CN102617560A - Preparation method of furilazole - Google Patents
Preparation method of furilazole Download PDFInfo
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- CN102617560A CN102617560A CN2011100328756A CN201110032875A CN102617560A CN 102617560 A CN102617560 A CN 102617560A CN 2011100328756 A CN2011100328756 A CN 2011100328756A CN 201110032875 A CN201110032875 A CN 201110032875A CN 102617560 A CN102617560 A CN 102617560A
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Abstract
The invention discloses a preparation method of furilazole, which comprises the following steps: 1, carrying out a nucleophilic addition reaction on furfural and trimethylsilyl cyanide; 2, reducing a-(2-furan)-a-trimethylsiloxy acetonitrile; 3, carrying out an addition elimination reaction on a-aminomethyl-2-furancarbinol and acetone; and 4, amidating 5-(2-furan)-2,2-dimethyloxazolidine. The preparation method has the advantages of simple process operation, and pureness and high yield of the target product, and provides another approach for the synthesis of like herbicide safeners.
Description
Technical field
The invention belongs to the synthetic field of organic synthesis and agricultural chemicals, particularly a kind of preparation method of novel dichloroacetyl oxazolidine herbicide-safener.
Background technology
The dichloroacetyl oxazolidine compound is a kind of novel herbicide-safener.Abroad just begun one's study to reach synthesizing of herbicide-safener and used, and developed many different kinds (for example: AD-67, R-28725, R-29148 etc.) in succession from the seventies.Synthetic and the bioactivity research of the relevant herbicide-safener of China is started late; Wherein studying more is the herbicide-safener of dichloro acetamide class formation; This type of safener can protect crops such as corn, Chinese sorghum and paddy rice to avoid the injury of chloro acetanilide class (like acetochlor) and dithiocarbamate herbicide (like EPTC) preferably; Especially sulfonylurea and imidazolinone herbicide there are detoxifying effect preferably, can reduce the caused injury of weedicide.Comparatively comprehensively study about them, the substituting group difference that is particularly connected on the Zai oxazole ring to the active influence of safener still among exploring.
Safener and weedicide are mixed and form new mixed agent will be the developing direction of safener; And the research of the development of safener and use technology will help the exploitation of novel herbicide and the safe handling of weedicide; Minimizing because of the use of weedicide to the loss that agriculture prodn caused, be beneficial to the sustainable development of agriculture prodn.
China does not also have the patent about the furilazole compound method at present, a preparation method (CN200410012505.6) relevant for oxazolidine, but the reaction conditions requirement is high, and method is complicated, and yield is low.
Summary of the invention
The object of the present invention is to provide a kind of simple to operate, productive rate is high, can industrialized furilazole preparation method.
The technical solution that realizes the object of the invention is: a kind of preparation method of furilazole, and step is following:
The first step: the nucleophilic addition of furtural and trimethyl silicane nitrile: furtural is added drop-wise in the flask that (CH3) 3SiCN and lewis acid catalyst are housed, obtains solution A;
Second step: the reduction reaction of а-(2-furans)-а-trimethylammonium silica acetonitrile: solution A is added drop-wise in the non-protonic solvent that lithium aluminum hydride is housed; Back flow reaction; Question response liquid adds NaOH solution and at room temperature continues reaction after being cooled to room temperature; Filter, filtrating obtains solid B through drying, after revolving steaming;
In the 3rd step, reaction is eliminated in the addition of а-aminomethyl-2-furfuralcohol and acetone: acetone is joined in the benzole soln of solid B and tosic acid, back flow reaction obtains solution C;
The 4th step: 5-(2-furans)-2; The amidate action of 2-Er Jia Ji oxazolidine: in solution C, add NaOH and dichloroacetyl chloride; At stirring reaction below 0 ℃, reaction adds water after finishing, and separatory is got organic phase; Organic phase obtains solid D through saturated common salt water washing, anhydrous magnesium sulfate drying, after revolving steaming, is further purified and obtains target compound.
The present invention compared with prior art, its remarkable advantage: the 3rd step is synthetic to be back flow reaction Xing Cheng oxazolidine, and the too high meeting of temperature causes open loop; Make solvent with toluene in the prior art; Its boiling point is higher, and the formation of the too high Bu Li of reflux temperature Yu oxazolidine is used benzene to make solvent and obviously improved productive rate; It is more that synthetic middle background technology of the 4th step is done the acid binding agent side reaction with triethylamine, and purifying products is complicated, does its side reaction of acid binding agent with the sodium hydroxide mineral alkali and obviously reduces; Adopted the method purified product of post in the document, and be unfavorable for realizing industriallization, the employing ethyl alcohol recrystallization is simple to operate, productive rate is high.
Description of drawings
Fig. 1 is the nuclear-magnetism phenogram of the midbody-а-aminomethyl-2-furfuralcohol among the present invention, wherein, and (a)
1HNMR characterization result figure, (b)
13CNMR characterization result figure.
Fig. 2 is the makings phenogram of the midbody-а-aminomethyl-2-furfuralcohol among the present invention.
Fig. 3 is the nuclear-magnetism phenogram of the title product-furilazole among the present invention, wherein, and (c)
1HNMR characterization result figure, (d)
13CNMR characterization result figure.
Fig. 4 is the mass spectral characteristi figure of the title product-furilazole among the present invention.
Fig. 5 is the synthesis process flow diagram of the midbody-а-aminomethyl-2-furfuralcohol among the present invention.
Fig. 6 is the synthesis process flow diagram of the title product-furilazole among the present invention.
Embodiment
Below in conjunction with accompanying drawing the present invention is described in further detail.
The preparation method of furilazole of the present invention, its step is following:
The first step: with ZnI
2, CuI
2, in the KI lewis acid catalyst any one be catalyzer; Add furtural and trimethyl silicane nitrile; Wherein, the mol ratio of furtural and trimethyl silicane nitrile is 1:1.0 ~ 1.5, and temperature of reaction is 5 ~ 20 ℃; Reaction times is 1.0 ~ 4.0h, and reaction makes а-(2-furans)-а-trimethylammonium silica acetonitrile.
Second step: with a kind of in ether, the THF is solvent, and with lithium aluminium hydride reduction а-(2-furans)-а-trimethylammonium silica acetonitrile, reflux conditions reacts 1.0 ~ 3.0h down, obtains а-aminomethyl-2-furfuralcohol with acetonitrile, methyl alcohol equal solvent recrystallization.
The 3rd the step: with any one solvent in benzene, ETHYLE ACETATE, chloroform, the toluene as entrainment agent; Add а-aminomethyl-2-furfuralcohol, toluenesulphonic acids, acetone; Wherein, the mol ratio of а-aminomethyl-2-furfuralcohol and acetone is 1:1 ~ 5, and 1 ~ 4h refluxes; Reaction makes 5-(2-furans)-2,2-Er Jia Ji oxazolidine.
The 4th step: with a kind of in sodium hydroxide, the triethylamine is acid binding agent, adds 5-(2-furans)-2,2-Er Jia Ji oxazolidine and dichloroacetyl chloride; Wherein, 5-(2-furans)-2, the mol ratio of 2-Er Jia Ji oxazolidine and dichloroacetyl chloride is 1:1.0 ~ 1.3, temperature of reaction is at-10 ~ 5 ℃; Reaction times is 8 ~ 14h, obtains target compound-furilazole with ethanol, benzene, acetonitrile equal solvent recrystallization.
The first step: in the four-hole boiling flask of 100ml, add 0.10mol (CH
3)
3SiCN and 30mgZnI
2The slow furtural that drips, both mol ratios are 1:1.0, after dropping finishes, continue reaction 1h under 5 ~ 10 ℃; Reaction finish the back with diatomite filtration to remove ZnI
2Solid, products obtained therefrom are the yellow oily liquid A.
Second step: in the four-hole boiling flask of 250ml, add the 100ml anhydrous diethyl ether, treat that temperature reduces to 0 ℃ and add 2.09 gLiAlH again
4, slowly dripping the 0.1mol liquid A, dropping is under refluxad reacted 1 h after finishing; Reaction finishes the back and is cooled to 5 ℃ with the cryosel bath, slowly drips the aqueous solution of 3ml frozen water and 3ml33%NaOH again, and dropping is reacted 2h after finishing again at ambient temperature; Suction filtration; Filter cake washs with ether, and merging filtrate is used anhydrous MgSO
4Revolve after the drying to steam and obtain yellow solid, filter cake and revolving steams the yellow solid that obtains with 100ml THF heating for dissolving and suction filtration, and filter cake washs with a small amount of THF again, and merging filtrate is used anhydrous MgSO
4Revolve after the drying steam yellow solid, get light yellow crystal B with recrystallizing methanol.
The 3rd step: in the 100ml four-hole boiling flask, add 0.01mol crystal B, 40mg tosic acid and 30.0mL benzene, reacting by heating adds acetone after temperature rises to 50 ℃, and the mol ratio of crystal B and acetone is 1:1.0, and at 50-54 ℃ of following stirring reaction 2h; Back flow reaction 1h obtains flaxen liquid C again.
The 4th step: in the 100ml four-hole boiling flask, add 0.01mol liquid C, be cooled to below 0 ℃, add 0.01molNaOH as acid binding agent; After stirring 30min, slowly drip dichloroacetyl chloride, both mol ratios are 1:1.0, after dropping finishes, at stirring reaction 8h below-10 ~-5 ℃; Reaction finishes the back and adds 50ml water; Pour reaction system into separating funnel, organic layer is used saturated common salt water washing, anhydrous magnesium sulfate drying; Revolve and steam solvent and obtain yellow solid, ethyl alcohol recrystallization obtains white needle-like crystals-furilazole.
The structural characterization of а-aminomethyl-2-furfuralcohol:
m.p.?82.9~84.3℃
Ultimate analysis: C
6H
9NO
2
% calculated value measured value
C 56.69 55.85
H 7.09 7.13
N 11.02 10.55
Nuclear magnetic spectrogram is as shown in Figure 1: wherein
1H-NMR (500 MHz, CDC13) ppm: δ=2.268,2.432 (dd, 3H, NH2, OH); δ=2.997,3.008 (d, 2H, CH2); δ=4.618,4.630,4.641 (s, lH, CH); δ=6.253,6.256,6.333,7.368 (m., 3H, furan-H); δ=7.280 (solvent peak).
13C-NMR (500 MHz, CDC13) ppm: δ=45.97 (s, 1C ,-CH2); δ=68.16 (s, 1C ,-CH); δ=106.30,110.18,142.00,155.44 (s, 4C, furan-C); δ=76.80,77.06,77.31 (dd, solvent peaks).
The makings spectrogram is as shown in Figure 2: wherein
M+=126.89
The structural characterization of furilazole:
m.p.?93.5~96.2℃
Ultimate analysis: C11H13NO3Cl
% calculated value measured value
C 47.48 46.90
H 4.68 4.74
N 5.03 4.74
Nuclear magnetic spectrogram is as shown in Figure 3: wherein
1H-NMR (500 MHz, CDC1
3) ppm: δ=1.677,1.732 (s, 6H, CH
3); δ=3.992,4.011,4.029,4.169,4.184,4.196 (m, 2H, CH
2); δ=5.209,5.224,5.237 (t, lH, CH); δ=6.084 (s, 1H, NH); δ=6.413,6.502,7.481 (s, 3H, furan-H); δ=7.278 (solvent peak).
13C-NMR (500 MHz, CDC1
3) ppm: δ=23.47,25.28 (s, 1C ,-CH
3); δ=66.95,69.93 (s, 2C ,-CH); δ=96.87 (s, 1C ,-C); δ=109.93,110.60,143.60,148.99 (s, 4C, furan-C); δ=159.63 (s, 1C ,-CO); δ=76.78,77.04,77.29 (solvent peaks).
Mass spectrum such as Fig. 4: wherein
High resolution mass spectrum: M+Na=299.95, M+K=318.01
Reactions step and embodiment 1 are identical, difference: select CuI for the first step
2Be lewis acid catalyst, the mol ratio of reactant is 1:1.3,10 ~ 15 ℃ of temperature of reaction, and the reaction times is 2.5h; It is reaction solvent that second step was selected THF, and the reaction times is 2h, adopts the acetonitrile recrystallization; The 3rd step used ETHYLE ACETATE to be entrainment agent, and the mol ratio of reactant is 1:1.3, and reflux time is 2.5h; Selecting triethylamine in the 4th step is acid binding agent, and the mol ratio of reactant is 1:1.2; Temperature of reaction is-5 ~ 0 ℃, and the reaction times is 10h, and employing benzene is recrystallization solvent.
The confirmation method of the compound of this embodiment is identical with embodiment 1.
Reactions step and embodiment 1 are identical, difference: selecting KI for the first step is lewis acid catalyst, and the mol ratio of reactant is 1:1.5,15 ~ 20 ℃ of temperature of reaction, and the reaction times is 4h; Second reaction times in step was 3h; Use chloroform to be entrainment agent in the 3rd step, the mol ratio of reactant is 1:1.5, and reflux time is 4h; The mol ratio of reactant is 1:1.3 in the 4th step; Temperature of reaction is 0 ~ 5 ℃, and the reaction times is 14h, and the employing acetonitrile is a recrystallization solvent.
The confirmation method of the compound of this embodiment is identical with embodiment 1.
Reactions step and embodiment 1 are identical, difference: for adopting toluene in the 3rd step is entrainment agent.
The confirmation method of the compound of this embodiment is identical with embodiment 1.
Claims (9)
1. the preparation method of a furilazole is characterized in that step is following:
The first step: the nucleophilic addition of furtural and trimethyl silicane nitrile: furtural is added drop-wise in the flask that (CH3) 3SiCN and lewis acid catalyst are housed, obtains solution A;
Second step: the reduction reaction of а-(2-furans)-а-trimethylammonium silica acetonitrile: solution A is added drop-wise in the non-protonic solvent that lithium aluminum hydride is housed; Back flow reaction; Question response liquid adds NaOH solution and at room temperature continues reaction after being cooled to room temperature; Filter, filtrating obtains solid B through drying, after revolving steaming;
In the 3rd step, reaction is eliminated in the addition of а-aminomethyl-2-furfuralcohol and acetone: acetone is joined in the benzole soln of solid B and tosic acid, back flow reaction obtains solution C;
The 4th step: 5-(2-furans)-2; The amidate action of 2-Er Jia Ji oxazolidine: in solution C, add NaOH and dichloroacetyl chloride; At stirring reaction below 0 ℃, reaction adds water after finishing, and separatory is got organic phase; Organic phase obtains solid D through saturated common salt water washing, anhydrous magnesium sulfate drying, after revolving steaming, is further purified and obtains target compound.
2. the preparation method of furilazole according to claim 1, it is characterized in that: lewis acid catalyst is ZnI
2, CuI
2Or KI, the reaction times is 3 ~ 4 hours.
3. the preparation method of furilazole according to claim 1, it is characterized in that: the mol ratio of said furtural and trimethyl silicane nitrile is 1:1.0 ~ 1:1.5, and temperature of reaction is at 5 ~ 20 ℃, and the reaction times is 1.0 ~ 4.0h.
4. the preparation method of furilazole according to claim 1; It is characterized in that: the non-protonic solvent in the said step 2 is ether or THF; Reflux time is 2.5 hours, and the concentration of the NaOH solution of adding is 10%, and the time of at room temperature continuing reaction is 2 hours.
5. the preparation method of furilazole according to claim 1; It is characterized in that: in the said step 3; Acetone joins under 50 ℃ in the benzole soln of solid B and tosic acid, and the following reaction times of reflux conditions is 1.0 ~ 3.0h, with acetonitrile, recrystallizing methanol.
6. the preparation method of furilazole according to claim 1, it is characterized in that: in the said step 4, the stirring reaction time is 12h.
7. the preparation method of furilazole according to claim 1 is characterized in that: ammonia alcohol is Chenged oxazolidine with acetone Huanization, tosic acid is an acid catalyst.
8. the preparation method of furilazole according to claim 1 is characterized in that: ammonia alcohol is 1:1 ~ 1:5 with the mol ratio of Compound C, and benzene, ETHYLE ACETATE, chloroform, toluene are entrainment agent, the about 1 ~ 4h of reflux time.
9. the preparation method of furilazole according to claim 1; It is characterized in that: sodium hydroxide is acid binding agent, and ammonia alcohol is 1:1.0 ~ 1:1.5 with the mol ratio of sodium hydroxide, and temperature of reaction is at-10 ~ 5 ℃; Reaction times is 8 ~ 14h, with ethanol, benzene, acetonitrile recrystallization.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110041294A (en) * | 2019-05-13 | 2019-07-23 | 河北科技大学 | The synthetic method and its application of the chloro- N- of 2,2- bis- [2- (2- furyl) -2- hydroxyethyl] acetamide |
| CN114989115A (en) * | 2022-07-01 | 2022-09-02 | 河北科技大学 | Improved synthesis of alpha- (nitromethyl) -2-furancarbinols and method for maintaining catalyst activity in such a process |
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| CN1031375A (en) * | 1987-08-13 | 1989-03-01 | 孟山都公司 | The oxazolidine dihaloacetamides class of 5-heterocyclic substituted |
| US5428172A (en) * | 1993-09-21 | 1995-06-27 | Monsanto Company | Preparation of 3-dihaloacetyl oxazolidines |
| CN1229405A (en) * | 1996-09-06 | 1999-09-22 | 日本化药株式会社 | Novel acetamide derivatives and protease inhibitors |
| CN1603315A (en) * | 2004-09-02 | 2005-04-06 | 季宝 | Method for preparing oxazolidine |
| CN101274958A (en) * | 2008-05-17 | 2008-10-01 | 中国海洋大学 | Bioactive peptide, preparation thereof and application thereof |
-
2011
- 2011-01-30 CN CN2011100328756A patent/CN102617560A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1031375A (en) * | 1987-08-13 | 1989-03-01 | 孟山都公司 | The oxazolidine dihaloacetamides class of 5-heterocyclic substituted |
| US5428172A (en) * | 1993-09-21 | 1995-06-27 | Monsanto Company | Preparation of 3-dihaloacetyl oxazolidines |
| CN1229405A (en) * | 1996-09-06 | 1999-09-22 | 日本化药株式会社 | Novel acetamide derivatives and protease inhibitors |
| CN1603315A (en) * | 2004-09-02 | 2005-04-06 | 季宝 | Method for preparing oxazolidine |
| CN101274958A (en) * | 2008-05-17 | 2008-10-01 | 中国海洋大学 | Bioactive peptide, preparation thereof and application thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110041294A (en) * | 2019-05-13 | 2019-07-23 | 河北科技大学 | The synthetic method and its application of the chloro- N- of 2,2- bis- [2- (2- furyl) -2- hydroxyethyl] acetamide |
| CN114989115A (en) * | 2022-07-01 | 2022-09-02 | 河北科技大学 | Improved synthesis of alpha- (nitromethyl) -2-furancarbinols and method for maintaining catalyst activity in such a process |
| CN114989115B (en) * | 2022-07-01 | 2024-04-30 | 兰升生物科技集团股份有限公司 | Improved synthesis of alpha- (nitromethyl) -2-furanmethanol and method for maintaining catalyst activity in the process |
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Application publication date: 20120801 |