CN102382028A - Maleimide compound, its preparation and application - Google Patents
Maleimide compound, its preparation and application Download PDFInfo
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- CN102382028A CN102382028A CN2011102492011A CN201110249201A CN102382028A CN 102382028 A CN102382028 A CN 102382028A CN 2011102492011 A CN2011102492011 A CN 2011102492011A CN 201110249201 A CN201110249201 A CN 201110249201A CN 102382028 A CN102382028 A CN 102382028A
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- APDHLESCAVRSHH-UHFFFAOYSA-N CC(C(N1c2cc(Cl)cc(Cl)c2)=O)=C(C)C1=O Chemical compound CC(C(N1c2cc(Cl)cc(Cl)c2)=O)=C(C)C1=O APDHLESCAVRSHH-UHFFFAOYSA-N 0.000 description 1
- XCOLWDZEHYDCOP-UHFFFAOYSA-N CC(C(N1c2ccccc2)=O)=C(C)C1=O Chemical compound CC(C(N1c2ccccc2)=O)=C(C)C1=O XCOLWDZEHYDCOP-UHFFFAOYSA-N 0.000 description 1
- QWSRARTUANJAIV-UHFFFAOYSA-N CCCCN(C(C(C)=C1C)=O)C1=O Chemical compound CCCCN(C(C(C)=C1C)=O)C1=O QWSRARTUANJAIV-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a maleimide compound as shown in the formula (I). In the formula (I), R is C1-C16 fatty alkyl, phenyl or substituted phenyl, wherein the fatty alkyl is C1-C16 straight-chain alkyl group, C1-C16 branched-chain alkyl group or C1-C16 cycloalkyl; and the substituent of the substituted phenyl is C1-C3 alkyl group, p-chloro group, 3,5-dichloroyl, 2-methyl-3-nitroyl, benzimidazolyl, 3,4,5-trifluoroyl. The preparation method of the maleimide compound is to use 2,3-dimethyl maleic anhydride and organic amine as raw materials to perform amidation reaction and dehydration ring-closing reaction in an organic solvent under the action of a catalyst, a polymerization inhibitor and/or a dehydrant to obtain the maleimide compound as shown in the formula (I). The preparation method of the compound is simple and is convenient to operate; with the adoption of the preparation method, the effect of inhibiting Sclerotinia sclerotiorum is raised and the toxicity is low.
Description
(1) technical field
The present invention relates to a kind of preparation and application of antiseptic-germicide, particularly a kind of maleimide compounds and preparation thereof and its application in the control sclerotinia rot of colza.
(2) background technology
Sclerotinia rot of colza is the important rape disease that is caused by sclerotium germ (Sclerotmia sclerotiorum) by a kind of, and it can occur in each period of growth of rape, causes that seedling is rotted, death or poor growth.Sclerotinia rot of colza distributes very extensively in China, especially in the Yangtze valley and south often take place, more than 5000 mu of area takes place throughout the year, account for more than 50% of sown area, the rape production safety is constituted a serious threat.The medicament that is used for the sclerotinia rot of colza control at present mainly contains dimetachlone, derosal and procymidone etc.But long-time the use can make germ produce corresponding resistance with a kind of sterilant, and in recent years, and the residual close attention with food-safety problem to chemical pesticide of Along with people's invents that antibacterial agent is extremely urgent safely and efficiently.
Maleimide is claimed maleimide (Maleimide) again, is a five-membered heterocycles that contains N.The α of maleimide compounds, the unsaturated imide ring texture of β can combine with mercapto functional group, thereby influence numerous enzymes that contain sulfydryl in the body, and then influence the growth of thalline.Show after deliberation; This compounds has good inhibitory effect to mikrobes such as many bacteriums, yeast, fungies; Can effectively treat yam branches and leaves canker; Hemintho-sporum leaf spot of rice plants, hypochnus, Kidney bean stem rot, sclerotium disease and gray mold, the shot hole of apple core pear scab, oranges and tangerines, the corps diseases such as late blight of tomato, and have efficient, low toxicity, advantage such as nuisanceless.Therefore the present invention's antibacterial agent that contains the maleimide structure of preparing gained is expected to become one type of efficient, safe antiseptic-germicide of control sclerotinia rot of colza.
(3) summary of the invention
The object of the invention provides a kind of maleimide compounds and preparation thereof and uses, and such compounds process for production thereof is simple, has the control sclerotinia rot of colza and gets one type of efficient, safe antiseptic-germicide.
The technical scheme that the present invention adopts is:
Maleimide compounds shown in a kind of formula (I),
In the formula (I), R is aliphatic group, phenyl or the substituted-phenyl of C1～C16; Said aliphatic group is C1～C16 straight-chain alkyl, C1～C16 branched hydrocarbyl or C1～C16 naphthenic base; The substituting group of said substituted-phenyl is C1～C3 alkyl, to chloro, 3,5-dichloride base, 2-methyl-3-nitro, benzimidazolyl-, 3,4,5-three is fluorine-based.
Described maleimide compounds is preferably one of following compounds:
The present invention provides a kind of method for preparing described maleimide compounds; Described method is: with 2,3-dimethyl maleate acid anhydride and organic amine are raw material, in organic solvent; Under the effect of catalyzer, stopper and/or dewatering agent; Through amidate action and dehydration closed-loop reaction, after reaction finished, the reaction solution separation and purification made the maleimide compounds shown in the formula (I); Described organic solvent is acetone or toluene; Described catalyzer is that mass concentration is the triethylamine solution of the sodium acetate of 0.03～0.1g/mL; Described stopper is cuprous iodide (CuI) or Resorcinol; Described dewatering agent is a diacetyl oxide; Described organic amine adds with the form of the organic solution of organic amine after with described organic solvent dissolution.
Described in the preparation method of maleimide compounds of the present invention 2; 3-dimethyl maleate acid anhydride (dimethyl maleic anhydride) is 1: 0.23～0.56: 0.01～0.12 with the mass ratio of catalyzer, stopper, and described catalyst quality is in the triethylamine solution quality of sodium acetate; Described 2; 3-dimethyl maleate acid anhydride is 1: 0.82～0.99 with organic amine amount of substance ratio; Described dewatering agent is with 2, and 3-dimethyl maleate acid anhydride quality is counted 0.8～1.7mL/g, and said organic solvent is with 2; 3-dimethyl maleate acid anhydride quality is counted 4～16mL/g; Said consumption of organic solvent does not comprise the organic solvent that dissolves organic amine, and the amount of the organic solvent described in said organic amine adds with the organic solution form of organic amine after with said organic solvent dissolution can be dissolved organic amine and get final product not influence of the present invention.
Organic amine of the present invention is one of following: n-Butyl Amine 99, isobutylamine, normal hexyl Amine, hexahydroaniline, amino dodecane, aniline, benzylamine, phenylethylamine, p-Chlorobenzoic acid amide, para-totuidine, 3; 5-dichlorphenamide bulk powder, 2-methyl-3-nitro aniline, the amino benzoglyoxaline, 3 of 2-; 4, the 5-trifluoromethyl aniline.
Further, the preparation method of described maleimide compounds recommends to carry out according to following steps: with 2,3-dimethyl maleate acid anhydride is dissolved in the organic solvent; Slowly drip the organic solution that is dissolved with organic amine, be heated to 25～60 ℃, stir 1.5～8.5h; Add catalyzer, stopper and/or dewatering agent successively, heat up 50～101 ℃, stir 3～24h; Reaction finishes, and the reaction solution separation and purification obtains described maleimide compounds; Described catalyzer is the sodium acetate triethylamine solution of mass concentration 0.03～0.1g/mL, and described stopper is Resorcinol or cuprous iodide, and described dewatering agent is a diacetyl oxide, and said organic solvent is acetone or toluene; Described 2, the mass ratio of 3-dimethyl maleate acid anhydride and catalyzer, stopper is 1: 0.40: 0.06, and described catalyst quality is in the triethylamine solution quality of sodium acetate; Described 2; 3-dimethyl maleate acid anhydride is 1: 0.95 with organic amine amount of substance ratio, and described dewatering agent is with 2, and 3-dimethyl maleate acid anhydride quality is counted 1.2mL/g; Said organic solvent is with 2, and 3-dimethyl maleate acid anhydride quality is counted 12mL/g.
The method of reaction solution separation and purification is one of following among the preparation method of maleimide compounds of the present invention: after (1) reaction finishes; Reaction solution is cooled to room temperature, steams and removes organic solvent, n-hexane extraction; Merge organic subtracting each other and press distillation; Obtain liquid concentrator or crystal, it is dry through silica gel column chromatography/crystal that liquid concentrator or crystal are dissolved in acetone, obtains described maleimide compounds; (2) after reaction finished, reaction solution was washed to water layer neutral, and organic layer is used anhydrous sodium sulfate drying, heated absorption, decolouring with gac and silica gel respectively, filtered, and filtrate decompression concentrates, and obtains described maleimide compounds; (3) reaction finishes, and reaction solution is washed to water layer neutral with the washing of mass concentration 5% sodium hydroxide solution again; Get organic layer and use anhydrous sodium sulfate drying; Filter, filtrating concentrates, and obtains liquid concentrator or crystal; Liquid concentrator obtains described maleimide compounds through silica gel column chromatography or crystal is dry; (4) reaction finishes, and reaction solution filters with the washing of mass concentration 5% sodium hydroxide solution, and filter cake is water, toluene wash successively, filters, and drying obtains described maleimide compounds; (5) reaction finishes, the cooling of reaction solution room temperature, and reaction solution washs with mass concentration 5% sodium hydroxide solution, or with reacting liquid filtering; Filtrating is washed to water layer neutrality, organic layer anhydrous sodium sulfate drying with the washing of mass concentration 5% sodium hydroxide solution again; Filter, filtrate decompression concentrates, and obtains liquid concentrator or crystal; Liquid concentrator is used the recrystallization solvent recrystallization, and drying obtains described maleimide compounds; Described recrystallization solvent is normal hexane, ETHYLE ACETATE, sherwood oil or toluene.
The application of maleimide compounds of the present invention in the antibacterial reaction of control Sclerotinia sclerotiorum.
Further; The application of described maleimide compounds in the control Sclerotinia sclerotiorum; Described being applied as: in the PDA substratum, add maleimide compounds of the present invention; Adopt the mycelial growth rate method to measure the inhibiting rate of maleimide compounds to Sclerotinia sclerotiorum (S.sclerotiorum) mycelial growth: using diameter to get the bacterium dish as the punch tool of 6mm at the S.sclerotiorum of PDA culture medium culturing colony edge, be seeded to the culture medium flat plate centre that contains the maleimide compounds respectively, is contrast with the flat board that contains solubility promoter; In 23 ℃ constant incubator, cultivate; Wait to contrast colony growth 50mm at least, but when not covering with full ware, adopt the right-angled intersection method to measure the colony growth diameter of pastille culture medium culturing; Said compound adds the PDA substratum with the form of the mixed solution of maleimide compounds and solubility promoter and water; Be mixed with the pastille culture medium flat plate that maleimide compounds concentration is 0.01～100 μ g/mL; Said solubility promoter is a tween-80, and said solubility promoter is the tween-80 aqueous solution of mass concentration 0.2%; Said PDA substratum final concentration consists of: yam 200g/L, and glucose 20g/L, agar 20g/L, solvent are water, natural pH.
The present invention adopts the right-angled intersection method to measure the colony growth diameter.The mycelial growth inhibition rate calculation formula (unit of length: mm) as follows:
Compared with prior art, beneficial effect of the present invention is mainly reflected in: (1) 2,3-dimethyl-maleimide makes maleimide class thing through amidation, and the preparation method is simple, easy to operate; (2) maleimide class thing not only improved the inhibition effect to Sclerotinia sclerotiorum, and toxicity is lower.
(4) embodiment
Below in conjunction with specific embodiment the present invention is described further, but protection scope of the present invention is not limited in this.
Embodiment 1:N-normal-butyl-2,3-dimethyl-maleimide (I-1)
Take by weighing 2,3-dimethyl maleate acid anhydride (dimethyl maleic anhydride) 5.0g (0.04mol) adds in the there-necked flask and uses the 30mL acetone solution, measures 3.7mL (0.038mol) n-Butyl Amine 99; Use the 20mL acetone diluted; Be added drop-wise in the there-necked flask with constant pressure funnel again, stir about 8min while dripping.System is heated to 35 ℃ of stirring reaction 3.0h, is cooled to 0 ℃, adds the triethylamine solution 2.28g (0.1g NaAc and 3.0mL triethylamine) of sodium acetate successively, 0.1g CuI, and the 8.0mL diacetyl oxide stirs, and is heated to 80 ℃, stirring and refluxing reaction 6h.After reaction finished, reaction solution was cooled to room temperature (25 ℃), steamed and removed part acetone in the reaction solution, and with 50mL n-hexane extraction 3 times, merging organic phase, underpressure distillation obtains the yellow oily liquid concentrator.Liquid concentrator is separated with 200 order silica gel upper props, and moving phase is petrol ether/ethyl acetate (4: 1), collects target liquid and concentrates, and obtains golden yellow oily liquids product.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-normal-butyl-2,3-dimethyl-maleimide (I-1) 5.52g, productive rate 76.2% (with 2,3-dimethyl maleate acid anhydride quality meter, as follows).
1H?NMR(CDCl
3)：δ3.30-3.38(m，2H)，1.89(s，6H)，1.42-1.48(m，2H)，1.18-1.25(m，2H)，0.84-0.87(t，3H)ESI-MS?m/z：181.1
(I-1) structural formula:
Embodiment 2:N-isobutyl--2,3-dimethyl-maleimide (I-2)
Take by weighing in dimethyl maleic anhydride 5.0g (0.04mol) the adding there-necked flask and also use the 30mL acetone solution, measure 3.8mL (0.038mol) isobutylamine, use the 20mL acetone diluted, be added drop-wise in the there-necked flask with constant pressure funnel again, stir about 10min while dripping.System is heated to 45 ℃ of stirring reaction 4.0h, is cooled to 0 ℃, adds the triethylamine solution 2.76g (0.15g NaAc and 3.6mL triethylamine) of sodium acetate successively, 0.1g CuI, and the 8.5mL diacetyl oxide stirs, and is heated to 70 ℃, stirring and refluxing reaction 6.5h.After reaction finished, reaction solution was cooled to room temperature, boils off part acetone in the reaction solution, and with 50mL n-hexane extraction 3 times, merging organic phase, underpressure distillation obtains reddish-brown oily liquid concentrator.Liquid concentrator is separated with 200 order silica gel upper props, and moving phase is petrol ether/ethyl acetate (10: 1), collects target liquid and concentrates, and obtains safran oily product.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-isobutyl--2,3-dimethyl-maleimide (I-2) 4.95g, productive rate 68.3%.
1H?NMR(CDCl
3)：δ3.28-3.29(d，2H)，1.96(s，6H)，1.97-2.03(m，1H)，0.86-0.88(d，6H)ESI-MS?m/z：181.1
(I-2) structural formula:
Embodiment 3:N-n-hexyl-2,3-dimethyl-maleimide (I-3)
Taking by weighing dimethyl maleic anhydride 2.5g (0.02mol) adds in the there-necked flask also with about 20mL toluene dissolving; Measure 2.5mL (0.019mol) normal hexyl Amine,, be added drop-wise in the there-necked flask with constant pressure funnel with about 10mL dilution with toluene; Stir while dripping; About 15min at 40 ℃ of following stirring reaction 4.0h, obtains glassy yellow liquid.The triethylamine solution 0.81g (0.08gNaAc and 1.0mL triethylamine) that adds sodium acetate successively, the 0.08g Resorcinol, the 3.0mL diacetyl oxide stirs, and is heated to 75 ℃, constant temperature backflow 8.0h.After reaction finished, reaction solution repeatedly was neutral to water layer with washing, and toluene layer is used anhydrous Na
2SO
4Drying is adsorbed, is decoloured with gac and silica gel heating respectively then, and filtration, filtrate decompression concentrate, and obtain brown oily liquids.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-n-hexyl-2,3-dimethyl-maleimide (I-3) 3.09g, productive rate 73.9%.
1H?NMR(CDCl
3)：δ3.45-3.48(t，2H)，1.95(s，6H)，1.54-1.56(t，2H)，1.26-1.29(t，6H)，0.86-0.88(t，3H)ESI-MS?m/z：209.1
(I-3) structural formula:
Embodiment 4:N-cyclohexyl-2,3-dimethyl-maleimide (I-4)
Take by weighing in dimethyl maleic anhydride 2.5g (0.02mol) the adding there-necked flask and also use the 20mL acetone solution, measure 2.0mL (0.019mol) hexahydroaniline,, be added drop-wise in the there-necked flask with constant pressure funnel again, stir about 10min while dripping with the acetone diluted of 10mL.System is heated to 35 ℃ of stirring reaction 2.0h, obtains weak yellow liquid.The triethylamine solution 0.78g (0.05g NaAc and 1.0mL triethylamine) that adds sodium acetate successively, 0.05g CuI, the 3.0mL diacetyl oxide stirs, and is heated to 60 ℃, stirring and refluxing reaction 6.0h; Reaction is cooled to room temperature (25 ℃) after finishing, and steams and removes part acetone in the reaction solution, uses the 50mL n-hexane extraction again 3 times, merges organic phase, and underpressure distillation obtains white needle-like crystals, and drying makes title product.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-cyclohexyl-2,3-dimethyl-maleimide (I-4) 2.95g, productive rate 71.2%.
1H?NMR(CDCl
3)：δ3.84-3.89(m，1H)，1.93(s，6H)，1.26-2.08(m，10H)，ESI-MS?m/z：207.1
(I-4) structural formula:
Embodiment 5::N-n-octyl-2,3-dimethyl-maleimide (I-5)
Take by weighing in dimethyl maleic anhydride 2.5g (0.02mol) the adding there-necked flask and and dissolve, measure 3.1mL (0.019mol) NSC 9824,, be added drop-wise in the there-necked flask stirring while dripping, about 10min with about 15mL dilution with toluene with constant pressure funnel with about 20mL toluene.At 45 ℃ of following stirring reaction 6.0h, obtain weak yellow liquid.The triethylamine solution 0.81g (0.08g NaAc and 1.0mL triethylamine) that adds sodium acetate successively, the 0.08g Resorcinol, the 3.0mL diacetyl oxide stirs, and is heated to 70 ℃, constant temperature backflow 7.5h.After reaction finished, it was that 5% NaOH solution is washed once that reaction solution uses massfraction, then with washing repeatedly, is neutral until water layer; Toluene layer is used anhydrous Na
2SO
4Drying, organic phase concentrates and obtains brown oily liquid concentrator after filtering, and liquid concentrator separates with 200 order silicagel columns, and moving phase is petrol ether/ethyl acetate (10: 1), collects target appearance and concentrates, and obtains colourless transparent oil liquid, warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-n-octyl-2,3-dimethyl-maleimide (I-5) 3.53g, yield 74.4%.
1H?NMR(CDCl
3)：δ3.46-3.49(t，2H)，1.96(s，6H)，1.53-1.59(m，2H)，1.26-1.31(m，10H)，0.86-0.89(t，3H)ESI-MS?m/z：237.1
(I-5) structural formula:
Embodiment 6:N-dodecyl-2,3-dimethyl-maleimide (I-6)
Take by weighing in dimethyl maleic anhydride 2.5g (0.02mol) the adding there-necked flask and and dissolve, measure 3.3g (0.018mol) amino dodecane, dissolve, be added drop-wise in the there-necked flask, stir about 10min while dripping with constant pressure funnel with about 15mL toluene with about 20mL toluene.At 55 ℃ of following stirring reaction 6.0h, obtain weak yellow liquid.The triethylamine solution 0.81g (0.08g NaAc and 1.0mL triethylamine) that adds sodium acetate successively, the 0.08g Resorcinol, the 3.0mL diacetyl oxide stirs, and is heated to 85 ℃, and constant temperature backflow 10.0h obtains greenish orange look oily liquids.It is that 5% NaOH solution is washed once that reaction solution uses mass concentration, then with washing repeatedly, is neutral until water layer; Toluene layer is used anhydrous Na
2SO
4Drying, organic phase concentrates and obtains brown oily liquid concentrator after filtering, and liquid concentrator separates with 200 order silicagel columns, and moving phase is petrol ether/ethyl acetate (30: 1), collects target appearance and concentrates, and obtains colourless transparent oil liquid.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-n-octyl-2,3-dimethyl-maleimide (I-6) 3.76g, yield 64.1%.
1H?NMR(CDCl
3)：δ3.42(t，2H)，1.93(s，6H)，1.52(m，2H)，1.24(m，18H)，0.84(t，3H)ESI-MS?m/z：293.1
(I-6) structural formula:
Embodiment 7:N-phenyl-2,3-dimethyl-maleimide (I-7)
Take by weighing 6.5g (0.052mol) dimethyl maleic anhydride, add in the there-necked flask and also use the 30mL acetone solution, measure 4.0mL (0.044mol) aniline, be added drop-wise in the there-necked flask, stir about 8min while dripping with constant pressure funnel; At 25 ℃ of following stirring reaction 1.5h of room temperature, be cooled to 5 ℃.The triethylamine solution 1.55g (0.1g NaAc and 2mL triethylamine) that adds sodium acetate successively, 0.1g CuI, 5.7mL diacetyl oxide stir and form emulsion, are heated to 65 ℃, constant temperature backflow 3h.After reaction finished, reaction solution was cooled to room temperature, boils off part acetone, with the n-hexane extraction of 50mL 3 times, collected organic phase, and underpressure distillation obtains the white powder crystal, dry acquisition title product.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-phenyl-2,3-dimethyl-maleimide (I-7) 7.48g, yield 71.5%.
1H?NMR(CDCl
3)：δ7.46(m，2H)，7.31(m，2H)，7.10(m，1H)，2.12(s，6H)ESI-MS?m/z：201.1
(I-7) structural formula:
Embodiment 8:N-benzyl-2,3-dimethyl-maleimide (I-8)
Take by weighing in dimethyl maleic anhydride 2.5g (0.02mol) the adding there-necked flask and, measure 2.1mL (0.019mol) benzylamine,, be added drop-wise in the there-necked flask with constant pressure funnel again, stir about 10min while dripping with the dilution with toluene of 15mL with the dissolving of 20mL toluene.System is heated to 45 ℃, and stirring reaction 6.5h adds the triethylamine solution 0.81g (0.05g NaAc and 1.0mL triethylamine) of sodium acetate then successively, 0.05g CuI, and the 3.0mL diacetyl oxide stirs, and is heated to 70 ℃, back flow reaction 15.5h.After reaction finished, reaction solution was cooled to room temperature, boils off part toluene, and with the n-hexane extraction of 50mL 3 times, collection organic phase, underpressure distillation obtains golden yellow oily liquids, becomes crystal after the cooling.Crystal separates with 200 order silica gel upper props after with the 3mL acetone solution, and moving phase is chloroform/acetone (20: 1), obtains title product.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-benzyl-2,3-dimethyl-maleimide (I-8) 3.70g, yield 86.0%.
1H?NMR(CDCl
3)：δ7.28-7.37(m，5H)，4.56(s，1H)，1.96(s，6H)ESI-MSm/z：215.1
(I-8) structural formula:
Embodiment 9:N-styroyl-2,3-dimethyl-maleimide (I-9)
Take by weighing in dimethyl maleic anhydride 2.5g (0.02mol) the adding there-necked flask and and dissolve, measure 2.4mL (0.019mol) phenylethylamine,, be added drop-wise in the there-necked flask stirring while dripping, about 10min with about 15mL dilution with toluene with constant pressure funnel with about 20mL toluene.At 45 ℃ of following stirring reaction 4.0h, obtain weak yellow liquid, add the triethylamine solution 0.81g (0.08g NaAc and 1.0mL triethylamine) of sodium acetate successively, the 0.08g Resorcinol, the 3.0mL diacetyl oxide stirs, and is heated to 75 ℃, constant temperature backflow 8.0h.After reaction finished, reaction solution was cooled to room temperature, washed 3 times with the NaOH solution of mass concentration 5%, and water is washed till water layer and is neutrality again, and toluene layer is used anhydrous Na
2SO
4Dry; Filter, toluene is removed in the filtrate decompression distillation, obtains liquid concentrator, and liquid concentrator is with normal hexane recrystallization twice then, and drying obtains the white powder solid of yellowing.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-styroyl-2,3-dimethyl-maleimide (I-9) 3.32g, yield 72.4%.
1H?NMR(CDCl
3)：δ7.21-7.31(m，5H)，3.71-3.74(m，2H)，2.87-2.90(t，2H)，1.95(s，6H)ESI-MS?m/z：229.1
(I-9) structural formula:
Embodiment 10:N-rubigan-2,3-dimethyl-maleimide (I-10)
Take by weighing in dimethyl maleic anhydride 1.25g (0.01mol) the adding there-necked flask and and dissolve, take by weighing 1.2g (0.009mol) p-Chlorobenzoic acid amide, dissolve, be added drop-wise in the there-necked flask, stir about 8min while dripping with constant pressure funnel with about 15mL toluene with about 15mL toluene.At 55 ℃ of following stirring reaction 8.5h, obtain golden yellow liquid, add the triethylamine solution 0.63g (0.05g NaAc and 0.8mL triethylamine) of sodium acetate successively; 0.15g Resorcinol stirs, and is heated to 101 ℃; Constant temperature backflow 10.0h removes the water that reaction generates through water trap.After reaction finished, the cooling of reaction solution room temperature had small amount of crystal to separate out; Reaction solution is with the NaOH solution washing twice of mass concentration 5%, and water is washed till water layer and is neutral then, toluene layer with anhydrous sodium sulfate drying after; Filter, filtrate decompression concentrates, and liquid concentrator is used re-crystallizing in ethyl acetate then; Cooling obtains the crystal grain of milk yellow, oven dry.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-rubigan-2,3-dimethyl-maleimide (I-10), 1.87g, yield 80.0%.
1H?NMR(CDCl
3)：δ7.32-7.35(m，2H)，7.41-7.44(m，2H)，2.07(s，6H)ESI-MS?m/z：235.0
(I-10) structural formula:
Embodiment 11:N-p-methylphenyl-2,3-dimethyl-maleimide (I-11)
Take by weighing in dimethyl maleic anhydride 1.25g (0.01mol) the adding there-necked flask and also dissolve with 15mL toluene; Take by weighing para-totuidine 1.0g (0.009mol) with the dissolving of 15mL toluene, be added drop-wise in the there-necked flask with constant pressure funnel at ambient temperature, stir while dripping; About 8min; Temperature is adjusted to 45 ℃, and stirring reaction 7.5h obtains brown liquid.Add the triethylamine solution 0.63g (0.05g NaAc and 0.8mL triethylamine) of sodium acetate successively, the 0.15g Resorcinol stirs, and is heated to 101 ℃, and constant temperature backflow 10.0h removes the water that reaction generates through water trap.After reaction finishes, the cooling of reaction solution room temperature, reaction solution is with the NaOH solution washing twice of mass concentration 5%, and water is washed till water layer and is neutral then, and toluene layer use anhydrous sodium sulfate drying, filters, and filtrating is concentrated to obtain cyan crystal grain, dries.The products therefrom warp
1Are are H NMR, MS spectroscopic analysis proved conclusively and N-p-methylphenyl-2,3-dimethyl-maleimide (I-11) 1.78? G, yield 82.8%.
1H?NMR(CDCl
3)：δ7.21-7.27(m，4H)，7.38(s，3H)，2.06(s，6H)，ESI-MS?m/z：215.1
(I-11) structural formula:
Embodiment 12:N-(3, the 5-dichlorophenyl)-2,3-dimethyl-maleimide (I-12)
Take by weighing in dimethyl maleic anhydride 1.25g (0.01mol) the adding there-necked flask and, take by weighing 1.53g (0.009mol) 3, the 5-dichlorphenamide bulk powder with the dissolving of 15mL toluene; With about 15mL toluene dissolving; Be added drop-wise in the there-necked flask with constant pressure funnel, stir about 8min while dripping.At 60 ℃ of following stirring reaction 7.0h, obtain atropurpureus liquid, add the triethylamine solution 0.63g (0.05g NaAc and 0.8mL triethylamine) of sodium acetate successively; 0.15g Resorcinol; Stir, be heated to 101 ℃, constant temperature stirring reaction 24.0h; The water that reaction generates is removed with water trap, obtains brown liquid.Reaction solution cools off in room temperature, washes twice removal with the NaOH solution of mass concentration 5% and reacts remaining dimethyl maleic anhydride, and water is washed till water layer and is neutral then; Toluene layer is used anhydrous sodium sulfate drying, filters, and filtrating concentrates; Liquid concentrator is used the sherwood oil recrystallization, and drying obtains the grey crystal.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-(3, the 5-dichlorophenyl)-2,3-dimethyl-maleimide (I-12) 2.31g, yield 85.9%.
1H?NMR(CDCl
3)：δ7.39(d，2H)，7.33(d，2H)，2.07(s，6H)ESI-MS?m/z：269.0
(I-12) structural formula:
Embodiment 13:N-(2-methyl-3-nitro phenyl)-2,3-dimethyl-maleimide (I-13)
Taking by weighing dimethyl maleic anhydride 1.25g (0.01mol) adds in the there-necked flask also with about 15mL toluene dissolving; Take by weighing 1.44g (0.009mol) 2-methyl-3-nitro aniline,, be added drop-wise in the there-necked flask with constant pressure funnel with about 20mL toluene dissolving; Stir about 10min while dripping.At 50 ℃ of following stirring reaction 4.5h, obtain yellow-green liquid, add the triethylamine solution 0.41g (0.05g NaAc and 0.5mL triethylamine) of sodium acetate successively, the 0.05g Resorcinol, the 1.5mL diacetyl oxide stirs, and is heated to 70 ℃, constant temperature backflow 6.5h.After reaction finished, reaction solution was cooled to room temperature (25 ℃), has many solids to separate out solids removed by filtration; Filtrating is washed 2 times with the NaOH of mass concentration 5% and is removed remaining dimethyl maleic anhydride, washes to water layer neutrality again, and organic layer is used anhydrous sodium sulfate drying then; Filter; Filtrate decompression concentrates, and liquid concentrator is used re-crystallizing in ethyl acetate, and drying obtains white powdery solid.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-(2-methyl-3-nitro phenyl)-2,3-dimethyl-maleimide (I-13) 1.79g, yield 73.6%.
1H?NMR(CDCl
3)：δ7.95-7.97(d，1H)，7.42-7.46(t，1H)，7.37-7.38(t，1H)，2.31(s，3H)，2.10(s，6H)ESI-MS?m/z：243.1
(I-13) structural formula:
Embodiment 14:N-(2-benzimidazolyl-)-2,3-dimethyl-maleimide (I-14)
Take by weighing in the amino benzoglyoxaline 1.21g of 2-(0.009mol) the adding there-necked flask and dissolve with 20mL toluene; Take by weighing dimethyl maleic anhydride 1.25g (0.01mol) and use about 20mL toluene dissolving; Be added drop-wise in the there-necked flask with constant pressure funnel at ambient temperature, stir about 10min while dripping.Temperature is adjusted to 65 ℃, and stirring reaction 6.0h has a large amount of yellow powders to produce; Add the triethylamine solution 0.41g (0.05g NaAc and 0.5mL triethylamine) of sodium acetate successively, the 0.15g Resorcinol stirs; Be heated to 101 ℃, constant temperature back flow reaction 11.0h, the water of generation is removed with water trap.After reaction finished, reaction solution washed twice with the NaOH solution of mass concentration 5%, filtered, and filter cake is washed 2 times with 30mL water, toluene respectively, and oven dry obtains yellow powder shape crystal.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-(2-benzimidazolyl-)-2,3-dimethyl-maleimide (I-14) 1.88g, yield 78.0%.
1H?NMR(CDCl
3)：δ7.55-7.65(m，2H)，7.23-7.27(m，2H)，2.04(s，6H)ESI-MS?m/z：241.1
(I-14) structural formula:
Embodiment 15:N-(3,4, the 5-trifluorophenyl)-dimethyl-maleimide (I-15)
Take by weighing 3,4, dissolve with 15mL toluene in 5-trifluoromethyl aniline 1.39g (0.009mol) the adding there-necked flask; Take by weighing dimethyl maleic anhydride 1.40g (0.011mol) and use about 15mL toluene dissolving; Under room temperature (25 ℃) condition, be added drop-wise in the there-necked flask, stir about 10min while dripping with constant pressure funnel.Temperature is adjusted to 60 ℃, and stirring reaction 7.0h adds the triethylamine solution 0.63g (0.05g NaAc and 0.8mL triethylamine) of sodium acetate successively, and the 0.15g Resorcinol stirs, and is heated to 101 ℃, constant temperature back flow reaction 11.0h, and the water of generation is removed with water trap.After reaction finishes, produce saffron liquid in the system, reaction solution respectively with the NaOH solution of mass concentration 5%, wash 2 times, toluene layer is used anhydrous Na
2SO
4After the drying, filter, filtrating concentrating obtains brown particle shape crystal, 90 ℃ of oven dry.The products therefrom warp
1H NMR, MS spectroscopic analysis are proved conclusively and are N-(3,4, the 5-trifluorophenyl)-dimethyl-maleimide (I-15) 1.94g, yield 76.0%.
1H NMR (CDCl
3): δ 7.18-7.21 (m, 2H), 2.07 (s, 6H) ESI-MS m/z:255.1 (I-15) structural formula:
Embodiment 16: the mensuration of maleimide compounds bacteriostatic activity
(S.sclerotiorum) is model with Sclerotinia sclerotiorum, tested the bacteriostatic activity of maleimide compounds of the present invention.
Respectively embodiment 1～15 prepared maleimide compounds (I-1)～(I-15) is mixed with tween-80 and water; Obtain mixed solution; Mixed solution is the drug solns that contains that the maleimide compounds (I-1)～(I-15) of 0.01g and the aqueous solution of 10mL tween-80 (mass concentration 0.2% of tween-80) are mixed with 1000 μ g/mL; Get 1000 μ g/mL then and contain drug solns 5mL, be diluted to the drug solns that contains of 500 μ g/mL with the 0.2% tween-80 aqueous solution; According to aforesaid method; The drug solns 2mL that contains that gets 500 μ g/mL again is diluted to 100 μ g/mL and contains drug solns; The drug solns 5mL that contains that gets 100 μ g/mL is diluted to 50 μ g/mL and contains drug solns; The drug solns 2mL that contains that gets 50 μ g/mL is diluted to 10 μ g/mL and contains drug solns, and the drug solns 1mL that contains that gets 10 μ g/mL is diluted to 1 μ g/mL and contains drug solns, and the drug solns 1mL that contains that gets 1 μ g/mL is diluted to 0.1 μ g/mL and contains drug solns.That gets each concentration then respectively contains drug solns 1mL, adds in the PDA substratum of 9mL, is mixed with the pastille culture medium flat plate that maleimide compounds concentration is 0.01,0.1,1,5,10,50,100 μ g/mL respectively, each gradient establish 3 parallel.Adopt the mycelial growth rate method to measure the inhibiting rate of maleimide compounds: to use diameter to get the bacterium dish as the punch tool of 6mm at the pre-incubated S.sclerotiorum colony edge of PDA substratum to the S.sclerotiorum mycelial growth; Be seeded to series concentration pastille culture medium flat plate centre respectively; With the flat board that contains 0.2% tween-80 is contrast, in 23 ℃ constant incubator, cultivates 36h, waits to contrast colony growth 50mm at least; But when not covering with full ware; Adopt the right-angled intersection method to measure the colony growth diameter of pastille culture medium culturing, calculate mycelial growth inhibition rate according to formula (1), the result is as shown in table 1.
Said PDA substratum final concentration consists of: yam 200g, and glucose 20g, agar 20g adds water to 1000mL, natural pH.
The mycelial growth inhibition rate calculation formula (unit of length: mm) as follows:
Table 1 maleimide compounds is to the bacteriostatic activity of Sclerotinia sclerotiorum
Claims (8)
1. the maleimide compounds shown in the formula (I),
In the formula (I), R is aliphatic group, phenyl or the substituted-phenyl of C1～C16; Said aliphatic group is C1～C16 straight-chain alkyl, C1～C16 branched hydrocarbyl or C1～C16 naphthenic base; The substituting group of said substituted-phenyl is C1～C3 alkyl, to chloro, 3,5-dichloride base, 2-methyl-3-nitro, benzimidazolyl-, 3,4,5-three is fluorine-based.
2. maleimide compounds as claimed in claim 1 is characterized in that described compound is one of following:
3. the preparation method of a maleimide compounds as claimed in claim 1; It is characterized in that described method is: with 2,3-dimethyl maleate acid anhydride and organic amine are raw material, in organic solvent; Under the effect of catalyzer, stopper and/or dewatering agent; Through amidate action and dehydration closed-loop reaction, after reaction finished, the reaction solution separation and purification made the maleimide compounds shown in the formula (I); Described organic solvent is acetone or toluene; Described catalyzer is that mass concentration is the triethylamine solution of the sodium acetate of 0.03～0.1g/mL; Described stopper is cuprous iodide or Resorcinol; Described dewatering agent is a diacetyl oxide; Described organic amine adds with the form of the organic solution of organic amine after with described organic solvent dissolution.
4. the preparation method of maleimide compounds as claimed in claim 3; It is characterized in that described 2; The mass ratio of 3-dimethyl maleate acid anhydride and catalyzer, stopper is 1: 0.23～0.56: 0.01～0.12, and described catalyst quality is in the triethylamine solution quality of sodium acetate; Described 2; 3-dimethyl maleate acid anhydride is 1: 0.82～0.99 with organic amine amount of substance ratio, and described dewatering agent is with 2, and 3-dimethyl maleate acid anhydride quality is counted 0.8～1.7mL/g; Said organic solvent is with 2, and 3-dimethyl maleate acid anhydride quality is counted 4～16mL/g.
5. like the preparation method of claim 3 or 4 described maleimide compounds; It is characterized in that described organic amine is one of following: n-Butyl Amine 99, isobutylamine, normal hexyl Amine, hexahydroaniline, amino dodecane, aniline, benzylamine, phenylethylamine, p-Chlorobenzoic acid amide, para-totuidine, 3; 5-dichlorphenamide bulk powder, 2-methyl-3-nitro aniline, the amino benzoglyoxaline, 3 of 2-; 4, the 5-trifluoromethyl aniline.
6. the preparation method of maleimide compounds as claimed in claim 3, it is characterized in that described method carries out according to following steps: with 2,3-dimethyl maleate acid anhydride is dissolved in the organic solvent; Slowly drip the organic solution that is dissolved with organic amine; Be heated to 25～60 ℃, stir 1.5～8.5h, add catalyzer, stopper and/or dewatering agent successively; Heat up 50～101 ℃; Stir 3～24h, reaction finishes, and the reaction solution separation and purification obtains described maleimide compounds; Described catalyzer is the sodium acetate triethylamine solution of mass concentration 0.03～0.1g/mL, and described stopper is Resorcinol or cuprous iodide, and described dewatering agent is a diacetyl oxide; Said organic solvent is acetone or toluene; Described 2, the mass ratio of 3-dimethyl maleate acid anhydride and catalyzer, stopper is 1: 0.40: 0.06, and described catalyst quality is in the triethylamine solution quality of sodium acetate; Described 2; 3-dimethyl maleate acid anhydride is 1: 0.95 with organic amine amount of substance ratio, and described dewatering agent is with 2, and 3-dimethyl maleate acid anhydride quality is counted 1.2mL/g; Said organic solvent is with 2, and 3-dimethyl maleate acid anhydride quality is counted 12mL/g.
7. like the preparation method of claim 3 or 6 described maleimide compounds, the method that it is characterized in that described reaction solution separation and purification is one of following: after (1) reaction finished, reaction solution was cooled to room temperature; Steam and remove organic solvent; N-hexane extraction merges organic subtracting each other and presses distillation, obtains liquid concentrator or crystal; Liquid concentrator or crystal are dissolved in acetone through silica gel column chromatography or crystal is dry, obtain described maleimide compounds; (2) after reaction finished, reaction solution was washed to water layer neutral, and organic layer is used anhydrous sodium sulfate drying, heated absorption, decolouring with gac and silica gel respectively, filtered, and filtrate decompression concentrates, and obtains described maleimide compounds; (3) reaction finishes, and reaction solution washs with mass concentration 5% sodium hydroxide solution, washes to water layer to be neutral again; Get organic layer and use anhydrous sodium sulfate drying; Filter, filtrating concentrates, and obtains liquid concentrator or crystal; Liquid concentrator obtains described maleimide compounds through silica gel column chromatography or crystal is dry; (4) reaction finishes, and reaction solution filters with the washing of mass concentration 5% sodium hydroxide solution, and filter cake is water, toluene wash successively, filters, and drying obtains described maleimide compounds; (5) reaction finishes, the cooling of reaction solution room temperature, and reaction solution washs with mass concentration 5% sodium hydroxide solution, or with reacting liquid filtering; Filtrating is washed with mass concentration 5% sodium hydroxide solution, washes to water layer to be neutral again, and organic layer is used anhydrous sodium sulfate drying; Filter, filtrate decompression concentrates, and obtains liquid concentrator or crystal; Liquid concentrator is used the recrystallization solvent recrystallization, and drying obtains described maleimide compounds; Described recrystallization solvent is normal hexane, ETHYLE ACETATE, sherwood oil or toluene.
8. the application of maleimide compounds as claimed in claim 1 in the antibacterial reaction of control sclerotinia rot of colza.
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| CN103113279A (en) * | 2013-02-06 | 2013-05-22 | 浙江工业大学 | Maleimide type compound, as well as preparation and application thereof |
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| CN105777582A (en) * | 2016-05-05 | 2016-07-20 | 青岛辰达生物科技有限公司 | Method for preparing anticarcinogen vorinostat |
| CN109453167A (en) * | 2018-10-29 | 2019-03-12 | 浙江工业大学 | Maleimide class compound is preparing the application in Li Shiman protozoon insecticide |
| CN110105574A (en) * | 2019-05-06 | 2019-08-09 | 深圳职业技术学院 | A kind of polythiaether maleimide optical resin and preparation method thereof |
| CN113582905A (en) * | 2021-09-06 | 2021-11-02 | 福建师范大学泉港石化研究院 | Imide derivative and preparation method thereof |
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| CN103113279A (en) * | 2013-02-06 | 2013-05-22 | 浙江工业大学 | Maleimide type compound, as well as preparation and application thereof |
| CN105198785A (en) * | 2015-09-29 | 2015-12-30 | 浙江工业大学 | Maleimide compound and preparation and application thereof |
| CN105777582A (en) * | 2016-05-05 | 2016-07-20 | 青岛辰达生物科技有限公司 | Method for preparing anticarcinogen vorinostat |
| CN109453167A (en) * | 2018-10-29 | 2019-03-12 | 浙江工业大学 | Maleimide class compound is preparing the application in Li Shiman protozoon insecticide |
| CN110105574A (en) * | 2019-05-06 | 2019-08-09 | 深圳职业技术学院 | A kind of polythiaether maleimide optical resin and preparation method thereof |
| CN110105574B (en) * | 2019-05-06 | 2022-03-15 | 深圳职业技术学院 | Polythioether maleimide optical resin and preparation method thereof |
| CN113582905A (en) * | 2021-09-06 | 2021-11-02 | 福建师范大学泉港石化研究院 | Imide derivative and preparation method thereof |
| CN113582905B (en) * | 2021-09-06 | 2022-12-09 | 福建师范大学泉港石化研究院 | Imide derivative and preparation method thereof |
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