, 4, 6-triene di-tert-butyl ester.
The invention also aims to provide a synthesis method of the 4-aryl substituted 2,4, 6-triene suberate, which adopts the following technical scheme:
placing N- (2-styryl) pyrazine-2-amide derivatives (formula II), acrylate compounds (formula III), palladium salt catalysts, acids and oxidants in an organic solvent, heating and reacting for a period of time at a certain temperature in a certain gas atmosphere, and after the reaction is finished, carrying out post-treatment on reaction liquid to obtain 4-aryl substituted 2,4, 6-triene suberate ester compounds shown in formula (I) corresponding to reactants; the reaction formula is as follows:
Figure BDA0003399709500000031
preferably, the molar ratio of the N- (2-styryl) pyrazine-2-amide derivative to the acrylate compound to the palladium salt catalyst is 1: (1.5-5.0): (0.1-0.15).
Preferably, the organic solvent is one or more of ethanol, acetonitrile, dichloromethane, toluene, 1, 3-dichloroethane, ethyl acetate and methanol.
Preferably, the acid is pivalic acid; the oxidant adopts MnO2And benzoquinone BQ.
More preferably, the molar ratio of pivalic acid to the N- (2-styryl) pyrazine-2-amide derivative is (1.5 to 3): 1, the molar ratio of the BQ to the N- (2-styryl) pyrazine-2-amide derivative is (0.01-0.5): 1, MnO2The molar ratio of the N- (2-styryl) pyrazine-2-amide derivative to the N- (2-styryl) pyrazine-2-amide derivative is (1.0-6.0): 1.
Preferably, the palladium salt catalyst is palladium acetate.
Preferably, the amount of the organic solvent is 5-20L per mole of the N- (2-styryl) pyrazine-2-amide derivative.
Preferably, the gas atmosphere is one of air, argon and oxygen.
Further, the N, N-bidentate guide group in the N- (2-styryl) pyrazine-2-amide derivative is pyrazine-2-formamide, pyridine-2-formamide and N- (2- (pyridine-2-yl) isopropyl) amide.
Preferably, the heating reaction temperature is 60 ℃, and the reaction time is 16-48 hours.
Preferably, the post-treatment is: cooling to room temperature, concentrating the reaction solution under reduced pressure, loading the reaction solution into a column, dissolving and transferring the residual reaction solution by using dichloromethane, performing column chromatography separation by using 300-mesh silica gel, collecting eluent containing a target compound, concentrating and drying to obtain a corresponding target product, wherein the eluent is a mixed solution of ethyl acetate and petroleum ether.
The 4-aryl substituted 2,4, 6-triene suberate compound prepared by the invention is not reported and belongs to a brand new synthesis method.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention provides a method for efficiently synthesizing a 4-aryl substituted 2,4, 6-triene suberate compound, and the obtained products are all brand new and have not been reported.
(2) The synthesis method is simple to operate, the simple transition metal salt is used as the catalyst under relatively mild conditions, the reaction can be carried out in the air environment, and the reaction yield is high and reaches 81% at most.
(3) The synthesis method adopts the method of synthesizing the 4-aryl substituted 2,4, 6-triene suberate compound by the guide group N, N-bidentate coupling reaction, has simple and efficient operation, does not need the protection of inert gas and has stronger practicability.
(4) The invention adopts pivalic acid as a ligand, promotes the activation step of a carbon-hydrogen bond, and stabilizes the ring metal palladium intermediate.
(5) The invention adopts MnO2The combination of benzoquinone BQ as an oxidant enables the C-H/C-H oxidative coupling reaction to be smoothly carried out.
(6) The substrate has the advantages of wide application range, high yield (51-81%), good stereoselectivity, wide functional group compatibility and very good economic value.
(7) The synthetic raw materials are economical and easy to obtain, are suitable for the high-efficiency preparation of the 4-aryl substituted 2,4, 6-triene suberate compound, have wide application prospect, and are an effective supplement to the existing method in the preparation method.
Detailed Description
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto.
The column chromatography separation described in the following examples is performed by using 300 mesh silica gel, the eluent is a mixed solution of ethyl acetate and petroleum ether, the eluent containing the target compound is collected, concentrated and dried to obtain the compound shown in formula (1).
Example 1: preparation of (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene dibutyl ester
Figure BDA0003399709500000041
A screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and butyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was separated by direct column chromatography to give a colorless liquid (59.7mg, yield 81%).1H NMR(500MHz,CDCl3) δ9.35(d,J＝1.0Hz,1H),8.69(d,J＝2.5Hz,1H),8.39(q,J＝1.5Hz,1H),7.86(t,J ＝5.5Hz,1H),7.57(d,J＝15.5Hz,1H),7.53(d,J＝7.5Hz,1H),7.44–7.37(m,2H), 7.06(dd,J＝7.5,1.0Hz,1H),6.92(dd,J＝15.0,11.5Hz,1H),6.79(d,J＝12.0Hz, 1H),6.05(d,J＝15.0Hz,1H),5.45(d,J＝15.5Hz,1H),4.51–4.38(m,2H),4.09– 4.05(m,2H),4.02(t,J＝6.5Hz,2H),1.60–1.52(m,2H),1.37–1.33(m,2H),1.32 –1.28(m,2H),0.92(t,J＝7.5Hz,3H),0.88(d,J＝7.5Hz,3H)；13C NMR(125MHz, CDCl3)δ165.41,165.15,161.37,146.10,145.13,144.37,143.35,143.17,141.35, 138.48,135.13,134.73,133.46,129.06,128.74,128.17,127.34,124.93,122.81, 63.55,63.45,40.40,29.61,29.53,18.09,18.07,12.67,12.66；HRMS(ESI):m/z for C28H33N3O5Na[M+Na]+:514.2312,found:514.2308；FTIR(KBr,cm-1):3481.31, 3456.07,3428.04,3422.43,3405.61,2357.01,2331.78,1644.86,1633.64,1628.04, 1619.63,1608.41,1543.93,1507.48,1403.74,1395.33,1381.31.
Example 2: preparation of (2E,4Z,6E) -4- (2- ((pyrazine-2-formamide) methyl) phenyl) octa-2, 4, 6-triene di-tert-butyl ester
Figure BDA0003399709500000051
Filling a screw cap small bottle with acetic acidPalladium (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and tert-butyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was separated by direct column chromatography to give a colorless liquid (56.7mg, yield 77%).1H NMR(500MHz,CDCl3) δ9.36(d,J＝1.5Hz,1H),8.69(d,J＝2.5Hz,1H),8.43–8.42(m,1H),7.87(s,1H), 7.51(d,J＝7.0Hz,1H),7.47(d,J＝15.5Hz,1H),7.42–7.35(m,2H),7.06(dd,J＝ 7.5,1.5Hz,1H),6.86(dd,J＝15.0,12.0Hz,1H),6.73(d,J＝11.5Hz,1H),5.98(d,J ＝15.0Hz,1H),5.36(d,J＝15.0Hz,1H),4.52–4.39(m,2H),1.42(s,9H),1.39(s, 9H)；13C NMR(125MHz,CDCl3)δ164.68,164.54,146.11,144.38,144.05,143.33, 141.44,137.72,134.80,134.68,133.69,129.13,128.56,128.04,127.26,126.61, 124.44,98.96,79.75,79.69,40.38,28.68,27.05,27.02；HRMS(ESI):m/z for C28H33N3O5Na[M+Na]+:514.2312,found:514.2306；FTIR(KBr,cm-1):3414.02, 3405.61,2354.21,2328.97,1675.7,1658.88,1653.27,1644.86,1633.64,1619.63, 1616.82,1557.94,1541.12,1510.28,1459.81,1403.74,1392.52,1386.92.
Example 3: preparation of (2E,4Z,6E) -4- (2- ((pyrazine-2-formamide) methyl) phenyl) octa-2, 4, 6-triene dimethyl ester
Figure BDA0003399709500000061
A screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and methyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was applied directly to flash column chromatography (PE/EA),the reaction mixture was subjected to direct column chromatography to give a yellow liquid (33.0mg, yield 54%).1H NMR(500MHz,CDCl3) δ9.35(d,J＝1.5Hz,1H),8.70(d,J＝2.5Hz,1H),8.40–8.39(m,1H),7.86(s,1H), 7.58(d,J＝15.5Hz,1H),7.53(d,J＝7.5Hz,1H),7.45–7.37(m,2H),7.06(d,J＝ 8.5Hz,1H),6.91(dd,J＝15.0,11.5Hz,1H),6.78(d,J＝11.5Hz,1H),6.04(d,J＝ 15.0Hz,1H),5.45(d,J＝15.5Hz,1H),4.50–4.38(m,2H),3.67(s,3H),3.62(s, 3H)；13C NMR(125MHz,CDCl3)δ165.69,165.43,161.37,146.12,145.39,144.41, 143.38,143.15,141.34,138.59,135.23,134.73,133.35,129.04,128.78,128.24, 127.38,124.60,122.43,50.65,40.40,28.68；HRMS(ESI):m/z for C22H21N3O5Na [M+Na]+:430.1373,found:430.1363；FTIR(KBr,cm-1):3425.23,3414.02,2359.81, 2334.58,1661.638,1653.27,1636.45,1625.23,1538.32,1510.28,1406.54,1395.33.
Example 4: preparation of (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-trienediphenyl ester
Figure BDA0003399709500000062
A screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then, pivalic acid (1.5equiv,0.23 mmol) and phenyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was directly separated by column chromatography to obtain 53.0mg of a yellow liquid, yield 66%).1H NMR(500MHz,CDCl3) δ9.39(d,J＝1.5Hz,1H),8.65(d,J＝2.5Hz,1H),8.35(dd,J＝2.5,1.5Hz,1H), 7.93(t,J＝5.5Hz,1H),7.79(d,J＝15.5Hz,1H),7.57(d,J＝8.5Hz,1H),7.48– 7.41(m,2H),7.39–7.34(m,4H),7.25–7.20(m,2H),7.16–7.15(m,1H),7.12(dd, J＝13.0,9.0Hz,1H),7.04–7.00(m,4H),6.93(d,J＝11.5Hz,1H),6.28(d,J＝15.0 Hz,1H),5.69(d,J＝15.5Hz,1H),4.58–4.48(m,2H)；13C NMR(125MHz,CDCl3) δ163.62,163.33,161.42,149.46,149.44,146.80,146.28,145.05,143.36,143.08, 141.50,140.03,135.70,134.77,133.09,129.08,128.89,128.50,128.44,128.34, 127.52,124.89,124.84,124.46,122.37,120.31,40.44,28.68；HRMS(ESI):m/z for C32H26N3O5[M+H]+:532.1867,found:532.1873；FTIR(KBr,cm-1):3447.66, 3422.43,2357.01,1656.07,1650.47,1633.64,1619.63,1400.93.
Example 5: preparation of (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene dibenzyl ester
Figure BDA0003399709500000071
A screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and benzyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was directly separated by column chromatography to obtain 46.1mg of a yellow liquid, yield 55%).1H NMR(500MHz,CDCl3) δ9.31(d,J＝1.5Hz,1H),8.54(d,J＝2.5Hz,1H),8.14(dd,J＝2.5,1.5Hz,1H), 7.82(t,J＝5.5Hz,1H),7.61(d,J＝15.5Hz,1H),7.51(d,J＝7.5Hz,1H),7.43– 7.40(m,1H),7.39–7.31(m,9H),7.30–7.27(m,2H),7.05(dd,J＝7.5,1.0Hz,1H), 6.97(dd,J＝15.5,11.5Hz,1H),6.78(d,J＝11.5Hz,1H),6.08(d,J＝15.0Hz,1H), 5.50(d,J＝15.5Hz,1H),5.11–5.04(m,4H),4.48–4.38(m,2H)；13C NMR(125 MHz,CDCl3)δ165.07,164.84,161.32,146.09,145.64,144.61,143.23,143.04, 141.31,139.05,135.25,134.72,134.71,134.58,133.36,129.06,128.87,128.25, 127.59,127.53,127.43,127.41,127.39,127.26,127.14,124.55,122.55,65.52,65.28, 40.42；HRMS(ESI):m/z for C34H29N3O5Na[M+Na]+:582.1999,found:582.1997； FTIR(KBr,cm-1):3475.70,3456.07,3442.06,3422.43,3408.41,2354.21,2320.56, 1684.11,1672.90,1658.88,1656.07,1633.64,1622.43,1611.21,1557.94,1538.32, 1504.67,1417.76,1403.74,1392.52,1384.11.
Example 6: preparation of (2E,4Z,6E) -4- (2- ((pyrazine-2-formamide) methyl) phenyl) octa-2, 4, 6-triene diethyl ester
Figure BDA0003399709500000081
A screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and ethyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was directly separated by column chromatography to obtain 46.2mg of a yellow liquid, yield 71%).1H NMR(500MHz,CDCl3) δ9.35(d,J＝1.5Hz,1H),8.69(d,J＝2.5Hz,1H),8.40(dd,J＝2.5,1.5Hz,1H), 7.86(t,J＝5.5Hz,1H),7.57(d,J＝15.5Hz,1H),7.52(dd,J＝7.5,1.0Hz,1H),7.44 –7.36(m,2H),7.06(dd,J＝7.5,1.5Hz,1H),6.92(dd,J＝15.0,11.5Hz,1H),6.78 (d,J＝11.5Hz,1H),6.04(d,J＝15.5Hz,1H),5.44(d,J＝15.5Hz,1H),4.50–4.39 (m,2H),4.15–4.10(m,2H),4.08(q,J＝7.5Hz,2H),1.23(t,J＝7.5Hz,3H),1.20(t, J＝7.5Hz,3H)；13C NMR(125MHz,CDCl3)δ165.30,165.07,161.37,146.10, 145.21,144.33,143.36,143.18,141.34,138.42,135.18,134.72,133.44,129.07, 128.74,128.19,127.35,125.01,122.79,59.54,40.40,13.17；HRMS(ESI):m/z for C24H25N3O5Na[M+Na]+:458.1686,found:458.1684；FTIR(KBr,cm-1):3456.07, 3444.86,2354.21,2326.17,1684.11,1670.09,1650.47,1636.45,1622.43,1557.94, 1538.32,1507.48,1473.83,1454.21,1395.33,1386.92.
Example 7: preparation of (2E,4Z,6E) -4- (2-methyl-6- (pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene di-tert-butyl ester
Figure BDA0003399709500000091
The screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (3-methyl-2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then, pivalic acid (1.5equiv,0.23 mmol) and phenyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was directly separated by column chromatography to give 45.7mg of a yellow solid with a yield of 60%). m.p. 149.2 ℃.1H NMR(500MHz,CDCl3)δ9.36(d,J＝1.5Hz,1H),8.68(d,J＝2.5Hz,1H),8.42(dd, J＝2.5,1.5Hz,1H),7.83(t,J＝5.5Hz,1H),7.47(d,J＝15.5Hz,1H),7.33–7.28(m, 2H),7.23(d,J＝7.0Hz,1H),6.80–6.74(m,2H),6.01–5.94(m,1H),5.33(d,J＝ 15.5Hz,1H),4.45–4.35(m,2H),2.08(s,3H),1.42(s,9H),1.39(s,9H)；13C NMR (125MHz,CDCl3)δ164.74,164.52,161.27,146.04,143.58,143.30,143.26,143.23, 141.44,137.41,135.74,135.02,134.45,133.09,128.96,127.79,126.86,125.99, 123.46,79.76,79.68,40.67,27.05,27.02,18.58；HRMS(ESI):m/z for C29H36N3O5[M+H]+:506.2649,found:506.2662；FTIR(KBr,cm-1):3481.31,3456.07,3444.86, 2357.01,1653.27,1650.47,1633.64,1622.43,1417.76,1403.74,1395.33.
Example 8: preparation of (2E,4Z,6E) -4- (3-methyl-2- (pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene di-tert-butyl ester
Figure BDA0003399709500000092
A screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (2-methyl-6-vinylphenyl) pyrazine-2-carboxamide(1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and tert-butyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was directly separated by column chromatography to give 46.8mg of a yellow solid, yield 51%). m.p. ═ 61.5 oC.1H NMR(500MHz,CDCl3)δ9.34(d,J＝1.5Hz,1H),8.66(d,J＝2.5Hz,1H),8.38(dd, J＝2.5,1.5Hz,1H),7.59(t,J＝4.5Hz,1H),7.48(d,J＝15.5Hz,1H),7.29(d,J＝ 7.5Hz,1H),7.26(d,J＝5.5Hz,1H),6.91–6.86(m,2H),6.72(d,J＝12.0Hz,1H), 5.94(s,1H),5.36(d,J＝15.5Hz,1H),4.51–4.41(m,2H),2.48(s,3H),1.42(s,9H), 1.39(s,9H)；13C NMR(125MHz,CDCl3)δ164.64,164.58,161.15,145.99,144.83, 144.80,143.20,141.41,137.84,137.37,135.03,134.78,132.33,130.16,130.14, 127.43,126.83,126.37,124.53,79.71,79.64,37.58,27.05,27.04,18.74；HRMS (ESI):m/z for C29H36N3O5Na[M+Na]+:528.2469,found:528.2453；FTIR(KBr, cm-1):3414.02,2317.76,1748.60,1731.78,1712.15,1656.07,1636.45,1622.43.
Example 9: preparation of (2E,4Z,6E) -4- (4-methoxy-2- (pyrazine-2-carboxamide) methyl) phenyl) octa-2, 4, 6-triene di-tert-butyl ester
Figure BDA0003399709500000101
The screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (5-methoxy-2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and tert-butyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was directly separated by column chromatography to obtain 47.1mg of a yellow liquid with a yield of 60%).1H NMR(500 MHz,CDCl3)δ9.36(d,J＝1.5Hz,1H),8.69(d,J＝2.5Hz,1H),8.43(dd,J＝2.5, 1.5Hz,1H),7.87(t,J＝5.5Hz,1H),7.46(d,J＝15.5Hz,1H),7.03(d,J＝2.5Hz, 1H),6.97(d,J＝8.0Hz,1H),6.93–6.87(m,2H),6.72(d,J＝11.5Hz,1H),5.98(d, J＝15.0Hz,1H),5.40(d,J＝15.5Hz,1H),4.47–4.35(m,2H),3.84(s,3H),1.43(s, 9H),1.40(s,9H)；13C NMR(125MHz,CDCl3)δ164.76,164.65,161.44,158.90, 146.12,144.80,144.02,143.33,143.22,141.45,137.93,136.15,135.12,130.29, 126.35,125.60,124.36,114.04,112.57,79.69,79.67,54.36,40.51,28.68,27.04； HRMS(ESI):m/z for C29H35N3O5K[M+K]+:560.2157,found:560.2164；FTIR(KBr, cm-1):3475.70,3456.07,3447.66,2351.40,2326.17,1684.11,1670.09,1653.27, 1636.45,1622.43,1538.32,1504.67,1406.54,1400.93.
Example 10: preparation of (2E,4Z,6E) -4- (2- ((pyrazine-2-carboxamide) methyl) -5-trifluoromethylphenyl) octa-2, 4, 6-triene di-tert-butyl ester
Figure BDA0003399709500000111
The screw cap vial was charged with palladium acetate (15 mol%, 0.023mmol), manganese dioxide (3.0equiv,0.45 mmol), benzoquinone (10 mol%, 0.015mmol), N- (4-trifluoromethyl-2-vinylphenyl) pyrazine-2-carboxamide (1.0equiv,0.15mmol), ethanol (1.0 mL). Then pivalic acid (1.5equiv,0.23 mmol) and tert-butyl acrylate (2.5equiv,0.38mmol) were added to the solution in this order. The vial was sealed under air and heated to 60 ℃ and stirred for 24 hours. After cooling, the mixture was directly applied to flash column chromatography (PE/EA), and the reaction solution was directly separated by column chromatography to obtain 61.6mg of a yellow liquid, yield 73%).1H NMR(500 MHz,CDCl3)δ9.30(d,J＝1.5Hz,1H),8.65(d,J＝2.5Hz,1H),8.38(dd,J＝2.5, 1.5Hz,1H),7.88(t,J＝6.0Hz,1H),7.60(d,J＝1.0Hz,2H),7.42(d,J＝15.5Hz, 1H),7.26(s,1H),6.74–6.66(m,2H),5.96(d,J＝14.0Hz,1H),5.24–5.21(m,1H), 4.49–4.37(m,2H),1.37(s,9H),1.32(s,9H)；13C NMR(125MHz,CDCl3)δ164.39, 164.26,161.67,146.36,143.66,143.38,142.92,142.24,141.49,136.84(d,JCF＝1.4 Hz),136.79,135.37,134.36,199.61(q,JCF＝32.8Hz),128.99,127.70,125.78(q,JCF＝3.9Hz),125.48(q,JCF＝254.7Hz),125.00(q,JCF＝3.5Hz),124.58,80.05,79.96, 39.91,27.04,26.98；19F NMR(470MHz,CDCl3)δ-62.51；HRMS(ESI):m/z for C29H32N3O5F3K[M+K]+:598.1926,found:598.1927；FTIR(KBr,cm-1):3453.23, 3439.25,2362.62,2326.17,1667.29,1656.07,1633.64,1557.94,1535.51,1504.67。

Claims (10)

  1. A 4-aryl substituted 2,4, 6-triene octanedioate compound characterized by the following chemical structural formula:
    Figure FDA0003399709490000011
    in the formula (I), R1Is hydrogen, a C1-C3 alkyl, alkoxy, or halohydrocarbon group; r2Is an ester group.
  2. 2. The 4-aryl-substituted 2,4, 6-triene octanedioate compound as claimed in claim 1, wherein R in the formula (I)1When it is hydrogen or trifluoromethyl, R2Is a butyl ester group, an ethyl ester group or a tert-butyl ester group.
  3. 3. The 4-aryl-substituted 2,4, 6-triene octanedioate compound as claimed in claim 1, wherein R in the formula (I)1When it is hydrogen, R2Is tert-butyl ester group.
  4. A process for the synthesis of 4-aryl-substituted 2,4, 6-triene octanedioates, characterized in that the process is as follows:
    placing the N- (2-styryl) pyrazine-2-amide derivative shown in the formula II, the acrylate compound shown in the formula III, a palladium salt catalyst, an acid and an oxidant in an organic solvent, heating and reacting for a period of time at a certain temperature in a certain gas atmosphere, and after the reaction is finished, carrying out post-treatment on reaction liquid to obtain a 4-aryl substituted 2,4, 6-triene octanedioate compound shown in the formula (1) corresponding to the reactant; the reaction formula is as follows:
    Figure FDA0003399709490000012
  5. 5. the synthesis method according to claim 4, wherein the molar ratio of the N- (2-styryl) pyrazine-2-amide derivative to the acrylate compound to the palladium salt catalyst is 1: (1.5-5.0): (0.1-0.15).
  6. 6. The method of claim 4, wherein the acid is pivalic acid; the oxidant adopts MnO2Benzoquinone BQ; the molar ratio of the pivalic acid to the N- (2-styryl) pyrazine-2-amide derivative is (1.5-3): 1, the molar ratio of the BQ to the N- (2-styryl) pyrazine-2-amide derivative is (0.01-0.5): 1, MnO2The molar ratio of the N- (2-styryl) pyrazine-2-amide derivative to the N- (2-styryl) pyrazine-2-amide derivative is (1.0-6.0): 1.
  7. 7. The method of claim 4, wherein the palladium salt catalyst is palladium acetate.
  8. 8. The method of claim 4, wherein said atmosphere is one of air, argon and oxygen.
  9. 9. The synthesis method according to claim 4, wherein the heating reaction temperature is 60 ℃ and the reaction time is 16-48 hours.
  10. 10. The method of claim 4, wherein the organic solvent is one or more of ethanol, acetonitrile, dichloromethane, toluene, 1, 3-dichloroethane, ethyl acetate, and methanol.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110627717A (en) * 2019-09-30 2019-12-31 杭州师范大学 Branched 1, 4-diene amide derivative and synthesis method thereof
CN110642737A (en) * 2019-09-30 2020-01-03 杭州师范大学 Amide-substituted (E, E) -configuration branched conjugated diene derivative and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110627717A (en) * 2019-09-30 2019-12-31 杭州师范大学 Branched 1, 4-diene amide derivative and synthesis method thereof
CN110642737A (en) * 2019-09-30 2020-01-03 杭州师范大学 Amide-substituted (E, E) -configuration branched conjugated diene derivative and preparation method thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BENEDIKT S.等: "Palladium-Catalyzed Regioselective C-H Iodination of Unactivated Alkenes" *
CONG SHEN等: "Bidentate auxiliary-directed alkenyl C-H allylation via exo-palladacycles: synthesis of branched 1,4-dienes" *
MINGYU LIU等: "C(alkenyl)-H Activation via Six-Membered Palladacycles: Catalytic 1,3-Diene Synthesis" *

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