A kind of 2-[4-(hydroxyphenoxy)] synthetic method of propionic acid
Technical field
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The invention belongs to chemosynthesis technical field, relate to a kind of compound 2-[4-(hydroxyphenoxy)] synthetic method of propionic acid.Synthesizing of pesticide intermediate.
Background technology
China is a large agricultural country, and the consumption of agricultural chemicals is very big, and weedicide is reliable, the most most economical means in the farmland weeding technology as the important component of modern agriculture production system.Yet traditional weedicide is big because of its toxicity, efficient is low, dosage is big, just progressively be eliminated to environmental influence is very big.Therefore, modern agricultural chemicals is had higher requirement to weedicide: efficient, low toxicity.A series of weedicides such as diphenyl ether and phenoxy propionic acid class, sulfonylurea and imidazolone type, the ureas that contains pyridine ring, pyridazine class etc. have been developed in recent years in succession.The phenoxy propionic acid compounds has efficiently, low toxicity, herbicidal spectrum is wide, selectivity is high, the phase of using is long, to characteristics such as succession crop safety, be one of best weedicide of performance up to now.
2-[4-(hydroxyphenoxy)] propionic acid is the important intermediate of synthesis of phenoxy and heterocyclic oxy group phenoxy propionic acid class weedicide.At present, preparing 2-[4-(hydroxyphenoxy)] method of propionic acid has: (1) is that raw material and alpha-halogen propionic ester react ([P] .US 614 814 that finishes with the Resorcinol; [P] .US 4 489 207); (2) with the parahydroxyacet-ophenone be initiator, with alpha-halogen propionic ester reaction, again through oxidation, hydrolysis and get ([P] .EP 0 334 595); (3) adopting ethyl lactate is raw material, is under the acid binding agent condition at the triethylamine organic weak base, through acidylate, condensation reaction synthetic (Jiamusi University's journal, ,23 (2), 260-264) etc.Some reaction process generates a large amount of by products in these methods, and is difficult to remove, and has a strong impact on the purification and the productive rate of target product; Some method long reaction time, and total recovery is on the low side; Also some method need be used catalyzer, severe reaction conditions, and the production cost height is not suitable for industrial production.
Summary of the invention
The objective of the invention is in order to solve problems of the prior art, a kind of cost cheapness, pesticide intermediate 2-[4-(hydroxyphenoxy) efficiently be provided] synthetic method of propionic acid.
2-[4-of the present invention (hydroxyphenoxy)] synthetic method of propionic acid, comprise following processing step:
(1) makes solvent with dehydrated alcohol, with mono-benzyl ether of hydroquinone, sodium hydroxide and 2 bromopropionic acid ethyl ester mixed in molar ratio, stirring at normal temperature 4&#;6h with 1: 1: 1.2&#;1: 1: 1.5; Extraction, drying concentrates, and separates, and gets compound 2-(4-(benzyloxy) phenoxy group) ethyl propionate;
(2) under protection of inert gas, in 2-(4-(benzyloxy) phenoxy group) ethyl propionate, add reductive agent boron trifluoride-ether and Na I, stir 1&#;3h down at 0&#;5 &#;; Extraction, drying concentrates, and separates, and gets 2-(4-hydroxyphenoxy) ethyl propionate.
The add-on of described boron trifluoride-ether is 1&#;3 times of 2-(4-hydroxyphenoxy) ethyl propionate molar weight, and the add-on of NaI is 1&#;3 times of 2-(4-(benzyloxy) phenoxy group) ethyl propionate molar weight.
(3) 2-(4-hydroxyphenoxy) ethyl propionate is joined in mass concentration 5%&#;10%NaOH solution stirring at normal temperature 2&#;4h; Reaction 0&#;5 &#; of following dripping hydrochloric acid, makes pH=1&#;3 of reaction solution after finishing, and continues to stir 1&#;2h; Extraction, drying concentrates, and uses pure recrystallization again, promptly gets white solid 2-[4-(hydroxyphenoxy)] propionic acid.
Above-mentioned separating technology adopts silica gel column chromatography to separate.
Described mono-benzyl ether of hydroquinone is by following prepared: under alkaline condition, with DMF is solvent, and Resorcinol and Benzyl Chloride are under the condition of 280&#;350W with 1.2: 1&#;1.5: 1 mixed in molar ratio at microwave irradiation power, radioreaction 1&#;2min, be cooled to room temperature, suction filtration, filtrate separates out mono-benzyl ether of hydroquinone with hcl acidifying fully, again after suction filtration and frozen water washing, use pure recrystallization, activated carbon decolorizing gets the white solid mono-benzyl ether of hydroquinone.Described alkaline condition is an aqueous sodium hydroxide solution, and sodium hydroxide and Resorcinol equimolar amount.
Described 2 bromopropionic acid ethyl ester is by following prepared: under protection of inert gas, with ethyl lactate and phosphorus tribromide mixed in molar ratio with 3: 1&#;2: 1, stirring at normal temperature reaction 3&#;6h, extraction, dry, concentrate, separate, colourless liquid 2 bromopropionic acid ethyl ester.
Synthetic route is as follows:
Reaction product is through magnetic resonance detection, and product is pure product.
The relative prior art of the present invention is compared and is had the following advantages:
The present invention is a raw material with Resorcinol and ethyl lactate; prevented the generation of bis ether through the monohydroxy protection; make 2-[4-(hydroxyphenoxy) through hydroxyl deprotection, hydrolysis again] propionic acid; mild condition; reaction times is short, and aftertreatment is simple, the yield height; production cost is low, has better industrial application prospects.
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Embodiment
Below by specific embodiment to 2-[4-of the present invention (hydroxyphenoxy)] synthetic method of propionic acid is described further.
(1) preparation of 2 bromopropionic acid ethyl ester
Under nitrogen environment, get the there-necked flask of a dried and clean, add ethyl lactate 3.54g (0.03mol), phosphorus tribromide 3.25g (0.012mol) successively, stirring at normal temperature 5h, reaction process is followed the tracks of with thin layer chromatography.Reaction finishes the back and drips saturated sodium bicarbonate solution generate to there being gas in reaction solution, adds the ethyl acetate extraction three times that volume adds the saturated sodium bicarbonate solution twice approximately again, gets extraction liquid.Extraction liquid is through dried over mgso, after filtering filtrate, must concentrated solution after the RE-52AA type Rotary Evaporators that filtrate is produced with the inferior Rong Shenghua in Shanghai company limited concentrates; The silica gel (300&#;400 order) that adds 2&#;3 times of concentrated solution quality again in concentrated solution is mixed sample, to mix sample and put into chromatography column, the mixed solution that adds volume ratio and be 20: 1 sherwood oil and ethyl acetate carries out wash-out to be separated, collect elutriant at last, elutriant is put into Rotary Evaporators concentrate, promptly get colourless liquid 2 bromopropionic acid ethyl ester 4.8g.Reaction yield is 88%.
(2) preparation of mono-benzyl ether of hydroquinone
In the 100mL flask, add Resorcinol 3.08g (0.028mol).
Take by weighing 1.12g (0.028mol) sodium hydroxide, add 8mL water, treat to drop to after the dissolution of sodium hydroxide in the above-mentioned flask that fills Resorcinol, fully shake up, adding 15mL DMF and 2.52g (0.02mol) Benzyl Chloride again, is under the condition of 320W at microwave irradiation power, radioreaction 60s.Reaction finishes postcooling to room temperature.Earlier transfer to alkalescence with 10% sodium hydroxide, suction filtration, filter cake wash to filtrate with 10% sodium hydroxide and are colourless (filter cake is quinhydrones pair benzyl oxides, recyclable utilization).Filtrate separates out mono-benzyl ether of hydroquinone with hcl acidifying fully, after suction filtration and frozen water washing, uses ethyl alcohol recrystallization again, and activated carbon decolorizing gets white solid mono-benzyl ether of hydroquinone 2.56g, and yield is 64%.
(3) preparation of 2-(4-(benzyloxy) phenoxy group) ethyl propionate
In the 100mL flask, take by weighing 2.50g (0.mol) mono-benzyl ether of hydroquinone, 0.5g (0.mol) sodium hydroxide and 2.90g (0.016mol) 2 bromopropionic acid ethyl ester successively, add the 15mL dehydrated alcohol again, stirring at normal temperature 5h, reaction process is followed the tracks of with TLC (thin layer chromatography).Reaction finishes the back removes ethanol in the reaction solution earlier with Rotary Evaporators, toward wherein adding the 10mL saturated ammonium chloride solution, use 3 * 15mL ethyl acetate extraction then 3 times again.Extraction liquid gets filtrate after filtering through dried over mgso, gets concentrated solution after filtrate is concentrated with Rotary Evaporators; The silica gel that adds 2&#;3 times of concentrated solution quality in concentrated solution is mixed sample again, to mix sample and put into chromatography column, the mixed solution that adds volume ratio and be 10: 1 sherwood oil and ethyl acetate carries out wash-out to be separated, collect elutriant at last, elutriant is put into Rotary Evaporators concentrate, promptly get compound 2-(4-(benzyloxy) phenoxy group) ethyl propionate 2.1g.The mono-benzyl ether of hydroquinone transformation efficiency is 58%, and the residue mono-benzyl ether of hydroquinone is recyclable to be utilized again; Reaction yield is 56%.
Warp
1HNMR,
13CNMR detects, and its product is pure product.Its each performance index or characterization data are as follows:
1H NMR (400MHz, CDCl
3): δ=7.40-7.29 (m, 4H), 6.88-6.80 (m, 4H), 4.97 (s, 2H), 4.64 (dd, J
1=1.6Hz, J
2=6.8Hz, 1H), 4.21 (m, 2H), 1.56 (d, J=1.6Hz, 3H), 1.24-1.19 (m, 3H);
13C NMR (100MHz, CDCl
3): δ=172.45,153.96,150.25,142.21,130.19,128.57,128.21,116.69,115.78,70.56,69.38,61.53,16.35,14.98.
(4) preparation of 2-(4-hydroxyphenoxy) ethyl propionate
Under nitrogen environment, with 2-(4-(benzyloxy) phenoxy group) ethyl propionate 2.0g (0.mol), boron trifluoride-ether 2.82g (0.02mol) and NaI 1.5g (0.01mol) join in the 100mL flask, stir 1.5h in ice-water bath.Reaction drips saturated sodium bicarbonate solution after finishing in reaction solution, stirring at normal temperature does not produce to there being bubble; Add volume again and add approximately the ethyl acetate extraction three times of saturated sodium bicarbonate solution twice, must extraction liquid.Extraction liquid gets filtrate after filtering through dried over mgso, gets concentrated solution after filtrate is concentrated with Rotary Evaporators; The silica gel that adds 2&#;3 times of concentrated solution quality in concentrated solution is mixed sample again, to mix sample and put into chromatography column, the mixed solution that adds volume ratio and be 20: 1 sherwood oil and ethyl acetate carries out wash-out to be separated, collect elutriant at last, elutriant is put into Rotary Evaporators concentrate, promptly get compound 2-(4-hydroxyphenoxy) ethyl propionate 1.2g.Reaction yield 86%.
Warp
1HNMR,
13CNMR detects, and its product is pure product.Its each performance index or characterization data are as follows:
1H NMR (400MHz, CDCl
3): δ=6.78-6.71 (m, 4H), 5.62 (s, 1H), 4.65 (q, J=6.8Hz, 1H), 4.22 (dd, J
1=0.8Hz, J
2=7.2Hz, 2H), 1.59 (d, J=6.8Hz, 3H), 1.25 (t, J=7.6Hz, 3H);
13C NMR (100MHz, CDCl
3): δ=172.48,153.69,151.28,118.67,117.53,70.36,59.66,16.27,14.86.
(5) 2-[4-(hydroxyphenoxy)] preparation of propionic acid
2-(4-hydroxyphenoxy) ethyl propionate 1.05g (0.005mol) is joined in the 8mL 10%NaOH solution stirring at normal temperature 3h.Under the ice-water bath cooling, drip 2mol/L hydrochloric acid then, continue to stir 1h to reaction solution pH=1.With the reaction solution ethyl acetate extraction, extraction liquid gets filtrate more after filtering through dried over mgso, filtrate is concentrated with Rotary Evaporators obtain crude product afterwards.Crude product further promptly gets white solid 2-[4-(hydroxyphenoxy) with ethyl alcohol recrystallization] propionic acid 0.85g.Reaction yield is 93%.
Warp
1HNMR,
13CNMR detects, and its product is pure product.Its each performance index or characterization data are as follows:
1H NMR (400MHz, DMSO-d
6): δ=11.6 (s, 1H), 6.68-6.61 (m, 4H), 4.65 (m, 1H), 1.36 (d, J=6.8Hz, 3H);
13C NMR (100MHz, DMSO-d
6): δ=174.26,153.22,151.76,120.35,119.55,72.36,16.84.
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