1,2,3-trisubstituted indolizine derivative and preparation method thereof

An indolizine derivative and tri-substitution technology, which is applied in the field of 1,2,3-trisubstituted indolizine derivatives and their preparation, can solve the problems of fast forward and reverse reactions, harsh conditions, complex reactions, etc., and achieves energy reduction. The effect of low consumption, mild reaction conditions and high reaction yield

Inactive Publication Date: 2018-09-14
ANHUI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The methods of the multi-substituted indolizines and derivatives thereof reported in the literature include: (1) Scholtz reaction, utilizing 2-substituted pyridine and acid anhydride to cyclize at 200-220° C. to obtain acyl-substituted indolizine compounds, and then Obtain indolizine derivatives by hydrolysis reaction, although this reaction has a wide range of sources of raw materials, the reaction yield is low and the conditions are harsh; (2) Tschitschibabin reaction, utilizing 2-alkyl substituted pyridine halocarbonyl compounds as substrates, first forming Pyridinium quaternary ammonium salts are then subjected to intramolecular condensation to obtain indolizine skeletons, but this method can only obtain indolizine skeletons with alkyl or aryl substitutions at the 2-position
Like the Scholtz reaction, the Tschitschibabin reaction also has the disadvantages of harsh reaction conditions (240-260°C) and low reaction yield; (3) cycloaddition reaction, which synthesizes the middle nitrogen band by 1,3-dipolar cycloaddition reaction Skeleton compounds are mainly generated from N-ylides and electron-deficient alkenes, alkynes and their derivatives as substrates. The source of substrates is limited. The obtained indolizine structure only contains electron-withdrawing groups, and the positions of substituents have Larger limitations; and 1,5-dipolar cycloaddition reactions often require multiple steps to obtain the indolizine structure, which also results in low overall yields
(4) Photodecomposition reaction, compared with the chemical reaction in the traditional sense, the

Method used

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  • 1,2,3-trisubstituted indolizine derivative and preparation method thereof
  • 1,2,3-trisubstituted indolizine derivative and preparation method thereof
  • 1,2,3-trisubstituted indolizine derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Add bromoacetophenone (1.0mmol), methyl azidocinnamate (0.5mmol) and pyridine (0.75mmol), DMSO (3mL) to a 25mL reaction tube, react at 100°C for 3h, TLC (thin layer chromatography method) tracking reaction, after the reaction was finished, extracted with dichloromethane, anhydrous Na 2 SO 4 After drying and column chromatography (developer petroleum ether / ethyl acetate v / v=3:1), a yellow solid A1 can be obtained in a yield of 78%. The reaction principle is as follows.

[0035] The H NMR and C NMR spectra of compound A1 correspond to figure 1 , figure 2 , the obtained data are as follows: Methyl1,3-dibenzoylindolizine-2-carboxylate(A1), 1 H NMR (300MHz, CDCl 3 )δ9.61(d, J=7.2Hz, 1H), 8.21(d, J=9.0Hz, 1H), 7.71(d, J=7.2Hz, 3H), 7.56-7.49(m, 3H), 7.46- 7.40(m,4H),7.16(t,J=6.9Hz,1H),2.82(s,3H); 13 C NMR (75MHz, CDCl 3 )δ 191.1, 187.1, 164.5, 151.1, 140.2, 140.0, 138.0, 132.1, 132.0, 128..5, 128.5, 128.3, 127.7, 127.6, 119.9, 116.3, 51.7. It can be seen that the sin...

Embodiment 2

[0038] Add 4-methylbromoacetophenone (1.0mmol), methyl azidocinnamate (0.5mmol) and pyridine (0.75mmol), DMSO (3mL) to a 25mL reaction tube, react at 100°C for 3h, TLC Follow up the reaction, after the reaction is finished, extract with dichloromethane, anhydrous Na 2 SO 4 After drying and column chromatography (developer petroleum ether / ethyl acetate v / v=3:1), a yellow solid A2 can be obtained in a yield of 75%. The reaction principle is as follows.

[0039]

[0040] The results of the H NMR and C NMR spectra of compound A2 are as follows: Methyl1,3-bis(4-methylbenzoyl)indolizine-2-carboxylate(A2), 1 H NMR (300MHz, CDCl 3 )δ9.51(d, J=6.9Hz, 1H), 8.12(d, J=9.0Hz, 1H), 7.64-7.61(m, 4H), 7.40(t, J=7.8Hz, 1H), 7.24- 7.21(m,4H),7.11(t,J=6.9Hz,1H),2.89(s,3H),2.41(s,6H); 13 C NMR (75MHz, CDCl 3 )δ 190.8, 186.9, 164.6, 142.9, 142.7, 137.7, 137.5, 137.3, 129.7, 128.9, 128.8, 128.7, 127.6, 127.1, 121.3, 119.8, 116.0, 113.5, 51.7, 21.5. It can be seen that the single peaks at ...

Embodiment 3

[0042] Add bromoacetophenone (1.0mmol), ethyl azide cinnamate (0.5mmol) and pyridine (0.75mmol), DMSO (3mL) to a 25mL reaction tube, react at 100°C for 3h, track the reaction by TLC, and wait for the reaction After the end, extract with dichloromethane, anhydrous Na 2 SO 4 After drying and column chromatography (developer petroleum ether / ethyl acetate v / v=3:1), a yellow solid A3 can be obtained in a yield of 78%. The reaction principle is as follows.

[0043]

[0044] The results of the H NMR and C NMR spectra of compound A3 are as follows: Ethyl1,3-dibenzoylindolizine-2-carboxylate (A3), 1 H NMR (300MHz, CDCl 3 )δ9.54 (d, J = 6.3Hz, 1H), 8.16 (d, J = 8.7Hz, 1H), 7.69 (d, J = 8.4Hz, 3H), 7.48-7.26 (m, 8H), 7.12- 7.10(m,1H),3.20-3.13(m,2H),0.73-0.64(m,3H); 13 C NMR (75MHz, CDCl 3 )δ 191.1, 187.1, 164.1, 151.0, 140.2, 140.0, 138.0, 133.6, 132.1, 132.1, 130.1, 129.1, 128.6, 128.4, 128.2, 128.2, 127.6, 127.4, 119.8, 114.2, 13.1. It can be seen that the multiplets at 0.73-...

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Abstract

The present invention relates to an indolizine derivative, and specifically discloses a 1,2,3-trisubstituted indolizine derivative and a preparation method thereof, wherein the chemical structure formula of the indolizine derivative is I as shown in the specification. The 1,2,3-trisubstituted indolizine derivative has benzoyl groups at both 1 and 3 positions, and an ester group at 2-position, namely, the 1,2,3-trisubstituted indolizine derivative has substituents containing carbonyl groups, benzene rings and the ester group, and further modification and processing of the product structure arefacilitated by the chemical nature of the benzoyl groups and the ester group, and more possibilities are provided for the construction of more complex indolizine derivatives. Moreover, the preparationmethod of the 1,2,3-trisubstituted indolizine derivative does not require addition of a metal catalyst, does not require inert gas protection, and has the advantages of easy-to-obtain reaction raw materials, high reaction yield, and mild reaction conditions.

Description

technical field [0001] The invention relates to indolizine compounds, in particular to a 1,2,3-trisubstituted indolizine derivative and a preparation method thereof. Background technique [0002] Indolizine compounds are a class of very useful compounds that are widely used in the fields of medicine, organic light-emitting materials and organic synthesis. Indolizine is a heterocyclic compound consisting of a five-membered and six-membered fused ring and a bridgehead nitrogen atom. It exhibits excellent properties in many biological activities and can be used as various inhibitors and antiviral, antibacterial, antibacterial, and antibacterial agents. Drugs such as tumors; in addition, indolizine derivatives are key intermediates for the synthesis of a class of alkaloids with physiological activity, and complex molecules containing indolizine skeletons can also be found in natural product molecules isolated and extracted from some plants and marine organisms . In addition, i...

Claims

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Application Information

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IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 叶青青左有鹏何心伟商永嘉
Owner ANHUI NORMAL UNIV
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