CN108456149A - A kind of synthetic method of oat alkaloid - Google Patents
A kind of synthetic method of oat alkaloid Download PDFInfo
- Publication number
- CN108456149A CN108456149A CN201810474217.4A CN201810474217A CN108456149A CN 108456149 A CN108456149 A CN 108456149A CN 201810474217 A CN201810474217 A CN 201810474217A CN 108456149 A CN108456149 A CN 108456149A
- Authority
- CN
- China
- Prior art keywords
- reaction
- oat alkaloid
- oat
- carboxyls
- acetylamino
- 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.)
- Pending
Links
Classifications
-
- 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
-
- 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
Abstract
The present invention provides a kind of chemical synthesis process of oat alkaloid, have studied oat alkaloid A, B, the chemical synthesis process of C, with 2 amino, 5 hydroxybenzoic acid, Michaelis acid and 4 hydroxy benzaldehydes, 4 hydroxyl, 3 methoxybenzaldehyde, 3, 4 4-dihydroxy benzaldehydes are raw material, oat alkaloid A is synthesized by Knoevenagel condensation reactions, B, C, using infrared spectrum, nuclear magnetic resoance spectrum, the analysis means such as mass spectrum and elemental analysis have carried out structural characterization to compound, demonstrate the feasibility of synthesis oat alkaloid process route, optimize synthetic technological condition, have the function of that the application of the multiple biological activities oat alkaloid such as anti-oxidant has important research meaning further to develop, the exploitation of this chemical synthesis process possesses very wide application prospect.
Description
Technical field：
The present invention relates to a kind of preparation methods applied to organic-biological alkali in the products such as skin care item, external preparation for skin emulsifiable paste, especially
It is a kind of synthetic method of oat alkaloid.
Background technology：
Modern medicine study shows that oat is mainly reflected in the following aspects to the effect of health：Anti-oxidant radiation is put down
Weighing apparatus blood glucose, strengthen immunity, relax bowel, stabilizing blood pressure, weight-reducing body shaping etc..This healthcare function of oat contains except being attributed to height
Outside the beta glucan of amount, it is also due to its polyphenoils containing there are many, one type is the nitrogenous phenolic acid class for having unique texture
Derivative ----oat alkaloid.Oat alkaloid not only has very strong antioxidation, and has antipruritic, antiproliferative, resists
The multiple biological activities such as inflammation also play important role to the prevention of coronary heart disease, colon cancer and cutaneous pruritus, cause the country
The great interest of outer scholar.
Oat alkaloid is to detach identification for the first time by Canadian scientist Collins, and be named as
Avenanthramides accounts for oat life respectively wherein main three kinds are oat alkaloid A, B and the C defined by Collins
35%, 21% and the 44% of alkaloids.Structural formula such as formula（1）It is shown：
（1）Wherein R is H or OCH3 or OH, respectively corresponds to oat alkaloid A, B, C.
In recent years, both at home and abroad mainly using Avena stivai as primary raw material study the content of oat alkaloid, extraction process and its
Bioactivity etc., although alkaloid activity it is higher, the content of alkaloid is but very low in oat, in wheat bran highest containing about
400 mg/kg, and different extraction processes has different degrees of influence to oat alkaloid and its bioactivity.At present
Almost without to oat alkaloid structure identification and structure-activity relationship in terms of report, the chemical synthesis process in relation to oat alkaloid
Research is also considerably less.Chinese patent notification number is disclosed in CN 106631865A《A kind of system of oat alkaloid and its derivative
Preparation Method》, it is oat alkaloid and its derivative to be synthesized by three-step approach, but this synthetic method needs to use thionyl chloride
Activated carboxyl prepares acyl chlorides, is then reacted with aminobenzoic acid, needs anhydrous solvent and nitrogen protection etc., severe reaction conditions,
And preparation process is complicated.
How a kind of chemical synthesis process of oat alkaloid provided, with 2- amino -5- hydroxybenzoic acids and Michaelis acid
Reaction synthesis 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acids, with 2- Methyl anthranilates and Michaelis acid reaction synthesis 2-
(2- carboxyls acetylamino) benzoic acid, then respectively with 4- hydroxy benzaldehydes, 3-methoxy-4-hydroxybenzaldehyde, 3,4- dihydroxies
Knoevenagel condensation reactions synthesis oat alkaloid A, B, C occur for benzaldehyde etc., optimum synthesis process conditions, to for
Further exploitation has the function of that the application of the multiple biological activities oat alkaloid such as anti-oxidant has important research meaning, this chemistry
The exploitation of synthesis technology possesses very wide application prospect.
Invention content：
Present invention aim to provide a kind of synthetic method of oat alkaloid, with 2- amino -5- hydroxybenzoic acids, Michaelis
Acid and 4- hydroxy benzaldehydes, 3-methoxy-4-hydroxybenzaldehyde, 3,4- 4-dihydroxy benzaldehydes are raw material, pass through Knoevenagel
Condensation reaction synthesizes oat alkaloid A, B, C, and the oat alkaloid prepared is applied to the productions such as skin care item, external preparation for skin emulsifiable paste
In product.
A kind of synthetic method of oat alkaloid of the present invention, structure such as formula（1）It is shown：
（1）Wherein R is H or OCH3Or OH, respectively correspond to oat alkaloid A, B, C.
The synthetic method of oat alkaloid of the present invention, with 2- amino -5- hydroxybenzoic acids, Michaelis acid and 4- hydroxyls
Benzaldehyde, 3-methoxy-4-hydroxybenzaldehyde, 3,4- 4-dihydroxy benzaldehydes are raw material comprising following methods step：
(a), the preparation of 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acids：Take 2- amino -5- hydroxybenzoic acids and Michaelis
Acid is that solvent is fully dispersed uniformly with toluene, at a temperature of 100-120 DEG C 6 ~ 8 hours postcoolings of heating reflux reaction to room temperature,
Suction filtration obtains pale solid, washs solid with toluene, is recrystallized after dry, 2- (2- carboxyls acetylamino) -5- hydroxyls processed
Yl benzoic acid head product；
(b), by step（a）2- (2- carboxyls acetylamino) -5- hydroxybenzoic acid head products of preparation, are stirred evenly with ice water,
Sodium hydroxide solution is slowly added dropwise, until all products dissolve, continues to stir 20-40 min, cold hydrochloric acid solution is then added,
Controlling reaction temperature is 20oC hereinafter, after continuing 20-40min of stirring, a large amount of solids are precipitated to 3-4 in tune pH value, take out by standing
Pale solid is obtained after filter, it is dry, obtain 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acid products；
(c), by step (b) prepare 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acids product respectively with 4- hydroxy benzaldehydes,
3-methoxy-4-hydroxybenzaldehyde, the reaction of 3,4- 4-dihydroxy benzaldehydes, are sufficiently uniformly dissolved with pyridine, add catalyst β-
Alanine is heated to 85-95oC is cooled to room temperature after isothermal reaction 20-28 hours, obtains reaction solution；
(d), by the reaction solution of step (c) in -2-0 oIn the ice-water bath of C, it is slowly added to dilute hydrochloric acid solution, adjusts pH value to 2-3,
A large amount of yellow solids are precipitated, stand, filters, is washed with a large amount of deionized waters, obtain reaction head product；
(e), it recrystallizes, further uses hot acetone and water to recrystallize the reaction head product obtained by the step (d), will react
Head product acetone heating stirring dissolves, then deionized water is slowly added into acetone soln, and a large amount of yellow solids are precipitated, quiet
It sets, filters, be finally washed with deionized, vacuum drying obtains yellow solid product oat alkaloid.
The synthetic method of oat alkaloid of the present invention, preferably, with molar ratio computing, the 2- in the step (a)
Amino -5- hydroxybenzoic acids：Michaelis acid=1:1.05.
Further, it is with molar ratio computing, to control 2- in the step (c)（2- carboxyl acetylaminos）- 5- hydroxy benzenes first
Acid：4- hydroxy benzaldehydes or Vanillin or 4-dihydroxy benzaldehyde=1 3,4-:1.05.
Preferably, the dosage of control catalyst Beta-alanine is 2- (2- carboxyls acetylamino) -5- hydroxyls in the step (c)
1.0-1.2mol% of yl benzoic acid.
Further, the temperature of heating reaction is 90 DEG C in the step (c).
Preferably, the drying is vacuum drying.
The synthesis of oat alkaloid B, C of the present invention are similar with A, and 4- hydroxy benzaldehydes are substituted for corresponding 3- methoxies
Base -4- hydroxy benzaldehydes, 3,4- 4-dihydroxy benzaldehydes.Other preparation conditions are identical, and oat alkaloid B is pale yellow colored solid
Body；Oat alkaloid C is greenish yellow solid.
Below with regard to the synthetic method of oat alkaloid of the present invention, each reaction raw materials proportioning etc. is to reaction condition of the present invention
It influences, is further described in detail.
Influence of the raw material proportioning to reaction yield：
When being investigated to reacting required raw material proportioning, fixed other reaction conditions, 1.0 mol% of catalyst amount, reaction temperature
Degree 90 oC, reaction time are 24 h, the results are shown in Table 1：When raw material proportioning is by 1:1 increases to 1:Reaction yield is notable when 1.05
Enhancing, when raw material proportioning increases to 1:Reaction yield reaches higher level when 1.05, but continues growing raw material proportioning to 1:
When 1.08, yield increasing degree is small, and product detached with raw material 4- hydroxy benzaldehydes it is more difficult.
Influence of 1 raw material proportioning of table to reaction yield
| 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acids/4- hydroxy benzaldehydes | Reaction yield % |
| 1:1 | 66 |
| 1:1.03 | 69 |
| 1:1.05 | 74 |
| 1:1.08 | 75 |
Illustrate, can be seen that reaction raw materials 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acids and 4- hydroxyls from data shown in table 1
The molar ratio of benzaldehyde is 1:1.05 be the optimum material proportion of the condensation reaction.Raw material proportioning is to 1:When 1.08, production
Rate increasing degree is small, but product detached with raw material 4- hydroxy benzaldehydes it is more difficult, it is therefore preferable that reaction raw materials 2- (2- carboxyls
Acetylamino) molar ratio of -5- hydroxybenzoic acids and 4- hydroxy benzaldehydes is 1:1.05 be the best original of the condensation reaction
Material proportioning.Each mean quality molar ratio.
Influence of the catalyst amount to reaction yield：
When being investigated to catalyst amount, fixed other reaction conditions, raw material 2- (2- carboxyls acetylamino) -5- hydroxy benzenes first
The molar ratio of acid and 4- hydroxy benzaldehydes is 1:1.05, reaction temperature 90oC, reaction time are that for 24 hours, as a result see the table below 2,
When catalyst amount increases to 1.0 mol% by 0.25 mol%, reaction yield significantly increases, when the dosage of catalyst increases to
Reaction yield reaches higher level when 1.0 mol%, but continues growing after the dosage to 1.5 mol% of catalyst yield just no longer
It continues growing, this shows that the catalyst amount of 1.0 mol% is the optimal dose of the reaction.
Influence of the dosage of 2 catalyst of table to condensation reaction yield
| Dosage/mol% of catalyst | Reaction yield/% |
| 0.25 | 45 |
| 0.50 | 52 |
| 0.75 | 66 |
| 1.0 | 74 |
| 1.5 | 74 |
Influence of the reaction temperature to reaction yield：
When being investigated to the reaction temperature needed for the reaction, fixed other reaction conditions, raw material 2- (2- carboxyls acetylamino)-
The molar ratio of 5- hydroxybenzoic acids and 4- hydroxy benzaldehydes is 1:1.05, catalyst amount 1.0mol%, reaction time 24
H the results are shown in Table 3.When being increased to 90 DEG C by 60 DEG C to reaction temperature, reaction yield significantly increases, when reaction temperature is increased to 90
DEG C when reaction yield reach higher level, but continue to increase reaction temperature to yields after 100 DEG C and be declined instead, this shows
90 DEG C of reaction temperature is the optimal reaction temperature of the reaction.
Influence of 3 reaction temperature of table to condensation reaction yield
| Reaction temperature/DEG C | Reaction yield/% |
| 60 | 29 |
| 70 | 47 |
| 80 | 62 |
| 90 | 74 |
| 100 | 70 |
Influence of the reaction time to reaction yield：
When being investigated the time required to reaction, fixed other reaction conditions, raw material 2- (2- carboxyls acetylamino) -5- hydroxy benzenes
The molar ratio of formic acid and 4- hydroxy benzaldehydes is 1:1.05,1.0 mol% of catalyst amount, reaction temperature 90oC, as a result
It is shown in Table 4.Reaction yield significantly increases when increasing to 24 h by 12 h between when reacted, when reacted between increase to anti-at 24 hours
It answers yield to reach higher level, but continues extension reaction time to yield after 28 hours and just do not continue to increase, this shows 24
The reaction time of hour is the optimum reacting time of the reaction.
Influence of 4 reaction time of table to condensation reaction yield
| Reaction time/h | Reaction yield/% |
| 12 | 36 |
| 16 | 52 |
| 20 | 69 |
| 24 | 74 |
| 28 | 74 |
It is found after carrying out condition optimizing to the Knoevenagel condensation reactions：Reaction raw materials 2- (2- carboxyls acetylamino) -5- hydroxyls
The molar ratio of yl benzoic acid and 4- hydroxy benzaldehydes is 1:1.05 be the optimum material proportion of the condensation reaction, 1.0
The catalyst amount of mol% is the optimal dose of the reaction, and 90 DEG C of reaction temperature is the optimal reaction temperature of the reaction, and 24 is small
When reaction time be the reaction optimum reacting time.
Specific implementation mode：
Specific implementation mode by the following examples is again described in further detail the above of the present invention, but not only
It is limited to embodiment below, based on the embodiments of the present invention, those of ordinary skill in the art are not making creative work
Under the premise of the every other embodiment that is obtained, shall fall within the protection scope of the present invention.
In order to be better understood from the essence of invention, invention content, but the content of present invention is described in detail below by example
It is not limited thereto.
Embodiment 1
The synthesis of 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acids
Weigh 15.3 g of 2- amino -5- hydroxybenzoic acids（0.1 mol）With 15.1 g（0.105 mol）Michaelis acid, is added to 500
It is fully dispersed uniformly with 300 mL dry toluenes in the round-bottomed flask of mL, 6 ~ 8 hours postcoolings of heating reflux reaction to room temperature,
It filters removing toluene and obtains pale solid, washed twice with toluene, the pale solid of gained air-dries in draught cupboard, waits for first
Benzene volatilizees, and is recrystallized after product drying.By 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acid head product ice of synthesis
Water stirs evenly, and sodium hydroxide solution is slowly added dropwise, until all products dissolve, solution is in lilac, continues to stir 30 min.
Then cold hydrochloric acid solution is added（6 mol/L）, and ice block cooling is added in reaction solution, controlling reaction temperature is 20oC
Hereinafter, adjusting pH value to 3 ~ 4, continuing after stirring 30 min, solution starts that a large amount of solids are precipitated, and is further continued for being slowly stirred 2 h,
Solid precipitation no longer increases, and stands, and pale solid is obtained after suction filtration, is dried in vacuo to obtain 22.3 g of product, yield 93.1%；
Pale solid, mp.175-177 DEG C, 13C NMR (DMSO-d6, 100 MHz): 169.6, 169.1, 164.7,
153.4, 132.2, 123.0, 121.2, 118.5, 116.7, 44.8.It is characterized as 2- (2- carboxyls acetylamino) -5- hydroxyls
Yl benzoic acid product.
The synthesis of oat alkaloid A：
Weigh 2-（2- carboxyl acetylaminos）2.39 g of -5- hydroxybenzoic acids (10 mmol) and 1.28g (10.5 mmol)
4- hydroxy benzaldehydes are added into the neck round bottom flask of 100 mL, are sufficiently uniformly dissolved with 20 mL pyridines, add catalysis
Agent Beta-alanine (0.1 mmol), heated constant temperature to 90oC, 24 hours postcoolings of reaction to room temperature.Reaction terminates, and will react
Liquid pours into the beaker of 500 mL, and ice cube, cooling solution to 0 is added oC is slow added into dilute hydrochloric acid solution, adds ice cube in time
Temperature is controlled 0 oC or so adjusts pH value to 2 ~ 3, a large amount of yellow solids is precipitated, and stands, and filters, and product is washed with a large amount of deionizations
It washs, product oat alkaloid A further uses hot acetone and water to recrystallize, and head product acetone heating stirring is dissolved, then toward third
It is slowly added to deionized water in ketone solution, a large amount of yellow solids are precipitated, is stood, is filtered, product is washed with deionized, and vacuum is dry
It is dry to obtain 2.21 g of yellow solid, it is oat alkaloid A product, yield 74%.
Oat alkaloid A, yellow solid, mp.276-277 DEG C.1H NMR (DMSO-d6, 400 MHz): 6.56
(1H, d, J=15.5Hz), 6.85 (2H, d, J=8.5Hz), 7.07 (1H, dd, J=9.2Hz, J=3.0Hz),
7.42 (2H, d, J=8.5Hz), 7.49 (1H, d, J=3.0Hz), 7.55 (1H, d, J=15.5Hz), 8.58
(1H, d, J=9.2Hz), 9.54 (1H, s), 9.86 (1H, s), 10.87 (1H, s), 13.27 (1H, brs)
。13C NMR (DMSO-d6, 100 MHz): 169.3, 163.9, 159.4, 152.6, 140.8, 133.1, 129.9,
125.7, 122.5, 121.0, 119.1, 118.5, 116.6, 115.8。IR (KBr) ν: 3122(NH), 1720,
1688(NHCO), 1646(Ar-COOH), 1608, 1591, 1296 cm-1。MS m/z (%): 300.5 ([M+H]+,
100)。Anal. calcd for C16H13NO5: C, 64.21; H, 4.38; N, 4.68; found C, 64.03; H,
4.50; N, 4.52。
Embodiment 2
The synthesis of oat alkaloid B,
Weigh 2-（2- carboxyl acetylaminos）2.39 g of -5- hydroxybenzoic acids (10 mmol) and 3- methoxyl group -4- hydroxy benzenes
Formaldehyde 1.28g (10.5 mmol) is added into the neck round bottom flask of 100 mL, is sufficiently uniformly dissolved with 20 mL pyridines,
Add catalyst Beta-alanine (0.2 mmol), heated constant temperature to 90oC, 24 hours postcoolings of reaction to room temperature.Reaction knot
Beam pours into reaction solution in the beaker of 500 mL, and ice cube, cooling solution to 0 is added oC is slow added into dilute hydrochloric acid solution, and
When add ice cube control temperature 0 oC or so adjusts pH value to 2 ~ 3, a large amount of faint yellow solids is precipitated, and stands, and filters, and product is with greatly
Deionized water washing is measured, product oat alkaloid B further uses hot acetone and water to recrystallize, by head product acetone heating stirring
Dissolving, then deionized water is slowly added into acetone soln, a large amount of faint yellow solids are precipitated, stand, filter, product deionization
Water washing, vacuum drying obtain faint yellow solid, yield 68%.
Oat alkaloid B, faint yellow solid, mp.246-247 DEG C.1H NMR (DMSO-d6, 400 MHz): 3.77
(3H, s), 6.67 (1H, d, J=15.5Hz), 6.81 (1H, d, J=8.1Hz), 7.04 (1H, dd, J=
9.0Hz, J=3.0Hz), 7.10 (1H, dd, J=8.1Hz, J=1.8Hz), 7.29 (1H, d, J=1.8Hz), 7.41
(1H, d, J=3.0Hz), 7.49 (1H, d, J=15.5Hz), 8.40 (1H, d, J=9.0Hz), 9.44 (1H,
s), 9.56 (1H, s), 10.77 (1H, s), 13.31 (1H, brs)。13C NMR (DMSO-d6, 100 MHz):
169.5, 164.1, 152.8, 149.1, 148.1, 141.4, 133.3, 126.4, 122.8, 121.0, 119.5,
118.6, 116.8, 111.5, 115.9, 55.9。IR (KBr) ν: 3126(NH), 1722, 1687(NHCO), 1645
(Ar-COOH), 1606, 1592, 1295 cm-1。MS m/z (%): 330.4 ([M+H]+, 100)。Anal. calcd
for C17H15NO6: C, 62.00; H, 4.59; N, 4.25; found C, 61.93; H, 4.65; N, 4.22。
Embodiment 3
The synthesis of oat alkaloid C,
Weigh 2-（2- carboxyl acetylaminos）2.39 g of -5- hydroxybenzoic acids (10 mmol) and 3,4- 4-dihydroxy benzaldehydes
1.28g (10.5 mmol) is added into the neck round bottom flask of 100 mL, is sufficiently uniformly dissolved with 20 mL pyridines, then adds
Enter catalyst Beta-alanine (0.2 mmol), heated constant temperature to 90oC, 24 hours postcoolings of reaction to room temperature.Reaction terminates,
Reaction solution is poured into the beaker of 500 mL, ice cube, cooling solution to 0 is added oC is slow added into dilute hydrochloric acid solution, mends in time
Control temperature on the rocks is 0 oC or so adjusts pH value to 2 ~ 3, a large amount of greenish yellow solids is precipitated, and stands, and filters, and product is with largely going
Ion water washing, product oat alkaloid C further uses hot acetone and water to recrystallize, and head product is molten with acetone heating stirring
Solution, then deionized water is slowly added into acetone soln, a large amount of greenish yellow solids are precipitated, stand, filter, product deionized water
Washing, vacuum drying obtain greenish yellow solid, yield 61%.
Oat alkaloid C, greenish yellow solid, mp.233-235 DEG C.1H NMR (DMSO-d6, 400 MHz): 6.47
(1H, d, J=15.5Hz), 6.71 (1H, d, J=8.1Hz), 6.82 (1H, dd, J=9.0Hz, J=3.0Hz),
6.90 (1H, dd, J=8.1Hz, J=1.8Hz), 7.04 (1H, d, J=1.8Hz), 7.31 (1H, d, J=
3.0Hz), 7.43 (1H, d, J=15.5Hz), 8.40 (1H, d, J=9.0Hz), 9.12 (1H, s), 9.44
(1H, s), 9.56 (1H, s), 10.77 (1H, s), 13.46 (1H, brs)。13C NMR (DMSO-d6, 100
MHz): 169.6, 164.1, 153.0, 148.2, 146.1, 141.5, 133.3, 126.5, 122.9, 121.4,
121.3, 119.2, 119.0, 117.0, 116.2, 114.9。IR (KBr) ν: 3123(NH), 1721, 1689
(NHCO), 1646(Ar-COOH), 1608, 1592, 1295 cm-1。MS m/z (%): 316.3 ([M+H]+, 100)。
Anal. calcd for C16H13NO6: C, 60.95; H, 4.16; N, 4.44; found C, 60.93; H, 4.21;
N, 4.48。
The present invention is with 2- amino -5- hydroxybenzoic acids, Michaelis acid and 4- hydroxy benzaldehydes, 4- hydroxy 3-methoxybenzene first
Aldehyde, 3,4- 4-dihydroxy benzaldehydes are raw material, synthesize oat alkaloid A, B, C by Knoevenagel condensation reactions, pass through nuclear-magnetism
Equal characterization methods confirmed that the alkaloid that synthesized compound and document report are extracted from oat is same substance, demonstrating
The feasibility for learning synthesis oat alkaloid process route, optimizes synthetic technological condition, is further development and application oat biology
The multiple biological activities function such as anti-oxidant of alkali provides substance source, has important research significance.
Claims (7)
1. a kind of synthetic method of oat alkaloid, structure such as formula（1）It is shown：
（1）Wherein R is H or OCH3Or OH, respectively correspond to oat alkaloid A, B, C.
2. the synthetic method of oat alkaloid according to claim 1, with 2- amino -5- hydroxybenzoic acids, Michaelis acid and
4- hydroxy benzaldehydes, 3-methoxy-4-hydroxybenzaldehyde, 3,4- 4-dihydroxy benzaldehydes are raw material, it is characterized in that including with lower section
Method step：
(a), the preparation of 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acids：Take 2- amino -5- hydroxybenzoic acids and Michaelis
Acid is that solvent is fully dispersed uniformly with toluene, at a temperature of 100-120 DEG C 6 ~ 8 hours postcoolings of heating reflux reaction to room temperature,
Suction filtration obtains pale solid, washs solid with toluene, is recrystallized after dry, 2- (2- carboxyls acetylamino) -5- hydroxyls processed
Yl benzoic acid head product；
(b), by step（a）2- (2- carboxyls acetylamino) -5- hydroxybenzoic acid head products of preparation, are stirred evenly with ice water,
Sodium hydroxide solution is slowly added dropwise, until all products dissolve, continues to stir 20-40 min, cold hydrochloric acid solution is then added,
Controlling reaction temperature is 20oC hereinafter, after continuing 20-40min of stirring, a large amount of solids are precipitated to 3-4 in tune pH value, take out by standing
Pale solid is obtained after filter, it is dry, obtain 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acid products；
(c), by step (b) prepare 2- (2- carboxyls acetylamino) -5- hydroxybenzoic acid products, respectively with 4- hydroxy benzenes first
Aldehyde, 3-methoxy-4-hydroxybenzaldehyde, the reaction of 3,4- 4-dihydroxy benzaldehydes, are sufficiently uniformly dissolved with pyridine, add catalyst
Beta-alanine is heated to 85-95oC is cooled to room temperature after isothermal reaction 20-28 hours, obtains reaction solution；
(d), by the reaction solution of step (c) in -2-0 oIn the ice-water bath of C, it is slowly added to dilute hydrochloric acid solution, adjusts pH value to 2-3,
A large amount of yellow solids are precipitated, stand, filters, is washed with a large amount of deionized waters, obtain reaction head product；
(e), it recrystallizes, further uses hot acetone and water to recrystallize the reaction head product obtained by the step (d), will react
Head product acetone heating stirring dissolves, then deionized water is slowly added into acetone soln, and a large amount of yellow solids are precipitated, quiet
It sets, filters, be finally washed with deionized, vacuum drying obtains yellow solid product oat alkaloid.
3. the synthetic method of oat alkaloid according to claim 2, characterized in that with molar ratio computing, the step (a)
In 2- amino -5- hydroxybenzoic acids：Michaelis acid=1:1.05.
4. the synthetic method of oat alkaloid according to claim 2, characterized in that in the step (c), with molar ratio
Meter controls 2-（2- carboxyl acetylaminos）- 5- hydroxybenzoic acids：4- hydroxy benzaldehydes or Vanillin or
4-dihydroxy benzaldehyde=1 3,4-:1.05.
5. the synthetic method of oat alkaloid according to claim 2, characterized in that control catalysis in the step (c)
The dosage of agent Beta-alanine is the 1.0-1.2mol% of 2- (2- carboxyls acetylamino)-5- hydroxybenzoic acids.
6. the synthetic method of oat alkaloid according to claim 2, characterized in that heating reaction in the step (c)
Temperature be 90 DEG C.
7. the synthetic method of oat alkaloid according to claim 2, characterized in that the drying is vacuum drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810474217.4A CN108456149A (en) | 2018-05-17 | 2018-05-17 | A kind of synthetic method of oat alkaloid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810474217.4A CN108456149A (en) | 2018-05-17 | 2018-05-17 | A kind of synthetic method of oat alkaloid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108456149A true CN108456149A (en) | 2018-08-28 |
Family
ID=63215394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810474217.4A Pending CN108456149A (en) | 2018-05-17 | 2018-05-17 | A kind of synthetic method of oat alkaloid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108456149A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2018
- 2018-05-17 CN CN201810474217.4A patent/CN108456149A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106243031B (en) | A kind of Ah handkerchief replaces the preparation method of Buddhist nun | |
| CN104086379B (en) | The synthetic method of the clean intermediate of Da Gelie | |
| CN103936694A (en) | Preparation method of antidepressant vortioxetine | |
| CN112321496B (en) | Method for synthesizing 2-amino-3-chloro-5-trifluoromethylpyridine | |
| CN112062759B (en) | Ethylsulfonyl-containing pyridine-1, 2, 4-oxadiazole substituted benzamide compounds and preparation method and application thereof | |
| CN111943944B (en) | Ethylthio-containing pyridine-bis-1, 2, 4-oxadiazole substituted benzamide compound and preparation method and application thereof | |
| CN108456149A (en) | A kind of synthetic method of oat alkaloid | |
| CN111333613A (en) | Preparation method of trifluoromethyl tetralone compound | |
| CN106946887B (en) | A kind of preparation method introducing catalyst optimization synthesis Dipyridamole | |
| CN113387916A (en) | Urolithin PDE2 inhibitor compound and preparation method thereof | |
| CN109836382A (en) | The rich preparation method for replacing Buddhist nun and its intermediate of malic acid card | |
| CN110204542A (en) | A kind of synthetic method of JAK1 inhibitor Filgotinib | |
| CN103408525A (en) | Synthetic method and application of flavonoid | |
| CN105949124A (en) | Pyrazoline derivatives and application thereof | |
| CN103387570A (en) | Preparation method of rizatriptan benzoate | |
| CN106243009B (en) | A kind of preparation method of the bromo- N-phenylmaleimides of 3- n-butylamine-baseds -4- | |
| JPH0374671B2 (en) | ||
| CN102942553B (en) | Preparation method for 6-carboxylfluorescein | |
| CN106565657A (en) | Hesperetin cinnamate compound with anti-tumor activity and synthetic method thereof | |
| CN112174897A (en) | Preparation method of azoxystrobin intermediate | |
| CN109535087A (en) | A kind of synthetic method of -2 C-3 aroyl compounds of (1H) -one of quinoxaline | |
| CN108727261A (en) | A kind of preparation method of that pyridine of nitro substitution quinoline | |
| CN105111194B (en) | A kind of aphthopyrans ketone compound and its preparation method and application | |
| CN115108979A (en) | Preparation method of 8-hydroxyquinoline derivative | |
| CN113004161B (en) | Preparation method of (2R, 3R) -3-methyl-3-phenylalanine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180828 |
|
| RJ01 | Rejection of invention patent application after publication |