CN106631865A - Preparation method of avenanthramide and derivative thereof - Google Patents
Preparation method of avenanthramide and derivative thereof Download PDFInfo
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- CN106631865A CN106631865A CN201611174814.2A CN201611174814A CN106631865A CN 106631865 A CN106631865 A CN 106631865A CN 201611174814 A CN201611174814 A CN 201611174814A CN 106631865 A CN106631865 A CN 106631865A
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- oat alkaloid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/287—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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Abstract
The invention provides a preparation method of avenanthramide and a derivative thereof. The avenanthramide and the derivative thereof are synthesized and obtained by mainly utilizing an organic acid and aminobenzoic acid as major reactants. The method is high in yield, few in by-products and applicable to the industrialized production of the avenanthramide and the derivative thereof. The avenanthramide has multiple bioactivities of anti-oxidation, anti-anaphylaxis, anti-proliferation and itching relief, meanwhile, also has certain effects of treating coronary disease and colonic cancer, and is often used in products of a emulsion skincare article, an after-sun repairing article, a rhinitis spray, a skin itching relieving infantile product, an externally used cream for treating dermatitis and the like.
Description
Technical field
The present invention relates to the preparation method of a kind of oat alkaloid and its derivative, is mainly used in skin care item, hair washing and produces
In the products such as product, baby products, external preparation for skin emulsifiable paste.
Background technology
Oat alkaloid exists only in oat grain and silkworm seed, with anti-oxidant, antiallergy, antiproliferative and antipruritic various
Biologically active, while also having certain effect to treating coronary heart disease, colon cancer, is usually used in emulsion skincare product, after-sun, nose
In the products such as scorching spray, skin antipruritic baby's children's product, the medicinal external emulsifiable paste for the treatment of dermatitis.
Oat alkaloid is a class phenolic compound, is to be connected to hydroxyl by amido link by ortho-aminobenzoic acid to replace
Constitute on cinnamic acid.Oat alkaloid types have kind more than 20, mainly there is tri- kinds of structures of Bf, Bp, Bc, structural formula such as formula（1）Institute
Show, substituted radical is shown in Table 1：
（1）
。
Oat alkaloid is mainly present in aleurone with of a relatively high content, about 400mg/kg, but thus direct
The oat alkaloid that extraction is obtained is low.Traditional synthetic method is carboxylic acid and the reaction of amino Direct Dehydration, and the method is reacted
Temperature is high, causes coloured product depth, and low yield, high cost.
This patent provides the synthetic method of a kind of new oat alkaloid and its derivative, not only increases yield, and suitable
It is wide with scope, it is possible to increase the product quality of oat alkaloid and its derivative, reduces cost.
The content of the invention
It is an object of the invention to provide the preparation method of a kind of oat alkaloid and its derivative, can be applicable to skin care
In the products such as product, hair washing product, baby products, external preparation for skin emulsifiable paste.
Described oat alkaloid and its structure such as formula of derivative（2）It is shown：
（2）
Wherein,
R1、R2、R3It is each, independently of the other H, OH, OCH3, or OCOCH3；
R4, R6 each, independently of the other be H, OH, or OCH3；
R5For H or OH；
Z is that Z is-(CH2)m—(CH=CH)n—(CH2) p-, wherein m, n, p is 0-5.
The invention provides a kind of method of synthesis oat alkaloid and its derivative, synthetic schemes step and thinking are such as
Under：
1. sour chlorination：General structure such as formula（3）Compound be suspended in suitable solvent, quickly instill protochloride
Sulfone, after reaction overnight, 80 DEG C are reacted 2-5h, recycling design and excess thionyl chloride, obtain general structure such as formula（4）Acyl chlorides in the middle of
Body.
2. the amidation process of acyl chlorides and aminobenzoic acid：General structure such as formula（5）Compound be suspended in suitable solvent,
Nitrogen is protected, and under the conditions of 5-10 DEG C, general structure such as formula is added dropwise successively（4）Acid chloride intermediate and alkali, be subsequently adding hydrochloric acid acid
Change, suction filtration, drying is obtained product.
3. deacetylation is hydrolyzed：If general structure such as formula（2）Compound contain acetoxyl group, can further be hydrolyzed
Reaction.Aqueous alkali is added in step product 2., then regulation pH is acid, and suction filtration, drying is obtained product.
For step, 1. middle general structure is formula（3）Compound in, R1, R2, R3 be each independently H, OH, OCH3, or
OCOCH3；Z is-(CH2)m—(CH=CH)n—(CH2) p-, wherein m, n, p is 0-5.
For step, 2. middle general structure is formula（5）Chemicals in, R4, R6 be each independently H, OH, or OCH3；R5
For H or OH.
Specific embodiment by the following examples is described in further detail again to the above of the present invention, but
It is not limited only to below example.The present invention in the case where above-mentioned technological thought is instructed, according to ordinary skill knowledge and usual
Various replacements or change that means are made, all should be included within the scope of the invention.
Specific embodiment
For the essence for being better understood from inventing, the content of the invention, but present invention are described in detail below by example
It is not limited thereto.
Embodiment 1
1. weigh 180.0g to be suspended in acetoxyl group benzenpropanoic acid in 90mL toluene, quickly drip 400.0g thionyl chlorides under room temperature
Enter, overnight after, 80 DEG C of reaction 2h, distillation to steaming without obvious cut, obtains brown color liquid-to acetyloxy phenyl propionyl chloride, receives
Rate 94.0%.
2. weigh 100.0g ortho-aminobenzoic acids to be suspended in 1200mL dichloromethane, under nitrogen protection, 10 DEG C of temperature control is added dropwise
220.0g steps 1. obtained by method to acetyloxy phenyl propionyl chloride, about 2.0h is dripped off.Then 120.0g triethylamines are added dropwise again, are controlled
10 DEG C of temperature, about 1h is dripped off, insulated and stirred 0.5h, adds the cold hydrochloric acid (2.0%) of 500.0g, and dichloromethane is evaporated off, and suction filtration, washing is done
It is dry, obtain yellow-brown solid, yield 81.1%.
3. 600.0g NaOH is added in the step 2. product of gained（15%）, continue to stir 30min, hydrochloric acid is added dropwise
Adjust pH to 4.5, suction filtration, washing, dry yellow-brown solid, yield 89.0%.
Embodiment 2
1. weigh 160.0g to be suspended in acetoxyl group cinnamic acid in 100mL chloroforms, it is under room temperature that 400.0g thionyl chlorides is fast
Speed is instilled, and after being stirred overnight, 80 DEG C of reaction 3.0h are distilled off excessive solvent and thionyl chloride, obtain brown color liquid-to second
Acyloxy acryloyl chloride, yield 93.0%.
2. 100.0g ortho-aminobenzoic acids are suspended in 1200mL dichloromethane, under nitrogen protection, 10 DEG C of temperature control is added dropwise
222.0g steps 1. obtained by method to acetoxyl group acryloyl chloride, about 2.5h is dripped off.Then 150.0g hydroxides are added dropwise again
Sodium（30%）, 5-10 DEG C of temperature control, about 1h drip off, continue to stir 1.5h, the cold hydrochloric acid of addition 500mL（2%）, dichloromethane is evaporated off, take out
Filter, washing, dry light tan solid, yield is 91.2%.
3. 600.0g NaOH is added in step product 2.（15%）, continue to stir 30min, hydrochloric acid is added dropwise and adjusts
PH to 4.5, suction filtration, filter cake washing, suction filtration obtains brown color sandy solid, yield 89.5%.
Embodiment 3
1. weigh 180.0g 2- methoxyl group -3- acetoxyl group cinnamic acids to be suspended in 100mL hexamethylenes, will under room temperature
400.0g thionyl chlorides are quickly instilled, overnight after, 80 DEG C reaction 2.5h, excessive solvent and thionyl chloride is distilled off, obtain brown
Yellow liquid, it is standby.
2. 2- amino -5- hydroxybenzoic acid 120.0g are suspended in 1500.0g chloroforms, under nitrogen protection, 10 DEG C of temperature control,
Step 3- methoxyl group -4- acetoxyl group acryloyl chloride 240.0g 1. obtained by method are added dropwise, about 2.5h is dripped off, then is added dropwise
110.0g triethylamines, 10 DEG C of temperature control, about 1h is dripped off, insulated and stirred 0.5h, adds the cold hydrochloric acid of 100.0g（10%）, remove two under reduced pressure
Chloromethanes, suction filtration, water washing, suction filtration obtains light yellow solid, yield 91.8%.
3. 310.0g NaOH is added in step product 2.（30%）, continue to stir 30min, hydrochloric acid is added dropwise and adjusts
PH to 4.5, suction filtration, filter cake is washed with water, suction filtration, dry yellow-brown solid, yield 92.3%.
Embodiment 4
1. weigh 160.0g to be suspended in acetoxyl group cinnamic acid in 100mL chloroforms, it is under room temperature that 400.0g thionyl chlorides is fast
Speed is instilled, and after being stirred overnight, 80 DEG C of reaction 3.0h are distilled off excessive solvent and thionyl chloride, obtain brown color liquid-to second
Acyloxy acryloyl chloride, yield 93.0%.
2. 110.0g 2- amino-4-hydroxy benzoic acid is suspended in 1000mL dichloromethane, under nitrogen protection, 10 DEG C of temperature control,
Be added dropwise 222.0g steps 1. obtained by method to acetoxyl group acryloyl chloride, about 2.5h is dripped off.Then 200.0g hydrogen is added dropwise again
Sodium oxide molybdena（30%）, 5-10 DEG C of temperature control, about 1h drip off, continue to stir 1.5h, the cold hydrochloric acid of addition 600mL（2%）, dichloromethane is evaporated off
Alkane, suction filtration, washing, dry light tan solid, yield is 81.4%.
3. 650.0g NaOH is added in step product 2.（15%）, continue to stir 30min, hydrochloric acid is added dropwise and adjusts
PH to 4.5, suction filtration, filter cake washing, suction filtration, dry brown color sandy solid, yield 81.5%.
Embodiment 5
1. weigh 160.0g to be suspended in acetoxyl group cinnamic acid in 100mL chloroforms, it is under room temperature that 400.0g thionyl chlorides is fast
Speed is instilled, and after being stirred overnight, 80 DEG C of reaction 3.0h are distilled off excessive solvent and thionyl chloride, obtain brown color liquid-to second
Acyloxy acryloyl chloride, yield 93.0%.
2. by 118.0g 2- amino -4,6- dihydroxy-benzoic acids are suspended in 1500mL dichloromethane, under nitrogen protection, temperature control
10 DEG C, be added dropwise 232.0g steps 1. obtained by method to acetoxyl group acryloyl chloride, about 2.5h is dripped off.Then it is added dropwise again
350.0g NaOH（30%）, 5-10 DEG C of temperature control, about 1h drip off, continue to stir 1.5h, the cold hydrochloric acid of addition 700mL（2%）, it is evaporated off
Dichloromethane, suction filtration, washing, dry light tan solid, yield is 69.2%.
3. 900.0g NaOH is added in step product 2.（20%）, continue to stir 30min, hydrochloric acid is added dropwise and adjusts
PH to 4.5, suction filtration, filter cake washing, suction filtration, dry brown color sandy solid, yield 80.5%.
Claims (7)
1. the preparation method of a kind of oat alkaloid and its derivative, it is characterised in that：The oat alkaloid and its derivative
Structural formula such as formula（2）It is shown：
（2）
Wherein,
R1、R2、R3It is each, independently of the other H, OH, OCH3, or OCOCH3；
R4, R6 each, independently of the other be H, OH, or OCH3；
R5For H or OH；
Z is-(CH2)m—(CH=CH)n—(CH2) p-, wherein m, n, p is 0-5.
2. according to the preparation method of oat alkaloid and its derivative in claim 1, it is characterised in that concretely comprise the following steps：
1. acyl chloride reaction；
2. amidation process；
3. deacetylation.
3. according to the preparation method of oat alkaloid and its derivative in claim 2, it is characterised in that step concrete behaviour 1.
It is as step：General structure such as formula（3）Compound be suspended in suitable solvent, quickly instill thionyl chloride, reaction is overnight
Afterwards, 80 DEG C of reaction 2-5h, recycling design and excess thionyl chloride, obtain general structure such as formula（4）Acid chloride intermediate.
4. according to the preparation method of oat alkaloid and its derivative in claim 2, it is characterised in that step concrete behaviour 2.
It is as step：General structure such as formula（5）Compound be suspended in suitable solvent, nitrogen protection, under the conditions of 5-10 DEG C, successively
Structure such as formula is added dropwise（4）Acid chloride intermediate and alkali, be subsequently adding hydrochloric acid acidifying, suction filtration, be dried.
5. according to the preparation method of oat alkaloid and its derivative in claim 2, it is characterised in that step concrete behaviour 3.
It is as step：Aqueous alkali is added in step product 2., then with salt acid for adjusting pH to acidity, suction filtration is dried.
6. according to the preparation method of oat alkaloid and its derivative in claim 4, it is characterised in that the alkali of dropwise addition can be
Triethylamine, NaOH, potassium hydroxide, pyridine, sodium carbonate, potassium carbonate etc..
7. according to the preparation method of oat alkaloid and its derivative in claim 2-5, it is characterised in that：General structure such as formula
（3）、（4）、（5）Compound in, R1, R2, R3 be each independently H, OH, OCH3, or OCOCH3；Z is-(CH2)m—(CH=
CH)n—(CH2) p-, wherein m, n, p is 0-5；R4, R6 be each independently H, OH, or OCH3；R5For H or OH.
Priority Applications (1)
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| CN201611174814.2A CN106631865A (en) | 2016-12-19 | 2016-12-19 | Preparation method of avenanthramide and derivative thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019108800A1 (en) * | 2017-11-29 | 2019-06-06 | The Regents Of The University Of California | Compounds and methods for hematopoietic regeneration |
| CN109970593A (en) * | 2019-03-14 | 2019-07-05 | 北京工商大学 | The extracting method and its extract of a kind of oat extract and application |
| US10822299B2 (en) | 2016-05-26 | 2020-11-03 | The Regents Of The University Of California | Compounds and methods for hematopoietic regeneration |
| CN112939803A (en) * | 2021-02-07 | 2021-06-11 | 郑州轻工业大学 | Preparation process of dihydrooat alkaloid D |
| CN114292204A (en) * | 2022-01-15 | 2022-04-08 | 重庆美杉蓝科技发展有限公司 | Preparation method of dihydrooat alkaloid |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4070484A (en) * | 1973-01-18 | 1978-01-24 | Kissei Pharmaceutical Co., Ltd. | Antiallergic composition containing aromatic carboxylic amide derivatives and method of using the same |
| CN1713904A (en) * | 2002-11-25 | 2005-12-28 | 西姆莱斯有限责任两合公司 | Anthranilic acid amides and the derivatives thereof as cosmetic and pharmaceutical agents |
| CN104418764A (en) * | 2013-09-11 | 2015-03-18 | 上海伊明化学科技有限公司 | Method for synthesizing 4-hydroxy benzenepropionamido benzoic acid |
-
2016
- 2016-12-19 CN CN201611174814.2A patent/CN106631865A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4070484A (en) * | 1973-01-18 | 1978-01-24 | Kissei Pharmaceutical Co., Ltd. | Antiallergic composition containing aromatic carboxylic amide derivatives and method of using the same |
| CN1713904A (en) * | 2002-11-25 | 2005-12-28 | 西姆莱斯有限责任两合公司 | Anthranilic acid amides and the derivatives thereof as cosmetic and pharmaceutical agents |
| CN104418764A (en) * | 2013-09-11 | 2015-03-18 | 上海伊明化学科技有限公司 | Method for synthesizing 4-hydroxy benzenepropionamido benzoic acid |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10822299B2 (en) | 2016-05-26 | 2020-11-03 | The Regents Of The University Of California | Compounds and methods for hematopoietic regeneration |
| WO2019108800A1 (en) * | 2017-11-29 | 2019-06-06 | The Regents Of The University Of California | Compounds and methods for hematopoietic regeneration |
| CN109970593A (en) * | 2019-03-14 | 2019-07-05 | 北京工商大学 | The extracting method and its extract of a kind of oat extract and application |
| CN109970593B (en) * | 2019-03-14 | 2019-11-08 | 北京工商大学 | The extracting method and its extract of a kind of oat extract and application |
| CN112939803A (en) * | 2021-02-07 | 2021-06-11 | 郑州轻工业大学 | Preparation process of dihydrooat alkaloid D |
| CN114292204A (en) * | 2022-01-15 | 2022-04-08 | 重庆美杉蓝科技发展有限公司 | Preparation method of dihydrooat alkaloid |
| CN114292204B (en) * | 2022-01-15 | 2024-01-30 | 重庆美杉蓝科技发展有限公司 | Preparation method of dihydro oat alkaloid |
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Application publication date: 20170510 |