CN103333145B - Preparation method of 3-(alpha- methoxyl) methylene benzofuran-2(3H)-ketone - Google Patents
Preparation method of 3-(alpha- methoxyl) methylene benzofuran-2(3H)-ketone Download PDFInfo
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- CN103333145B CN103333145B CN201310310216.3A CN201310310216A CN103333145B CN 103333145 B CN103333145 B CN 103333145B CN 201310310216 A CN201310310216 A CN 201310310216A CN 103333145 B CN103333145 B CN 103333145B
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Abstract
The invention discloses a preparation method of 3-(alpha- methoxyl) methylene benzofuran-2(3H)-ketone. The method comprises the following steps of mixing benzofuran-2(3H)-ketone, trimethyl orthoformate and lewis acid, heating the mixture, adding recrystallization solvent after the reaction is ended, and cooling, crystallizing, filtering and drying the product to obtain the 3-(alpha- methoxyl) methylene benzofuran-2(3H)-ketone. The preparation method of the 3-(alpha- methoxyl) methylene benzofuran-2(3H)-ketone adopts the lewis acid catalysis. Compared with the prior art, no anhydride is added in the reaction, the high vacuumness and high temperature are not needed to recycle the excessive anhydride and byproducts produced by the anhydride after the reaction, so that the coking and sublimation phenomenon of the product can be avoided, and the recycling process is simple and convenient; and meanwhile, compared with preparation method adopting acetic acid as the catalyst, the consumption of the lewis acid is less, the consumption of raw materials can be greatly reduced, and the atom economy is good.
Description
Technical field
The present invention relates to the preparation method of a kind of 3-(α-methoxyl group) methene cumarone-2 (3H)-one.
Background technology
3-(α-methoxyl group) methene cumarone-2 (3H)-one is the important intermediate of synthesizing fungicide Azoxystrobin, and the method that bibliographical information produces 3-(α-methoxyl group) methene cumarone-2 (3H)-one has three kinds:
1, o-hydroxy phenylacetic acid dewater under the katalysis of acid generate cumarone-2 (3H)-one, separation and purification or one kettle way and diacetyl oxide and trimethyl orthoformate are obtained by reacting target compound, by-product acetic acid and methyl acetate simultaneously, reaction can use toluene equal solvent or not use any solvent, and reaction formula is as follows:
Detailed preparation method is shown in that publication number is the patent of US5760250, and publication number is the patent of CN1219537A, agricultural chemicals, 2004,43 (9), 414-416.
2, o-hydroxy phenylacetic acid directly and acid anhydrides and trimethyl orthoformate be obtained by reacting target compound, reaction equation is as follows:
Conventional acid anhydrides has diacetyl oxide, propionic anhydride and isobutyric anhydride etc., the corresponding carboxylic acid of by-product and carboxylate methyl ester.Detailed preparation method is shown in that publication number is the patent of US5760250, Chin.J.Chem.2012,30,1517-1524, Bull.Korean Chem.Soc., 2012,33 (8), 2627-2634. etc.
All there is following shortcoming in above two kinds of methods:
1) diacetyl oxide is excessive, and need after reaction terminates to reclaim acetic acid and diacetyl oxide mixture, and need rectifying purifies and separates acetic acid and diacetyl oxide, process is complicated, and energy consumption is high;
2) because diacetyl oxide boiling point is high, need high temperature high vacuum when reclaiming excessive acetic acid acid anhydride, product easily distils and carbonization;
3) trimethyl orthoformate is excessive, and not only production cost is high, in reaction process, easily resolve into methyl-formiate, steam reaction system together with by-product methyl acetate, need directly discarded or rectifying separation to obtain methyl acetate and methyl-formiate respectively, process is complicated, add energy consumption, raw materials consumption is high.
3, solvent made by acetic acid
For avoiding above shortcoming, Journal of the American Chemical Society, 2007,12 (41), 12396-12397, report the method that cumarone-2 (3H)-one and trimethyl orthoformate synthesize target compound in acetic acid, material ratio is cumarone-2 (3H)-one: trimethyl orthoformate: acetic acid=1:1.5:7, yield 69%.The usage quantity of acetic acid is excessive, still uneconomical.
Summary of the invention
In view of this, the invention provides the preparation method of a kind of 3-(α-methoxyl group) methene cumarone-2 (3H)-one, reaction does not need to add acid anhydrides, the by product not needing high vacuum and high-temperature to reclaim excessive acid anhydrides and produced by acid anhydrides after reaction terminates, and raw materials consumption reduces greatly, Atom economy is good.
The preparation method of 3-of the present invention (α-methoxyl group) methene cumarone-2 (3H)-one, cumarone-2 (3H)-one, trimethyl orthoformate and Lewis acid mixing post-heating are reacted, add recrystallization solvent after reaction terminates, then crystallisation by cooling, filtration drying obtain 3-(α-methoxyl group) methene cumarone-2 (3H)-one product.
Further, described Lewis acid is aluminum chloride, iron trichloride, zinc chloride, tin tetrachloride or titanium tetrachloride.
Further, described cumarone-2 (3H)-one, trimethyl orthoformate and lewis acidic mol ratio are 1:1.05 ~ 2:0.01 ~ 0.05.
Further, the Heating temperature of described reacting by heating is 60 ~ 110 DEG C.
Further, termination reaction when described reacting by heating to the mass content of cumarone-2 (3H)-one is less than 2%.
Further, before described reacting by heating, in reaction system, add aromatic hydrocarbon solvent; Reaction terminates first to reclaim aromatic hydrocarbon solvent afterwards, and then adds recrystallization solvent, and crystallisation by cooling, filtration drying obtain 3-(α-methoxyl group) methene cumarone-2 (3H)-one product.
Further, described recrystallization solvent is methyl alcohol.
Beneficial effect of the present invention is: the present invention is a kind of preparation method of 3-(α-methoxyl group) methene cumarone-2 (3H)-one of Louis acid catalysis, and reaction equation is as follows:
The preparation method of the present invention's Louis acid catalysis is compared with existing preparation method, reaction does not need to add acid anhydrides, the by product not needing high vacuum and high-temperature to reclaim excessive acid anhydrides and produced by acid anhydrides after reaction terminates, thus there will not be product coking and distillation phenomenon, removal process is simple, convenient; Meanwhile, compared with the preparation method making solvent with acetic acid, lewis acidic usage quantity is very little, and raw materials consumption reduces greatly, and Atom economy is good; Products obtained therefrom purity of the present invention is greater than 97%, and yield is greater than 85%.
Embodiment
Below will be described in detail the preferred embodiments of the present invention.
Embodiment 1
Take cumarone-2 (3H)-one 54.7g(content 98%, 0.4mol), trimethyl orthoformate 46.7g(0.44mol) and aluminum trichloride (anhydrous) 0.55g(0.004mol) mixing, reacting by heating, regulate oil bath temperature to 110 DEG C, sample after 4 hours, the mass content that HPLC detects cumarone-2 (3H)-one is 1.41%, termination reaction; Add 150mL methyl alcohol, mixing, crystallisation by cooling, filtration drying obtain faint yellow 3-(α-methoxyl group) methene cumarone-2 (3H)-one product 61.2g, and it is 98.2% that HPLC detects purity, yield 85.4%.
Embodiment 2
Take cumarone-2 (3H)-one 54.7g(content 98%, 0.4mol), trimethyl orthoformate 46.7g(0.44mol) and zinc chloride 0.65g(0.0048mol) mixing, reacting by heating, regulate oil bath temperature to 110 DEG C, sample after 4 hours, the mass content that HPLC detects cumarone-2 (3H)-one is 1.38%, termination reaction; Add 150mL methyl alcohol, mixing, crystallisation by cooling, filtration drying obtain faint yellow 3-(α-methoxyl group) methene cumarone-2 (3H)-one product 63.5g, and it is 98.0% that HPLC detects purity, yield 88.4%.
Embodiment 3
Take cumarone-2 (3H)-one 54.7g(content 98%, 0.4mol), trimethyl orthoformate 63.7g(0.6mol) and zinc chloride 0.65g(0.0048mol) mixing, reacting by heating, regulate oil bath temperature to 110 DEG C, sample after 4 hours, the mass content that HPLC detects cumarone-2 (3H)-one is 0.56%, termination reaction; Add 150mL methyl alcohol, mixing, crystallisation by cooling, filtration drying obtain faint yellow 3-(α-methoxyl group) methene cumarone-2 (3H)-one product 65.4g, and it is 98.5% that HPLC detects purity, yield 91.5%.
Embodiment 4
Take cumarone-2 (3H)-one 54.7g(content 98%, 0.4mol), trimethyl orthoformate 63.7g(0.6mol) and zinc chloride 0.65g(0.0048mol) mixing, add 300mL toluene, reacting by heating, regulate oil bath temperature to 110 DEG C, sample after 4 hours, the mass content that HPLC detects cumarone-2 (3H)-one is 0.79%, termination reaction; Distillation recovery toluene, then adds 150mL methyl alcohol, mixing, and crystallisation by cooling, filtration drying obtain faint yellow 3-(α-methoxyl group) methene cumarone-2 (3H)-one product 62.0g, and it is 97.8% that HPLC detects purity, yield 86.2%.
In the present invention, the Lewis acid of catalyzed reaction is not limited to aluminum chloride and the zinc chloride of above-described embodiment, and all the other common Lewis acids, such as iron trichloride, tin tetrachloride, titanium tetrachloride etc., all can reach identical effect.The principle that Louis acid catalysis 3-(α-methoxyl group) methene cumarone-2 (3H)-one building-up reactions occurs is first cumarone-2 (3H)-one carbonyl and Lewis acid complexing, enhance the nucleophilicity of alpha-carbon, make it very easily be obtained by reacting target product with trimethyl orthoformate and discharge Lewis acid simultaneously, whole reaction process Lewis acid only plays katalysis and is not consumed, therefore, lewis acidic usage quantity is very little, raw materials consumption reduces greatly, and Atom economy is good.
In the present invention, cumarone-2 (3H)-one, trimethyl orthoformate and the preferred mol ratio of Lewis acid are 1:1.05 ~ 2:0.01 ~ 0.05; The preferred Heating temperature of reacting by heating is 60 ~ 110 DEG C; Can not add solvent in reaction system, also can carry out in a solvent, solvent can select aromatic hydrocarbon solvent, as toluene, dimethylbenzene, chlorobenzene etc.
What finally illustrate is, above embodiment is only in order to illustrate technical scheme of the present invention and unrestricted, although by referring to the preferred embodiments of the present invention, invention has been described, but those of ordinary skill in the art is to be understood that, various change can be made to it in the form and details, and not depart from the spirit and scope of the present invention that appended claims limits.
Claims (6)
1. the preparation method of 3-(α-methoxyl group) methene cumarone-2 (3H)-one, it is characterized in that: cumarone-2 (3H)-one, trimethyl orthoformate and Lewis acid mixing post-heating are reacted, add recrystallization solvent after reaction terminates, then crystallisation by cooling, filtration drying obtain 3-(α-methoxyl group) methene cumarone-2 (3H)-one product; Described Lewis acid is aluminum chloride, iron trichloride, zinc chloride, tin tetrachloride or titanium tetrachloride.
2. the preparation method of 3-according to claim 1 (α-methoxyl group) methene cumarone-2 (3H)-one, is characterized in that: described cumarone-2 (3H)-one, trimethyl orthoformate and lewis acidic mol ratio are 1:1.05 ~ 2:0.01 ~ 0.05.
3. the preparation method of 3-according to claim 1 (α-methoxyl group) methene cumarone-2 (3H)-one, is characterized in that: the Heating temperature of described reacting by heating is 60 ~ 110 DEG C.
4. the preparation method of 3-according to claim 1 (α-methoxyl group) methene cumarone-2 (3H)-one, is characterized in that: termination reaction when described reacting by heating to the mass content of cumarone-2 (3H)-one is less than 2%.
5. the preparation method of 3-according to claim 1 (α-methoxyl group) methene cumarone-2 (3H)-one, is characterized in that: before described reacting by heating, in reaction system, adds aromatic hydrocarbon solvent; Reaction terminates first to reclaim aromatic hydrocarbon solvent afterwards, and then adds recrystallization solvent, and crystallisation by cooling, filtration drying obtain 3-(α-methoxyl group) methene cumarone-2 (3H)-one product.
6. the preparation method of 3-according to claim 1 (α-methoxyl group) methene cumarone-2 (3H)-one, is characterized in that: described recrystallization solvent is methyl alcohol.
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