CN102795994B - 5-cyclopropyl-2-hydroxy-benzoic acid, its synthetic method and application method - Google Patents
5-cyclopropyl-2-hydroxy-benzoic acid, its synthetic method and application method Download PDFInfo
- Publication number
- CN102795994B CN102795994B CN201210284007.1A CN201210284007A CN102795994B CN 102795994 B CN102795994 B CN 102795994B CN 201210284007 A CN201210284007 A CN 201210284007A CN 102795994 B CN102795994 B CN 102795994B
- Authority
- CN
- China
- Prior art keywords
- cyclopropyl
- degrees celsius
- hydroxy
- benzoic acid
- heated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The invention, relating to the technical field of synthesizing 5-cyclopropyl-2-hydroxy-benzoic acid by using salicylic acid, discloses 5-cyclopropyl-2-hydroxy-benzoic acid, its synthetic method and application method. The 5-cyclopropyl-2-hydroxy-benzoic acid is represented by C10H10O3, and has a molecular weight of 178.18. According to the invention, the process of synthesizing the 5-cyclopropyl-2-hydroxy-benzoic acid is simple with high yield, the application of the 5-cyclopropyl-2-hydroxy-benzoic acid in agricultural food preservation has significant effect, and the fruit respiration can be inhibited after using the 5-cyclopropyl-2-hydroxy-benzoic acid to process the fruits to increase the activity of polyphenoloxidase, effectively reduce the fruit hardness, and reduce the content of titratable acids, thus the storage and quality of the fruits are guaranteed.
Description
Technical field
The present invention relates to the technical field with the synthetic 5-cyclopropyl-2-hydroxy-benzoic acid of Whitfield's ointment, is a kind of 5-cyclopropyl-2-hydroxy-benzoic acid and synthetic method and application.
Background technology
Whitfield's ointment (Salicylic Acid, be called for short SA), is a kind of simple phenolic compound being extensively present in higher plant, can carry out the fruit after ability fresh-keeping, it is found that after SA processes, can reduce adopt after fruit rot; Delayed fruit is old and feeble; Can effectively keep fruit-vegetable quality; Strengthen the cold resistance of fruit; Rear fruit resistance enzymic activity is adopted in induction.But under Whitfield's ointment condition of normal pressure, be easy to resolve into phenol and carbonic acid gas, be difficult for preserving and using, restricted the application of Whitfield's ointment aspect fresh-keeping function.Except common preservation agent, also occurred some composite antistaling agents in the market, but composite antistaling agent is because formula is complicated, applies restricted.
Summary of the invention
The invention provides a kind of 5-cyclopropyl-2-hydroxy-benzoic acid and synthetic method and application, overcome the deficiency of above-mentioned prior art, it can effectively solve, and existing fruit freshness preserving agent prescription is complicated, the conditional problem of fresh-keeping application.Synthetic method craft process of the present invention is simple, yield is high.
One of technical scheme of the present invention realizes by following measures: a kind of 5-cyclopropyl-2-hydroxy-benzoic acid, its molecular formula is: C
10h
10o
3, molecular weight is: 178.18, and chemical structural formula is:
。
Two of technical scheme of the present invention realizes by following measures: a kind of synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid, carry out in the steps below:
The first step, halogenating reaction: Whitfield's ointment is dissolved in glacial acetic acid, then at room temperature add bromine and stir, after finishing, stirring carries out decompress filter, after decompress filter, obtain faint yellow solid filter cake, faint yellow solid filter cake water or ethyl alcohol recrystallization are obtained to white crystal, and white crystal is the bromo-2-hydroxy-benzoic acid of 5-;
Second step, alkylation or esterification: the bromo-2-hydroxy-benzoic acid of 5-and salt of wormwood are suspended in acetone, then at room temperature adding after methyl-sulfate is that 70 degrees Celsius to 75 degrees Celsius lower stirring and refluxing are spent the night in temperature, stirring and refluxing is cooled to room temperature and carries out decompress filter after having spent the night, after decompress filter, obtain filter cake and filtrate, filter cake washs by ethyl acetate, obtains washing lotion after washing; Washing lotion and filtrate are merged to rear pressure reducing and steaming solvent, resistates acetic acid ethyl dissolution after pressure reducing and steaming solvent, then with saturated aqueous common salt, wash, by anhydrous sodium sulphate, be dried, after dry, pressure reducing and steaming solvent obtains colourless liquid, and colourless liquid is the bromo-2-methoxyl group-methyl benzoate of 5-;
The 3rd step, linked reaction: by the bromo-2-methoxyl group-methyl benzoate of 5-, 1,1'-bis-(diphenyl phosphine) ferrocene palladium chloride, cyclopropylboronic acid and cesium carbonate are suspended in N, in the mixed solution that dinethylformamide and water form, be heated to 95 degrees Celsius to 105 degrees Celsius under the protection of nitrogen after, be cooled to room temperature, then cooled solution be poured into water, be then extracted with ethyl acetate water, extraction phase after aqueous phase extracted is organic phase, merges organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after being dried, uses column chromatography and obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-methoxyl group-methyl benzoate; Eluent during column chromatography for separation is ethyl acetate and sherwood oil, and the volume ratio of ethyl acetate and sherwood oil is 1: 10;
The 4th step, demethylation: 5-cyclopropyl-2-methoxyl group-methyl benzoate is dissolved in methylene dichloride, cooling rear dropping boron tribromide also stirs 1 hour to 1.5 hours, after completing, stirring is warming up to room temperature, then under ice-water bath is cooling, add saturated sodium bicarbonate solution to carry out separatory, after separatory, by methylene dichloride water aqueous phase extracted, merge organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after last pressure reducing and steaming solvent, obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters;
The 5th step, hydrolysis reaction: 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters is dissolved in tetrahydrofuran (THF), then add lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature, after cooling, carry out decompress filter, obtain filtrate after decompress filter, filtrate is extracted with ethyl acetate, with 1 N hydrochloric acid soln, the aqueous phase solution after extraction being adjusted to pH value is 1, then carries out decompress filter; After decompress filter, obtain white solid, white solid obtains white crystal with ethyl alcohol recrystallization, and this white crystal is 5-cyclopropyl-2-hydroxy-benzoic acid.
The further optimization and/or improvements to two of foregoing invention technical scheme below:
In above-mentioned the first step halogenating reaction, in every 250ml glacial acetic acid, dissolve in 13g to 15g Whitfield's ointment, then at room temperature add 15g to 17g bromine and stir.
In above-mentioned second step alkylation or esterification, in every 150ml acetone, be suspended with the bromo-2-hydroxy-benzoic acid of 5-of 12g to 14g and the salt of wormwood of 19g to 21g, then at room temperature adding after 13ml to 15ml methyl-sulfate is that 70 degrees Celsius to 75 degrees Celsius lower stirring and refluxing are spent the night in temperature.
In above-mentioned the 3rd step linked reaction; every 40mlN; in the mixed solution that dinethylformamide and 4ml water form, be suspended with 1g to 3g the bromo-2-methoxyl group-methyl benzoate of 5-, 0.5g 1; 1'-bis-(diphenyl phosphine) ferrocene palladium chloride, the cyclopropylboronic acid of 1.5g to 2g and the cesium carbonate of 6g to 7g; under the protection of nitrogen, be heated to 95 degrees Celsius to 105 degrees Celsius; heat and be cooled to room temperature after 3 hours to 6 hours, and cooled solution is poured into water.
In above-mentioned the 4th step demethylation, in the dry methylene dichloride of every 50ml, dissolve in 5-cyclopropyl-2-methoxyl group-methyl benzoate of 1.5g to 3g, drip boron tribromide and stir 1 hour to 1.5 hours at-80 degrees Celsius to-60 degrees Celsius after being cooled to-70 degrees Celsius to-80 degrees Celsius.
In above-mentioned the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of above-mentioned 5-cyclopropyl-2-hydroxy-benzoic acid, carry out in the steps below:
The first step, halogenating reaction: dissolve in 13g to 15g Whitfield's ointment in every 250ml glacial acetic acid, then at room temperature add 15g to 17g bromine and stir, after finishing, stirring carries out decompress filter, after decompress filter, obtain faint yellow solid filter cake, faint yellow solid filter cake water or ethyl alcohol recrystallization are obtained to white crystal, and white crystal is the bromo-2-hydroxy-benzoic acid of 5-;
Second step, alkylation or esterification: in every 150ml acetone, be suspended with the bromo-2-hydroxy-benzoic acid of 5-of 12g to 14g and the salt of wormwood of 19g to 21g, then at room temperature adding after 13ml to 15ml methyl-sulfate is that 70 degrees Celsius to 75 degrees Celsius lower stirring and refluxing are spent the night in temperature, stirring and refluxing is cooled to room temperature and carries out decompress filter after having spent the night, after decompress filter, obtain filter cake and filtrate, filter cake washs by ethyl acetate, obtains washing lotion after washing; Washing lotion and filtrate are merged to rear pressure reducing and steaming solvent, resistates acetic acid ethyl dissolution after pressure reducing and steaming solvent, then with saturated aqueous common salt, wash, by anhydrous sodium sulphate, be dried, after dry, pressure reducing and steaming solvent obtains colourless liquid, and colourless liquid is the bromo-2-methoxyl group-methyl benzoate of 5-;
The 3rd step, linked reaction: every 40mlN, in the mixed solution that dinethylformamide and 4ml water form, be suspended with 1g to 3g the bromo-2-methoxyl group-methyl benzoate of 5-, 0.5g 1,1'-bis-(diphenyl phosphine) ferrocene palladium chloride, the cyclopropylboronic acid of 1.5g to 2g and the cesium carbonate of 6g to 7g, under the protection of nitrogen, be heated to 95 degrees Celsius to 105 degrees Celsius, heat and be cooled to room temperature after 3 hours to 6 hours, and cooled solution is poured into water, then be extracted with ethyl acetate water, extraction phase after aqueous phase extracted is organic phase, merges organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after being dried, uses column chromatography and obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-methoxyl group-methyl benzoate; Eluent during column chromatography for separation is that the volume ratio of ethyl acetate and sherwood oil is 1: 10; Eluent during column chromatography for separation is ethyl acetate and sherwood oil, and the volume ratio of ethyl acetate and sherwood oil is 1: 10;
The 4th step, demethylation: the 5-cyclopropyl-2-methoxyl group-methyl benzoate that dissolves in 1.5g to 3g in the dry methylene dichloride of every 50ml, after being cooled to-70 degrees Celsius to-80 degrees Celsius, drip boron tribromide and stir 1 hour to 1.5 hours at-80 degrees Celsius to-60 degrees Celsius, after completing, stirring is warming up to room temperature, then under ice-water bath is cooling, add saturated sodium bicarbonate solution to carry out separatory, after separatory, by methylene dichloride water aqueous phase extracted, merge organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after last pressure reducing and steaming solvent, obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters;
The 5th step, hydrolysis reaction: the 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters that dissolves in 1g to 2g in every 20ml tetrahydrofuran (THF), then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature, after cooling, carry out decompress filter, obtain filtrate after decompress filter, filtrate is extracted with ethyl acetate, with 1 N hydrochloric acid soln, the aqueous phase solution after extraction being adjusted to pH value is 1, then carries out decompress filter; After decompress filter, obtain white solid, white solid obtains white crystal with ethyl alcohol recrystallization, and this white crystal is 5-cyclopropyl-2-hydroxy-benzoic acid.
Three of technical scheme of the present invention realizes by following measures: a kind of using method of 5-cyclopropyl-2-hydroxy-benzoic acid, during use, first 5-cyclopropyl-2-hydroxy-benzoic acid is made into 5-cyclopropyl-2-hydroxy-benzoic acid aqueous solution that concentration range is 1mg/L～50mg/L, then 5-cyclopropyl-2-hydroxy-benzoic acid aqueous solution is sprayed on and needs on fresh-keeping fruit.
The synthetic 5-cyclopropyl-2-hydroxy-benzoic acid technological process of the present invention is simple, yield is high, 5-cyclopropyl-2-hydroxy-benzoic acid is remarkable for agricultural products fresh-keeping effect, through 5-cyclopropyl-2-hydroxy-benzoic acid, process the respiration that can significantly suppress fruit, make the increase of polyphenol oxidase activity, effectively delayed fruit hardness, and titratable acid content declines, and has guaranteed storage and the quality of fruit.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment 1, this 5-cyclopropyl-2-hydroxy-benzoic acid, and its molecular formula is: C
10h
10o
3, molecular weight is: 178.18, and chemical structural formula is:
.
Embodiment 2, the synthetic method of this 5-cyclopropyl-2-hydroxy-benzoic acid, carry out in the steps below: the first step, halogenating reaction: Whitfield's ointment is dissolved in glacial acetic acid, then at room temperature add bromine and stir, after stirring finishes, carrying out decompress filter, after decompress filter, obtaining faint yellow solid filter cake, faint yellow solid filter cake water or ethyl alcohol recrystallization are obtained to white crystal, and white crystal is the bromo-2-hydroxy-benzoic acid of 5-;
Second step, alkylation or esterification: the bromo-2-hydroxy-benzoic acid of 5-and salt of wormwood are suspended in acetone, then at room temperature adding after methyl-sulfate is that 70 degrees Celsius to 75 degrees Celsius lower stirring and refluxing are spent the night in temperature, stirring and refluxing is cooled to room temperature and carries out decompress filter after having spent the night, after decompress filter, obtain filter cake and filtrate, filter cake washs by ethyl acetate, obtains washing lotion after washing; Washing lotion and filtrate are merged to rear pressure reducing and steaming solvent, resistates acetic acid ethyl dissolution after pressure reducing and steaming solvent, then with saturated aqueous common salt, wash, by anhydrous sodium sulphate, be dried, after dry, pressure reducing and steaming solvent obtains colourless liquid, and colourless liquid is the bromo-2-methoxyl group-methyl benzoate of 5-;
The 3rd step, linked reaction: by the bromo-2-methoxyl group-methyl benzoate of 5-, 1,1'-bis-(diphenyl phosphine) ferrocene palladium chloride, cyclopropylboronic acid and cesium carbonate are suspended in N, in the mixed solution that dinethylformamide and water form, under the protection of nitrogen, be heated to 95 degrees Celsius to 105 degrees Celsius and be cooled to room temperature, cooled solution is poured into water, be then extracted with ethyl acetate water, extraction phase after aqueous phase extracted is organic phase, merges organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after being dried, uses column chromatography and obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-methoxyl group-methyl benzoate; Eluent during column chromatography for separation is ethyl acetate and sherwood oil, and the volume ratio of ethyl acetate and sherwood oil is 1: 10;
The 4th step, demethylation: 5-cyclopropyl-2-methoxyl group-methyl benzoate is dissolved in methylene dichloride, cooling rear dropping boron tribromide also stirs 1 hour to 1.5 hours, after completing, stirring is warming up to room temperature, then under ice-water bath is cooling, add saturated sodium bicarbonate solution to carry out separatory, after separatory, by methylene dichloride water aqueous phase extracted, merge organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after last pressure reducing and steaming solvent, obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters;
The 5th step, hydrolysis reaction: 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters is dissolved in tetrahydrofuran (THF), then add lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature, after cooling, carry out decompress filter, obtain filtrate after decompress filter, filtrate is extracted with ethyl acetate, with 1 N hydrochloric acid soln, the aqueous phase solution after extraction being adjusted to pH value is 1, then carries out decompress filter; After decompress filter, obtain white solid, white solid obtains white crystal with ethyl alcohol recrystallization, and this white crystal is 5-cyclopropyl-2-hydroxy-benzoic acid.
Embodiment 3, the synthetic method of this 5-cyclopropyl-2-hydroxy-benzoic acid, carry out in the steps below: the first step, halogenating reaction: dissolve in 13g to 15g Whitfield's ointment in every 250ml glacial acetic acid, then at room temperature add 15g to 17g bromine and stir, after stirring finishes, carrying out decompress filter, after decompress filter, obtaining faint yellow solid filter cake, faint yellow solid filter cake water or ethyl alcohol recrystallization are obtained to white crystal, and white crystal is the bromo-2-hydroxy-benzoic acid of 5-;
Second step, alkylation or esterification: in every 150ml acetone, be suspended with the bromo-2-hydroxy-benzoic acid of 5-of 12g to 14g and the salt of wormwood of 19g to 21g, then at room temperature adding after 13ml to 15ml methyl-sulfate is that 70 degrees Celsius to 75 degrees Celsius lower stirring and refluxing are spent the night in temperature, stirring and refluxing is cooled to room temperature and carries out decompress filter after having spent the night, after decompress filter, obtain filter cake and filtrate, filter cake washs by ethyl acetate, obtains washing lotion after washing; Washing lotion and filtrate are merged to rear pressure reducing and steaming solvent, resistates acetic acid ethyl dissolution after pressure reducing and steaming solvent, then with saturated aqueous common salt, wash, by anhydrous sodium sulphate, be dried, after dry, pressure reducing and steaming solvent obtains colourless liquid, and colourless liquid is the bromo-2-methoxyl group-methyl benzoate of 5-;
The 3rd step, linked reaction: every 40mlN, in the mixed solution that dinethylformamide and 4ml water form, be suspended with 1g to 3g the bromo-2-methoxyl group-methyl benzoate of 5-, 0.5g 1,1'-bis-(diphenyl phosphine) ferrocene palladium chloride, the cyclopropylboronic acid of 1.5g to 2g and the cesium carbonate of 6g to 7g, under the protection of nitrogen, be heated to 95 degrees Celsius to 105 degrees Celsius, heat and be cooled to room temperature after 3 hours to 6 hours, and cooled solution is poured into water, then be extracted with ethyl acetate water, extraction phase after aqueous phase extracted is organic phase, merges organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after being dried, uses column chromatography and obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-methoxyl group-methyl benzoate; Eluent during column chromatography for separation is ethyl acetate and sherwood oil, and the volume ratio of ethyl acetate and sherwood oil is 1: 10;
The 4th step, demethylation: the 5-cyclopropyl-2-methoxyl group-methyl benzoate that dissolves in 1.5g to 3g in the dry methylene dichloride of every 50ml, after being cooled to-70 degrees Celsius to-80 degrees Celsius, drip boron tribromide and stir 1 hour to 1.5 hours at-80 degrees Celsius to-60 degrees Celsius, after completing, stirring is warming up to room temperature, then under ice-water bath is cooling, add saturated sodium bicarbonate solution to carry out separatory, after separatory, by methylene dichloride water aqueous phase extracted, merge organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after last pressure reducing and steaming solvent, obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters;
The 5th step, hydrolysis reaction: the 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters that dissolves in 1g to 2g in every 20ml tetrahydrofuran (THF), then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature, after cooling, carry out decompress filter, obtain filtrate after decompress filter, filtrate is extracted with ethyl acetate, with 1 N hydrochloric acid soln, the aqueous phase solution after extraction being adjusted to pH value is 1, then carries out decompress filter; After decompress filter, obtain white solid, white solid obtains white crystal with ethyl alcohol recrystallization, and this white crystal is 5-cyclopropyl-2-hydroxy-benzoic acid.
Embodiment 4, the synthetic method of this 5-cyclopropyl-2-hydroxy-benzoic acid, carry out in the steps below: the first step, halogenating reaction: dissolve in 13.8g Whitfield's ointment in every 250ml glacial acetic acid, then at room temperature add 16g bromine and stir, carry out decompress filter after stirring finishes, after decompress filter, obtain faint yellow solid filter cake, faint yellow solid filter cake water or ethyl alcohol recrystallization are obtained to white crystal 15.1g, and white crystal is the bromo-2-hydroxy-benzoic acid of 5-, and yield is 69%;
Second step, alkylation or esterification: in every 150ml acetone, be suspended with the bromo-2-hydroxy-benzoic acid of 13g5-and 20g salt of wormwood, then at room temperature adding after 14ml methyl-sulfate is that 70 degrees Celsius of lower stirring and refluxing are spent the night in temperature, stirring and refluxing is cooled to room temperature and carries out decompress filter after having spent the night, after decompress filter, obtain filter cake and filtrate, filter cake washs by ethyl acetate, obtains washing lotion after washing; Washing lotion and filtrate are merged to rear pressure reducing and steaming solvent, resistates acetic acid ethyl dissolution after pressure reducing and steaming solvent, then with saturated aqueous common salt, wash, by anhydrous sodium sulphate, be dried, after dry, pressure reducing and steaming solvent obtains colourless liquid 13.2g, colourless liquid is the bromo-2-methoxyl group-methyl benzoate of 5-, and yield is 93%;
The 3rd step, linked reaction: every 40mlN, in the mixed solution that dinethylformamide and 4ml water form, be suspended with the bromo-2-methoxyl group-methyl benzoate of 1.7 g 5-, 0.5g 1,1'-bis-(diphenyl phosphine) ferrocene palladium chloride, 1.8g cyclopropylboronic acid and 6.8g cesium carbonate, under the protection of nitrogen, be heated to 100 degrees Celsius, heat and be cooled to room temperature after 5 hours, and cooled solution is poured into water, then be extracted with ethyl acetate water, extraction phase after aqueous phase extracted is organic phase, merges organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, then by anhydrous sodium sulphate, be dried, after dry, use column chromatography and obtain colourless liquid 0.6g, this colourless liquid is 5-cyclopropyl-2-methoxyl group-methyl benzoate, and yield is 42%; Eluent during column chromatography for separation is ethyl acetate and sherwood oil, and the volume ratio of ethyl acetate and sherwood oil is 1: 10;
The 4th step, demethylation: dissolve in 2.1g5-cyclopropyl-2-methoxyl group-methyl benzoate in the dry methylene dichloride of every 50ml, after being cooled to-78 degrees Celsius, drip boron tribromide and under-70 degrees Celsius, stir 1 hour, after completing, stirring is warming up to room temperature, then under ice-water bath is cooling, add saturated sodium bicarbonate solution to carry out separatory, after separatory, use dichloromethane extraction water, merge organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, then by anhydrous sodium sulphate, be dried, after last pressure reducing and steaming solvent, obtain colourless liquid 1.6g, this colourless liquid is 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters, and yield is 85%;
The 5th step, hydrolysis reaction: dissolve in 1.5g5-cyclopropyl-2-hydroxy-benzoic acid methyl esters in every 20ml tetrahydrofuran (THF), then add 2N lithium hydroxide solution and be heated to 45 degrees Celsius, after having heated, naturally cool to room temperature, after cooling, carry out decompress filter, obtain filtrate after decompress filter, filtrate is extracted with ethyl acetate, with 1 N hydrochloric acid soln, the aqueous phase solution after extraction being adjusted to pH value is 1, then carries out decompress filter; After decompress filter, obtain white solid, white solid obtains white crystal 1.1g with ethyl alcohol recrystallization, and this white crystal is 5-cyclopropyl-2-hydroxy-benzoic acid, and yield is 81%.
Embodiment 5, the using method of this 5-cyclopropyl-2-hydroxy-benzoic acid, during use, first 5-cyclopropyl-2-hydroxy-benzoic acid is made into 5-cyclopropyl-2-hydroxy-benzoic acid aqueous solution that concentration range is 1mg/L～50mg/L, then 5-cyclopropyl-2-hydroxy-benzoic acid aqueous solution is sprayed on and needs on fresh-keeping fruit.
5-cyclopropyl-2-hydroxy-benzoic acid is to retain in the situation of Whitfield's ointment script anti-corrosion function group, and Whitfield's ointment is carried out to addition, and fresh-keeping function group 1-methyl cyclopropane group is stable fixing, thereby makes synthetic product possess two fresh-keeping function groups.
Test shows: by 5-cyclopropyl-2-hydroxy-benzoic acid, be made into 5-cyclopropyl-2-hydroxy-benzoic acid aqueous solution of concentration range position 1mg/L～50mg/L, the fruit of processing through 5-cyclopropyl-2-hydroxy-benzoic acid aqueous solution is as sample sets, and undressed fruit is control group;
Under other condition same cases, sample sets and control group compare discovery:
(1) sample sets ethene average rate of release is 17.09 % of control group, and sample sets is breathed peak value arrival time average and extended 3 times, average peak be control group on average breathe peak value 45.33%;
(2), in the situation that preservation period is identical, it is 69.31% of control group that sample sets average hardness declines;
(3) sample sets titratable acid average content is 71.84% of control group;
(4) the average polyphenol oxidase activity of sample sets is 65.71% of control group;
Evidence: process the respiration that can significantly suppress fruit through 5-cyclopropyl-2-hydroxy-benzoic acid, make the increase of polyphenol oxidase activity, effectively delayed fruit hardness, and titratable acid content declines, and has guaranteed storage and the quality of fruit.
Within the scope of 5-cyclopropyl-2-hydroxy-benzoic acid concentration of aqueous solution, under different concns value, the data obtained is as follows respectively:
| NO. | 5-cyclopropyl-2-hydroxy-benzoic acid concentration (mg/L) | Sample sets Ethylene Production Rate is the percentage (%) of control group | Peak value is the percentage (%) that control group is breathed peak value | In the situation of preservation period identical (5d), it is the percentage (%) of control group that sample sets hardness declines |
| 1 | 1.0 | 11.03 | 31.44 | 40.68 |
| 2 | 10 | 17.09 | 45.33 | 69.31 |
| 3 | 30 | 16.82 | 40.12 | 70.24 |
| 4 | 50 | 15.91 | 34.56 | 68.83 |
Claims (17)
1. a synthetic method for 5-cyclopropyl-2-hydroxy-benzoic acid, is characterized in that carrying out in the steps below:
The first step, halogenating reaction: Whitfield's ointment is dissolved in glacial acetic acid, then at room temperature add bromine and stir, after finishing, stirring carries out decompress filter, after decompress filter, obtain faint yellow solid filter cake, faint yellow solid filter cake water or ethyl alcohol recrystallization are obtained to white crystal, and white crystal is the bromo-2-hydroxy-benzoic acid of 5-;
Second step, alkylation and esterification: the bromo-2-hydroxy-benzoic acid of 5-and salt of wormwood are suspended in acetone, then at room temperature adding after methyl-sulfate is that 70 degrees Celsius to 75 degrees Celsius lower stirring and refluxing are spent the night in temperature, stirring and refluxing is cooled to room temperature and carries out decompress filter after having spent the night, after decompress filter, obtain filter cake and filtrate, filter cake washs by ethyl acetate, obtains washing lotion after washing; Washing lotion and filtrate are merged to rear pressure reducing and steaming solvent, resistates acetic acid ethyl dissolution after pressure reducing and steaming solvent, then with saturated aqueous common salt, wash, by anhydrous sodium sulphate, be dried, after dry, pressure reducing and steaming solvent obtains colourless liquid, and colourless liquid is the bromo-2-methoxyl group-methyl benzoate of 5-;
The 3rd step, linked reaction: by the bromo-2-methoxyl group-methyl benzoate of 5-, 1,1'-bis-(diphenyl phosphine) ferrocene palladium chloride, cyclopropylboronic acid and cesium carbonate are suspended in N, in the mixed solution that dinethylformamide and water form, be heated to 95 degrees Celsius to 105 degrees Celsius under the protection of nitrogen after, be cooled to room temperature, then cooled solution be poured into water, be then extracted with ethyl acetate water, extraction phase after aqueous phase extracted is organic phase, merges organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after being dried, uses column chromatography and obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-methoxyl group-methyl benzoate; Eluent during column chromatography for separation is ethyl acetate and sherwood oil, and the volume ratio of ethyl acetate and sherwood oil is 1: 10;
The 4th step, demethylation: 5-cyclopropyl-2-methoxyl group-methyl benzoate is dissolved in methylene dichloride, cooling rear dropping boron tribromide also stirs 1 hour to 1.5 hours, after completing, stirring is warming up to room temperature, then under ice-water bath is cooling, add saturated sodium bicarbonate solution to carry out separatory, after separatory, by methylene dichloride water aqueous phase extracted, merge organic phase; Organic phase after being combined with saturated sodium bicarbonate solution and saturated aqueous common salt is successively washed, and then by anhydrous sodium sulphate, is dried, and after last pressure reducing and steaming solvent, obtains colourless liquid, and this colourless liquid is 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters;
The 5th step, hydrolysis reaction: 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters is dissolved in tetrahydrofuran (THF), then add lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature, after cooling, carry out decompress filter, obtain filtrate after decompress filter, filtrate is extracted with ethyl acetate, with 1 N hydrochloric acid soln, the aqueous phase solution after extraction being adjusted to pH value is 1, then carries out decompress filter; After decompress filter, obtain white solid, white solid obtains white crystal with ethyl alcohol recrystallization, and this white crystal is 5-cyclopropyl-2-hydroxy-benzoic acid;
Wherein: the molecular formula of 5-cyclopropyl-2-hydroxy-benzoic acid is: C
10h
10o
3, chemical structural formula is:
。
2. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 1, is characterized in that in the first step halogenating reaction, in every 250ml glacial acetic acid, dissolves in 13g to 15g Whitfield's ointment, then at room temperature adds 15g to 17g bromine and stirs.
3. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 1 and 2, it is characterized in that in second step alkylation and esterification, in every 150ml acetone, be suspended with the bromo-2-hydroxy-benzoic acid of 5-of 12g to 14g and the salt of wormwood of 19g to 21g, then at room temperature adding after 13ml to 15ml methyl-sulfate, is that 70 degrees Celsius to 75 degrees Celsius lower stirring and refluxing are spent the night in temperature.
4. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 1 and 2; it is characterized in that in the 3rd step linked reaction; every 40mlN; in the mixed solution that dinethylformamide and 4ml water form, be suspended with 1g to 3g the bromo-2-methoxyl group-methyl benzoate of 5-, 0.5g 1; 1'-bis-(diphenyl phosphine) ferrocene palladium chloride, the cyclopropylboronic acid of 1.5g to 2g and the cesium carbonate of 6g to 7g; under the protection of nitrogen, be heated to 95 degrees Celsius to 105 degrees Celsius; heat and be cooled to room temperature after 3 hours to 6 hours, and cooled solution is poured into water.
5. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 3; it is characterized in that in the 3rd step linked reaction; every 40mlN; in the mixed solution that dinethylformamide and 4ml water form, be suspended with 1g to 3g the bromo-2-methoxyl group-methyl benzoate of 5-, 0.5g 1; 1'-bis-(diphenyl phosphine) ferrocene palladium chloride, the cyclopropylboronic acid of 1.5g to 2g and the cesium carbonate of 6g to 7g; under the protection of nitrogen, be heated to 95 degrees Celsius to 105 degrees Celsius; heat and be cooled to room temperature after 3 hours to 6 hours, and cooled solution is poured into water.
6. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 1 and 2, it is characterized in that in the 4th step demethylation, in the dry methylene dichloride of every 50ml, dissolve in 5-cyclopropyl-2-methoxyl group-methyl benzoate of 1.5g to 3g, drip boron tribromide and stir 1 hour to 1.5 hours at-80 degrees Celsius to-60 degrees Celsius after being cooled to-70 degrees Celsius to-80 degrees Celsius.
7. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 3, it is characterized in that in the 4th step demethylation, in the dry methylene dichloride of every 50ml, dissolve in 5-cyclopropyl-2-methoxyl group-methyl benzoate of 1.5g to 3g, drip boron tribromide and stir 1 hour to 1.5 hours at-80 degrees Celsius to-60 degrees Celsius after being cooled to-70 degrees Celsius to-80 degrees Celsius.
8. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 4, it is characterized in that in the 4th step demethylation, in the dry methylene dichloride of every 50ml, dissolve in 5-cyclopropyl-2-methoxyl group-methyl benzoate of 1.5g to 3g, drip boron tribromide and stir 1 hour to 1.5 hours at-80 degrees Celsius to-60 degrees Celsius after being cooled to-70 degrees Celsius to-80 degrees Celsius.
9. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 5, it is characterized in that in the 4th step demethylation, in the dry methylene dichloride of every 50ml, dissolve in 5-cyclopropyl-2-methoxyl group-methyl benzoate of 1.5g to 3g, drip boron tribromide and stir 1 hour to 1.5 hours at-80 degrees Celsius to-60 degrees Celsius after being cooled to-70 degrees Celsius to-80 degrees Celsius.
10. the synthetic method of 5-cyclopropyl-2-hydroxy-benzoic acid according to claim 1 and 2, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of 11. 5-cyclopropyl-2-hydroxy-benzoic acids according to claim 3, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of 12. 5-cyclopropyl-2-hydroxy-benzoic acids according to claim 4, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of 13. 5-cyclopropyl-2-hydroxy-benzoic acids according to claim 5, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of 14. 5-cyclopropyl-2-hydroxy-benzoic acids according to claim 6, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of 15. 5-cyclopropyl-2-hydroxy-benzoic acids according to claim 7, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of 16. 5-cyclopropyl-2-hydroxy-benzoic acids according to claim 8, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
The synthetic method of 17. 5-cyclopropyl-2-hydroxy-benzoic acids according to claim 9, it is characterized in that in the 5th one-step hydrolysis reaction, in every 20ml tetrahydrofuran (THF), dissolve in 5-cyclopropyl-2-hydroxy-benzoic acid methyl esters of 1g to 2g, then add 2N lithium hydroxide solution and be heated to 40 degrees Celsius to 50 degrees Celsius, after having heated, naturally cool to room temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210284007.1A CN102795994B (en) | 2012-08-10 | 2012-08-10 | 5-cyclopropyl-2-hydroxy-benzoic acid, its synthetic method and application method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210284007.1A CN102795994B (en) | 2012-08-10 | 2012-08-10 | 5-cyclopropyl-2-hydroxy-benzoic acid, its synthetic method and application method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102795994A CN102795994A (en) | 2012-11-28 |
| CN102795994B true CN102795994B (en) | 2014-12-03 |
Family
ID=47195335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210284007.1A Expired - Fee Related CN102795994B (en) | 2012-08-10 | 2012-08-10 | 5-cyclopropyl-2-hydroxy-benzoic acid, its synthetic method and application method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102795994B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113801011A (en) * | 2021-08-25 | 2021-12-17 | 江西麦豪化工科技有限公司 | Stannous salicylate and application thereof in polyurethane foam |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1998750A (en) * | 1931-12-30 | 1935-04-23 | Resinous Prod & Chemical Co | Salicylic acid derivative |
| US2022185A (en) * | 1931-09-17 | 1935-11-26 | Resinous Prod & Chemical Co | Fungicide |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2726468B1 (en) * | 1994-11-03 | 1996-12-13 | Oreal | USE OF SALICYLIC ACID DERIVATIVE AS AN OIL-IN-WATER EMULSION STABILIZER |
-
2012
- 2012-08-10 CN CN201210284007.1A patent/CN102795994B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2022185A (en) * | 1931-09-17 | 1935-11-26 | Resinous Prod & Chemical Co | Fungicide |
| US1998750A (en) * | 1931-12-30 | 1935-04-23 | Resinous Prod & Chemical Co | Salicylic acid derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102795994A (en) | 2012-11-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104311448B (en) | A kind of preparation method of dinitolmide | |
| CN104974073A (en) | Preparation method of silodosin intermediate | |
| CN102795994B (en) | 5-cyclopropyl-2-hydroxy-benzoic acid, its synthetic method and application method | |
| CN107311875A (en) | The synthetic method of aramine | |
| CN103665057A (en) | Synthetic method of bromotetracetylglucose | |
| Xu et al. | Natural products-based insecticidal agents 5. Design, semisynthesis and insecticidal activity of novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin against Mythimna separata Walker in vivo | |
| CN107216289A (en) | A kind of preparation method of Edaravone | |
| CN101343241A (en) | Purification process for Oseltamivir Phosphate | |
| CN102070596B (en) | Preparation method for dihydrosafrole | |
| CN104086545A (en) | Synthesis method of 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridyl-3-formamidine hydrochloride | |
| CN104262249A (en) | Environmental-friendly and efficient preparation method of quinolone compound | |
| CN102838579B (en) | Method for preparing 1,3,6,7-tetrahydroxy xanthone | |
| CN106496300A (en) | Semen arachidis hypogaeae cholic acid and its preparation method of intermediate | |
| CN110483433A (en) | The synthetic method of 4- methyl -5- ethyoxyl oxazole acetoacetic ester | |
| CN105566405A (en) | Preparation method of high-purity topiramate | |
| CN108129279B (en) | Preparation method of bisdemethoxycurcumin | |
| CN102329201B (en) | Method for refining 1,3-cyclohexanedione crude product prepared by adopting m-dihydroxybenzene through hydrogenation | |
| US20090054667A1 (en) | Transition metal catalyzed cross-coupling of 1-halo-1-haloalkene compounds | |
| WO2008051541A3 (en) | Process for preparing anhydrous aripirazole type i | |
| CN109761785A (en) | The synthetic method of one kind (1R, 2R) -2- (3,4- difluorophenyl) cyclopropane-carboxylic acid | |
| CN105330704B (en) | The preparation method of 2-deoxy-D-glucose | |
| CN104478851A (en) | Method for preparing articaine hydrochloride | |
| CN107162937A (en) | A kind of synthesis technique of high-quality diuron | |
| CN103172527A (en) | Method for preparing clopidogrel synthetic intermediate-L-2-chlorophenylglycine methyl ester | |
| CN102633725A (en) | Synthetic method of N-heptafluorobutyrylimidazole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141203 Termination date: 20210810 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |