CN103254028A - Method for synthesizing carboxylic acid by removing benzyl protection of benzyl carboxylate - Google Patents
Method for synthesizing carboxylic acid by removing benzyl protection of benzyl carboxylate Download PDFInfo
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- CN103254028A CN103254028A CN2013101926703A CN201310192670A CN103254028A CN 103254028 A CN103254028 A CN 103254028A CN 2013101926703 A CN2013101926703 A CN 2013101926703A CN 201310192670 A CN201310192670 A CN 201310192670A CN 103254028 A CN103254028 A CN 103254028A
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- benzyl
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- toluene
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
The invention provides a method for synthesizing carboxylic acid by removing benzyl protection of benzyl carboxylate, and relates to a method for removing benzyl protection of benzyl carboxylate. The method comprises the following steps: performing one-step reaction on various kinds of benzyl carboxylate used as raw materials, toluene used as reaction reagent and solvent and boron trifluoride etherate used as additive, concentrating, and purifying to obtain the finished product. The method has the characteristics that the method is easy and simple to operate, no metal participates in the catalysis, the yield is high, the application and popularization are convenient to realize and the like; and by adopting the method provided by the invention, benzyl protecting groups on carboxyl can be effectively removed. The method provided by the invention can be widely used for industrial production of various kinds of carboxylic acid; and the product prepared by the method can be widely used in the fields such as medicine, agriculture chemicals, paint, daily chemicals, chemical raw materials and the like, and can meet the requirements of the market for high demand in multiple fields.
Description
Technical field
The invention belongs to the organic chemical synthesis technical field, be specifically related to the method that benzyl carboxylate removes the benzyl protection synthesis of carboxylic acid.
Background technology
Carboxyl extensively is present in the material of biologically active, as the fundamental unit amino acid that constitutes protein etc.Though carboxyl is more stable generally speaking, in specific synthesizing, also often need protection, so that react at other position of molecule.The protective devices that carboxylic acid is commonly used is to introduce benzyl by benzyl halide to form benzyl carboxylate.The deprotection of benzyl carboxylate goes the benzyl method normally in acid, under the alkaline condition, hydrolysis reaction takes place or realizes through the Pd/C catalytic hydrogenation.The method of existing benzyl carboxylate debenzylation, for example the disclosed patent No. in 2011 is in the patent of 102219736 " preparation method of 8-quinoline methyl ester and 8-quinolinecarboxylic acid ", disclosed method is to be raw material with 8-quinolinecarboxylic acid benzyl ester, methyl alcohol is solvent, and Pd/C is catalyzer, falls air with hydrogen exchange, reaction vessel is forced into 0.3MPa, the complete after-filtration of room temperature reaction falls Pd/C, and filtrate concentrating drained and obtained the 8-quinolinecarboxylic acid, and productive rate reaches 99%.This method is at room temperature carried out, and yield is higher, but mainly there is following deficiency in this method:
1. used the expensive precious metals pd/C of price as catalyzer;
2. reaction needed is carried out under the hydrogen condition, and needs pressurization, and complex operation has certain requirement to reaction vessel, the production cost height;
3. the use of hydrogen is dangerous big, and sneaks into metallic impurity such as Pd in the product unavoidably.
Summary of the invention
The objective of the invention is provides a kind of benzyl carboxylate to go the method for benzyl protection synthesis of carboxylic acid at having the weak point that benzyl carboxylate removes the benzyl protection synthesis of carboxylic acid now.Present method has the preparation feedback production safety, and processing condition are not harsh, production unit is required low, and reaction reagent cheaply is easy to get, and technology is simple, and production cost is low, and product is purified simple, and environmental pollution is little and do not have an advantage such as metal participation.
The present invention has adopted eco-friendly, and cheap efficient reagent boron trifluoride diethyl etherate provides a kind of simple, green cleaning, that economical and practical benzyl carboxylate removes benzyl protection synthesis of carboxylic acid method.
The technical scheme that realizes the object of the invention is: a kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, is raw material with the benzyl carboxylate, and toluene is reaction reagent and solvent, and boron trifluoride diethyl etherate is additive, generates carboxylic acid through single step reaction.Its concrete grammar step is as follows:
(1) reacts
Be raw material with the benzyl carboxylate, being reaction reagent and solvent with toluene, is additive with the boron trifluoride diethyl etherate, and according to the benzyl carboxylate mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: (2.0～4.0): the ratio of (1.2～2.4), in reaction vessel, add benzyl carboxylate earlier, under the stirring action, add toluene, add boron trifluoride diethyl etherate again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution of benzyl carboxylate synthesis of carboxylic acid.
(2) carry out that product concentrates, purifying
(1) step finish after, go on foot the carboxylic acid reaction liquid of preparing to (1), naturally cooling in air, use is revolved and is steamed instrument rotary evaporation concentration of reaction solution, to concentrated solution through purification by silica gel column chromatography, carry out wash-out with elutriant, to the effluent liquid of silica gel column chromatography through rotary evaporation concentrate, drain the pure product of product;
Described elutriant is pure sherwood oil, ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (2～50) and methyl alcohol: the volume ratio of ethyl acetate is 1: 3 mixed solution.
After the present invention adopts technique scheme, mainly contain following effect:
(1) the reaction additives boron trifluoride diethyl etherate cheaply is easy to get, and no metal participates in, economic environmental protection.
(2) be reflected under the open reflux conditions and carry out, need not extra operating equipment such as pressurization, sealing, working condition requires not harsh, simple to operate, and production cost is low.
(3) avoid the Pd/C catalytic hydrogenation method used always, production safety.
Embodiment
Below in conjunction with embodiment, further specify the present invention.
Embodiment 1
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are as follows:
(1) with the peruscabin is raw material, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to the peruscabin mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add peruscabin 212.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains peruscabin and generates benzoic reaction solution.
(2) carry out that product concentrates, purifying
(1) step finish after, go on foot the benzoic acid liquid of preparing to (1), naturally cooling in air, use is revolved and is steamed instrument rotary evaporation concentration of reaction solution, to concentrated solution through purification by silica gel column chromatography, carry out wash-out with elutriant, to the effluent liquid of silica gel column chromatography through rotary evaporation concentrate, drain white solid phenylformic acid 111.1mg (yield 91%).
Described elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50).
Embodiment 2
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with m-phthalic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to m-phthalic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 4: 2.4 ratio, in reaction vessel, add m-phthalic acid dibenzyl ester 346.1mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that the m-phthalic acid dibenzyl ester generates m-phthalic acid.
In the step (2), elutriant is pure sherwood oil, ethyl acetate: the volume ratio of sherwood oil is 1: 40 mixed solution and methyl alcohol: the volume ratio of ethyl acetate is 1: 3 mixed solution, gets white solid m-phthalic acid 164.4mg (yield 99%).
Embodiment 3
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with the NSC 25467, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to the NSC 25467 mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add NSC 25467 226.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that NSC 25467 generates p-methylbenzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid p-methylbenzoic acid 127.0mg (yield 93%).
Embodiment 4
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with m-methyl benzoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to m-methyl benzoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add m-methyl benzoic acid benzyl ester 226.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that m-methyl benzoic acid benzyl ester generates m-methyl benzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid m-methyl benzoic acid 125.8mg (yield 92%).
Embodiment 5
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with o-toluic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to o-toluic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add o-toluic acid benzyl ester 226.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that o-toluic acid benzyl ester generates o-toluic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid o-toluic acid 132.0mg (yield 97%).
Embodiment 6
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with Chlorodracylic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to Chlorodracylic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add Chlorodracylic acid benzyl ester 246.7mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that Chlorodracylic acid benzyl ester generates Chlorodracylic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid Chlorodracylic acid 151.4mg (yield 97%).
Embodiment 7
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with m-chlorobenzoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to m-chlorobenzoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add m-chlorobenzoic acid benzyl ester 246.6mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that m-chlorobenzoic acid benzyl ester generates m-chlorobenzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid m-chlorobenzoic acid 142.9mg (yield 91%).
Embodiment 8
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with 0-chloro-benzoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to 0-chloro-benzoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add 0-chloro-benzoic acid benzyl ester 246.6mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that 0-chloro-benzoic acid benzyl ester generates 0-chloro-benzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid 0-chloro-benzoic acid 143.9mg (yield 92%).
Embodiment 9
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with p-nitrobenzoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to p-nitrobenzoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add p-nitrobenzoic acid benzyl ester 257.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that p-nitrobenzoic acid benzyl ester generates p-nitrobenzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid p-nitrobenzoic acid 161.5mg (yield 97%).
Embodiment 10
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with M-NITROBENZOIC ACID benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to M-NITROBENZOIC ACID benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add M-NITROBENZOIC ACID benzyl ester 257.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that M-NITROBENZOIC ACID benzyl ester generates M-NITROBENZOIC ACID.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid M-NITROBENZOIC ACID 162.3mg (yield 97%).
Embodiment 11
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with parafluorobenzoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to parafluorobenzoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add parafluorobenzoic acid benzyl ester 230.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that parafluorobenzoic acid benzyl ester generates parafluorobenzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid parafluorobenzoic acid 133.5mg (yield 95%).
Embodiment 12
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with o-iodobenzoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to o-iodobenzoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add o-iodobenzoic acid benzyl ester 338.1mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that o-iodobenzoic acid benzyl ester generates o-iodobenzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid o-iodobenzoic acid 241.4mg (yield 97%).
Embodiment 13
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with paracyanobenzoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to paracyanobenzoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add paracyanobenzoic acid benzyl ester 237.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that paracyanobenzoic acid benzyl ester generates paracyanobenzoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (2～50) gets white solid paracyanobenzoic acid 144.1mg (yield 98%).
Embodiment 14
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with anisic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to anisic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 2 ratio, in reaction vessel, add anisic acid benzyl ester 242.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that anisic acid benzyl ester generates anisic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid anisic acid 132.3mg (yield 87%).
Embodiment 15
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with the cinnamein, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to the cinnamein mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add cinnamein 238.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that cinnamein generates styracin.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid styracin 137.4mg (yield 93%).
Embodiment 16
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with Alpha-Methyl-cinnamein, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to Alpha-Methyl-cinnamein mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add Alpha-Methyl-cinnamein 252.3mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that Alpha-Methyl-cinnamein generates Alpha-Methyl-styracin.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid Alpha-Methyl-styracin 158.8mg (yield 98%).
Embodiment 17
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with the phenylpropyl alcohol acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to phenylpropyl alcohol acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 2 ratio, in reaction vessel, add phenylpropyl alcohol acid benzyl ester 240.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that phenylpropionic acid benzyl ester generates phenylpropionic acid.
In the step (2), elutriant is pure sherwood oil, ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) and pure ethyl acetate get white solid phenylpropionic acid 147.1mg (yield 98%).
Embodiment 18
A kind of benzyl carboxylate goes the benzyl protection symphysis to become the method for carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with α-Nai Jiasuan benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to α-Nai Jiasuan benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add α-Nai Jiasuan benzyl ester 262.3mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that α-Nai Jiasuan benzyl ester generates α-Nai Jiasuan.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid α-Nai Jiasuan 170.3mg (yield 99%).
Embodiment 19
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with β-naphthoic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to β-naphthoic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add β-naphthoic acid benzyl ester 262.3mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that β-naphthoic acid benzyl ester generates β-naphthoic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid β-naphthoic acid 170.4mg (yield 99%).
Embodiment 20
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with 2-thiophenic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to 2-thiophenic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add 2-thiophenic acid benzyl ester 218.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that 2-thiophenic acid benzyl ester generates the 2-thiophenic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid 2-thiophenic acid 126.8mg (yield 99%).
Embodiment 21
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with 2-furancarboxylic acid benzyl ester, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to 2-furancarboxylic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2 ratio, in reaction vessel, add 2-furancarboxylic acid benzyl ester 202.2mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that 2-furancarboxylic acid benzyl ester generates the 2-furancarboxylic acid.
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid 2-furancarboxylic acid 111.2mg (yield 99%).
Embodiment 22
A kind of benzyl carboxylate goes the method for benzyl protection synthesis of carboxylic acid, and its concrete steps are with embodiment 1, wherein:
Step (1) is raw material with the benzyl laurate, be reaction reagent and solvent with toluene, be additive with the boron trifluoride diethyl etherate, according to the benzyl laurate mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 2 ratio, in reaction vessel, add benzyl laurate 290.4mg (1mmol) earlier, under the stirring action, add toluene 2mL, add boron trifluoride diethyl etherate 151 μ L (1.2mmol) again, finish, oil bath is warming up to 80 ℃, continues stirring and refluxing reaction 2 hours, just obtains the reaction solution that benzyl laurate generates laurostearic acid.
In the step (2), elutriant is pure sherwood oil, ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) and pure ethyl acetate get white solid laurostearic acid 184.3mg (yield 92%).
Claims (5)
1. method that benzyl carboxylate removes the benzyl protection synthesis of carboxylic acid is characterized in that concrete method steps is as follows:
(1) reacts
Be raw material with the benzyl carboxylate, being reaction reagent and solvent with toluene, is additive with the boron trifluoride diethyl etherate, and according to the benzyl carboxylate mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: (2.0～4.0): the ratio of (1.2～2.4), in reactor, add benzyl carboxylate earlier, under the stirring action, add toluene, add boron trifluoride diethyl etherate again, finish, oil bath temperature rises to 80 ℃ of open backflows, continues stirring reaction 2 hours, just obtains the reaction solution that benzyl carboxylate generates carboxylic acid;
(2) carry out that product concentrates, purifying
(1) step finish after, go on foot the carboxylic acid reaction liquid of preparing to (1), naturally cooling in air, use is revolved and is steamed instrument rotary evaporation concentration of reaction solution, to concentrated solution through purification by silica gel column chromatography, carry out wash-out with elutriant, to the effluent liquid of silica gel column chromatography through rotary evaporation concentrate, drain the pure product of product;
Described elutriant is pure sherwood oil, ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (2～50) and methyl alcohol: the volume ratio of ethyl acetate is 1: 3 mixed solution.
2. the method for removing the benzyl protection synthesis of carboxylic acid according to the described a kind of benzyl carboxylate of claim 1, it is characterized in that: in the step (1), raw material is peruscabin, reaction reagent and solvent are toluene, additive is boron trifluoride diethyl etherate, peruscabin mmole: toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2, and oil bath temperature rises to 80 ℃, continues stirring reaction 2 hours;
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets the white solid phenylformic acid.
3. the method for removing the benzyl protection synthesis of carboxylic acid according to the described a kind of benzyl carboxylate of claim 1, it is characterized in that: in the step (1), raw material is the m-phthalic acid dibenzyl ester, reaction reagent and solvent are toluene, additive is boron trifluoride diethyl etherate, m-phthalic acid dibenzyl ester mmole: toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 4: 2.4, and oil bath temperature rises to 80 ℃, continues stirring reaction 2 hours;
In the step (2), elutriant is pure sherwood oil, ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) and methyl alcohol: the volume ratio of ethyl acetate is 1: 3 mixed solution, gets the white solid m-phthalic acid.
4. the method for removing the benzyl protection synthesis of carboxylic acid according to the described a kind of benzyl carboxylate of claim 1, it is characterized in that: in the step (1), raw material is α-Nai Jiasuan benzyl ester, reaction reagent and solvent are toluene, additive is boron trifluoride diethyl etherate, α-Nai Jiasuan benzyl ester mmole: toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2, and oil bath temperature rises to 80 ℃, continues stirring reaction 2 hours;
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets the white solid α-Nai Jiasuan.
5. the method for removing the benzyl protection synthesis of carboxylic acid according to the described a kind of benzyl carboxylate of claim 1, it is characterized in that: in the step (1), raw material is 2-thiophenic acid benzyl ester, reaction reagent and solvent are toluene, additive is boron trifluoride diethyl etherate, 2-thiophenic acid benzyl ester mmole: the toluene milliliter: the ratio of boron trifluoride diethyl etherate mmole is 1: 2: 1.2, and oil bath temperature rises to 80 ℃, continues stirring reaction 2 hours;
In the step (2), elutriant is pure sherwood oil and ethyl acetate: the volume ratio of sherwood oil is 1: the mixed solution of (4～50) gets white solid 2-thiophenic acid.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4223132A (en) * | 1976-03-03 | 1980-09-16 | Shionogi & Co., Ltd. | Selective conversion of benzyl alcohol carboxylates to the free acid form |
| CN101010276A (en) * | 2004-07-26 | 2007-08-01 | 中外制药株式会社 | Novel cyclohexane derivative, prodrug thereof and salt thereof, and therapeutic agent containing the same for diabetes |
-
2013
- 2013-05-14 CN CN2013101926703A patent/CN103254028A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4223132A (en) * | 1976-03-03 | 1980-09-16 | Shionogi & Co., Ltd. | Selective conversion of benzyl alcohol carboxylates to the free acid form |
| CN101010276A (en) * | 2004-07-26 | 2007-08-01 | 中外制药株式会社 | Novel cyclohexane derivative, prodrug thereof and salt thereof, and therapeutic agent containing the same for diabetes |
Non-Patent Citations (2)
| Title |
|---|
| 康军: "三氟化硼乙醚络合物的合成与应用", 《上海化工》, vol. 24, no. 9, 30 September 1999 (1999-09-30) * |
| 朱华等: "一种选择性脱苄基方法在天然产物结构修饰中的应用", 《中南医药》, vol. 10, no. 6, 30 June 2012 (2012-06-30), pages 425 - 427 * |
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