What Are Some Coumarin Derivatives?

Coumarin, English name is Coumarin, molecular formula: C9H6O2, relative molecular weight 146.15, white crystalline solid, melting point 68 ~ 70 ° C, boiling point 298 ° C / 266Pa, relative density 0.9350. It is found naturally in black fragrant beans, cockleburs, wild vanilla, orchids, and has fresh hay and fragrant fragrant incense. Generally it is not edible, and tobacco and external use are allowed [1] .

Coumarin, English name is Coumarin, molecular formula: C9H6O2, relative molecular weight 146.15, white crystalline solid, melting point 68 ~ 70 , boiling point 298 / 266Pa, relative density 0.9350. It is found naturally in black fragrant beans, cockleburs, wild vanilla, orchids, and has fresh hay and fragrant fragrant incense. Generally it is not edible, and tobacco and external use are allowed [1] .
On October 27, 2017, the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization initially compiled the reference, and coumarin was in the list of 3 types of carcinogens. [2]
Chinese name
Coumarin
English name
Coumarin
nickname
Xanthonyl ketone; Coumarin lactone; Oxonaphthone; 2H-1-benzopyran-2-one
Chemical formula
C9H6O2
Molecular weight
146.14
CAS Registry Number
91-64-5
EINECS registration number
202-086-7
Melting point
69
Boiling point
297 ~ 299
Water soluble
Insoluble in water, easily soluble in hot water
Density
0.935 g / mL, 20/4
Exterior
Colorless flake or powder crystal
Flash point
162 ° C
Application
spices

Coumarin Profile

WinID: 023V
Chinese name: Coumarin
English name: o-Naphthyl ketone oxygen
Alias names: Coumarin lactone, oxonaphthone, oxonaphthone [3] , o-hydroxylaurolactone, 1,2-benzopyrone, o-hydroxycinnamate, etc.
More aliases: Coumarin Oxygen phthalazinon adjacent ketone Salicylic acid lactone 1,2-Benzopyrone 1-Benzopyran-2-one o-Hydroxycinamic acid lactone (Z) -o-Coumarinic acid lactone
Molecular formula: C 9 H 6 O 2
Molecular weight: 146.14
CAS number: 91-64-5
MDL number: MFCD00006850
EINECS number: 202-086-7
RTECS number: GN4200000
BRN number: 383644
PubChem number: 24892679

Coumarin classification

  1. Simple coumarins: Only coumarins with substituents on the benzene ring.
  2. Furocoumarins (furocoumarins): The isoprenyl group on the coumarin core often synthesizes a furan or pyran ring with an ortho-phenolic hydroxyl (7-hydroxy) ring. The former is called furanocoumarin.
  3. Pyranocoumarins: Coumarin C-6 or C-8 isopentenyl is cyclized with o-phenol hydroxyl groups to form a 2,2-dimethyl--pyran ring structure to form pyran Coumarin.
  4. Double coumarins, isocoumarins and other coumarins.

Coumarin preparation method

In a 250 mL three-necked flask equipped with a distillation device, a dropping funnel and a thermometer, add 40 g of salicylaldehyde, 73 g of freshly distilled acetic anhydride, and 1 g of treated anhydrous potassium acetate, and then heat up the temperature in the three-necked bottle. Controlled at 145 ~ 150 , steam temperature controlled below 120 . At this point, the acetic acid began to evaporate. When the amount of distillate is about 15g, 15g of acetic anhydride is added dropwise, and its dropping speed should be equivalent to the speed of acetic acid distilling. After the dropwise addition of acetic acid, after a certain period of time, it is found that when the temperature is not easy to control at 120 ° C, the internal temperature can be continuously increased to about 208 ° C, and maintained for 15min to half an hour, and then naturally cooled.
When the temperature is cooled to about 80 ° C, wash with hot water under stirring, let stand and separate the water layer, and the oil layer is neutralized with 10% sodium carbonate solution, becomes slightly alkaline, and then washed with hot water to neutrality, remove The water layer was distilled under reduced pressure, and the crude product was collected at 150 ~ 160 ° C / 1866Pa. The crude product was recrystallized with 95% ethanol (the mass ratio of ethanol to the crude product was 1: 1) to obtain white granular crystals, which were pure coumarin products [1] .

Coumarin activity

Antitumor; antibacterial (Escherichia coli); antifungal; anticoagulant effect; hypoglycemic (rat); larvicides (housefly larva) [4]

Coumarin Properties

  1. Properties: colorless flake or powder, light yellow crystal with aromatic odor.
  2. Density (g / mL, 20/4 ° C): 0.935
  3. Melting point (ºC): 69
  4. Boiling point (ºC, atmospheric pressure): 297 ~ 299
  5. Boiling point (ºC, 1.3kPa): 154
  6. Boiling point (ºC, 0.67kPa): 139
  7. Flash point (ºC): 162
  8. Sublimation temperature (ºC): 100
  9. Solubility (g / 100mL, 25ºC, water): 0.25
  10. Solubility (g / 100mL, 100ºC, water): 2.0
  11. Solubility: Insoluble in cold water, easily soluble in hot water, alcohol, ether, chloroform and sodium hydroxide solution.

Coumarin molecular structure data

  1. Molar refractive index: 39.76
  2. Molar volume (m / mol): 117.0
  3. Isometric Zhang Rong (90.2K): 305.6
  4. Surface tension (dyne / cm): 46.4
  5. Polarizability (10cm): 15.76

Coumarin chemical data

  1. Number of hydrogen-bonded donors: 0
  2. Number of hydrogen bond acceptors: 2
  3. Number of rotatable chemical bonds: 0
  4. Topological molecular polar surface area: 26.3
  5. Number of heavy atoms: 11
  6. Surface charge: 0
  7. Complexity: 196
  8. Number of covalent bond units: 1

Coumarin detection response

  1. Iron hydroxamate reaction: Under basic conditions, coumarin lactones can be ring-opened, and hydroxamic acid condensed to hydroxamic acid, and then complexed with ferric ions in red under acidic conditions.
  2. Ferric chloride reaction: Coumarin containing phenolic hydroxyl groups can react with ferric chloride reagents in color.
  3. Gibbs reaction: 2,6-dichloro (bromo) benzoquinone chloroimine can be condensed with active hydrogen para-positioned with phenolic hydroxyl group to form a blue compound under weakly basic conditions.
  4. Emerson reaction: Aminoantipyrine and potassium ferricyanide can form a red condensate with para-active hydrogen of phenolic hydroxyl group.
    Both 3 and 4 require that the coumarin molecule must have a free phenolic hydroxyl group, and the phenolic hydroxyl group has a positive reaction only when there is no substituent at the para position.
    Fragrance: sweet and sweet like peas, with dried herbs, anise, and diluted like hay, nuts, tobacco leaves, dull and lasting.

Coumarin synthesis method

Coumarin is made using the Perkin W reaction. Under the action of sodium acetate, salicylaldehyde and acetic anhydride obtain coumarin in one step. It is a lactone of coumaric acid. Note that this lactone is obtained from cis-coumaric acid. The two large groups (HOC 6 H 4- , -COOH) in the product are always in the trans form, but the trans form cannot produce lactones, so the formation of cyclic lactones may promote the production of cis isomers. For one reason, in fact a small amount of trans-coumaric acid is also obtained in this reaction, and lactones cannot be formed. [3]

Coumarin related drugs

Coumarins Coumarins

Coumarins are a class of oral anticoagulants. Their common structure is 4-hydroxycoumarin. At the same time, dicoumarin can also be used against rodents. The coumarins that were discovered in the process of death caused by internal bleeding caused by anticoagulation in pasture animals were aware of the anticoagulant effect of this type of substance, which led to the subsequent research and synthesis of coumarin drugs, which has become a medical science. The world offers one more important coagulation drug.
Common coumarins are dicoumarol, warfarin (benzylacetone coumarin), and acenocoumarol (new anticoagulant).

Coumarin Chinese Medicine Chemistry

The coumarin (+) calanolide A in Calophyllum lanigerum is a powerful HIV-1 reverse transcriptase inhibitor. As an AIDS drug, the US FDA has approved its entry into phase III clinical trials.

Coumarin Toxicology Data

  1. Acute toxicity: oral-rat LD50: 293 mg / kg; oral-mouse LD50: 196 mg / kg.
  2. The highest dosage in food is 5mg / kg food; in alcoholic beverages is 10mg / kg beverage. The United States Alcohol, Tobacco, and Weapons Administration (BATF) 1974 stipulated that the coumarin content in alcohol should not exceed 5 mg / kg.

Coumarin pharmacological action

Coumarins inhibit the synthesis of coagulation factors in the liver. Coumarins are similar in structure to vitamin K. Coumarins bind to vitamin K epoxide reductase in the liver, inhibit the conversion of vitamin K from epoxide to hydroquinone, and inhibit the circulation of vitamin K. Coumarins can be said to be vitamin K antagonists or competitive inhibitors (see enzymes). The carboxylation of coagulation factors II, IX, IX, X, and X containing glutamic acid residues is inhibited, and its precursors are not coagulant, so the coagulation process is suppressed. But it has no effect on established clotting factors.

Coumarin adverse reactions and contraindications

Prothrombin time should be controlled at 25-20 seconds (normal value 12 seconds), excessive bleeding is prone to bleeding. It can be counteracted with vitamin K, and fresh plasma or whole blood can be transfused to supplement clotting factors if necessary. Contraindications are the same as heparin.

Coumarin bioactivity

  1. toxicity
  2. Antiviral effect
  3. Antitumor effect
  4. Anti-osteoporosis
  5. Anticoagulant effect
  6. Effects on the cardiovascular system
  7. Photosensitivity

Coumarin properties and stability

  1. Coumarin is a lactone of cis ortho-hydroxycinnamic acid. Can occur halogenation, nitration, sulfonation, hydrogenation and other reactions.
  2. Toxic, LD50293mg / kg in rats, LD50196mg / kg in mice, and LD50220mg / kg in mice. The workplace should be well ventilated, the equipment should be sealed, and operators should wear protective gear.
  3. It is found in burley tobacco leaves.
  4. It is found naturally in black fragrant beans, vanilla beans, lavender oil, cinnamon oil, citronella oil, and Peruvian balsam.

Coumarin storage method

  1. This product should be sealed in a cool, dry place and protected from light.
  2. 50kg cardboard drum lined with plastic bag. Pay attention to dryness, ventilation, sun protection, moisture resistance and heat insulation during storage and transportation.

Coumarin Standard Atlas

The standard map of coumarin is as follows:
Coumarin NMR
Coumarin infrared
Coumarin mass spectrometry

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