CN105085255B - A kind of synthesis technique of the oxo succinate of 2 alkoxy of imidazolinone herbicide intermediate 3 - Google Patents
A kind of synthesis technique of the oxo succinate of 2 alkoxy of imidazolinone herbicide intermediate 3 Download PDFInfo
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- CN105085255B CN105085255B CN201510492032.2A CN201510492032A CN105085255B CN 105085255 B CN105085255 B CN 105085255B CN 201510492032 A CN201510492032 A CN 201510492032A CN 105085255 B CN105085255 B CN 105085255B
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- succinate
- alkoxy
- oxos
- added dropwise
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C67/32—Decarboxylation
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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Abstract
The invention discloses a kind of synthesis technique of the oxo succinate of 2 alkoxy of imidazolinone herbicide intermediate 3, belong to Technology of Fine Chemical Industry technical field.The technique is with alkoxy acetic acid ester, and oxalate diester is raw material, and in the presence of alkali, the oxo succinate of 2 alkoxy 3 is made through condensation reaction, compared with prior art, simple to operate, and yield improves notable.Sodium alkoxide alcoholic solution is replaced with solid sodium ethanol simultaneously, reduces solvent species and solution usage, reduces three wastes yield, is a kind of efficient, economic, environmentally friendly oxo succinate preparation method of 2 alkoxy 3.
Description
Technical field
The present invention relates to technical field of fine, and in particular to a kind of imidazolinone herbicide intermediate 2- alcoxyls
The synthesis technique of base -3- oxos-succinate.
Background technology
Imidazolinone herbicide is a kind of highy potent herbicide of American Cyanamid Company's research and development the 1980s, and its mu is used
Measure as 2.3~16.7g active ingredients, be mainly used in the dry crops such as soybean, peanut, vegetables.Prevent and kill off annual and perennial standing grain
The weeds such as undergraduate course weeds and broad leaved weed, Cyperaceae.It is widely used, is a kind of environmentally friendly efficient farmland weeding of low toxicity
Agent.Thus increasingly paid attention to by various countries, turn into the focus agricultural chemicals competitively researched and developed, produce and applied.
Imidazolinone herbicide mainly includes four kinds of Arsenal, Imazethapyr, imazapic and imazamox, and it is made
Standby process all refers to the synthesis of different substitution -2, the 3- pyridine dicarboxylates of key intermediate 5, and 2- alkoxy -3- oxos -
Succinate is the important as precursors compound for preparing the intermediate.Therefore, the system of 2- alkoxies -3- oxos-succinate
Standby cost is just particularly important for reducing imidazolinone herbicide synthesis technique cost.
The common technology scheme of 2- alkoxies -3- oxos-succinate is prepared at present mainly to synthesize based on single ester.
Scheme one（US6080867）Synthetic route such as formula（2）Shown, the conversion of program raw material is slower, and consumption alkali number is big, and yield is relatively low,
It is unsuitable for industrialized production.
（2）
Scheme two（US6080867）Synthetic route such as formula（3）Shown, the conversion of this method raw material is slower, and product has stronger wave
Hair property, post processing are more difficult.
（3）
Scheme three（J. Org. Chem. 50(22), 4404,1985）Synthetic route such as formula（4）It is shown, this method raw material into
This is higher, while raw material has higher risk, and product yield is relatively low, is not suitable for industrialized production.
（4）.
The content of the invention
For raw material conversion is slow, yield is low, alkali and solvent-oil ratio are big, environmental pollution is tight existing for techniques described above scheme
Drawback, the present invention propose a kind of mixed ester preparation technology again etc., i.e., and a kind of imidazolinone herbicide intermediate 2- alkoxies-
The synthesis technique of 3- oxos-succinate.
The technical scheme is that：
A kind of synthesis technique of imidazolinone herbicide intermediate 2- alkoxies -3- oxos-succinate, the synthesis
Technique is using methoxy menthyl acetate and diethy-aceto oxalate as raw material, in the presence of sodium alkoxide, is substituted reaction and hydrochloric acid successively
Acidifying prepares the 2- alkoxies -3- oxos-succinate.The synthesis technique specifically comprises the following steps：
（1）Substitution reaction：
In equipped with thermometer and churned mechanically four-hole bottle, the first solvent and solid sodium ethanol are added, is stirred at room temperature 10 points
Zhong Hou, methoxy menthyl acetate and diethy-aceto oxalate are well mixed, are added dropwise in four-hole bottle in reaction solution, are warming up to 40~70
DEG C, stir 1~3 hour；Wherein：The molar ratio of the diethy-aceto oxalate, methoxy menthyl acetate and sodium alkoxide is 1:(1.0~
1.5):(1.0~1.5)；The part by weight of the diethy-aceto oxalate and the first solvent is 1:（5~15）；
（2）Hydrochloric acid is acidified：
To step（1）Watery hydrochloric acid is added dropwise in reaction system, control temperature of reaction system is below 25 DEG C, by controlling dilute salt
The rate of addition regulation reaction system pH scopes of acid are 2~3, are stirred 1~3 hour；
（3）Intermediate separates：
Will be through step（2）Reaction system after hydrochloric acid acidifying stands liquid separation, retains organic phase；Aqueous phase adds the second solvent extraction
Take twice；Merge organic phase, concentrated acquisition brown yellow oil 2- alkoxies -3- oxos-succinate.
Above-mentioned steps（1）In, first solvent be benzene, toluene, tetrahydrofuran, 1,2 dichloroethanes, methanol, ethanol and
One or more of mixed solvents in acetonitrile.
Above-mentioned steps（1）Substitution reaction and step（2）Acidization is to carry out under nitrogen protection.
Above-mentioned steps（2）In, it is 0.1~0.2 mol/L that watery hydrochloric acid concentration, which is added dropwise,.
Above-mentioned steps（3）In, second solvent is benzene, toluene, ethyl acetate, 1,2 dichloroethanes, dichloroethanes and chlorine
One or more in imitative.
The imidazolinone herbicide intermediate 2- alkoxies -3- oxos-succinate prepared using above-mentioned technique
Formula such as following formula（1）It is shown：
（1）；
Formula（1）In, R1, R2And R3Respectively-CH3Or-CH2CH3, and R1, R2And R3It is identical or different.
Through intermediate synthesized by above-mentioned technique be 2- methoxyl groups -3- oxos-dimethyl succinate, 2- ethyoxyl -3- oxos -
Diethyl succinate, 2- methoxyl groups -3- oxos-succinic acid -1- methyl esters -4- ethyl esters and 2- methoxyl groups -3- oxos-succinic acid -1-
The mixed ester of ethyl ester -4- methyl esters.
The present invention has advantages below and beneficial effect：
1st, the cost of material selected by the present invention is low, and simple and easy to get, reaction condition is gentle, and post processing is simple, and yield is by 40%
Improve to more than 90%, significantly reduce process costs.
2nd, present invention process is reduced solvent species, is easy to single solvent recovery again with solid sodium ethanol substituted alcohols sodium solution
Utilize, while the dosage of sodium alkoxide significantly reduces, and reduces the discharge of the three wastes, is advantageous to environmental protection.Therefore, the present invention is a kind of
More it is adapted to the synthetic method of industrialized production.
Brief description of the drawings
Fig. 1 is intermediate GC-MS spectrograms (GC-MS prepared by the embodiment of the present invention 3:190[M]+)。
Fig. 2 is intermediate GC-MS spectrograms (GC-MS prepared by the embodiment of the present invention 3:204[M]+)。
Fig. 3 is intermediate GC-MS spectrograms (GC-MS prepared by the embodiment of the present invention 3:218[M]+)。
Embodiment
The present invention is further described with reference to embodiments.
The present invention is the synthesis technique of imidazolinone herbicide intermediate 2- alkoxies -3- oxos-succinate, its
Synthetic route such as reaction equation（5）It is shown：
（5）
Four kinds of different esters of the above, 2- alkoxies -3- oxos-succinate mixed ester is constituted, in subsequent technique,
These four esters can be effectively from different methacrylaldehyde cyclizations, and corresponding 5 of generation is different to substitute -2,3- pyridinedicarboxylic acids
Ester.Therefore, these four esters are the target products of the present invention.
Embodiment 1
2- methoxyl groups -3- oxos-dimethyl succinate
At 40 DEG C, to the g of methanol solution 5.9 of 25wt.% sodium methoxides（0.11 mol,1.1 eq）Middle addition toluene（52
mL）, reaction system is in little cloudy liquid.By the g of dimethyl oxalate 20.0（0.11 mol, 1.1 eq）With methoxy menthyl acetate
10.4 g（0.10 mol, 1.0 eq）It is well mixed, is added dropwise in above-mentioned dirty solution, reaction system is gradually by dirty solution at room temperature
It is changed into light yellow transparent solution, is warming up to 45~50 DEG C, stirs 1 hour.Add the g of methanol solution 5.9 of 25wt.% sodium methoxides
（0.11 mol,1.1 eq）Continue reaction 2 hours.Below 25 DEG C of ice-water bath temperature control, 14 % HCl 37g are added dropwise into system
（0.14 mol, 1.28 eq）, pH=2~3 are adjusted, are stirred 1.5 hours at room temperature.Filtering, filtrate stratification, organic phase are protected
Stay, aqueous phase toluene（90 mL×2）It is extracted twice, merges organic phase, be concentrated to give the g of yellow oily target product 7.6, yield 40
%。GC-MS:190[M]+。
Embodiment 2
2- ethyoxyls -3- oxos-diethyl succinate
The g of ethoxy ethyl acetate 3.0 is sequentially added into 100 mL there-necked flasks（23 mmol, 1.0 eq）, oxalic acid diethyl
The g of ester 4.0（27 mmol, 1.2 eq）, the g of 19.5 % alcohol sodium alcohol solutions 9.5（27 mol, 1.2 eq）And toluene（15
mL）, it is warming up to 55 DEG C of stirrings.Reaction 2 hours, adds the g of 19.5 % alcohol sodium alcohol solutions 1.6（4.5 mmol,0.2 eq）Stir
Mix 2 hours.Below 25 DEG C of ice-water bath temperature control, 14 % HCl6.0 g are added dropwise into system（29.4 mmol,1.28eq）, adjust pH
=2~3, stir 1.5 hours at room temperature.Filtering, filtrate stratification, organic phase retain, aqueous phase toluene（15 mL×2）Extraction
Twice, merge organic phase, be concentrated to give the g of yellow oily target product 4.0, the % of yield 80.5.GC-MS:232[M]+。
Embodiment 3
2- methoxyl groups -3- oxos-succinate
Under nitrogen protection, into the 10 L four-hole bottles equipped with mechanical agitation and thermometer, toluene is sequentially added（3.5 L）、
The g of 96 % solid sodium ethanols 572（8.07 mol, 1.2 eq）, it is stirred at room temperature 10 minutes.By the g of 99 % methoxy menthyl acetates 700
（6.72 mol, 1.0 eq）With the g of 99 % diethy-aceto oxalates 1179（8.07 mol, 1.2 eq）It is well mixed, it is added dropwise to above-mentioned anti-
Answer in liquid, be added dropwise and be warming up to 40~45 DEG C and react 1 hour, reaction system be in rufous clarified solution, and ice-water bath cools down, to anti-
Answer and the g of 14 % aqueous hydrochloric acid solutions 2244 is added dropwise in liquid（8.61 mol, 1.28 eq）, temperature is controlled below 25 DEG C, tune pH=2~
3.Stirring 1.5~2 hours, filtering, filtrate stratification, organic phase retain, aqueous phase chloroform（2.1 L）Extraction once, merges
Organic phase is simultaneously concentrated to give the g of yellow oily target product 1435.7, with 2- methoxyl groups -3- oxos-diethyl succinate calculated yield
For 97.8 %. GC-MS:190[M]+, 204 [M]+, 218 [M]+。
Embodiment 4
2- methoxyl groups -3- oxos-succinate
Under nitrogen protection, into the 2 L four-hole bottles equipped with mechanical agitation and thermometer, 99 % methoxyacetic acids are sequentially added
The g of methyl esters 120（1.15 mol, 1.0 eq）, the g of 99 % diethy-aceto oxalates 202（1.38 mol, 1.2 eq）With 19.6 % caustic alcohols
The g of ethanol solution 480（1.38 mol, 1.2 eq）, it is warming up to 50 DEG C and reacts 4 hours, reaction system is in rufous clarified solution.Add
Enter toluene（480 mL）, ice-water bath cooling, the g of 14 % aqueous hydrochloric acid solutions 384 is added dropwise into reaction solution（1.76 mol, 1.28
eq）, control temperature is below 25 DEG C, tune pH=2~3.Stirring 0.5 hour, stratification, organic phase retain, aqueous phase toluene
（250 mL）Extraction once, merges organic phase and is concentrated to give the g of yellow oily target product 201, with 2- methoxyl groups -3- oxos-fourth
Diethyl adipate calculated yield is 80 %. GC-MS:190[M]+, 204 [M]+, 218 [M]+。
Claims (1)
1. a kind of synthesis technique of imidazolinone herbicide intermediate 2- methoxyl groups -3- oxos-succinate, its feature exist
In：
Under nitrogen protection, into the 10L four-hole bottles equipped with mechanical agitation and thermometer, 3.5L toluene and 8.07mol are sequentially added
96% solid sodium ethanol, it is stirred at room temperature 10 minutes, 6.72mol methoxy menthyl acetates and the diethy-aceto oxalates of 8.07mol 99% is mixed
Close uniform, be added dropwise in above-mentioned reaction solution, be added dropwise and be warming up to 40 ~ 45 DEG C and react 1 hour, reaction system is in rufous clarification
Liquid, ice-water bath cooling, the aqueous hydrochloric acid solutions of 8.61mol 14% are added dropwise into reaction solution, control below 25 DEG C of temperature, adjust pH=2 ~ 3,
Stirring 1.5 ~ 2 hours, filtering, filtrate stratification, organic phase retain, and aqueous phase is extracted once with 2.1L chloroforms, merge organic phase
And yellow oily target product is concentrated to give, using 2- methoxyl groups -3- oxos-diethyl succinate calculated yield as 97.8%.
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| CN114644565B (en) * | 2020-12-17 | 2024-05-03 | 江苏中旗科技股份有限公司 | Synthesis method of key intermediate of imidazolinone compound |
| CN113292487B (en) * | 2021-06-06 | 2022-04-08 | 江苏省农用激素工程技术研究中心有限公司 | Preparation method of pyroxsulam intermediate |
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|---|---|---|---|---|
| US6080867A (en) * | 1998-06-15 | 2000-06-27 | American Cyanamid Company | Process and intermediates for the manufacture of pyridine-2,3-dicarboxylate compounds |
| CN102304094A (en) * | 2011-09-23 | 2012-01-04 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine and intermediate thereof |
| CN103864700A (en) * | 2014-03-10 | 2014-06-18 | 常熟市金申医化制品有限责任公司 | Method for preparing 5-methoxy-4,6-dihydroxy pyrimidine disodium |
| CN104447327A (en) * | 2014-12-13 | 2015-03-25 | 常熟市金申医化制品有限责任公司 | Preparation method of methyl ethyl methoxymalonate |
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| CN103910629A (en) * | 2014-03-10 | 2014-07-09 | 常熟市南湖实业化工有限公司 | Method used for smooth and steady preparation of 2-methoxypropandioic acid ethyl methyl ester |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6080867A (en) * | 1998-06-15 | 2000-06-27 | American Cyanamid Company | Process and intermediates for the manufacture of pyridine-2,3-dicarboxylate compounds |
| CN102304094A (en) * | 2011-09-23 | 2012-01-04 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine and intermediate thereof |
| CN103864700A (en) * | 2014-03-10 | 2014-06-18 | 常熟市金申医化制品有限责任公司 | Method for preparing 5-methoxy-4,6-dihydroxy pyrimidine disodium |
| CN104447327A (en) * | 2014-12-13 | 2015-03-25 | 常熟市金申医化制品有限责任公司 | Preparation method of methyl ethyl methoxymalonate |
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