CN101555213A - Preparation method of N-(phenelyl)-2-hydroxybenzamide - Google Patents
Preparation method of N-(phenelyl)-2-hydroxybenzamide Download PDFInfo
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- CN101555213A CN101555213A CNA2009100591710A CN200910059171A CN101555213A CN 101555213 A CN101555213 A CN 101555213A CN A2009100591710 A CNA2009100591710 A CN A2009100591710A CN 200910059171 A CN200910059171 A CN 200910059171A CN 101555213 A CN101555213 A CN 101555213A
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- phenelyl
- hydroxybenzamide
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- bigcatkin willow
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Abstract
The invention belongs to the technical field of medicine and discloses a preparation method of N-(phenelyl)-2-hydroxybenzamide. The method is characterized in that salicylic acid is firstly prepared into salicyloyl chloride and then reacted with 4-ethoxyaniline to obtain N-(phenelyl)-2-hydroxybenzamide. The method has the advantages of few reaction process, mild reaction condition, high yield, fine product purity and low cost which are applicable to industrial production.
Description
Technical field:
The invention belongs to medical technical field, be specifically related to the preparation method of N-(phenelyl)-2-hydroxybenzamide.
Background technology:
N-(phenelyl)-2-hydroxybenzamide (ethoxy benzene willow amine) is a kind of nonsteroidal anti-inflammatory Claritin, be the kind new medicine that China develops voluntarily, clinical study finds that N-(phenelyl)-2-hydroxybenzamide has obviously definite curative effect to neurodermatitis, eczema, acne.
Chinese patent CN1050588A discloses the synthetic method of a kind of N-(phenelyl)-2-hydroxybenzamide. promptly: earlier Whitfield's ointment is made phenyl ester or methyl esters, carry out the ester amine exchange reaction with the 4-phenetidine then and obtain target compound, ester amine exchange reaction temperature is many more than 130 ℃ in this method, find in the actually operating because temperature of reaction is very high, make in the final product impure more, and the product color is deep, has influenced the quality of finished product.In the disclosed N-of Chinese patent CN1166484A and CN101085746A (phenelyl)-2-hydroxybenzamide synthetic method, used a large amount of benzene class aromatic hydrocarbons as reaction solvent, though reaction yield is than higher, but because benzene class aromatic hydrocarbons great majority all have more intense toxicity, therefore scale operation is restricted, and is unfavorable for environmental protection and HUMAN HEALTH.
Summary of the invention:
The objective of the invention is to overcome present N-(phenelyl)-2-hydroxybenzamide preparation method's deficiency, provide a kind of raw material economics to be easy to get, reaction scheme is short, reaction conditions is gentle, yield is high, the preparation method of good product purity.
The objective of the invention is to be achieved through the following technical solutions:
Preparation method of the present invention is undertaken by following reaction scheme:
Whitfield's ointment is mixed with sulfur oxychloride, and back flow reaction obtains the bigcatkin willow acyl chlorides under the situation of not using any solvent.
The bigcatkin willow acyl chlorides is mixed with the 4-phenetidine, with organic bases or mineral alkali as acid scavenger, in aprotic polar solvent, react and obtain N-(phenelyl)-2-hydroxybenzamide, the acid scavenger that adopts is specially: Anhydrous potassium carbonate, triethylamine, pyridine, reaction solvent is specially: DMF, methylene dichloride or acetone.
The starting raw material that the present invention selects is simple and easy to, and cheap, reaction scheme is short, and the reaction conditions gentleness does not produce the strong acid and strong base waste material, and post-reaction treatment is easy, and preparation yield height is suitable for industrialized production.
The invention will be further described by the following examples, it should be noted that reaction conditions and raw material purpose that following examples are related are the present invention is done better explanation, rather than limitation of the present invention.
Embodiment
Embodiment 1
The preparation of bigcatkin willow acyl chlorides
13.7g (0.1mol) Whitfield's ointment is mixed with 23.8g (0.2mol) sulfur oxychloride, and back flow reaction is 30 minutes under stirring, and removes excessive sulfur oxychloride in underpressure distillation below 50 ℃, obtains colorless oil 15.5g.
1H-NMR(CDCl
3)：4.92(s，1H)；6.91(d，1H)；7.05(m，1H)；7.46(m，1H)；7.94(d，1H)。
Embodiment 2
The preparation of N-(phenelyl)-2-hydroxybenzamide
31.3g (0.2mol) bigcatkin willow acyl chlorides is dissolved in the 200ml dry DMF, stir and add 24.7g (0.18mol) 4-phenetidine down, mixture is cooled to 0 ℃ subsequently, add Anhydrous potassium carbonate 33.1g (0.24mol), be warming up to stirring at room reaction 2 hours after 4 hours in 0 ℃ of stirring reaction.In reaction solution, add the 500ml frozen water, stirred 1 hour, use the ethyl acetate extraction reaction solution, tell ethyl acetate, water, saturated common salt water washing successively, anhydrous magnesium sulfate drying, concentrating under reduced pressure obtains light yellow solid 42.5g.Use recrystallization from ethyl acetate/petroleum ether, obtain white solid 38 4g. yields 83%.Fusing point: 140.5～142 ℃.
1H-NMR(CDCl
3)：1.33(t.3H)；3.95(q，2H)；5.05(s，1H)；6.72(d，2H)；6.93(d，1H)；6.98(m，1H)；7.31(m，1H)；7.59(d，2H)；7.78(d，1H)；8.14(s，br，1H)。
Embodiment 3
The preparation of N-(phenelyl)-2-hydroxybenzamide
31.3g (0.2mol) bigcatkin willow acyl chlorides is dissolved in the 150ml acetone, stir and add 24.7g (0.18mol) 4-phenetidine down, mixture is cooled to 0 ℃ subsequently, slowly dripped pyridine 23.7g (0.3mol) in 2 hour time, after dropwising, keep this temperature to continue to stir 2 hours, be warming up to stirring at room reaction 2 hours subsequently, solids removed by filtration, with the reaction solution evaporate to dryness, add 200ml water, use ethyl acetate extraction, tell ethyl acetate, water, saturated common salt water washing successively, anhydrous magnesium sulfate drying, concentrating under reduced pressure obtains light yellow solid 41.6g.Use recrystallization from ethyl acetate/petroleum ether, obtain white solid 35.9g, yield 78%.Fusing point: 140.5～141.5 ℃.
1H-NMR(CDCl
3)：1.33(t，3H)；3.95(q，2H)；5.05(s，1H)；6.72(d，2H)；6.93(d，1H)；6.98(m，1H)；7.31(m，1H)；7.59(d，2H)；7.78(d，1H)；8.14(s，br，1H)。
Embodiment 4
The preparation of N-(phenelyl)-2-hydroxybenzamide
31.3g (0.2mol) bigcatkin willow acyl chlorides is dissolved in the 150ml methylene dichloride, stir and add 24.7g (0.18mol) 4-phenetidine down, mixture is cooled to 0 ℃ subsequently, slowly dripped triethylamine 30g (0.3mol) in 2 hour time, after dropwising, keep this temperature to continue to stir 2 hours, be warming up to stirring at room reaction 1 hour subsequently, solids removed by filtration, with the reaction solution evaporate to dryness, add 200ml water, use ethyl acetate extraction, tell ethyl acetate, water successively, the saturated common salt water washing, anhydrous magnesium sulfate drying, concentrating under reduced pressure obtains light yellow solid 43.1g.Use recrystallization from ethyl acetate/petroleum ether, obtain white solid 40.2g, yield 87%.Fusing point: 141～142 ℃.
1H-NMR(CDCl
3)：1.33(t，3H)；3.95(q，2H)；5.05(s，1H)；6.72(d，2H)；6.93(d，1H)；6.98(m，1H)；7.31(m，1H)；7.59(d，2H)；7.78(d，1H)；8.14(s，br，1H)。
Claims (6)
1. the preparation method of a N-(phenelyl)-2-hydroxybenzamide is characterized in that earlier Whitfield's ointment being made the bigcatkin willow acyl chlorides, obtains N-(phenelyl)-2-hydroxybenzamide with the reaction of 4-phenetidine again.
2. preparation method according to claim 1 when preparing the bigcatkin willow acyl chlorides by Whitfield's ointment, except acid of reactant bigcatkin willow and sulfur oxychloride, does not use any solvent.
3. preparation method according to claim 1, during preparation N-(phenelyl)-2-hydroxybenzamide, the solvent that uses is methylene dichloride, acetone or DMF.
4. preparation method according to claim 1, during preparation N-(phenelyl)-2-hydroxybenzamide, the acid scavenger that uses is triethylamine, Anhydrous potassium carbonate or pyridine.
5. preparation method according to claim 1, during preparation N-(phenelyl)-2-hydroxybenzamide, range of reaction temperature at 0 ℃ between the room temperature.
6. preparation method according to claim 1, during preparation N-(phenelyl)-2-hydroxybenzamide, the reaction times is 1 to 10 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009100591710A CN101555213A (en) | 2009-05-04 | 2009-05-04 | Preparation method of N-(phenelyl)-2-hydroxybenzamide |
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| CNA2009100591710A CN101555213A (en) | 2009-05-04 | 2009-05-04 | Preparation method of N-(phenelyl)-2-hydroxybenzamide |
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| CN101555213A true CN101555213A (en) | 2009-10-14 |
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| CNA2009100591710A Pending CN101555213A (en) | 2009-05-04 | 2009-05-04 | Preparation method of N-(phenelyl)-2-hydroxybenzamide |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108727442A (en) * | 2018-04-21 | 2018-11-02 | 浙江大学 | A kind of preparation method and applications of Osalmid glucuronidation product |
-
2009
- 2009-05-04 CN CNA2009100591710A patent/CN101555213A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108727442A (en) * | 2018-04-21 | 2018-11-02 | 浙江大学 | A kind of preparation method and applications of Osalmid glucuronidation product |
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Application publication date: 20091014 |