CN101381305A - Bactericidal agent intermediate (E)-2-(2'-bromomethyl)phenyl-3-methoxylacrylate preparation method - Google Patents
Bactericidal agent intermediate (E)-2-(2'-bromomethyl)phenyl-3-methoxylacrylate preparation method Download PDFInfo
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Abstract
The invention provides a method for preparing intermediate compound (E)-2-(2'-bromomethyl) phenyl-3-methoxy methyl acrylate of bactericide. The method comprises the following steps: 1) in the presence of a catalyst, o-tolyl-acetic acid reacts with methanol, and the catalyst is selected from sulfuric acid or paratoluenesulfonic acid; 2) in the presence of alkali, the product of step 1) reacts with alkyl formate; 3) in the presence of alkali, the product of step 2) reacts with methylating reagent; 4) in the presence of catalyst, the product of step 3) reacts with halogen, wherein the dosage of the halogen is between 1.0 and 1.5 mol against that of the product of step 3), and the obtained product is recrystallized in solvent methanol to obtain a pure compound, the catalyst is selected from azodiisobutyronitrile or dibenzoyl peroxide, and the solvent is selected from benzene, carbon tetrachloride or cyclohexane. The method avoids using expensive solvent, or methyl chloride gas which has higher toxicity and influences the atmospheric ozone layer as the methylating reagent, thereby meeting the requirement of environmental protection.
Description
Technical field
The present invention relates to a kind of formula (I) intermediates preparation, be specifically related to a kind ofly when producing agricultural fungicidal medicament methoxy acrylic, be used as the preparation method of compound (E)-2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate of chemical intermediate.
Background technology
Methoxy acrylic is a kind of widely used agricultural fungicidal medicament, for example compound known among patent CN1030749, CN1201657, CN1646472, WO90/07493, WO92/18494, EP-178826, EP-370629, EP-414153, EP-460575 or the WO94/08968.Generally can adopt (E)-2-(2 '-chloromethyl) phenyl-3-methoxy-methyl acrylate as intermediate when producing this medicament.Patent WO95/25729 has instructed the preparation method of compound (E)-2-(2 '-chloromethyl) phenyl-3-methoxy-methyl acrylate of a kind of formula (I) intermediate, this method uses isochromanome to be starting raw material, source, isochromanome market difficulty, cost an arm and a leg, and described respectively to go on foot reaction yield relatively low.
The method of patent WO97/30020 report is the product of step 3) of the present invention, but it has used relative more expensive N-Methyl pyrrolidone to make solvent and toxicity is higher, the methyl chloride gas that influences atmospheric ozone layer is made methylating reagent.
Summary of the invention
At the above-mentioned deficiency of existing method, the purpose of this invention is to provide the preparation method of a kind of intermediate (E)-2-that in the preparation process of mycocidal methoxy acrylic derivative, is suitable for (2 '-brooethyl) phenyl-3-methoxy-methyl acrylate.Present method will be got rid of more expensive solvent and the toxicity methyl chloride gas higher, that influence atmospheric ozone layer of use and make methylating reagent.
The scheme of finishing the foregoing invention task is: the method for preparation formula (I) compound,
Wherein X is a haloid element, and preferred X is bromine and chlorine (particularly bromine), and this method may further comprise the steps:
1). in the presence of catalyzer, make the 2-methylphenyl acetic acid and the methyl alcohol reaction of following formula (II), it is characterized in that methanol usage is 2.0～50mol of o-Tolylacetic acid, preferred 10～16.5mol; Catalyst levels is 0.0015～1.0mol of o-Tolylacetic acid, preferred 0.15～0.5mol;
Described catalyzer is selected from sulfuric acid or tosic acid, preferably sulfuric acid;
2). in the presence of suitable alkali, make the product and the alkyl formate reaction of step 1), it is characterized in that the consumption of alkyl formate is 1.0～10mol of the o-Tolylacetic acid methyl esters of step 1), preferred 2.0～4.0mol; The consumption of alkali is 1.0～2.0mol of the o-Tolylacetic acid methyl esters of step 1);
Described suitable alkali is selected from: sodium hydride or sodium methylate;
Described alkyl formate is selected from: methyl-formiate, ethyl formate, formic acid n-propyl ester, formic acid isopropyl esters, formic acid n-butyl or formic acid tertiary butyl ester, preferable formic acid methyl esters.
3). in the presence of suitable alkali, make step 2) product and methylating reagent reaction, it is characterized in that the consumption of methylating reagent is a step 2) 1.0～3.0mol of product, preferred 2.0～2.5mol; The consumption of alkali is a step 2) 1.0～3.0mol of product, preferred 2.0～2.5mol;
Described suitable alkali is selected from: sodium hydroxide, potassium hydroxide, sodium bicarbonate or salt of wormwood;
Described methylating reagent is selected from: methyl-sulfate, methyl-iodide or methylcarbonate, preferably sulfuric acid dimethyl ester;
4). in the presence of catalyzer, make the product and the halogen reaction of step 3), it is characterized in that the consumption of halogen is 0.6～1.2mol of the product of step 3), catalyst consumption is 0.001～0.005mol of the product of step 3); And make so obtain product recrystallization in solvent methanol obtain pure product.
Described catalyzer is selected from: Diisopropyl azodicarboxylate or dibenzoyl peroxide;
Solvent is selected from: benzene, tetracol phenixin or hexanaphthene, preferred benzene.It is characterized in that the consumption of benzene is 3.5～5.0 times of product of step 3).
Method provided by the invention is suitable for large-scale commercial production, has avoided using more expensive solvent and toxicity methyl chloride gas higher, that influence atmospheric ozone layer to make methylating reagent in the technology, meets requirement on environmental protection.
Description of drawings
Fig. 1 is the process flow sheet of the inventive method.
Embodiment
The following examples have illustrated the present invention.Wherein
1The H-NMR spectrum is to use CDCl
3The solvent record.Abbreviation used in the experiment below is as follows:
The bimodal m=multimodal of the unimodal d=of NMR=nucleus magnetic resonance s=
The MS=mass spectrum
The MTBE=methyl tertiary butyl ether
The AIBN=Diisopropyl azodicarboxylate.
Step 1)
The preparation of o-Tolylacetic acid methyl esters
151.7g (1.0mol, 99%) o-Tolylacetic acid is added in the 1000ml reaction flask, adds the 500ml dissolve with methanol under stirring, add the 25ml vitriol oil, reflux 6～12 hours, the decompression of cooling back steams solvent, steam excess and add methylbenzene extraction, add water washing three times, use anhydrous magnesium sulfate drying, decompression steams solvent, and decompression steams product again, gets 162.1g, content 99.3%, yield 98%, colourless liquid
1H-NMR(CDCl
3，TMS)δ:7.21-7.01(m，4H)，3.61(s，3H)，3.60(s，2H)，2.35(s，3H)；MS(m/e)：164(M
+，42)，133(100)，31(82)。
Step 2)
The preparation of 2-(2 '-methyl) phenyl-acrolactic acid methyl esters
600ml MTBE, 28.5g (0.75mol, 97% * 65%) sodium hydride, 82.7g (0.5mol, 99.3%) in o-Tolylacetic acid methyl esters, the input 1000ml reaction flask, stirring down, controlled temperature drips 91.8g (1.5mol at 20 ℃～25 ℃, 98%) methyl-formiate has a large amount of gases to produce, and adds in 2 hours, room temperature insulation 10 hours has solid to separate out between soak.Insulation finishes 200ml/ water extraction of usefulness 2～3 times, extracting solution merges the enriching hcl acidifying, with 150ml/ MTBE extraction 3～4 times, extracting solution merges, and washes neutrality with water, use anhydrous magnesium sulfate drying, MTBE is taken off in air distillation, 2-(2 '-methyl) phenyl-acrolactic acid methyl esters 96g, content 95.3%, yield 95.2%, colourless liquid.
1H-NMR(CDCl
3，TMS)δ:11.92(d，1H)，7.32-7.01(m，4H)3.71(s，3H)，2.21(s3H)；MS(m/e)：192(M
+，26)，160(52)，132(48)，84(100)。
Step 3)
The preparation of 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate
96g (0.476mol, 95.3%) 2-(2 '-methyl) phenyl-acrolactic acid methyl esters, 133g (1.0mol) methyl-sulfate drop in the 1000ml reaction flask, stir cooling down, controlled temperature drips 383.4g (1.15mol below 5 ℃, 12%) aqueous sodium hydroxide solution, drip and finish to be warming up to 20 ℃～25 ℃ insulations 6 hours, move into the separating funnel layering, lower layer of water is used hydrochloric acid furnishing acidity after using 200ml/ toluene extracting twice, use 200ml/ time new toluene extracting twice again, divide and abandon water layer.Merge the organic layer water washing to neutral, use anhydrous magnesium sulfate drying, air distillation piptonychia benzene, adopt 0.5mmHg reduce pressure steam 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate 89.8g, colourless liquid, content 98.4%, yield 90%.E body/Z body=82%/18%.
E isomer
1H-NMR(CDCl
3，TMS)δ:7.51(s，1H)，7.35-6.98(m，4H)，3.79(s，3H)，3.68(s，3H)，2.21(s，3H)；
MS(m/e)：206(M
+，10)，176(73)，117(100)，77(57)。
Z isomer
1H-NMR(CDCl
3，TMS)δ:7.34-6.98(m，4H)，6.50(s，1H)，3.85(s，3H)，3.68(s，3H)，2.21(s，3H)；
MS(m/e)：206(M
+，10)，176(100)，117(92)，77(30)。
Step 4)
(E)-preparation of 2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate
89.8g (0.428mol, 98.4%) 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate, 0.35g (2.1mmol, 99%) AIBN and 400ml benzene drop in the 1000ml reaction flask, stirring is warming up to little backflow, drip the solution of 76g (0.47mol, 99%) bromine and 100ml benzene, added with 4 hours, back flow reaction is 3 hours again, the material color is slowly become by redness to be cooled off reaction when light yellow slightly and finishes, and stirs to add 300ml water down, moves into the separating funnel layering, divide and abandon lower layer of water, add small amount of carbon acid sodium aqueous solution furnishing weakly alkaline, be washed to neutrality again, anhydrous magnesium sulfate drying, benzene is taken off in air distillation, gets crude product 121.8g.Add 120g methyl alcohol, being warming up to refluxes makes its dissolving, is cooled to 10 ℃ of suction filtrations, the product 97.2g that must wet, 40～50 ℃ dry 87.5g, content 95%.Yield 68.5%.Fusing point 94-96 ℃, white crystals.
1H-NMR(CDCl
3，TMS)δ:7.63(s，1H)，7.51-7.09(m，4H)，4.40(s，2H)，3.82(s，3H)，3.69(s，3H)；
MS(m/e)：284(M
+，10)，253(12)，205(21)，173(38)，145(100)。
(E)-preparation of 2-(2 '-chloromethyl) phenyl-3-methoxy-methyl acrylate
21g (0.1mol, 98%) 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate, 0.42g (2.5mmol, 99%) AIBN and 60ml benzene drop in the 100ml reaction flask, heat up 80 ℃, slowly feed chlorine, adopt the gas-chromatography trace analysis, logical chlorine finishes after 2 hours, steams solvent on rotatory evaporator, adopt the chromatographic column purifying, with n-hexane/ethyl acetate=4/1 wash-out, 18.25g (E)-2-(2 '-chloromethyl) phenyl-3-methoxy-methyl acrylate, be faint yellow colloid.
1H-NMR(CDCl
3，TMS)δ:7.61(s，1H)，7.5-7.0(m，4H)，4.49(s，2H)，3.80(s，3H)，3.69(s，3H)；
MS(m/e)：240(M
+，10)，210(12)，196(21)，149(38)，129(100)。
The catalyzer of step 1) changes into: tosic acid;
151.7g (1.0mol, 99%) o-Tolylacetic acid is added in the 1000ml reaction flask, adds the 500ml dissolve with methanol under stirring, add 26.4g (0.15mol, 98%) tosic acid, reflux 6～12 hours, the decompression of cooling back steams solvent, steams excess and adds methylbenzene extraction, adds water washing three times, use anhydrous magnesium sulfate drying, decompression steams solvent, and decompression steams product again, get 159.9g, content 99.6%, yield 97%, colourless liquid
Step 2) alkali changes sodium methylate into; Alkyl formate changes into: ethyl formate;
600ml toluene, 216g (2.0mol, 50%) sodium methylate, 82.7g (0.5mol, 99.3%) in o-Tolylacetic acid methyl esters, the input 1000ml reaction flask, stirring down, controlled temperature drips 112g (1.5mol at 20 ℃～25 ℃, 98%) ethyl formate has a large amount of gases to produce, and adds in 2 hours, room temperature insulation 10 hours has solid to separate out between soak.Insulation finishes 200ml/ water extraction of usefulness 2～3 times, extracting solution merges the enriching hcl acidifying, with 150ml/ toluene extraction 3～4 times, extracting solution merges, and washes neutrality with water, uses anhydrous magnesium sulfate drying, air distillation piptonychia benzene, 2-(2 '-methyl) phenyl-acrolactic acid methyl esters 91.2g, yield 89%, weak yellow liquid.
The alkali of step 3) changes into: potassium hydroxide;
101g (0.5mol, 95.3%) 2-(2 '-methyl) phenyl-acrolactic acid methyl esters, 133.6g (1.05mol, 99%) methyl-sulfate drops in the 1000ml reaction flask, stirs down and cool off, controlled temperature drips 402.5g (1.15mol below 5 ℃, 16%) potassium hydroxide aqueous solution, drip and finish to be warming up to 20 ℃～25 ℃ insulations 6 hours, move into the separating funnel layering, lower layer of water is used hydrochloric acid furnishing acidity after using 200ml/ toluene extracting twice, use 200ml/ time new toluene extracting twice again, divide and abandon water layer.Merge the organic layer water washing to neutral, use anhydrous magnesium sulfate drying, air distillation piptonychia benzene, adopt 0.5mmHg reduce pressure steam 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate 96.6g, colourless liquid, content 97.7%, yield 91.6%.
The catalyzer of step 4) changes into: dibenzoyl peroxide; Solvent changes into: tetracol phenixin.
104.8g (0.5mol, 98.4%) 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate, 1.7g (5.0mmol, 70%) dibenzoyl peroxide and 400ml tetracol phenixin drop in the 1000ml reaction flask, stirring is warming up to little backflow, drip 76g (0.47mol, 99%) solution of bromine and 100ml tetracol phenixin, added with 4 hours, back flow reaction is 3 hours again, the material color is slowly become by redness to be cooled off reaction when light yellow slightly and finishes, and stirs to add 300ml water down, moves into the separating funnel layering, divide and abandon lower layer of water, add small amount of carbon acid sodium aqueous solution furnishing weakly alkaline, be washed to neutrality again, anhydrous magnesium sulfate drying, tetracol phenixin is taken off in air distillation, gets crude product 141.2g.Add 140g methyl alcohol, being warming up to refluxes makes its dissolving, is cooled to 10 ℃ of suction filtrations, the product 112.5g that must wet, 40～50 ℃ dry (E)-2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate 101.4g, content 95.5%.Yield 68.0%.Fusing point 94-96 ℃, white crystals.
The alkyl formate of step 2 changes into: the formic acid isopropyl esters;
600ml MTBE, 28.5g (0.75mol, 97% * 65%) sodium hydride, 82.7g (0.5mol, 99.3%) in o-Tolylacetic acid methyl esters, the input 1000ml reaction flask, stirring down, controlled temperature drips 135g (1.5mol at 20 ℃～25 ℃, 98%) formic acid isopropyl esters has a large amount of gases to produce, and adds in 2 hours, room temperature insulation 10 hours has solid to separate out between soak.Insulation finishes 200ml/ water extraction of usefulness 2～3 times, extracting solution merges the enriching hcl acidifying, with 150ml/ MTBE extraction 3～4 times, extracting solution merges, and washes neutrality with water, use anhydrous magnesium sulfate drying, MTBE is taken off in air distillation, 2-(2 '-methyl) phenyl-acrolactic acid methyl esters 96.5g, content 93.2%, yield 93.6%, weak yellow liquid.
The alkali of step 3 changes into: salt of wormwood;
101g (0.5mol, 95.3%) 2-(2 '-methyl) phenyl-acrolactic acid methyl esters, 76.8g (0.55mol, 16%) salt of wormwood and 600ml acetone drop in the 1000ml reaction flask, stir down and cool off, controlled temperature drips 133.6g (1.05mol below 25 ℃, 99%) methyl-sulfate, drip and finish to be warming up to 65 ℃ of insulations 12 hours, decompression steams solvent, cooling adds water, move into the separating funnel layering, lower layer of water with hydrochloric acid furnishing acidity, is used new 200ml/ ethyl acetate extraction twice with twice back of 200ml/ ethyl acetate extraction again, divides and abandons water layer.Merge the organic layer water washing to neutral, use anhydrous magnesium sulfate drying, ethyl acetate is taken off in air distillation, adopt 0.5mmHg reduce pressure steam 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate 98.1g, colourless liquid, content 98.2%, yield 93.5%.
The alkyl formate of step 2 changes into: the formic acid tertiary butyl ester.
600ml toluene, 28.5g (0.75mol, 97% * 65%) sodium hydride, 82.7g (0.5mol, 99.3%) o-Tolylacetic acid methyl esters, drop in the 1000ml reaction flask, stirring down, controlled temperature drips 156.3g (1.5mol at 20 ℃～25 ℃, 98%) formic acid tertiary butyl ester, there are a large amount of gases to produce, added in 2 hours, room temperature insulation 10 hours, insulation finishes to use water extraction 2～3 times, extracting solution merges, and the enriching hcl acidifying is with 150ml/ toluene extraction 3～4 times, extracting solution merges, wash neutrality with water, use anhydrous magnesium sulfate drying, air distillation piptonychia benzene, 2-(2 '-methyl) phenyl-acrolactic acid methyl esters 95.4g, content 90.9%, yield 90.2%, weak yellow liquid.
Embodiment 7, and is substantially the same manner as Example 1, but step 4 wherein changes into:
(E)-preparation of 2-(2 '-chloromethyl) phenyl-3-methoxy-methyl acrylate, and use solvent instead hexanaphthene, catalyzer changes dibenzoyl peroxide into:
21g (0.1mol, 98%) 2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate, 0.7g (2.0mmol, 99%) dibenzoyl peroxide and 60ml hexanaphthene drop in the 100ml reaction flask, heat up 80 ℃, slowly feed chlorine, adopt the gas-chromatography trace analysis, logical chlorine finishes after 2 hours, on rotatory evaporator, steam solvent, adopt the chromatographic column purifying, with n-hexane/ethyl acetate=4/1 wash-out, 18.1g (E)-2-(2 '-chloromethyl) phenyl-3-methoxy-methyl acrylate, be faint yellow colloid.
Embodiment 8, and is substantially the same manner as Example 1, but following change is arranged:
Step 1). methanol usage is the 2.0mol of o-Tolylacetic acid; Catalyst levels is the 0.0015mol of o-Tolylacetic acid;
Step 2). the consumption of alkyl formate is the 1.0mol of the o-Tolylacetic acid methyl esters of step 1); The consumption of alkali is the 1.0mol of the o-Tolylacetic acid methyl esters of step 1);
Step 3). the consumption of methylating reagent is a step 2) the 1.0mol of product; The consumption of alkali is a step 2) the 1.0mol of product;
Step 4). the consumption of halogen is the 1.0mol of the product of step 3),
Catalyst consumption is the 0.001mol of the product of step 3).
Embodiment 9, and is substantially the same manner as Example 1, but following change is arranged:
Step 1). methanol usage is the 50mol of o-Tolylacetic acid; Catalyst levels is the 1.0mol of o-Tolylacetic acid;
Step 2). the consumption of alkyl formate is the 10mol of the o-Tolylacetic acid methyl esters of step 1); The consumption of alkali is the 5.0mol of the o-Tolylacetic acid methyl esters of step 1);
Step 3). the consumption of methylating reagent is a step 2) the 3.0mol of product; The consumption of alkali is a step 2) the 3.0mol of product;
Step 4). the consumption of halogen is the 1.5mol of the product of step 3),
Catalyst consumption is the 0.05mol of the product of step 3).
Embodiment 10, and is substantially the same manner as Example 1, but following change is arranged:
Step 1). methanol usage is the 10mol of o-Tolylacetic acid; Catalyst levels is the 0.25mol of o-Tolylacetic acid;
Step 2) consumption of alkyl formate is the 2.0mol of the o-Tolylacetic acid methyl esters of step 1);
The consumption of step 3) methylating reagent is a step 2) the 2.0mol of product;
The consumption of alkali is a step 2) the 2.0mol of product;
The consumption of step 4) solvent is 3.5 times of product of step 3).
Embodiment 11, and is substantially the same manner as Example 1, but following change is arranged:
Step 1). methanol usage is 16.5 of an o-Tolylacetic acid; Catalyst levels is the 0.5mol of o-Tolylacetic acid;
Step 2) consumption of alkyl formate is the 4.0mol of the o-Tolylacetic acid methyl esters of step 1);
The consumption of step 3) methylating reagent is a step 2) the 2.5mol of product;
The consumption of alkali is a step 2) the 2.5mol of product;
The consumption of step 4) solvent is 5.0 times of product of step 3).
Claims (5)
1, the preparation method of a kind of sterilant intermediate (E)-2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate, prepared compound is suc as formula shown in (I):
Wherein X is a haloid element,
This method may further comprise the steps:
1). in the presence of catalyzer, make the o-Tolylacetic acid and the methyl alcohol reaction of following formula (II), methanol usage is 2.0～50mol of o-Tolylacetic acid; Catalyst levels is 0.0015～1.0mol of o-Tolylacetic acid;
Described catalyzer is selected from sulfuric acid or tosic acid:
2). in the presence of suitable alkali, make the product and the alkyl formate reaction of step 1), the consumption of alkyl formate is 1.0～10mol of the o-Tolylacetic acid methyl esters of step 1); The consumption of alkali is 1.0～5.0mol of the o-Tolylacetic acid methyl esters of step 1);
Described suitable alkali is selected from: sodium hydride or sodium methylate;
Described alkyl formate is selected from: methyl-formiate, ethyl formate, formic acid n-propyl ester, formic acid isopropyl esters, formic acid n-butyl or formic acid tertiary butyl ester;
3). in the presence of suitable alkali, make step 2) product and methylating reagent reaction, the consumption of methylating reagent is a step 2) 1.0～3.0mol of product; The consumption of alkali is a step 2) 1.0～3.0mol of product;
Described suitable alkali is selected from: sodium hydroxide, potassium hydroxide, sodium bicarbonate or salt of wormwood;
Described methylating reagent is selected from: methyl-sulfate, methyl-iodide or methylcarbonate;
4). in the presence of catalyzer, make the product and the halogen reaction of step 3),
The consumption of halogen is 1.0～1.5mol of the product of step 3),
Catalyst consumption is 0.001～0.05mol of the product of step 3); And make so obtain product recrystallization in solvent methanol obtain pure product,
Described catalyzer is selected from: Diisopropyl azodicarboxylate or dibenzoyl peroxide;
Solvent is selected from: benzene, tetracol phenixin or hexanaphthene.
2, according to the preparation method of the described sterilant intermediate of claim 1 (E)-2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate, it is characterized in that,
The described catalyzer of step 1) is a sulfuric acid;
Described catalyst levels is 0.25～0.5mol of o-Tolylacetic acid;
Described methanol usage is 10～16.5mol of o-Tolylacetic acid;
Step 2) consumption of described alkyl formate is 2.0～4.0mol of the o-Tolylacetic acid methyl esters of step 1);
The consumption of the described methylating reagent of step 3) is a step 2) 2.0～2.5mol of product;
The consumption of described alkali is a step 2) 2.0～2.5mol of product;
The described halogen of step 4) is bromine or chlorine;
The consumption of described solvent is 3.5～5.0 times of product of step 3).
3, according to the preparation method of the described sterilant intermediate of claim 2 (E)-2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate, it is characterized in that,
Step 2) described alkyl formate is a methyl-formiate;
The described methylating reagent of step 3) is a methyl-sulfate;
The described halogen of step 4) is a bromine; Described solvent is a benzene.
4, according to the preparation method of claim 1 or 2 or 3 described disinfectant use in agriculture chemical intermediate (E)-2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate, it is characterized in that the concrete operations step is:
1) preparation of .2-methylphenyl acetic acid methyl esters
The o-Tolylacetic acid of regulation ratio is added in the reaction flask, adds dissolve with methanol under stirring, and adds the vitriol oil, reflux 6～12 hours, the decompression of cooling back steams solvent, steams excess and adds methylbenzene extraction, adds water washing three times, use anhydrous magnesium sulfate drying, decompression steams solvent, and decompression steams product again;
2) preparation of .2-(2 '-methyl) phenyl-acrolactic acid methyl esters
In the MTBE of regulation ratio, sodium hydride, o-Tolylacetic acid methyl esters, the input reaction flask, stirring down, controlled temperature has a large amount of gases to produce at 20 ℃～25 ℃ dropping methyl-formiates, added in 2 hours, room temperature insulation 10 hours has solid to separate out between soak, insulation finishes to use water extraction 2～3 times, extracting solution merges the enriching hcl acidifying, and with MTBE extraction 3～4 times, extracting solution merges, wash neutrality with water, use anhydrous magnesium sulfate drying, MTBE is taken off in air distillation, reduce pressure product;
3) preparation of .2-(2 '-methyl) phenyl-3-methoxy-methyl acrylate
The 2-of regulation ratio (2 '-methyl) phenyl-acrolactic acid methyl esters, methyl-sulfate drop in the reaction flask, stir cooling down, 5 ℃ of following dripping alkali liquid of controlled temperature, drip and finish to be warming up to 20 ℃～25 ℃ insulations 6 hours, move into the separating funnel layering, lower layer of water is used hydrochloric acid furnishing acidity after using the toluene extracting twice, use new toluene extracting twice again, divide and abandon water layer; Merge the organic layer water washing to neutral, use anhydrous magnesium sulfate drying, air distillation piptonychia benzene gets product;
4). (E)-preparation of 2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate
The 2-of regulation ratio (2 '-methyl) phenyl-3-methoxy-methyl acrylate, AIBN and benzene drop in the reaction flask, stirring is warming up to little backflow, the solution of dripping bromine and benzene, added with 4～5 hours, back flow reaction is 3 hours again, the material color is slowly become by redness to be cooled off reaction when light yellow slightly and finishes, add entry under stirring, move into the separating funnel layering, divide and abandon lower layer of water, add small amount of carbon acid sodium aqueous solution furnishing weakly alkaline, be washed to neutrality again, anhydrous magnesium sulfate drying, benzene is taken off in air distillation, gets crude product; Add methyl alcohol, being warming up to refluxes makes its dissolving, is cooled to 10 ℃ of suction filtrations, the product that must wet, and 40～50 ℃ of oven dry, must (E)-2-(2 '-brooethyl) phenyl-3-methoxy-methyl acrylate.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102115458A (en) * | 2010-11-25 | 2011-07-06 | 大连凯飞精细化工有限公司 | Synthesis method of 3-methoxy-2-aryl(methyl)acrylate compounds |
| CN103787915A (en) * | 2014-01-15 | 2014-05-14 | 京博农化科技股份有限公司 | Preparation method of trifloxystrobin intermediate (E)-2-(2-bromomethyl phenyl)-2-methoxylimidomethyl acetate |
| CN104529818A (en) * | 2014-12-16 | 2015-04-22 | 江苏耕耘化学有限公司 | Method for preparing (E)-2-(2-substituted phenyl)-2-methoxyimino acetic acid derivative |
| CN108299197A (en) * | 2018-02-06 | 2018-07-20 | 荆楚理工学院 | A kind of 3- alkoxy acrylic esters synthetic method |
| CN112624922A (en) * | 2020-11-26 | 2021-04-09 | 青岛科技大学 | Method for alkylation reaction by phase transfer catalysis |
-
2008
- 2008-10-21 CN CNA2008101553552A patent/CN101381305A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102115458A (en) * | 2010-11-25 | 2011-07-06 | 大连凯飞精细化工有限公司 | Synthesis method of 3-methoxy-2-aryl(methyl)acrylate compounds |
| CN102115458B (en) * | 2010-11-25 | 2019-12-13 | 大连九信精细化工有限公司 | Synthetic method of 3-methoxy-2-aryl methyl acrylate compound |
| CN103787915A (en) * | 2014-01-15 | 2014-05-14 | 京博农化科技股份有限公司 | Preparation method of trifloxystrobin intermediate (E)-2-(2-bromomethyl phenyl)-2-methoxylimidomethyl acetate |
| CN104529818A (en) * | 2014-12-16 | 2015-04-22 | 江苏耕耘化学有限公司 | Method for preparing (E)-2-(2-substituted phenyl)-2-methoxyimino acetic acid derivative |
| CN108299197A (en) * | 2018-02-06 | 2018-07-20 | 荆楚理工学院 | A kind of 3- alkoxy acrylic esters synthetic method |
| CN112624922A (en) * | 2020-11-26 | 2021-04-09 | 青岛科技大学 | Method for alkylation reaction by phase transfer catalysis |
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