CN106397381A - 2-alkoxy chromone oxime derivative and preparation method and application thereof - Google Patents
2-alkoxy chromone oxime derivative and preparation method and application thereof Download PDFInfo
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- CN106397381A CN106397381A CN201610813033.7A CN201610813033A CN106397381A CN 106397381 A CN106397381 A CN 106397381A CN 201610813033 A CN201610813033 A CN 201610813033A CN 106397381 A CN106397381 A CN 106397381A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/56—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 without hydrogen atoms in position 3
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Abstract
The invention discloses a 2-alkoxy chromone oxime derivative and a preparation method and application thereof. The preparation method includes: dissolving a 3-formyl chromone derivative, sodium nitrite, an alcohol derivative and an oxidizing agent into a solvent, and performing reaction under room temperature to obtain the 2-alcoxyl chromone oxime derivative. The preparation method has the advantages that the 3-formyl chromone derivative used as the initiator is easy to obtain, low in cost and many in variety; the sodium nitrite used as the oximation reagent is low in cost; metal catalysts are not needed, metal residues can be avoided, and the method is suitable for preparing medicine and biological preparations; the reaction of the method is performed in the air, and the method is mild in reaction condition, short in reaction time, high in target product yield, simple in reaction operation and post-treatment, low in environment pollution and suitable for industrial production.
Description
Technical field
The invention belongs to the preparing technical field of organic compound is and in particular to a kind of 2- alkoxyl chromone 9 oxime derivate
Preparation method；The invention still further relates to such compound is preparing the purposes that tumor cell rises in value in inhibitor and antibacterial preparation.
Background technology
Oxime is the important organic compound of a class, is widely used in synthesis chemistry, Coordinative Chemistry and biomedicine field.Oxime
Derivant has extensive physiologically active, such as antioxidation, antibacterial, parasite killing isoreactivity.
Linwood K. Payne, Jr. et al. report 9 oxime derivate has insecticidal activity, the knot of its representative compound
Structure is as follows（Referring to：Payne, Linwood K., Jr.; Stansbury, Harry A., Jr.; Weiden, M. H.
J.J.Agric. Food. Chem.1966,14(4), 356.）：
Filip Jaro et al. report 9 oxime derivate is nitric oxide production effective donor, and nitric oxide has promotion vasodilation
Effect；Bart omiej Potaniec et al. report compound IXNOX has very strong antioxidant activity, and it is active and anti-
Quite, the presence of wherein oxime functional group has a very important role bad hematic acid to antioxidant properties（Referring to：Jaroš, F. et
al.Eur. J. Pharmacol.2007,575, 122; Zhou, Z.-H., Deng, H.-W., Li, Y.-J.,
The depressor effect of nitroglycerin is mediated by calcitonin gene-related
peptide.Life Sci. 2001, 69, 1313–1320；Vetrovsky, P., Boucher, J.-L., Schott,
C., Beranova, P., Chalupsky, K., Callizot, N., Muller, B., Entlicher, G.,
Mansuy, D., Stoclet, J.-C., Involvement of NO in the endothelium-independent
relaxing effects of Nw-hydroxy-larginine and other compounds bearing a C_NOH
function in the rat aorta.J. Pharmacol. Exp. Ther. 2002,303,823 830;
Potaniec, B. et al.Spectrochim. Acta, Part A.2014,118, 716.
But during prior art prepares 9 oxime derivate, using metallic catalyst, and reaction condition requirement is very high；
It is thus desirable to the new method of research and development, multiple 9 oxime derivates are prepared with inexpensive, gentle condition, expand and widely apply.
Content of the invention
It is an object of the invention to provide a kind of 2- alkoxyl chromone 9 oxime derivate and preparation method thereof, it is simple that it has raw material
Be easy to get, without metallic catalyst, reaction condition gentle it is adaptable to the advantage of large-scale production.
To achieve the above object of the invention, the technical solution used in the present invention is：One kind is prepared 2- alkoxyl chromone oxime and is derived
The method of thing, comprises the following steps：3- formacyl chromone derivative, sodium nitrite, 01 derivatives and oxidant are dissolved in solvent
In, react at room temperature, obtain 2- alkoxyl chromone 9 oxime derivate；
Described 3- formacyl chromone derivative is as shown in following chemical structure of general formula：
Wherein R1It is selected from：One of alkyl, aryl, alkoxyl, halogen, nitro；
Described 01 derivatives are as shown in following chemical structure of general formula：
R2It is selected from：One of alkyl or aryl；
Described oxidant is selected from：Di-t-butyl peroxide, peroxidized t-butyl perbenzoate, cumyl peroxide, peroxidating uncle
One of butanol, potassium peroxydisulfate；
Described solvent is selected from：Acetonitrile, 1,2- dichloroethanes, acetone, water, toluene, N, one kind of N- dimethylformamide；
Described 2- alkoxyl chromone 9 oxime derivate is as shown in following chemical structure of general formula：
.
In technique scheme, described 3- formacyl chromone derivative is selected from：4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde,
6- fluorin-4-oxygen generation -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- chloro- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- bromo- 4- oxo -4H-
.alpha.-5:6-benzopyran -3- formaldehyde, 6- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- methyl -8- nitro -4- oxo -4H- benzo
Pyrans -3- formaldehyde, 6- chloro- 8- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- isopropyl -4- oxo -4H- benzo pyrrole
Mutter -3- formaldehyde, 7- fluorin-4-oxygen for -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 7- chloro- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 7- first
Epoxide -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 5- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- methoxyl group -4-
Oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 1- oxo -1H- benzo [f] pyrans -2- formaldehyde, 4- oxo -4H- benzo simultaneously [h] benzo
One of pyrans -3- formaldehyde.Described 01 derivatives are selected from：Methanol, ethanol, propanol, butanol, amylalcohol, hexanol, isobutanol, second
One of glycol monomethyl ether, propylene glycol, benzylalcohol.
In technique scheme, in molar ratio, 3- formacyl chromone derivative: sodium nitrite: oxidant is 1:（1~4）∶
（1~4）.
In technique scheme, using thin layer chromatography（TLC）Follow the tracks of reaction until being fully completed.
In technique scheme, reaction carries out column chromatography for separation purification processes to product after terminating.
The invention discloses the 2- alkoxyl chromone oxime of said method preparation, it is a kind of new 9 oxime derivate.Further
Anti tumor activity in vitro test and bacteriostatic test show, such compound has obvious tumor cell increment inhibitory action and suppression
Bacterium acts on.Therefore the present invention discloses above-mentioned 2- alkoxyl chromone 9 oxime derivate further in preparing tumor cell increment inhibitor
Application in preparing antibacterial of application and above-mentioned 2- alkoxyl chromone 9 oxime derivate.
The course of reaction of technique scheme is represented by：
Due to the utilization of technique scheme, the inventive method has following advantages：
1. the present invention uses 3- formacyl chromone derivative is starting material, in the presence of alcohol, sodium nitrite, prepares first
2- alkoxyl chromone oxime, is a kind of new 9 oxime derivate；Raw material is easy to get, with low cost, species is many, for expanding the knot of 9 oxime derivate
Structure, the application of abundant 9 oxime derivate provides more more options.
2. preparation method disclosed by the invention, without metallic catalyst, can avoid metal residual, is suitable for medicine and biology
The preparation of preparation；Avoid prior art and there is a problem of that metal residual is poisoned；And it is beneficial to the rear places such as purification without catalyst
Reason, and reduces cost.
3. in method disclosed by the invention, reaction is carried out in atmosphere, and reaction condition is gentle, and the response time is short, and target is produced
The high income of thing, operation and last handling process are simple, and environmental pollution is little；The product obtaining has obvious tumor cell and increases
Value inhibitory action and bacteriostasis, are suitable for industrialized production application.
Specific embodiment
With reference to embodiment, the invention will be further described：
Embodiment one：The synthesis of 2- methoxyl group chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.069 g, 1.0 mmol）, di-t-butyl peroxide（0.584 g, 4.0 mmol）, methanol（2 milliliters）And acetonitrile, room temperature is anti-
Should；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 70%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.55 (s, 1H), 7.90
(dd,J= 7.8, 1.4 Hz, 1H), 7.76 – 7.59 (m, 1H), 7.31 – 7.06 (m, 2H), 6.39 (s,
1H), 3.51 (s, 3H).
Embodiment two：The synthesis of 2- methoxyl group -6- fluorine chroman-4-on -3- oxime
Using 6- fluorin-4-oxygen generation -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
6- fluorin-4-oxygen generation -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.192 g, 1.0 mmol）, nitrous acid
Sodium（0.138 g, 2.0 mmol）, peroxidized t-butyl perbenzoate（0.776 g, 4.0 mmol）, methanol（2 milliliters）With 1,2-
Dichloroethanes, room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 90%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.70 (s, 1H), 8.13
– 7.36 (m, 2H), 7.43 – 6.97 (m, 1H), 6.34 (s, 1H), 3.48 (s, 3H).
Embodiment three：The synthesis of 2- methoxyl group -6- chlorine chroman-4-on -3- oxime
Using 6- chloro- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
6- chloro- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.209 g, 1.0 mmol）, nitrous acid
Sodium（0.207 g, 3.0 mmol）, cumyl peroxide（1.080 g, 4.0 mmol）, methanol（2 milliliters）And acetone, room temperature
Reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 86%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.76 (s, 1H), 7.81
(d,J= 2.7 Hz, 1H), 7.73 (dd,J= 8.8, 2.7 Hz, 1H), 7.25 (d,J= 8.8 Hz,
1H), 6.40 (s, 1H), 3.51 (s, 3H).
Example IV：The synthesis of 2- methoxyl group -6- bromine chroman-4-on -3- oxime
Using 6- bromo- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
6- bromo- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.253 g, 1.0 mmol）, nitrous acid
Sodium（0.276 g, 4.0 mmol）, tertbutanol peroxide（0.360 g, 4.0 mmol）, methanol（2 milliliters）And water, room temperature is anti-
Should；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 74%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.77 (s, 1H), 7.94
(d,J= 2.5 Hz, 1H), 7.86 (dd,J= 8.8, 2.6 Hz, 1H), 7.20 (d,J= 8.8 Hz,
1H), 6.40 (s, 1H), 3.51 (s, 3H).
Embodiment five：The synthesis of 2- methoxyl group -7- fluorine chroman-4-on -3- oxime
Using 7- fluorin-4-oxygen generation -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
7- fluorin-4-oxygen generation -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.192 g, 1.0 mmol）, nitrous acid
Sodium（0.276 g, 4.0 mmol）, potassium peroxydisulfate（0.27 g, 1.0 mmol）, methanol（2 milliliters）And toluene, room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 70%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.63 (s, 1H), 7.92
(t,J= 7.4 Hz, 1H), 6.96-7.11 (m, 2H), 6.37 (s, 1H), 3.50 (s, 3H).
Embodiment six：The synthesis of 2- methoxyl group -7- chlorine chroman-4-on -3- oxime
Using 7- chloro- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
7- chloro- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.209 g, 1.0 mmol）, nitrous acid
Sodium（0.276 g, 4.0 mmol）, potassium peroxydisulfate（0.54 g, 2.0 mmol）, methanol（2 milliliters）And N, N- dimethylformamide,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 78%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.70 (s, 1H), 7.89
(d,J= 8.4 Hz, 1H), 7.37 (d,J= 1.8 Hz, 1H), 7.29 (dd,J= 8.4, 1.9 Hz,
1H), 6.41 (s, 1H), 3.53 (s, 3H).
Embodiment seven：The synthesis of 2- methoxyl group -6- nitro chroman-4-on -3- oxime
Using 6- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
6- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.219 g, 1.0 mmol）, nitrous
Sour sodium（0.276 g, 4.0 mmol）, tertbutanol peroxide（0.270 g, 3.0 mmol）And methanol（5 milliliters）And acetonitrile, room
Temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 75%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.91 (s, 1H), 8.53
(d,J= 2.8 Hz, 1H), 8.44 (dd,J= 9.1, 2.9 Hz, 1H), 7.40 (d,J= 9.1 Hz,
1H), 6.48 (s, 1H), 3.53 (s, 3H).
Embodiment eight：The synthesis of 2- methoxyl group -6- methyl -8- nitro chroman-4-on -3- oxime
Using 6- methyl -8- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is such as
Under：
6- methyl -8- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.233 g, 1.0
mmol）, sodium nitrite（0.276 g, 4.0 mmol）, tertbutanol peroxide（0.360 g, 4.0 mmol）And methanol（5 milliliters）
And acetonitrile, room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 81%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.87 (s, 1H), 8.18
– 8.08 (m, 1H), 7.98 (dd,J= 2.2, 0.7 Hz, 1H), 6.49 (s, 1H), 3.57 (s, 3H),
2.40 (s, 3H).
Embodiment nine：The synthesis of 2- methoxyl group -6- chloro- 8- nitro chroman-4-on -3- oxime
Using 6- chloro- 8- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
6- chloro- 8- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.254 g, 1.0 mmol）、
Sodium nitrite（0.138 g, 2.0 mmol）, tertbutanol peroxide（0.180 g, 2.0 mmol）, methanol（2 milliliters）And acetone,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 71%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ14.03 (s, 1H), 8.49
(d,J= 2.7 Hz, 1H), 8.14 (d,J= 2.7 Hz, 1H), 6.58 (s, 1H), 3.59 (s, 3H).
Embodiment ten：The synthesis of 2- methoxyl group -6- isopropyl chroman-4-on -3- oxime
Using 6- isopropyl -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
6- isopropyl -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.216 g, 1.0 mmol）, sub-
Sodium nitrate（0.138 g, 2.0 mmol）, cumyl peroxide（0.540 g, 2.0 mmol）, methanol（2 milliliters）And acetone,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 74%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.56 (s, 1H), 7.72
(d,J= 2.3 Hz, 1H), 7.60 (dd,J= 8.5, 2.3 Hz, 1H), 7.12 (d,J= 8.5 Hz,
1H), 6.35 (s, 1H), 3.50 (s, 3H), 2.95 (dt,J= 13.8, 6.9 Hz, 1H), 1.22 (d,J
= 6.9 Hz, 6H).
Embodiment 11：The synthesis of 2,5- dimethoxy chroman-4-on -3- oxime
Using 5- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
5- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.204 g, 1.0 mmol）, sub-
Sodium nitrate（0.138 g, 2.0 mmol）, cumyl peroxide（0.810 g, 3.0 mmol）, methanol（2 milliliters）And acetone,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 73%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.25 (s, 1H), 7.55
(t,J= 8.3 Hz, 1H), 6.82 (d,J= 8.2 Hz, 1H), 6.71 (dd,J= 8.2, 0.7 Hz,
1H), 6.22 (s, 1H), 3.84 (s, 3H), 3.46 (s, 3H).
Embodiment 12：The synthesis of 2,6- dimethoxy chroman-4-on -3- oxime
Using 6- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
6- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.204 g, 1.0 mmol）, sub-
Sodium nitrate（0.138 g, 2.0 mmol）, cumyl peroxide（0.540 g, 2.0 mmol）, methanol（2 milliliters）And acetone,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 72%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.57 (s, 1H), 7.43
– 7.25 (m, 2H), 7.23 – 7.10 (m, 1H), 6.33 (s, 1H), 3.81 (s, 3H), 3.49 (s,
3H).
Embodiment 13：The synthesis of 2,7- dimethoxy chroman-4-on -3- oxime
Using 7- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
7- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.204 g, 1.0 mmol）, sub-
Sodium nitrate（0.138 g, 2.0 mmol）, cumyl peroxide（0.540 g, 2.0 mmol）, methanol（2 milliliters）And acetone,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 72%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.44 (s, 1H), 7.82
(d,J= 8.8 Hz, 1H), 6.80 (dd,J= 8.8, 2.3 Hz, 1H), 6.72 (d,J= 2.3 Hz,
1H), 6.36 (s, 1H), 3.89 (s, 3H), 3.53 (s, 3H).
Embodiment 14：2- methoxyl group -2H- benzo [h] chromane -4（3H）The synthesis of ketone -3- oxime
Using 4- oxo -4H- benzo [h] .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- benzo [h] .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.224 g, 1.0 mmol）, nitrous
Sour sodium（0.138 g, 2.0 mmol）, cumyl peroxide（0.540 g, 2.0 mmol）, methanol（2 milliliters）And acetone, room
Temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 71%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.65 (s, 1H), 8.31
(d,J= 8.2 Hz, 1H), 7.95 (d,J= 8.1 Hz, 1H), 7.83 (d,J= 8.7 Hz, 1H), 7.72
(t,J= 7.3 Hz, 1H), 7.63 (t,J= 8.7 Hz, 2H), 6.61 (s, 1H), 3.55 (s, 3H).
Embodiment 15：The synthesis of 3- methoxyl group -2,3- dihydro -1H- benzo [f] chromane -1- ketone -2- oxime
Using 1- oxo -1H- benzo [f] .alpha.-5:6-benzopyran -2- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
1- oxo -1H- benzo [f] .alpha.-5:6-benzopyran -2- formaldehyde is added in reaction bulb（0.224 g, 1.0 mmol）, nitrous
Sour sodium（0.138 g, 2.0 mmol）, potassium peroxydisulfate（0.81 g, 3.0 mmol）, methanol（2 milliliters）And acetone, room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 74%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.50 (s, 1H), 9.32
(d,J= 8.5 Hz, 1H), 8.25 (d,J= 8.9 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.71
(t, J = 7.5 Hz, 1H), 7.53 (t, J = 7.2 Hz, 1H), 7.33 (d, J = 8.8 Hz, 1H), 6.42
(s, 1H), 3.52 (s, 3H).
Embodiment 16：The synthesis of 2- ethyoxyl chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.207 g, 3.0 mmol）, potassium peroxydisulfate（0.54 g, 2.0 mmol）, ethanol（3 milliliters）And acetonitrile, room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 83%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.53 (s, 1H), 7.87
(d,J= 7.5 Hz, 1H), 7.65 (t,J= 7.4 Hz, 1H), 7.18 (t,J= 7.5 Hz, 1H), 7.12
(d,J= 8.2 Hz, 1H), 6.47 (s, 1H), 4.18 – 3.63 (m, 2H), 1.08 (s, 3H).
Embodiment 17：The synthesis of 2- propoxyl group chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.207 g, 3.0 mmol）, peroxidized t-butyl perbenzoate（0.388 g, 2.0 mmol）, normal propyl alcohol（3 milliliters）And acetonitrile,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 85%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.52 (s, 1H), 7.87
(dd,J= 7.8, 1.6 Hz, 1H), 7.79 – 7.58 (m, 1H), 7.28 – 7.14 (m, 1H), 7.12 (d,J= 8.2 Hz, 1H), 6.45 (s, 1H), 3.88 – 3.58 (m, 2H), 1.65 – 1.35 (m, 2H), 0.73
(t,J= 7.4 Hz, 3H).
Embodiment 18：The synthesis of 2- butoxy chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.207 g, 3.0 mmol）, peroxidized t-butyl perbenzoate（0.388 g, 2.0 mmol）, n-butyl alcohol（3 milliliters）And acetonitrile,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 90%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.53 (s, 1H), 7.86
(dd,J= 7.8, 1.6 Hz, 1H), 7.81 – 7.58 (m, 1H), 7.22 – 7.15 (m, 1H), 7.12 (d,J= 8.2 Hz, 1H), 6.45 (s, 1H), 3.74 (ddt,J= 32.4, 9.9, 6.4 Hz, 2H), 1.57 –
1.32 (m, 2H), 1.27 – 1.05 (m, 2H), 0.75 (t,J= 7.4 Hz, 3H).
Embodiment 19：The synthesis of 2- amoxy chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.207 g, 3.0 mmol）, peroxidized t-butyl perbenzoate（0.388 g, 2.0 mmol）, n-amyl alcohol（3 milliliters）And acetonitrile,
Room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 87%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.56 (s, 1H), 7.89
(dd,J= 7.8, 1.7 Hz, 1H), 7.69 (ddd,J= 8.8, 7.3, 1.7 Hz, 1H), 7.28 – 7.19
(m, 1H), 7.16 (d,J= 8.3 Hz, 1H), 6.47 (s, 1H), 3.92 – 3.62 (m, 2H), 1.49
(dt,J= 13.4, 6.6 Hz, 2H), 1.36 – 1.02 (m, 4H), 0.78 (t,J= 7.0 Hz, 3H).
Embodiment 20：The synthesis of 2- isobutoxy chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.276 g, 4.0 mmol）, potassium peroxydisulfate（0.54 g, 2.0 mmol）And isobutanol（5 milliliters）, and acetonitrile, room temperature reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 75%）Analytical data：1H NMR (400 MHz, DMSO-d 6):δ13.54 (s, 1H), 7.89 (dd,J=
7.8, 1.5 Hz, 1H), 7.79 – 7.56 (m, 1H), 7.22 (t,J= 7.5 Hz, 1H), 7.16 (d,J=
8.2 Hz, 1H), 6.47 (s, 1H), 3.55 (ddd,J= 20.0, 9.6, 6.8 Hz, 2H), 1.78 (dp,J
= 13.3, 6.6 Hz, 1H), 0.76 (dd,J= 14.7, 6.7 Hz, 6H).
Embodiment 21：2-（2- methoxy ethoxy）The synthesis of chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.276 g, 4.0 mmol）, potassium peroxydisulfate（0.54 g, 2.0 mmol）And glycol monoethyl ether（5 milliliters）And acetonitrile, room temperature
Reaction；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 71%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.55 (s, 1H), 7.87
(dd,J= 7.8, 1.6 Hz, 1H), 7.78 – 7.60 (m, 1H), 7.25 – 7.18 (m, 1H), 7.15 (d,J= 8.2 Hz, 1H), 6.52 (s, 1H), 3.87 (t,J= 4.7 Hz, 2H), 3.50 – 3.42 (m, 2H),
3.15 (s, 3H).
Embodiment 22：2-（3- hydroxy propyloxy group）The synthesis of chroman-4-on -3- oxime
Using 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, sodium nitrite as raw material, its reactions steps is as follows：
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde is added in reaction bulb（0.174 g, 1.0 mmol）, sodium nitrite
（0.276 g, 4.0 mmol）, potassium peroxydisulfate（0.54 g, 2.0 mmol）With 1,3- propylene glycol（5 milliliters）And acetonitrile, room temperature is anti-
Should；
TLC follows the tracks of reaction until being fully completed；
The crude by column chromatography that reaction obtains after terminating separates (petroleum ether:Ethyl acetate=4:1), obtain target product
（Yield 81%）.The analytical data of product is as follows：1H NMR (400 MHz, DMSO-d 6):δ13.53 (s, 1H), 7.86
(dd,J= 7.8, 1.4 Hz, 1H), 7.80 – 7.56 (m, 1H), 7.20 (t,J= 7.5 Hz, 1H),
7.14 (d,J= 8.2 Hz, 1H), 6.45 (s, 1H), 4.43 (s, 1H), 4.05 – 3.63 (m, 2H),
3.34 (t,J= 6.1 Hz, 2H), 1.64 (p,J= 6.4 Hz, 2H).
Embodiment 23：Anti tumor activity in vitro and bacteriostatic test
Anti tumor activity in vitro is tested：
(1) compound is configured to 10 with methanol respectively-4、10-5With 10-6The solution of mol/L concentration, for surveying activity；
(2) successive transfer culture of cell line and cell adopts human hepatocellular carcinoma BEL-7402 cell, human lung cancer SPC-A4 cell and mice white
The cancerous cell lines such as disorders of blood P388 cell.Various cells all with the RPMI-1640 culture medium containing 10% FBS, at 32 DEG C（P388 is thin
Born of the same parents) or at 37 DEG C（BEL-7402 and SPC-A4 cell) successive transfer culture in the incubator being passed through 5% carbon dioxide；
（3）Use Sulforhodamine B respectively（SRB）Method（For human hepatocellular carcinoma BEL-7402 cell and human lung cancer SPC-A4 cell）With
Tetrazolium（MTT）Method（For P 388 cells）, respectively obtain the cell increasing under each concentration of each compound
Grow suppression ratio (%)（It is shown in Table 1）.
It can be seen that, product of the present invention has obvious tumor cell increment inhibitory action, can be used for the research and development of antitumor drug.
Bacteriostatic test：
Using viewing test result after 37 DEG C of broth bouillon culture 24 hours, the minimum suppression being all this compound with asepsis growth
Bacteria concentration.Test shows, product of the present invention all has growth inhibited to make to staphylococcus aureuses, bacillus pyocyaneus and dysentery bacterium
With result of the test is shown in Table 2.From table 2, product of the present invention has obvious fungistatic effect, can be used for the research and development of antibacterial.
.
Claims (10)
1. a kind of method preparing 2- alkoxyl chromone 9 oxime derivate is it is characterised in that comprise the following steps：By 3- formyl primary colours
Ketone derivatives, sodium nitrite, 01 derivatives and oxidant are dissolved in solvent, react at room temperature, obtain 2- alkoxyl chromone oxime
Derivant；
Described 3- formacyl chromone derivative is as shown in following chemical structure of general formula：
Wherein R1It is selected from：One of alkyl, aryl, alkoxyl, halogen, nitro；
Described 01 derivatives are as shown in following chemical structure of general formula：
R2It is selected from：One of alkyl or aryl；
Described oxidant is selected from：Di-t-butyl peroxide, peroxidized t-butyl perbenzoate, cumyl peroxide, peroxidating uncle
One of butanol, potassium peroxydisulfate；
Described solvent is selected from：Acetonitrile, 1,2- dichloroethanes, acetone, water, toluene, N, one of N- dimethylformamide；
Described 2- alkoxyl chromone 9 oxime derivate is as shown in following chemical structure of general formula：
.
2. according to claim 1 2- alkoxyl chromone 9 oxime derivate preparation method it is characterised in that：In molar ratio, 3-
Formacyl chromone derivative: sodium nitrite: oxidant is 1:（1~4）∶（1~4）.
3. according to claim 1 2- alkoxyl chromone 9 oxime derivate preparation method it is characterised in that：Reaction is right after terminating
Product carries out column chromatography for separation purification processes.
4. according to claim 1 2- alkoxyl chromone 9 oxime derivate preparation method it is characterised in that：Described 3- formoxyl
Chromone derivative is selected from：4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- fluorin-4-oxygen generation -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- are chloro-
4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- bromo- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- nitro -4- oxo -4H- benzene
And pyrans -3- formaldehyde, 6- methyl -8- nitro -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- chloro- 8- nitro -4- oxo -4H-
.alpha.-5:6-benzopyran -3- formaldehyde, 6- isopropyl -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 7- fluorin-4-oxygen generation -4H- .alpha.-5:6-benzopyran -3-
Formaldehyde, 7- chloro- 4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 7- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 5- methoxy
Base -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 6- methoxyl group -4- oxo -4H- .alpha.-5:6-benzopyran -3- formaldehyde, 1- oxo -1H- benzene
And [f] pyrans -2- formaldehyde, 4- oxo -4H- benzo simultaneously one of [h] .alpha.-5:6-benzopyran -3- formaldehyde.
5. according to claim 1 2- alkoxyl chromone 9 oxime derivate preparation method it is characterised in that：TLC follows the tracks of reaction
Until being fully completed.
6. according to claim 1 2- alkoxyl chromone 9 oxime derivate preparation method it is characterised in that：Described 01 derivatives
It is selected from：Methanol, ethanol, propanol, butanol, amylalcohol, hexanol, isobutanol, glycol monoethyl ether, propylene glycol or benzylalcohol.
7. the 2- alkoxyl chromone oxime of the preparation method preparation of 2- alkoxyl chromone 9 oxime derivate according to claim 1 derives
Thing.
8. 2- alkoxyl chromone 9 oxime derivate described in claim 7 is preparing the application that tumor cell rises in value in inhibitor.
9. application in preparing antibacterial for the 2- alkoxyl chromone 9 oxime derivate described in claim 7.
10. application in preparing antitumor drug for the 2- alkoxyl chromone 9 oxime derivate described in claim 7.
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| CN110407716A (en) * | 2019-08-16 | 2019-11-05 | 山东省化工研究院 | A kind of method that oximate process inhibits nitroparaffins |
| CN115594655A (en) * | 2022-09-16 | 2023-01-13 | 桂林医学院（Cn） | Chromone oxime derivative and preparation method and application thereof |
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| CN110407716A (en) * | 2019-08-16 | 2019-11-05 | 山东省化工研究院 | A kind of method that oximate process inhibits nitroparaffins |
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| CN115594655A (en) * | 2022-09-16 | 2023-01-13 | 桂林医学院（Cn） | Chromone oxime derivative and preparation method and application thereof |
| CN115594655B (en) * | 2022-09-16 | 2023-08-15 | 桂林医学院 | Chromone oxime derivative and preparation method and application thereof |
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