CN110283133A - A kind of synthesis technology of metsulfuron-methyl-D3 - Google Patents
A kind of synthesis technology of metsulfuron-methyl-D3 Download PDFInfo
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- CN110283133A CN110283133A CN201910469257.4A CN201910469257A CN110283133A CN 110283133 A CN110283133 A CN 110283133A CN 201910469257 A CN201910469257 A CN 201910469257A CN 110283133 A CN110283133 A CN 110283133A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
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Abstract
The present invention provides the synthesis technologies of metsulfuron-methyl-D3 a kind of, specifically comprise the following steps: step 1), and in the ethanol solution of sodium ethoxide, chemical compounds I is added, compound ii is made；The compound ii of step 1) preparation is added in the tetrahydrofuran solution of deuterated methanol sodium step 2, and back flow reaction obtains compound III；Compounds Ⅳ is suspended in dry toluene by step 3), and compound V is added dropwise, and triethylene diamine is added, the toluene solution of compound VI is made under heating condition；Under nitrogen protection, compound III prepared by step 2 is suspended in ethyl acetate for step 4), under heating condition, a dropping step 3) made from compound VI toluene solution, react and final product metsulfuron-methyl-D3 be made.The present invention has the following technical effect that the compound III of the Synthesis by the functional group using relatively inexpensive compound I, although yield is lower, avoids cumbersome multistep synthesis and largely uses expensive deuterated methanol.
Description
Technical field
The invention belongs to technical field of organic synthesis, in particular to a kind of synthesis technology of metsulfuron-methyl-D3.
Background technique
Metsulfuron-methyl is a kind of efficient sulfonylurea herbicide of Uptake and translocation selectivity wheatland, by DuPont Corporation in 1980
Another efficient kind that year develops after chlorsulfuron, activity are higher than 3 times of chlorsulfuron.The mechanism of action and chlorine sulphur of metsulfuron-methyl
Grand approximation is absorbed by the root, stem and leaf of plant, in vivo conduction rapidly, is inhibited acetolactate synthestase (ALS) activity, is led to figured silk fabrics
Propylhomoserin is obstructed with isoleucine biosynthesis, to cause to grow suppressed and dead.After resistance crop wheat absorbs, in vivo
Phenyl ring hydroxylation is carried out, this hydroxylation product forms conjugates with glucose rapidly, thus loss of activity.
Metsulfuron-methyl is the highest kind of activity in existing sulfonylurea herbicide.Suitable for all kinds of soil, soil before seedling is carried out
Cauline leaf is spraying after processing or seedling, main to prevent and treat the most of broadleaf weeds of wheatland, and effect is also significantly inhibited to gramineae weed.It is dry
Shallowly mixing soil when carrying out soil treatment under the conditions of drought, after spray can be improved the effect of prevention and treatment gramineae weed.
The structural formula of metsulfuron-methyl-D3 (Metsulfuron-methylD3) is as follows:
Metsulfuron-methyl-D3 can be used for the research of metsulfuron-methyl mechanism of action.The synthesis of metsulfuron-methyl-D3 is had not been reported at present.
Metsulfuron-methyl regular course is usually by intermediate: 2- amino -4- methyl -6- methoxyl group -1,3,5- triazine and centre
Body neighbour's methyl formate benzenesulfonyl isocyanate is synthetically prepared to obtain metsulfuron-methyl, and intermediate neighbour's methyl formate benzenesulfonyl isocyanate
Not easy to maintain, preparation method is: o-methyl formate benzene sulfonamide and triphosgene (phosgene) or oxalyl chloride are synthetically prepared to obtain；
Metsulfuron-methyl regular course is as follows:
If carrying out the metsulfuron-methyl-D3 of synthetic isotope label according to the synthetic method of existing metsulfuron-methyl, need to prepare same position
The compound 2- amino -4- methyl -6- methoxyl group-D3-1 of element label, 3,5- triazines, preparing for the non-marked object of this compound are normal
There are two types of methods:
Method one: it is synthetically prepared using acetonitrile, methanol and dicyandiamide；
Method two: the chloro- 6- methyl-1 of 2,4- bis- is used, 3,5- triazine, ammonia and two step of sodium methoxide are prepared.
If using above two method, the 2- amino -4- methyl -6- methoxyl group-D3-1 of synthetic isotope label, 3,5-
Triazine can have the following technical problems:
Method one: preparing intermediate 2-amino -4- methyl -6- methoxyl group -1,3,5-triazines and need a large amount of deuterated compounds,
Such as deuterated methanol, synthesis cost is high, and is not easy to prepare in a small amount；
Method two: raw material is not easy to obtain, and reaction process needs to have higher requirements to equipment, operation using ammonia.
Summary of the invention
For overcome the deficiencies in the prior art, the present invention provides the synthesis technologies of metsulfuron-methyl-D3 a kind of.
The present invention is innovatively passed through using the 2- amino -4- methyl -6- methoxyl group -1,3,5- triazine that can directly buy
Ethyoxyl replaces methoxyl group, then the method for replacing ethyoxyl with deuterated methoxyl group, this method is easy to operate, does not need a large amount of deuterated
Object is closed, raw material is easy to get, advantage of lower cost.
Technical scheme is as follows:
A kind of synthesis technology of metsulfuron-methyl-D3, synthetic route are as follows:
Specifically comprise the following steps:
Chemical compounds I is added in the ethanol solution of sodium ethoxide in step 1), and compound ii is made；
Step 2) compound ii of step 1) preparation is added in the tetrahydrofuran solution of deuterated methanol sodium, back flow reaction,
Obtain compound III；
Compounds Ⅳ is suspended in dry toluene by step 3), and compound V is added dropwise, and triethylene diamine, fire-bar is added
The toluene solution of compound VI is made under part；
Under nitrogen protection, compound III prepared by step 2) is suspended in ethyl acetate for step 4), under heating condition,
A dropping step 3) made from compound VI toluene solution, react be made final product metsulfuron-methyl-D3.
Preferably,
In the step 1), the molar ratio of sodium ethoxide and chemical compounds I are as follows: 10.5:1.
In the step 2), the molar ratio of deuterated methanol sodium and compound ii are as follows: 37.8:1.
In the step 3), the molar ratio of compounds Ⅳ, compound V and triethylene diamine is 11.6:36:1.
In the step 4), compound III and VI molar ratio of compound are as follows: 1:7.1.
Preferably,
In the step 1), the reaction condition for synthesizing compound ii is as follows: being stirred overnight at room temperature.
In the step 2), the reaction condition for synthesizing compound III is as follows: back flow reaction 5h.
In the step 3), the reaction condition for synthesizing compound VI is as follows: 65 DEG C of reaction 6h, then is warming up to 110 DEG C instead
Answer 12h.
In the step 4), the reaction condition for synthesizing metsulfuron-methyl-D3 is as follows: reacting at 55 DEG C to reaction system dissolved clarification.
In the step 2), the anhydrous tetrahydrofuran solution of deuterated methanol sodium, the preparation method is as follows: deuterated methanol is added
Enter in anhydrous THF, metallic sodium be added, heat 50 DEG C, under nitrogen protection, after reacting 2h, stop heating, anhydrous THF dilution is added,
Sodium block is removed, the anhydrous tetrahydrofuran solution of deuterated methanol sodium is obtained.
The present invention has the following technical effect that the Synthesis by the functional group using relatively inexpensive compound I
Compound III avoids cumbersome multistep synthesis and largely uses expensive deuterated methanol although yield is lower.From
Embodiment 1 is as can be seen that using method synthesis 70mg metsulfuron-methyl-D3 of the invention, it is only necessary to 2 milliliters of deuterated methanols, if pressed
More solito synthesizes metsulfuron-methyl-D3 as much, needs ten times or more deuterated methanols, and there are starting material separation is tired
Difficult problem, present invention saves 90% or more costs.And means of purification of the present invention is relatively easy, it is easy to can isolate and purify out
Metsulfuron-methyl-D3.
Detailed description of the invention
Fig. 1 is the HNMR map of metsulfuron-methyl-D3.
Fig. 2 is the mass-spectrogram of metsulfuron-methyl-D3.
Specific embodiment
The present invention will be described in detail combined with specific embodiments below.
The synthesis technology of 1 metsulfuron-methyl-D3 of embodiment
Step 1:
5.0g sodium ethoxide (73.4mmol) is added in 15 milliliters of dehydrated alcohols, dissolved clarification is stirred, 976mg is added to enter chemical compounds I
(7.0mmol), is stirred overnight at room temperature, and chromatographs through column, obtains 920mg faint yellow solid, and ESI-MS:155 [M+1] is compound
II, yield 85.7%.
Step 2:
It prepares the tetrahydrofuran solution of deuterated methanol sodium: 2 milliliters of deuterated methanols is added in 20 milliliters of anhydrous THF, be added
2g metallic sodium heats 50 DEG C, under nitrogen protection, and reaction overnight, after reacting 2h, stops heating, it is dilute that 20 milliliters of anhydrous THF are added
It releases, removes sodium block, it is spare.The tetrahydrofuran solution of deuterated methanol sodium is obtained, wherein containing 49.2mmol deuterated methanol sodium.
200mg compound ii (1.3mmol) is taken to be added in above-mentioned solution, back flow reaction 5h, TLC detection, most of raw material
It is cooling after disappearance.Concentration rear pillar chromatographs to obtain 60mg compound III, yield 32.3%.
Step 3:
Under nitrogen protection, 2g compounds Ⅳ (9.3mmol) is suspended in 10 milliliters of dry toluenes, at room temperature, is added dropwise
2.44 milliliters of compounds V (28.8mmol), stirring after ten minutes, are added at one time 88mg DABCO (triethylene diamine)
(0.8mmol), then 65 DEG C of reaction 6h, then 110 DEG C of reaction 12h are warming up to, it is cooled to room temperature, filters, remove solid, no water beetle
Benzene washing, collects filtrate, yellow oil 1.8g is obtained after concentration, is dissolved in 5 milliliters of dry toluenes, obtains the first of compound VI
Benzole soln, for use.
Step 4:
Under nitrogen protection, 60mg compound III (0.42mmol) is suspended in 15 milliliters of ethyl acetate, at 55 DEG C of outer temperature, drop
Add 2 milliliters of the toluene solution (containing compound VI3.0mmmol) of above compound VI, reaction system dissolved clarification has been reacted to raw material
Afterwards, cooling, add 10 milliliters of water, 1N hydrochloric acid solution washs 2 times, and organic phase is dry with anhydrous sodium sulfate, and concentration rear pillar chromatographs to obtain
Final product 70mg, yield 43.8%.ESI-MS:385 [M+1].
Fig. 1 is the HNMR map of metsulfuron-methyl-D3.
Fig. 2 is the mass-spectrogram of metsulfuron-methyl-D3.
From Fig. 1 and Fig. 2, it can be seen that obtained product is metsulfuron-methyl-D3.98% or more purity.
It should be noted that above-described embodiment is only presently preferred embodiments of the present invention, there is no for the purpose of limiting the invention
Protection scope, the equivalent substitution or substitution made on the basis of the above all belong to the scope of protection of the present invention.
Claims (10)
1. a kind of synthesis technology of metsulfuron-methyl-D3, which is characterized in that synthetic route is as follows:
Specifically comprise the following steps:
Chemical compounds I is added in the ethanol solution of sodium ethoxide in step 1), and compound ii is made；
The compound ii of step 1) preparation is added in the tetrahydrofuran solution of deuterated methanol sodium step 2), and back flow reaction obtains
Compound III；
Compounds Ⅳ is suspended in dry toluene by step 3), dropwise addition compound V, addition triethylene diamine, under heating condition
The toluene solution of compound VI is made；
Under nitrogen protection, compound III prepared by step 2) is suspended in ethyl acetate for step 4), under heating condition, is added dropwise
The toluene solution of compound VI made from step 3) reacts and final product metsulfuron-methyl-D3 is made.
2. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 1), sodium ethoxide
With the molar ratio of chemical compounds I are as follows: 10.5:1.
3. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 2), deuterated first
The molar ratio of sodium alkoxide and compound ii are as follows: 37.8:1.
4. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 3), compound
IV, compound V and triethylene diamine molar ratio are 11.6:36:1.
5. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 4), compound
III with VI molar ratio of compound are as follows: 1:7.1.
6. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 1), synthesisization
The reaction condition for closing object II is as follows: being stirred overnight at room temperature.
7. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 2), synthesisization
The reaction condition for closing object III is as follows: back flow reaction 5h.
8. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 3), synthesisization
The reaction condition for closing object VI is as follows: 65 DEG C of reaction 6h, then is warming up to 110 DEG C of reaction 12h.
9. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that in the step 4), synthesize first
The reaction condition of the grand-D3 of sulphur is as follows: reacting at 55 DEG C to reaction system dissolved clarification.
10. the synthesis technology of metsulfuron-methyl-D3 according to claim 1, which is characterized in that deuterated in the step 2)
Metallic sodium, heating is added the preparation method is as follows: deuterated methanol is added in anhydrous THF in the anhydrous tetrahydrofuran solution of sodium methoxide
50 DEG C, under nitrogen protection, after reacting 2h, stop heating, anhydrous THF dilution is added, removes sodium block, obtains deuterated methanol sodium
Anhydrous tetrahydrofuran solution.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0030138A1 (en) * | 1979-11-30 | 1981-06-10 | E.I. Du Pont De Nemours And Company | Herbicidal sulfonamides, and compositions, preparation and use thereof |
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2019
- 2019-05-31 CN CN201910469257.4A patent/CN110283133B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0030138A1 (en) * | 1979-11-30 | 1981-06-10 | E.I. Du Pont De Nemours And Company | Herbicidal sulfonamides, and compositions, preparation and use thereof |
Non-Patent Citations (2)
| Title |
|---|
| QINGFU YE 等: "Causes of phytotoxicity of metsulfuron-methyl bound residues in soil", 《ENVIRONMENTAL POLLUTION》 * |
| 王娜 等: "三氟甲基嘧啶磺酰脲的合成与除草活性", 《合成化学》 * |
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