Synthesis method of N-aminoethyl terpinene maleimido imidazole derivative

Abstract

The invention provides a synthesis method of an N-aminoethyl terpinene maleimido imidazole derivative. The synthesis method comprises the following steps: converting alpha-pinene serving as a raw material into alpha-terpinene maleic anhydride adduct (called TMA for short), then reacting the alpha-terpinene maleic anhydride adduct with ethanediamine so as to prepare a midbody, namely N-aminoethyl terpinene maleimide (called ATM for short), and then synthesizing the N-aminoethyl terpinene maleimido imidazole derivative with potential biological activity through modified reaction of amino in the N-aminoethyl terpinene maleimide. The synthesis method has the advantages that the synthesis of the important imidazole ring-containing organic compound by introducing N atoms into the alpha-terpinene maleic anhydride structure is realized for the first time; the N-aminoethyl terpinene maleimido imidazole compound has multiple biological activity, particularly bactericidal activity, the applicant range of the alpha-pinene is widened, and a new approach is supplied for the deep development and utilization of natural organic green resources-turpentine.

Description

technical field

[0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing N-aminoethyl terpinene maleimido imidazole derivatives. Background technique

[0002] As the active center functional group of many natural enzymes and biological systems, imidazoles play an important role in the fields of medicine and pesticides. In the field of medicine, some imidazole compounds have antibacterial, anticancer, anti-inflammatory, analgesic, antiallergic and other medicinal activities. In the field of pesticides, many compounds containing imidazole groups can be used as fungicides, enzyme inhibitors, insecticides, plant growth regulators and herbicides. Imidazole compounds have the characteristics of high efficiency, low toxicity, not easy to produce drug resistance and environmental friendliness, and have attracted the attention of many scientists. In recent years, imidazole derivatives have become a research hotspot in the ...

Examples

Embodiment 1

[0023] Preparation of compound a:

[0024]

[0025] Add 0.6g ATM, 0.4g benzil, 0.26g benzaldehyde, 1.5g NH to the there-necked flask 4 OAc, 0.032g ZnO and 5ml toluene were stirred and refluxed for 2h, the reaction was terminated when no ATM was detected by TLC and ninhydrin hydrate, the solvent was evaporated, and the crude product was purified by silica gel column, and the eluent was petroleum ether / ethyl acetate: 10 / 1, 5 / 1, 3 / 1 gradient elution, and then recrystallized from a mixed solution of dichloromethane and petroleum ether to obtain the target product a. White crystal, m.p.187~188℃. IR(KBr,cm -1 )ν: 3030(Ar-H), 2958, 2869(C-H), 1771, 1700(C=O), 1601(Ar-C=C), 1502(C=N), 1125(C-N). 1 H NMR (600MHz, CDCl 3 )δ / ppm: 7.73~7.71(m, 2H, C 19 -H,C 23 -H),7.52~7.49(m,5H,C b1 -H,C c1 -H,C d1 -H,C e1 -H,C f1 -H),7.49~7.46(m,4H,C 20 -H,C 22 -H,C b -H,C f -H),7.45(t,J=7.4Hz,1H,C 21 -H),7.19(t,J=7.5Hz,2H,C c -H,C e -H),7.13(t,J=7.3Hz,1H,C d -H),5.74(d,J=8.4Hz,1H...

Embodiment 2

[0027] Preparation of compound b:

[0028]

[0029] Add 0.6g ATM, 0.4g benzil, 0.3g p-fluorobenzaldehyde, 1.5g NH to the there-necked flask 4OAc, 0.032g ZnO and 5ml toluene were stirred and refluxed for 2h, the reaction was terminated when no ATM was detected by TLC and ninhydrin hydrate, the solvent was evaporated, and the crude product was purified by silica gel column, and the eluent was petroleum ether / ethyl acetate: 10 / 1, 5 / 1, 3 / 1 gradient elution, and then recrystallized from a mixed solution of dichloromethane and petroleum ether to obtain the target product b. Light yellow powder, m.p.212~214℃. IR(KBr,cm -1 )ν: 3030(Ar-H), 2958, 2869(C-H), 1771, 1700(C=O), 1601(Ar-C=C), 1529(C=N), 1107(C-N). 1 H NMR (600MHz, CDCl 3 )δ / ppm: 7.73(m, 2H, C 19 -H,C 23 -H),7.50(m,5H,C b1 -H,C c1 -H,C d1 -H,C e1 -H,C f1 -H),7.47~7.44(m,2H,C b -H,C f -H),7.21(m,2H,C 20 -H,C 22 -H),7.19(m,2H,C c -H,C e -H),7.13(t,J=7.3Hz,1H,C d -H),5.76(d,J=8.4Hz,1H,C 8 -H),5.67(d,J=8.4H...

Embodiment 3

[0031] Preparation of compound c:

[0032]

[0033] Add 0.6g ATM, 0.4g benzil, 0.26g o-fluorobenzaldehyde, 1.5g NH to the there-necked flask 4 OAc, 0.032g ZnO and 5ml toluene were stirred and refluxed for 2h, the reaction was terminated when no ATM was detected by TLC and ninhydrin hydrate, the solvent was evaporated, and the crude product was purified by silica gel column, and the eluent was petroleum ether / ethyl acetate: 10 / 1, 7 / 1, 5 / 1, 3 / 1, 2 / 1 gradient elution, and then recrystallized with a mixed solution of dichloromethane and petroleum ether to obtain the target product c. Light yellow powder, m.p.65~68℃. IR(KBr,cm -1 )ν: 3039(Ar-H), 2958, 2869(C-H), 1771, 1700(C=O), 1601(Ar-C=C), 1580(C=N), 1017(C-N). 1 H NMR (600MHz, CDCl 3 )δ / ppm:7.71(td,J=7.5,1.7Hz,1H,C 23 -H),7.51(dd,J=7.3,6.0Hz,5H,C b1 -H,C c1 -H,C d1 -H,C e1 -H,C f1 -H),7.49~7.48(m,2H,C b -H,C f -H),7.47(m,1H,C 21 -H),7.31(td,J=7.5,0.9Hz,1H,C 20 -H),7.21(m,1H,C 22 -H),7.18(d,J=7.7Hz,2H,C c -H,...

technical field

[0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing N-aminoethyl terpinene maleimido imidazole derivatives. Background technique

[0002] As the active center functional group of many natural enzymes and biological systems, imidazoles play an important role in the fields of medicine and pesticides. In the field of medicine, some imidazole compounds have antibacterial, anticancer, anti-inflammatory, analgesic, antiallergic and other medicinal activities. In the field of pesticides, many compounds containing imidazole groups can be used as fungicides, enzyme inhibitors, insecticides, plant growth regulators and herbicides. Imidazole compounds have the characteristics of high efficiency, low toxicity, not easy to produce drug resistance and environmental friendliness, and have attracted the attention of many scientists. In recent years, imidazole derivatives have become a research hotspot in the ...

Examples

Embodiment 1

[0023] Preparation of compound a:

[0024]

[0025] Add 0.6g ATM, 0.4g benzil, 0.26g benzaldehyde, 1.5g NH to the there-necked flask 4 OAc, 0.032g ZnO and 5ml toluene were stirred and refluxed for 2h, the reaction was terminated when no ATM was detected by TLC and ninhydrin hydrate, the solvent was evaporated, and the crude product was purified by silica gel column, and the eluent was petroleum ether / ethyl acetate: 10 / 1, 5 / 1, 3 / 1 gradient elution, and then recrystallized from a mixed solution of dichloromethane and petroleum ether to obtain the target product a. White crystal, m.p.187~188℃. IR(KBr,cm -1 )ν: 3030(Ar-H), 2958, 2869(C-H), 1771, 1700(C=O), 1601(Ar-C=C), 1502(C=N), 1125(C-N). 1 H NMR (600MHz, CDCl 3 )δ / ppm: 7.73~7.71(m, 2H, C 19 -H,C 23 -H),7.52~7.49(m,5H,C b1 -H,C c1 -H,C d1 -H,C e1 -H,C f1 -H),7.49~7.46(m,4H,C 20 -H,C 22 -H,C b -H,C f -H),7.45(t,J=7.4Hz,1H,C 21 -H),7.19(t,J=7.5Hz,2H,C c -H,C e -H),7.13(t,J=7.3Hz,1H,C d -H),5.74(d,J=8.4Hz,1H...

Embodiment 2

[0027] Preparation of compound b:

[0028]

[0029] Add 0.6g ATM, 0.4g benzil, 0.3g p-fluorobenzaldehyde, 1.5g NH to the there-necked flask 4OAc, 0.032g ZnO and 5ml toluene were stirred and refluxed for 2h, the reaction was terminated when no ATM was detected by TLC and ninhydrin hydrate, the solvent was evaporated, and the crude product was purified by silica gel column, and the eluent was petroleum ether / ethyl acetate: 10 / 1, 5 / 1, 3 / 1 gradient elution, and then recrystallized from a mixed solution of dichloromethane and petroleum ether to obtain the target product b. Light yellow powder, m.p.212~214℃. IR(KBr,cm -1 )ν: 3030(Ar-H), 2958, 2869(C-H), 1771, 1700(C=O), 1601(Ar-C=C), 1529(C=N), 1107(C-N). 1 H NMR (600MHz, CDCl 3 )δ / ppm: 7.73(m, 2H, C 19 -H,C 23 -H),7.50(m,5H,C b1 -H,C c1 -H,C d1 -H,C e1 -H,C f1 -H),7.47~7.44(m,2H,C b -H,C f -H),7.21(m,2H,C 20 -H,C 22 -H),7.19(m,2H,C c -H,C e -H),7.13(t,J=7.3Hz,1H,C d -H),5.76(d,J=8.4Hz,1H,C 8 -H),5.67(d,J=8.4H...

Embodiment 3

[0031] Preparation of compound c:

[0032]

[0033] Add 0.6g ATM, 0.4g benzil, 0.26g o-fluorobenzaldehyde, 1.5g NH to the there-necked flask 4 OAc, 0.032g ZnO and 5ml toluene were stirred and refluxed for 2h, the reaction was terminated when no ATM was detected by TLC and ninhydrin hydrate, the solvent was evaporated, and the crude product was purified by silica gel column, and the eluent was petroleum ether / ethyl acetate: 10 / 1, 7 / 1, 5 / 1, 3 / 1, 2 / 1 gradient elution, and then recrystallized with a mixed solution of dichloromethane and petroleum ether to obtain the target product c. Light yellow powder, m.p.65~68℃. IR(KBr,cm -1 )ν: 3039(Ar-H), 2958, 2869(C-H), 1771, 1700(C=O), 1601(Ar-C=C), 1580(C=N), 1017(C-N). 1 H NMR (600MHz, CDCl 3 )δ / ppm:7.71(td,J=7.5,1.7Hz,1H,C 23 -H),7.51(dd,J=7.3,6.0Hz,5H,C b1 -H,C c1 -H,C d1 -H,C e1 -H,C f1 -H),7.49~7.48(m,2H,C b -H,C f -H),7.47(m,1H,C 21 -H),7.31(td,J=7.5,0.9Hz,1H,C 20 -H),7.21(m,1H,C 22 -H),7.18(d,J=7.7Hz,2H,C c -H,...

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