CN115197037B - Preparation method of acrylamide and triazole-enamide alternating copolymer - Google Patents

Preparation method of acrylamide and triazole-enamide alternating copolymer Download PDF

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CN115197037B
CN115197037B CN202210757690.XA CN202210757690A CN115197037B CN 115197037 B CN115197037 B CN 115197037B CN 202210757690 A CN202210757690 A CN 202210757690A CN 115197037 B CN115197037 B CN 115197037B
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propargyl ester
copper catalyst
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diisopropylethylamine
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宋汪泽
郑楠
段学伦
郑玉斌
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Dalian University of Technology
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Abstract

The invention is applied to the technical fields of organic synthesis and high polymer synthesis, and provides a preparation method of an acrylamide and triazole-enamide alternating copolymer. Weighing propargyl ester compounds, organic azide compounds, N-diisopropylethylamine and phosphite esters, and dissolving the propargyl ester compounds, the organic azide compounds, the N, N-diisopropylethylamine and the phosphite esters in an organic solvent to obtain a mixed solution; weighing copper catalyst and water, adding the copper catalyst and the water into the mixed solution, stirring the mixture for 8 to 24 hours at room temperature, and stopping the reaction; post-treatment to obtain the product. The method of the invention prepares the Z-acrylamide and triazole-enamide alternating copolymer with high selectivity, and the product yield is not lower than 50 percent. The Z-acrylamide compound has potential physiological activity, and the triazole-enamide alternating copolymer also provides basis and potential application value for subsequent biological and material science application. The method has the advantages of simple and easily obtained raw materials, wide substrate range, mild conditions, easy operation of reaction and medium to good yield.

Description

Preparation method of acrylamide and triazole-enamide alternating copolymer
Technical Field
The preparation method is applied to the technical fields of organic synthesis and high polymer synthesis, and can be used for respectively preparing the alternating copolymers of the Z-acrylamide and the triazole-Z-enamide. In an organic solvent, copper and HPO (OMe) 2 The method has the advantages of mild condition, simple operation, good compatibility of functional groups and extremely high Z-type selectivity.
Background
Alpha, beta-unsaturated amides are one of the most useful and fundamental building blocks in organic synthesis, drug discovery and functional materials (Eur. J. Med. Chem.2019,181,111561-111585; nat. Chem.2010,3,34-37; chem. Rev.2002,102, 3067-3083). Natural products containing acrylamide groups, such as cinnamon, have a variety of biological activities including anti-inflammatory, antimicrobial and antitumor properties (Eur.J.Med. Chem.2014,81,394-407; J.Med. Chem.2011,54,1449-1461; eur.J.Med. Chem.2004,39,827-834; J.am. Chem. Soc.2005,127, 8686-8696). In contrast to the E-isomer, Z-acrylamide can be widely used as a unique building block for synthetic transformation and drug delivery, or as an important structure for biologically active molecules (e.g., motualevic acid B and Basiliskamidea A) (chem. Soc. Rev.2020,49,3187-3210; J. Control. Release.2000,65,245-251; org. Lett.2009,11,1087-1090; J. Nat. Prod.2002,65, 1447-1451). However, the highly stereospecific synthesis of the Z-isomer remains a great challenge compared to the explicit preparation of E-acrylamide (J.Am. Chem. Soc.2020,142, 20987-20993). Due to the large thermodynamic gap, the synthesis routes of Z- α, β -unsaturated amides are very limited, such as the Wittig reaction and its variants, photoisomerization, metathesis, etc., but Z/E selectivity is poor and substrate range is narrow (Eur.J. Org. Chem.2021, 1737-1749; J.am. Chem. Soc.2019,141,7173-7146;Heteroatom Chem.2004,15,515-523).
Disclosure of Invention
Here, we have successfully solved the above problem by obtaining a library of alternating copolymers of Z-acrylamide and triazole-enamide with high selectivity under mild conditions. Z-alpha, beta-unsaturated amides (Z: E > 19:1) with good stereospecificity and a broad substrate range are obtained by multicomponent reaction (MCR) and multicomponent polymerization (MCP).
The technical scheme of the invention is as follows:
a preparation method of acrylamide and triazole-enamide alternating copolymer takes propargyl ester, organic azide and water as reaction raw materials, and the application of the three-component reaction in preparing small molecule synthesis and polymer synthesis comprises the following preparation steps:
weighing propargyl ester compounds, organic azide compounds, N-diisopropylethylamine and phosphite esters, and dissolving the propargyl ester compounds, the organic azide compounds, the N, N-diisopropylethylamine and the phosphite esters in an organic solvent to obtain a mixed solution; weighing copper catalyst and water, adding the copper catalyst and the water into the mixed solution, stirring the mixture for 8 to 24 hours at room temperature, and stopping the reaction; post-treatment to obtain a product;
when used in the preparation of Z-acrylamide,
the reaction general formula is as follows:
wherein R is 1 And R is 2 Is alkyl or aryl; 1 is propargyl ester compound, 2 is organic azide compound;
R 1 and R is 2 Wherein the alkyl is C1-C6 alkyl, C3-C8 cycloalkyl;
R 1 and R is 2 Wherein aryl is phenyl or phenyl optionally substituted at the position by Ra, ra is C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenoxy, halogen;
the reaction temperature is 0-60 ℃, preferably 20-30 ℃ and the reaction time is 8-24h;
the molar ratio of propargyl ester compound to organic azide compound to water is 1:1:1-1:10:4, preferably 1:1.5:1;
the dosage of the N, N-diisopropylethylamine is 2 times equivalent of the propargyl ester compound;
the phosphite ester comprises dimethyl phosphite, diethyl phosphite, diisopropyl phosphite and the like, preferably diethyl phosphite, and the dosage of the phosphite ester is 10mol percent to 100mol percent equivalent, preferably 10mol percent equivalent of propargyl ester compound;
the organic solvent is acetonitrile, toluene, chloroform, methylene dichloride, 1, 2-dichloroethane, tetrahydrofuran, acetone and the like, and the preferred solvent is chloroform;
the copper catalyst is a monovalent copper catalyst and mainly comprises copper tetraacetonitrile hexafluorophosphate, copper tetraacetonitrile tetrafluoroborate, copper toluene triflate, cuprous iodide, cuprous chloride, cuprous bromide and the like. Preferably, the copper catalyst is cuprous bromide, and the dosage is 10mol% to 100mol% equivalent of propargyl ester compound, preferably 10mol% equivalent;
the post-treatment mode is as follows: and (3) carrying out column chromatography separation after spin drying, and drying the product to constant weight in a vacuum drying oven.
When used to prepare the triazole-enamide alternating copolymer,
the reaction general formula is as follows:
the polymerization degree n is more than 5, and the number average molecular weight of the three-component polymer ranges from 17100 g/mol to 44300g/mol.
The organic azide 7 is mainly alkyl bis-azide, and the bis-azide monomer has the preferable structure that:
the amounts of the reaction substrates and additives are correspondingly adjusted according to the proportion of functional groups, such as: the molar ratio of propargyl ester compound to organic azide compound to water is preferably 1:1:2; the preferable dosage of the N, N-diisopropylethylamine is 4 times equivalent of the dipropargyl ester compound; the catalyst and phosphite are preferably used in an amount of 20mol% equivalent of the dipropargyl ester.
The post-treatment mode is as follows: the precipitate was collected by centrifugation, and the product was dried to constant weight in a vacuum oven.
The invention has the beneficial effects that:
1) According to the copper-catalyzed three-component reaction method of propargyl ester, azide and water, the Z-acrylamide and the unique poly (triazole- (Z-acrylamide)) structural compound are prepared with high selectivity, and the product yield is not lower than 50%.
2) The method has the advantages of simple and easily obtained raw materials, wide substrate range, mild conditions, easy operation of reaction and medium to good yield.
3) The Z-acrylamide compound prepared by the method has potential physiological activity. Meanwhile, the unique triazole-acrylamide alternating structure polymer prepared by the method also provides basis and potential application value for subsequent biological and material science application.
Drawings
FIG. 1 is a nuclear magnetic resonance diagram of a three-component poly (triazole- (Z-acrylamide)) P1 prepared in example 31 of the present invention.
FIG. 2 is a nuclear magnetic resonance diagram of a three-component poly (triazole- (Z-acrylamide)) P2 prepared in example 32 of the present invention.
FIG. 3 is a nuclear magnetic resonance diagram of a three-component poly (triazole- (Z-acrylamide)) P3 prepared in example 33 of the present invention.
FIG. 4 is a nuclear magnetic resonance diagram of a three-component poly (triazole- (Z-acrylamide)) P4 prepared in example 34 of the present invention.
FIG. 5 is a nuclear magnetic resonance diagram of a three-component poly (triazole- (Z-acrylamide)) P5 prepared in example 35 of the present invention.
Detailed Description
The following describes the embodiments of the present invention further with reference to the drawings and technical schemes.
Example 1:
preparation of (Z) -N-benzyl-3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), benzyl azide 2a (37.5 μl,0.3 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3a (36 mg, 75% yield) as a yellow solid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.42–7.37(m,2H),7.29–7.24(m,6H),7.14(dd,J＝7.4,1.9Hz,2H),6.78(d,J＝12.5Hz,1H),6.02(d,J＝12.5Hz,1H),5.79(s,1H),4.41(d,J＝5.8Hz,2H).
Compound 3a is a known compound whose spectrum is in complete agreement with literature reports (heteoatom chem.2004,15,515; chem.Commun.2010,46, 2462).
Example 2:
preparation of (Z) -N-benzyl-3- (4-methoxyphenyl) acrylamide
(4-methoxyphenyl) propargyl ester 1b (52.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave yellow liquid 3b (37 mg, 69% yield) after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.44–7.38(m,2H),7.30–7.23(m,3H),7.22–7.18(m,2H),6.79–6.76(m,2H),6.69(d,J＝12.5Hz,1H),5.89(s,1H),5.88(d,J＝12.5Hz,1H),4.44(d,J＝5.9Hz,2H),3.79(s,3H).
Compound 3b is a known compound whose spectrum is in complete agreement with literature reports (j.org.chem.2020, 85,12024).
Example 3:
preparation of (Z) -N-benzyl-3- (4-phenoxyphenyl) acrylamide
(4-phenoxyphenyl) propargyl ester 1c (64.8 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3c (39 mg, 60% yield) as a white solid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.46(d,J＝8.3Hz,2H),7.38(t,J＝7.7Hz,3H),7.31(dd,J＝13.1,5.9Hz,2H),7.24(d,J＝7.5Hz,2H),7.17(t,J＝7.0Hz,1H),7.03(d,J＝8.3Hz,2H),6.90(d,J＝8.2Hz,2H),6.74(d,J＝12.5Hz,1H),5.97(d,J＝12.5Hz,1H),5.88(s,1H),4.48(d,J＝5.8Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.9,157.9,156.5,137.7,136.3,130.9,129.9,129.6,128.7,128.1,127.6,123.8,123.3,119.4,118.2,43.7 high resolution mass spectrometry (ESI, m/z): c (C) 22 H 19 NO 2 [M+H] + Theoretical value: 330.1489; measurement value: 330.1498.
example 4:
preparation of (Z) -N-benzyl-3- (4-methylthiophenyl) acrylamide
(4-Methylsulfanyl phenyl) propargyl ester 1d (55.6 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave a white solid 3d (40 mg, 71% yield) after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.36(d,J＝8.0Hz,2H),7.29(d,J＝7.1Hz,3H),7.19(d,J＝7.4Hz,2H),7.10(d,J＝8.2Hz,2H),6.69(d,J＝12.5Hz,1H),5.95(d,J＝12.5Hz,1H),5.88(s,1H),4.43(d,J＝5.8Hz,2H),2.46(s,3H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.9,139.6,137.7,136.3,131.4,129.6,128.7,128.1,127.6,125.8,123.8,43.6,15.4 high resolution mass spectrometry (ESI, m/z): c (C) 17 H 17 NOS[M+H] + Theoretical value: 284.1104; measurement value: measurement value: 284.1109.
example 5:
preparation of (Z) -N-benzyl-3- (4-methylphenyl) acrylamide
(4-methylphenyl) propargyl ester 1e (49.2 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3e (38 mg, 76% yield) as a white solid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.32–7.23(m,5H),7.16–7.13(m,2H),7.06(d,J＝8.0Hz,2H),6.72(d,J＝12.5Hz,1H),5.94(d,J＝12.5Hz,1H),5.91(s,1H),4.39(d,J＝5.8Hz,2H),2.31(s,3H).
13 C NMR(100MHz,CDCl 3 )δ167.1,138.6,137.8,136.7,132.1,129.1,129.0,128.6,128.0,127.5,123.9,43.6,21.3 high resolution mass spectrometry (ESI, m/z): c (C) 17 H 17 NO[M+H] + Theoretical value: 252.1383; measurement value: 252.1390.
example 6:
preparation of (Z) -N-benzyl-3- (4-tert-butylphenyl) acrylamide
(4-tert-butylphenyl) propargyl ester 1f (57.6 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3f (35 mg, 60% yield) as a yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.34(d,J＝8.2Hz,3H),7.31–7.26(m,4H),7.18–7.14(m,2H),6.76(d,J＝12.5Hz,1H),5.97(d,J＝12.5Hz,1H),5.77(s,1H),4.43(d,J＝5.7Hz,2H),1.30(s,9H).
13 C NMR(100MHz,CDCl 3 ) Delta 167.0,151.9,137.6,136.4,131.9,128.8,128.7,128.1,127.5,125.4,124.0,43.7,34.7,31.2 high resolution mass spectrometry (ESI, m/z): c (C) 20 H 23 NO[M+H] + Theoretical value: 294.1852; measurement value: 294.1858.
example 7:
preparation of (Z) -N-benzyl-3- (4-fluorophenyl) acrylamide
(4-fluorophenyl) propargyl ester 1g (50.0 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin drying gave 3g (33 mg, 65% yield) of yellow liquid.
1 H NMR(400MHz,CDCl 3 )δ7.42–7.32(m,2H),7.24–7.16(m,3H),7.13–7.10(m,2H),6.86(t,J＝8.7Hz,2H),6.62(d,J＝12.5Hz,1H),5.89(d,J＝12.5Hz,1H),5.79(s,1H),4.35(d,J＝5.8Hz,2H).
13 C NMR(100MHz,CDCl 3 )δ166.6,164.00,161.5,137.6,135.9,131.2(d,J＝8.2Hz),128.7,128.0,127.6,124.1,115.3(d,J＝21.6Hz),43.6. 19 F NMR(565MHz,CDCl 3 ) Delta-112.2. High resolution Mass Spectrometry (ESI, m/z): c (C) 16 H 14 FNO[M+H] + Theoretical value: 256.1132; measurement value: 256.1138.
example 8:
preparation of (Z) -N-benzyl-3- (4-chlorophenyl) acrylamide
(4-chlorophenyl) propargyl ester 1h (53.2 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave a yellow liquid after spin-drying for 3h (33 mg, 60% yield).
1 H NMR(400MHz,CDCl 3 )δ7.37(d,J＝8.3Hz,2H),7.30(q,J＝5.9Hz,3H),7.22(d,J＝8.3Hz,2H),7.18(d,J＝7.4Hz,2H),6.69(d,J＝12.5Hz,1H),6.01(d,J＝12.5Hz,1H),5.85(s,1H),4.42(d,J＝5.8Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.5,137.5,135.7,134.5,133.3,130.5,128.7,128.6,128.1,127.7,124.9,43.6 high resolution mass spectrometry (ESI, m/z): c (C) 16 H 14 ClNO[M+H] + Theoretical value: 272.0834: measurement value: 272.0841.
example 9:
preparation of (Z) -N-benzyl-3- (4-bromophenyl) acrylamide
(4-bromophenyl) propargyl ester 1i (62 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave yellow liquid 3i (42 mg, 67% yield) after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.40(d,J＝8.3Hz,2H),7.36–7.23(m,5H),7.20(d,J＝7.4Hz,2H),6.72(d,J＝12.5Hz,1H),6.03(d,J＝12.5Hz,1H),5.88(s,1H),4.45(d,J＝5.8Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.5,137.5,135.7,133.8,131.5,130.7,128.7,128.1,127.7,125.0,122.8,43.6 high resolution mass spectrometry (ESI, m/z): c (C) 16 H 14 BrNO[M+H] + Theoretical value: 316.0332; measurement value: 316.0339.
example 10:
preparation of (Z) -N-benzyl-3- (4-iodophenyl) acrylamide
(4-iodophenyl) propargyl ester 1j (71.6 mg,0.2 mmol), benzyl azide 2a (37.5 μl,0.3 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave yellow liquid 3j (44 mg, 60% yield) after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.61(d,J＝8.3Hz,2H),7.39–7.31(m,3H),7.19(dd,J＝8.3,5.0Hz,4H),6.70(d,J＝12.5Hz,1H),6.05(d,J＝12.5Hz,1H),5.84(s,1H),4.45(d,J＝5.8Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.4,137.5,137.5,135.8,134.4,130.7,128.8,128.1,127.7,125.2,94.6,43.6 high resolution mass spectrometry (ESI, m/z): c (C) 16 H 14 INO[M+H] + Theoretical value: 364.0193; measurement value: 364.0200.
example 11:
preparation of (Z) -N-benzyl-3- (3-methoxyphenyl) acrylamide
(3-methoxyphenyl) propargyl ester 1k (52.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3k (35 mg, 65% yield) as a yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.32–7.25(m,4H),7.18–7.13(m,2H),7.03–6.97(m,2H),6.86(dd,J＝8.3,2.3Hz,1H),6.79(d,J＝12.5Hz,1H),6.05(d,J＝12.5Hz,1H),5.84(s,1H),4.43(d,J＝5.8Hz,2H),3.77(s,3H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.9,159.6,137.6,136.3,136.3,129.5,128.6,127.9,127.5,125.1,121.3,114.6,113.9,55.2,43.6 high resolution mass spectrometry (ESI, m/z): c (C) 17 H 17 NO 2 [M+H] + Theoretical value: 268.1332; measurement value: 268.1339.
example 12:
preparation of (Z) -N-benzyl-3- (3-methylphenyl) acrylamide
1L (49.2 mg,0.2 mmol) of (3-methylphenyl) propargyl ester, benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3l (34 mg, 68% yield) of yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.30–7.23(m,3H),7.22–7.16(m,3H),7.15–7.11(m,2H),7.09(d,J＝7.0Hz,1H),6.76(t,J＝9.7Hz,1H),6.01(d,J＝12.5Hz,1H),5.77(s,1H),4.41(d,J＝5.8Hz,2H),2.28(s,3H).
13 C NMR(100MHz,CDCl 3 ) Delta 167.0,138.2,137.7,136.5,135.0,129.5,129.4,129.1,128.6,128.4,127.9,127.5,125.9,124.8,43.6,21.3 high resolution mass spectrometry (ESI, m/z): c (C) 17 H 17 NO[M+H] + Theoretical value: 252.1383; measurement value: 252.1388.
example 13:
preparation of (Z) -N-benzyl-3- (3-chlorophenyl) acrylamide
(3-chlorophenyl) propargyl ester 1m (52.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin drying gave 3m (33 mg, 60% yield) as a yellow liquid.
1 H NMR(400MHz,CDCl 3 )δ7.38(d,J＝8.5Hz,2H),7.33–7.27(m,5H),7.20–7.15(m,2H),6.68(d,J＝12.5Hz,1H),6.02(d,J＝12.5Hz,1H),5.82(s,1H),4.42(d,J＝5.9Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.5,137.5,135.7,133.8,131.5,130.7,128.7,128.0,127.7,125.0,122.8,43.6 high resolution mass spectrometry (ESI, m/z): c (C) 16 H 14 ClNO[M+H] + Theoretical value: 272.0837; measurement value: 272.0844.
example 14:
preparation of (Z) -N-benzyl-3- (3-bromophenyl) acrylamide
(3-bromophenyl) propargyl ester 1N (62 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3n (38 mg, 61% yield) as a yellow solid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.60(s,1H),7.39(dd,J＝16.8,7.9Hz,2H),7.33–7.27(m,3H),7.18(d,J＝6.6Hz,2H),7.13(t,J＝7.9Hz,1H),6.68(t,J＝11.4Hz,1H),6.05(d,J＝12.5Hz,1H),5.77(s,1H),4.44(d,J＝5.8Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.3,137.4,137.0,135.1,131.8,131.6,130.0,128.8,128.0,127.7,127.6,125.8,122.5,43.7 high resolution mass spectrometry (ESI, m/z): c (C) 16 H 14 BrNO[M+H] + Theoretical value: 316.0332; measurement value: 316.0341.
example 15:
preparation of (Z) -N-benzyl-3- (2-methoxyphenyl) acrylamide
(2-methoxyphenyl) propargyl ester 1o (52.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3o (30 mg, 56% yield) as yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.37(d,J＝7.5Hz,1H),7.31–7.26(m,4H),7.08(d,J＝6.8Hz,2H),6.96(d,J＝12.4Hz,1H),6.89–6.77(m,2H),6.05(d,J＝12.5Hz,1H),5.87(s,1H),4.37(d,J＝5.7Hz,2H),3.78(s,3H).
13 C NMR(100MHz,CDCl 3 ) Delta 167.1,156.8,137.8,132.4,130.2,130.1,128.6,127.9,127.4,125.1,123.9,120.5,110.5,55.4,43.5 high resolution mass spectrometry (ESI, m/z): c (C) 17 H 17 NO 2 [M+H] + Theoretical value: 268.1332; measurement value: 268.1340.
example 16:
preparation of (Z) -N-benzyl-3- (2-chlorophenyl) acrylamide
(2-chlorophenyl) propargyl ester 1p (52.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3p (29 mg, 54% yield) as a yellow liquid after spin-drying.
1 H NMR(600MHz,CDCl 3 )δ7.45(dd,J＝7.7,1.3Hz,1H),7.37–7.34(m,1H),7.25–7.20(m,4H),7.14–7.10(m,1H),7.10–7.06(m,2H),6.96(d,J＝12.5Hz,1H),6.21(d,J＝12.5Hz,1H),5.76(s,1H),4.50(d,J＝3.9Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.2,137.5,133.8,133.6,133.3,130.6,129.7,129.4,128.6,127.9,127.5,126.7,126.4,43.5 high resolution mass spectrometry (ESI, m/z): c (C) 16 H 14 ClNO[M+H] + Theoretical value: 272.0837; measurement value: 272.0845.
example 17:
preparation of (Z) -N-benzyl-3- (1-naphthyl) acrylamide
(1-naphthalene) propargyl ester 1q (56.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin drying gave yellow liquid 3q (32 mg, yield 55%).
1 H NMR(400MHz,CDCl 3 )δ7.98–7.92(m,1H),7.89–7.85(m,1H),7.80(d,J＝8.2Hz,1H),7.53(dd,J＝6.1,3.3Hz,2H),7.46(d,J＝7.0Hz,1H),7.41–7.31(m,2H),7.19–7.09(m,3H),6.77(d,J＝7.0Hz,2H),6.34(d,J＝12.3Hz,1H),5.57(s,1H),4.22(d,J＝5.7Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.5,137.4,135.0,133.5,132.5,131.0,128.9,128.7,128.5,127.9,127.5,127.2,126.8,126.6,126.4,125.5,124.3,43.4 high resolution mass spectrometry (ESI, m/z): c (C) 20 H 17 NO[M+H] + Theoretical value: 288.1383; measurement value: 288.1389.
example 18:
preparation of (Z) -N-benzyl-3- (2-naphthyl) acrylamide
(2-naphthalene) propargyl ester 1r (56.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3r (36 mg, 62% yield) as a yellow solid after spin-drying.
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1 H NMR(400MHz,CDCl 3 )δ7.87(s,1H),7.84–7.70(m,3H),7.56–7.46(m,3H),7.21–7.13(m,3H),7.08(d,J＝6.6Hz,2H),6.94(d,J＝12.5Hz,1H),6.11(d,J＝12.5Hz,1H),5.82(s,1H),4.42(d,J＝5.8Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 167.0,137.6,136.5,133.2,133.1,132.5,128.7,128.6,128.3,128.1,127.9,127.7,127.5,126.7,126.4,126.3,125.0,43.6 high resolution mass spectrometry (ESI, m/z): c (C) 20 H 17 NO[M+H] + Theoretical value: 288.1383; measurement value: 288.1387.
example 19:
preparation of (Z) -N-benzyl-3- (3-thiophene) acrylamide
(3-thiophene) propargyl ester 1s (47.6 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin-drying gave 3s (30 mg, 61% yield) as a yellow solid
1 H NMR(400MHz,CDCl 3 )δ7.74(s,1H),7.41–7.27(m,5H),7.25–7.18(m,2H),6.68(d,J＝12.5Hz,1H),6.02(s,1H),5.82(d,J＝12.5Hz,1H),4.47(d,J＝5.5Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.6,137.9,136.3,131.5,129.1,128.7,128.0,128.0,127.6,125.3,121.6,43.7 high resolution mass spectrometry (ESI, m/z): c (C) 14 H 13 NOS[M+H] + Theoretical value: 244.0791; measurement value: 244.0796.
example 20:
preparation of (Z) -N-benzyl-3- (2-furan) acrylamide
(2-Furan) propargyl ester 1t (44.4 mg,0.2 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin drying gave 3t (30 mg, 65% yield) as a yellow solid
1 H NMR(400MHz,CDCl 3 )δ7.38–7.32(m,5H),7.29(dd,J＝8.4,3.9Hz,1H),7.21(d,J＝3.3Hz,1H),6.56(d,J＝13.0Hz,1H),6.44(s,1H),6.22(s,1H),5.73(d,J＝13.0Hz,1H),4.55(d,J＝5.7Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.0,150.7,143.4,138.1,128.7,128.0,127.6,125.0,118.9,115.4,112.2,43.7 high resolution mass spectrometry (ESI, m/z): c (C) 14 H 13 NO 2 [M+H] + Theoretical value: 228.1019; measurement value: 228.1025.
example 21:
preparation of (Z) -N- (4-methylbenzyl) -3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), 4-methylbenzyl azide 2b (44.1 mg,0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3u (37 mg, 74% yield) as a yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.43–7.37(m,2H),7.32–7.26(m,3H),7.08(d,J＝8.0Hz,2H),7.03(d,J＝8.0Hz,2H),6.77(d,J＝12.5Hz,1H),6.01(d,J＝12.5Hz,1H),5.75(s,1H),4.37(d,J＝5.7Hz,2H),2.32(s,3H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.9,137.2,136.4,135.0,134.6,129.3,128.9,128.6,128.5,128.0,124.8,43.4,21.1 high resolution Mass Spectrometry(ESI,m/z)：C 17 H 17 NO[M+H] + Theoretical value: 252.1383; measurement value: 252.1388.
example 22:
preparation of (Z) -N- (4-chlorobenzyl) -3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), 4-chlorobenzyl azide 2c (50.1 mg,0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin drying gave 3v (38 mg, 70% yield) as a yellow liquid.
1 H NMR(400MHz,CDCl 3 )δ7.40–7.34(m,2H),7.31–7.26(m,3H),7.23(d,J＝8.4Hz,2H),7.07(d,J＝8.4Hz,2H),6.80(d,J＝12.5Hz,1H),6.02(d,J＝12.5Hz,1H),5.80(s,1H),4.36(d,J＝5.9Hz,2H). 13 C NMR(100MHz,CDCl 3 ) Delta 167.0,136.7,136.2,134.9,133.3,129.3,128.9,128.7,128.6,128.5,124.7,42.8 high resolution mass spectrometry (ESI, m/z): c (C) 16 H 14 ClNO[M+H] + Theoretical value: 272.0837; measurement value: 272.0845.
example 23:
preparation of (Z) -N-phenyl-3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), phenyl azide 2d (35.7 mg,0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin drying gave 3w (22 mg, 50% yield) as a white solid.
1 H NMR(600MHz,CDCl 3 )δ7.50(d,J＝7.1Hz,2H),7.39–7.32(m,5H),7.30–7.26(m,2H),7.22(s,1H),7.09(t,J＝7.3Hz,1H),6.92(d,J＝12.5Hz,1H),6.11(d,J＝12.5Hz,1H).
Compound 3b is a known compound, and its spectrum is completely consistent with literature reports. (Heteroatom chem.2004,15,515; chem.Commun.2010,46, 2462)
Example 24:
preparation of (Z) -N-phenethyl-3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), phenethyl azide 2e (44.1 mg,0.3 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3x (40 mg, 74% yield) as yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.44–7.39(m,2H),7.36–7.29(m,3H),7.25–7.16(m,3H),7.03–6.99(m,2H),6.74(d,J＝12.5Hz,1H),5.96(d,J＝12.5Hz,1H),5.52(s,1H),3.50(dd,J＝13.0,7.0Hz,2H),2.71(t,J＝7.0Hz,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 167.1,138.6,136.2,135.1,128.9,128.6,128.6,128.5,126.5,125.0,40.4,35.2 high resolution mass spectrometry (ESI, m/z): c (C) 17 H 17 NO[M+Na] + Theoretical value: 274.1202; measurement value: 274.1210.
example 25:
preparation of (Z) -N- (phthalimido) butyl-3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), (phthalimido) butyl azide 2f (73.2 mg,0.3 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave yellow liquid 3y (51 mg, 73% yield) after spin-drying.
1 H NMR(600MHz,CDCl 3 )δ7.86–7.81(m,2H),7.74–7.69(m,2H),7.41(d,J＝7.5Hz,2H),7.31(t,J＝7.6Hz,2H),7.23(t,J＝7.4Hz,1H),6.76(d,J＝12.5Hz,1H),5.98(d,J＝12.5Hz,1H),5.67(s,1H),3.62(t,J＝7.1Hz,2H),3.26(dd,J＝13.2,6.9Hz,2H),1.63–1.54(m,2H),1.49–1.40(m,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 168.4,167.1,136.1,135.1,134.0,132.1,128.9,128.5,128.4,125.1,123.2,38.9,37.4,26.4,26.1 high resolution mass spectrometry (ESI, m/z): [ M+H ]] + Theoretical value: 349.1547; measurement value: 349.1556.
example 26:
preparation of (Z) -N- (4-azidobutyl) -3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), 2g of succinazide (42 mg,0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction.
Column chromatography gave 3z (29 mg, 60% yield) as a yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.42(d,J＝6.6Hz,2H),7.34(dd,J＝15.0,7.3Hz,3H),6.79(d,J＝12.5Hz,1H),6.00(d,J＝12.5Hz,1H),5.50(s,1H),3.28–3.19(m,4H),1.50–1.44(m,4H).
13 C NMR(100MHz,CDCl 3 )δ167.2,136.2,1351,128.8,128.7,128.5,125.2,51.0,38.8,26.5,26.3 high resolution mass spectrometry (ESI, m/z): c (C) 13 H 16 N 4 O[M+H] + Theoretical value: 245.1397; measurement value: 245.1404. example 27:
preparation of (Z) -N-cyclohexyl-3-phenylacrylamide
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), succinazide 2h (37.5 mg,0.3 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography separation after spin-drying gave 3aa (34 mg, 74% yield) as a yellow liquid.
1 H NMR(600MHz,CDCl 3 )δ7.38–7.33(m,2H),7.29–7.21(m,3H),6.68(d,J＝12.5Hz,1H),5.92(d,J＝12.5Hz,1H),5.29(s,1H),3.79–3.67(m,1H),1.78–1.71(m,2H),1.57–1.46(m,3H),1.28–1.16(m,2H),1.05–0.96(m,1H),0.93–0.80(m,2H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.1,135.6,135.1,128.9,128.5,128.4,125.6,48.0,32.6,25.4,24.7 high resolution mass spectrometry (ESI, m/z): c (C) 15 H 19 NO[M+H] + Theoretical value: 230.1539; measurement value: 230.1545. example 28:
(2R, 3S,4R,5R, 6R) -5-acetamido-2- (acetylmethyl) -6- ((Z) -3-phenylacrylamide) tetrahydro-2H-pyran-3, 4-diethyl ester
Phenyl propargyl ester 1a (46.4 mg,0.2 mmol), glycosylazide 2i (111.6 mg,0.3 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave yellow liquid 3ab (68 mg, 72% yield) after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.57(d,J＝7.7Hz,2H),7.37–7.31(m,3H),7.12(d,J＝8.3Hz,1H),6.80(d,J＝12.6Hz,1H),6.09(d,J＝8.3Hz,1H),5.90(d,J＝12.6Hz,1H),5.18–5.03(m,3H),4.32(dd,J＝12.4,4.2Hz,1H),4.12(dd,J＝16.4,8.0Hz,2H),3.83–3.69(m,1H),2.11(s,3H),2.07(d,J＝1.4Hz,3H),2.07(d,J＝1.4Hz,3H),1.83(s,3H).
13 C NMR(100MHz,CDCl 3 ) Delta 171.9,171.9,170.7,169.3,167.1,139.8,134.6,129.7,128.9,128.2,122.3,80.2,73.5,73.1,67.8,61.8,53.3,23.0,20.7,20.7,20.6 high resolution mass spectrometry (ESI, m/z): c (C) 23 H 28 N 2 O 9 [M+H] + Theoretical value: 477.1868; measurement value: 477.1875.
example 29:
preparation of (Z) - (1-benzyl-1H-1, 2, 3-triazol-4-yl) (4- (3- (benzylamino) -3-oxoprop-1-en-1-yl) phenyl) methyl tert-butyl carbonate
P-xylylene glycol 5a (38.6 mg,0.1 mmol), benzyl azide 2a (37.5. Mu.L, 0.3 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 10 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,20 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave 3ad (39 mg, 75% yield) as a yellow liquid after spin-drying.
1 H NMR(400MHz,CDCl 3 )δ7.44(d,J＝8.1Hz,2H),7.37(t,J＝6.1Hz,7H),7.27(s,4H),7.18(d,J＝6.9Hz,2H),6.80(s,1H),6.74(d,J＝12.6Hz,1H),6.03(d,J＝12.5Hz,1H),5.85(s,1H),5.56–5.41(m,2H),4.43(d,J＝5.8Hz,2H),1.47(s,9H).
13 C NMR(100MHz,CDCl 3 )δ166.7,152.4,147.4,138.8,137.6,136.1,134.9,134.3,129.4,129.2,128.8,128.7,128.1,128.0,127.6,126.9,124.8,122.2,83.0,72.8,54.2,43.6,27.8 high resolution mass spectrometry (ESI, m/z): c (C) 31 H 32 N 4 O 4 [M+H] + Theoretical value: 525.2496; measurement value: 525.2501.
example 30:
preparation of (Z) -1- (4- (3- (benzylamino) -3-oxoprop-1-en-1-yl) phenyl) propyl-2-yn-1-tert-butylcarbonate
P-xylylene glycol 5a (38.6 mg,0.1 mmol), benzyl azide 2a (12.5. Mu.L, 0.1 mmol), N-diisopropylethylamine (33. Mu.L, 0.2 mmol) and methyl phosphite (1. Mu.L, 10 mol%) were dissolved in chloroform. Water (1.8. Mu.L, 0.1 mmol) and cuprous bromide (1.9 mg,10 mol%) were then added to the mixed solution and stirred at room temperature for 8 hours, stopping the reaction. Column chromatography gave yellow liquid 6a (21 mg, 55% yield) after spin-drying.
1 H NMR(600MHz,CDCl 3 )δ7.43(q,J＝8.3Hz,4H),7.30(t,J＝7.2Hz,3H),7.15(d,J＝7.1Hz,2H),6.77(d,J＝12.5Hz,1H),6.21(d,J＝2.2Hz,1H),6.05(d,J＝12.5Hz,1H),5.72(s,1H),4.42(d,J＝5.8Hz,2H),2.70(d,J＝2.2Hz,1H),1.50(s,9H).
13 C NMR(100MHz,CDCl 3 ) Delta 166.7,152.4,137.5,136.5,135.7,129.2,128.7,128.0,127.8,127.6,125.4,83.3,79.7,76.1,67.7,43.7,29.7,27.8 high resolution mass spectrometry (ESI, m/z): c (C) 24 H 25 NO 4 [M+H] + Theoretical value: 392.1856; measurement value: 392.1863.
example 31:
preparation of Poly (triazole- (Z-enamide)) P1
P-xylylene glycol 5a (38.6 mg,0.1 mmol), benzodiazepine 7a (18.8 mg,0.1 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 20 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,20 mol%) were then added to the mixed solution and stirred at room temperature for 16 hours, stopping the reaction. The precipitate was collected by centrifugation, and the product was dried to constant weight in a vacuum oven to give product P1 (48 mg, yield 83%) as a powder.
1 H NMR(400MHz,DMSO)δ8.55(1H),8.07(1H),7.55–7.15(8H),6.62(1H),6.58(1H),5.98(1H),5.46(2H),4.27(2H),1.27(9H).
Example 32:
preparation of Poly (triazole- (Z-enamide)) P2
Paraphthalyn propyl ester 5a (38.6 mg,0.1 mmol), glycidyl ether diazide 7b (33.2 mg,0.1 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,20 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,20 mol%) were then added to the mixed solution and stirred at room temperature for 16 hours, stopping the reaction. The precipitate was collected by centrifugation, and the product was dried to constant weight in a vacuum oven to give product P2 (64 mg, 87%) as a powder.
1 H NMR(400MHz,DMSO)δ8.20(1H),8.05(1H),7.74–7.25(4H),6.73(1H),6.64(1H),6.02(1H),4.47(4H),3.78(4H),3.53–3.37(16H),1.38(9H).
Example 33:
preparation of Poly (triazole- (Z-enamide)) P3
Paraphthalyn propyl ester 5a (38.6 mg,0.1 mmol), succinazide 7c (14 mg,0.1 mmol), N-diisopropylethylamine (66 μl,0.4 mmol) and methyl phosphite (2 μl,20 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,20 mol%) were then added to the mixed solution and stirred at room temperature for 16 hours, stopping the reaction. The precipitate was collected by centrifugation, and the product was dried to constant weight in a vacuum oven to give product P3 (51 mg, 82%) as a powder.
1 H NMR(600MHz,DMSO)δ8.02(2H),7.61–7.11(4H),6.65(1H),6.55(1H),5.91(1H),4.26(4H),1.67(4H),1.29(9H).
Example 34:
preparation of Poly (triazole- (Z-enamide)) P4
Paradiphenylenedipropylenepropyl ester 5a (38.6 mg,0.1 mmol), glycidyl ether diazide 7d (24.4 mg,0.1 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 20 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,20 mol%) were then added to the mixed solution and stirred at room temperature for 16 hours, stopping the reaction. The precipitate was collected by centrifugation, and the product was dried to constant weight in a vacuum oven to give product P4 (55 mg, 85%) as a powder.
1 H NMR(400MHz,DMSO)δ8.18(1H),8.04(1H),7.72–7.10(4H),6.73(1H),6.62(1H),6.01(1H),4.46(4H),3.75(4H),3.43(8H),1.36(9H).
Example 35:
preparation of Poly (triazole- (Z-enamide)) P4
Paraphenyl dipropargyl ester 5a (38.6 mg,0.1 mmol), paraphenyl ethyl ether diazide 7e (24.8 mg,0.1 mmol), N-diisopropylethylamine (66. Mu.L, 0.4 mmol) and methyl phosphite (2. Mu.L, 20 mol%) were dissolved in chloroform. Water (3.6. Mu.L, 0.2 mmol) and cuprous bromide (3.8 mg,20 mol%) were then added to the mixed solution and stirred at room temperature for 16 hours, stopping the reaction. The precipitate was collected by centrifugation, and the product was dried to constant weight in a vacuum oven to give product P5 (57 mg, 88%) as a powder.
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1 H NMR(600MHz,DMSO)δ8.29(1H),8.07(1H),7.61–7.18(4H),6.82–6.50(6H),5.96(1H),4.60(4H),4.22(4H),1.28(9H).
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.

Claims (5)

1. A preparation method of Z-acrylamide is characterized by comprising the following steps: weighing propargyl ester compounds, organic azide compounds, N-diisopropylethylamine and phosphite esters, and dissolving the propargyl ester compounds, the organic azide compounds, the N, N-diisopropylethylamine and the phosphite esters in an organic solvent to obtain a mixed solution; weighing copper catalyst and water, adding the copper catalyst and the water into the mixed solution, stirring the mixture for 8 to 24 hours at room temperature, and stopping the reaction; then post-processing to obtain a product;
the structural formula of the propargyl ester compound is as follows:wherein R is 1 Phenyl or phenyl optionally substituted in position by Ra, ra being C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenoxy, halogen;
the structural formula of the organic azide compound is as follows: r is R 2 N 3 Wherein R is 2 Is alkyl or aryl; r is R 2 Wherein the alkyl is C1-C6 alkyl, C3-C8 cycloalkyl;
R 2 wherein aryl is phenyl or phenyl optionally substituted at the position by Ra, ra is C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenoxy, halogen;
the structural formula of the Z-acrylamide is as follows:
the copper catalyst is a monovalent copper catalyst, and the dosage of the copper catalyst is 10mol percent to 20mol percent equivalent of propargyl ester compounds.
2. A process for preparing Z-acrylamide according to claim 1,
when the product is a Z-acrylamide, the reaction product,
the reaction general formula is as follows:
wherein 1 is propargyl ester compound and 2 is organic azide compound;
the molar ratio of the propargyl ester compound to the organic azide compound to the water is 1:1:1-1:10:4;
the dosage of the N, N-diisopropylethylamine is 2 times equivalent of the propargyl ester compound;
the phosphite ester comprises dimethyl phosphite, diethyl phosphite and diisopropyl phosphite, and the dosage of the phosphite ester is 10mol percent to 100mol percent equivalent of propargyl ester compounds;
the organic solvent is acetonitrile, toluene, chloroform, methylene dichloride, 1, 2-dichloroethane, tetrahydrofuran and acetone;
the copper catalyst is cuprous iodide, cuprous chloride and cuprous bromide;
the post-treatment mode is as follows: and (3) carrying out column chromatography separation after spin drying, and drying the product to constant weight in a vacuum drying oven.
3. A process for producing Z-acrylamide according to claim 2, characterized in that,
the molar ratio of propargyl ester compounds to organic azide compounds to water is 1:1.5:1;
the phosphite ester is diethyl phosphite, and the dosage is 10mol percent equivalent of propargyl ester compounds;
the organic solvent is chloroform;
the copper catalyst is cuprous bromide, and the dosage of the copper catalyst is 10mol percent equivalent of propargyl ester compounds.
4. A preparation method of triazole-enamide alternating copolymer is characterized by comprising the following steps: weighing propargyl ester compounds, organic azide compounds, N-diisopropylethylamine and phosphite esters, and dissolving the propargyl ester compounds, the organic azide compounds, the N, N-diisopropylethylamine and the phosphite esters in an organic solvent to obtain a mixed solution; weighing copper catalyst and water, adding the copper catalyst and the water into the mixed solution, stirring the mixture for 8 to 24 hours at room temperature, and stopping the reaction; then post-processing to obtain a product;
the structural formula of the propargyl ester compound is as follows:
the structural formula of the organic azide compound is as follows:
the copper catalyst is a monovalent copper catalyst, and the dosage of the copper catalyst is 20mol percent equivalent of propargyl ester compounds.
5. A preparation method of triazole-enamide alternating copolymer is characterized by comprising the following steps: weighing propargyl ester compounds, organic azide compounds, N-diisopropylethylamine and dimethyl phosphite, and dissolving in an organic solvent to obtain a mixed solution; weighing copper catalyst and water, adding the copper catalyst and the water into the mixed solution, stirring the mixture for 8 to 24 hours at room temperature, and stopping the reaction; then post-processing to obtain a product;
when the product is a triazole-enamide alternating copolymer,
the reaction general formula is as follows:
the number average molecular weight of the triazole-enamide alternating copolymer ranges from 17100 g/mol to 44300g/mol, and the polymerization degree n is more than 5;
the structural formula of the propargyl ester compound is as follows:
the organic azide compound N 3 -R-N 3 The method comprises the following steps:
the molar ratio of propargyl ester compounds to organic azide compounds to water is 1:1:2; the dosage of the N, N-diisopropylethylamine is 4 times equivalent of that of the dipropargyl ester compound; the amount of the CuBr catalyst and the dimethyl phosphite are 20mol% equivalent of the dipropargyl ester;
the post-treatment mode is as follows: the precipitate was collected by centrifugation, and the product was dried to constant weight in a vacuum oven.
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Publication number Priority date Publication date Assignee Title
US5250629A (en) * 1990-12-10 1993-10-05 Idemitsu Kosan Co., Ltd. Graft copolymer and process for producing the same
CN114014802A (en) * 2021-07-30 2022-02-08 常州大学 Method for synthesizing enamide by palladium catalyst dehydrogenation coupling

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5250629A (en) * 1990-12-10 1993-10-05 Idemitsu Kosan Co., Ltd. Graft copolymer and process for producing the same
CN114014802A (en) * 2021-07-30 2022-02-08 常州大学 Method for synthesizing enamide by palladium catalyst dehydrogenation coupling

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