91-64-5

Basic information

• Product Name: Coumarin
• Synonyms: TIMTEC-BB SBB000094;O-HYDROXYCINNAMIC ACID LACTONE;TONKA BEAN CAMPHOR;5,6-BENZO-2-PYRONE;AKOS 212-75;2H-1-BENZOPYRAN-2-ONE;2H-1-BENZOPYAN-2-ONE;1,2-BENZOPYRONE
• CAS NO: 91-64-5
• Molecular Formula: C₉H₆O₂
• Molecular Weight: 146.14
• EINECS: 202-086-7
• Product Categories: FINE Chemical & INTERMEDIATES;Food & Feed ADDITIVES;Coumarins;Coumarin;Natural Plant Extract;Aromatics;Heterocycles;Pharmaceutical intermediates;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors;Fluorescent
• Mol File: 91-64-5.mol

Chemical Properties

• Melting Point: 68-73 °C(lit.)
• Boiling Point: 298 °C(lit.)
• Flash Point: 162 °C
• Appearance: White/Crystals or Crystalline Powder
• Density: 0.935
• Vapor Pressure: 0.01 mm Hg ( 47 °C)
• Refractive Index: 1.5100 (estimate)
• Storage Temp.: Refrigerator
• Solubility: 1.7g/l
• Water Solubility: 1.7 g/L (20 ºC)
• Merck: 14,2562
• BRN: 383644
• CAS DataBase Reference: Coumarin(CAS DataBase Reference)
• NIST Chemistry Reference: Coumarin(91-64-5)
• EPA Substance Registry System: Coumarin(91-64-5)

Safety Data

• Hazard Codes: Xn
• Statements: 22-40-36/37/38-20/21/22-43
• Safety Statements: 36-36/37-26
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 1
• RTECS: GN4200000
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 91-64-5(Hazardous Substances Data)

Usage

Uses

Used in Flavor and Fragrance Industry:
Coumarin is used as a spice for the preparation of floral fragrances such as lavender, rosemary, and sweet clover. It is used in perfumes, cosmetics, soaps, and detergents as a flavoring agent for blending fragrances to make the aroma lasting and unchanged.
Used in Electroplating Industry:
Coumarin is used as an electroplating additive to prevent the occurrence of pores in coating and can increase the brightness.
Used in Printing and Plastic Industry:
Coumarin is used as the flavor enhancer of printing ink and plastic.
Used in Pharmaceutical Industry:
Coumarin is considered a blood thinner, and it can also increase blood flow. Some sources cite anti-oxidant capacities as well. It is used as a pharmaceutical aid (flavor) and has anti-neoplastic, anti-inflammatory, and anti-hyperglycemic properties.
Used in Laser Technology:
Coumarin, as a laser dye, has an output laser range within the blue-green region (420 ~ 570nm) and has high fluorescence quantum efficiency, such as 7-ethylamino-6-methyl-4-trifluoromethyl coumarin Lactone 307.
Note: Coumarin was formerly used as spices and cigarettes spices but was banned from 1977. Since then, China had also prohibited its application in food.

Brief Introduction

It is also known as 1, 2-benzopyrone, cis ortho-caberillin, o-hydroxy cinnamon lactone and coumarin. It is contained in many natural plants in the form of glycosides and esters as vanillin instead of free-form. Coumarin will come out when certain plants are fermented and processed. Coumarin is found in the seeds of Dayton beans (Riccinechoides) in 1820 and is widely distributed in the plant kingdom, especially in plant species including Umbelliferae, Soybean, Rutaceae and Calyx. Seeds contain about 1.5% of the coumarin. In addition, coumarin is also contained in lavender oil, cinnamon oil and Peru balsam. Coumarin is spicy with sweet and lemongrass aroma. The aroma is emitted from the pink gum in the leaves of the fragrant beans, and the gum is made from the breakdown of the coumarin glycosides in the leaves. The aroma emitted by Sweet alfalfa is actually from the release of coumarin due to fermentation and decomposition during the stacking process. Precipitate from the ether appears as orthorhombic white pyramid or oblique sheet-like crystals with Lemongrass-type smell. It can subject to sublimation.

Preparation

Coumarin is currently produced by Perkin synthesis from salicylaldehyde. In the presence of sodium acetate, salicylaldehyde reacts with acetic anhydride to produce coumarin and acetic acid. The reaction is carried out in the liquid phase at elevated temperature.A process for the production of coumarin from hexahydrocoumarin by dehydrogenation has also been elaborated.Since the odor of coumarin is relatively weak, strong-smelling by-products (e.g., vinylphenol) must be removed. Many purification methods have been reported and patented.

Synthesis Reference(s)

The Journal of Organic Chemistry, 27, p. 4704, 1962 DOI: 10.1021/jo01059a541Tetrahedron Letters, 27, p. 3911, 1986 DOI: 10.1016/S0040-4039(00)83914-3

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Coumarin is sensitive to exposure to light. Coumarin is also sensitive to heat. Coumarin is incompatible with strong acids, strong bases and oxidizers. Coumarin is hydrolyzed by hot concentrated alkalis. Coumarin can be halogenated, nitrated and hydrogenated (in the presence of catalysts).

Hazard

Toxic by ingestion; carcinogenic. Use in food products prohibited (FDA). Questionable carcinogen.

Health Hazard

SYMPTOMS: Exposure to Coumarin may cause narcosis. It may also cause irritation and liver damage.

Fire Hazard

Coumarin is combustible.

Flammability and Explosibility

Nonflammable

Biological Activity

Oral anticoagulants can be prepared from compounds with coumarin as a base. Coumarin has been known for well over a century and, in addition to its use pharmaceutically, it is also an excellent odor-enhancing agent. However, because of its toxicity, it is not permitted in food products in the United States (Food and Drug Administration). One commercial drug is 3-(alpha-acetonyl-4-nitrobenzyl)- 4-hydroxycoumarin. This drug reduces the concentration of prothrombin in the blood and increases the prothrombin time by inhibiting the formation of prothrombin in the liver. The drug also interferes with the production of factors VII, IX, and X, so that their concentration in the blood is lowered during therapy. The inhibition of prothrombin involves interference with the action of vitamin K, and it has been postulated that the drug competes with vitamin K for an enzyme essential for prothrombin synthesis. Another commercial drug is bis-hydroxy-coumarin, C19H12O6. The actions of this drug are similar to those just described.

Contact allergens

Coumarin is an aromatic lactone naturally occurring in Tonka beans and other plants. As a fragrance allergen, it has to be mentioned by name in cosmetics within the EU

Safety Profile

Poison by ingestion, intraperitoneal, and subcutaneous routes. Questionable carcinogen with experimental tumorigenic data. Experimental teratogenic effects. Mutation data reported. Combustible when exposed to heat or flame. When heated to decomposition it emits acrid smoke and fumes. See also KETONES and ANHYDRIDES.

Synthesis

May be extracted from tonka beans; from salicylaldehyde and acetic anhydride in the presence of sodium acetate; also from o-cresol and carbonyl chloride followed by chlorination of the carbonate and fusion with a mixture of alkali acetate, acetic anhydride and a catalyst.

Environmental Fate

Coumarin toxicity is a function of blood and target tissue levels of coumarin relative to the metabolic capacity of the target organ. Cellular toxicity results when the formation of the toxic moieties exceeds the capacity of the cell to detoxify. This can have significant impact when comparing dosing by gavage to dietary exposure.

Purification Methods

Coumarin crystallises from ethanol or water and sublimes in vacuo at 43o [Srinivasan & deLevie J Phys Chem 91 2904 1987]. [Beilstein 17/10 V 143.]

Toxicity evaluation

Coumarin is readily biodegradable. Coumarin is unlikely to bind to soil. Coumarin does not bioaccumulate; the bioconcentration factor has been determined to be <10–40. Various environmental fate studies have shown that coumarin in the environment would biodegrade and be lost to volatilization. Losses resulting from photolysis may also occur.

Synthetic route

2-thiocoumarin (3986-98-9) → coumarin (91-64-5)

Conditions	Yield
With sodium hydroxide; copper(l) chloride In water; acetonitrile at 25℃; for 0.25h;	100%
With di(n-butyl)tin oxide In 1,4-dioxane Heating;	97%
With hydrogenchloride; N-nitrosopiperidine; potassium iodide In dichloromethane; water at 22℃; for 24h;	83%
With hydrogenchloride; sodium nitrite In dichloromethane; water at 45℃; for 22h;	64%
With sodium carbonate; trifluoroacetic anhydride 1) CH2Cl2, r.t., 2 h; Yield given. Multistep reaction;

palladium-on-activated carbon + Pd-on-carbon Powder + methyl 3-(2-oxocyclohexyl)propionate (10407-33-7) → coumarin (91-64-5) + C6H4(CH2CH2C(O)O) (119-84-6)

Conditions	Yield
In methyl 3-(2-oxcyclohexyl)propionate	A n/a B 100%

(E)-n-butyl 3-(2-hydroxyphenyl)acrylate (3487-90-9) → coumarin (91-64-5)

Conditions	Yield
In ethylene glycol at 200℃; for 12h;	99%

2-vinylphenyl acrylate → coumarin (91-64-5)

Conditions	Yield
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane at 45℃; for 24h;	99%
tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane at 20℃;	70%
With Grubbs catalyst first generation In toluene at 80℃; for 2h; Inert atmosphere;
With Hoveyda-Grubbs catalyst second generation In chloroform-d1 at 25℃; for 24h; Reagent/catalyst; Time; Inert atmosphere; Sealed tube; Darkness;	99 %Spectr.

2-oxo-2H-benzopyran-7-yl trifluoromethanesulfonate (108530-10-5) → coumarin (91-64-5)

Conditions	Yield
With methanol; zinc; Ni(Ph3P); 1,3-bis-(diphenylphosphino)propane; potassium iodide; zinc In N,N-dimethyl-formamide at 50℃; for 4h;	98%
With 1,1'-bis-(diphenylphosphino)ferrocene; formic acid; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 60℃; for 2h;	82%

methyl 2-coumarate (20883-98-1) → coumarin (91-64-5)

Conditions	Yield
In methanol at 40 - 50℃; for 14h; UV-irradiation;	96%
at 750℃;

(α6aH,β6bH,β12bH,α12cH)-cyclobuta<1,2-c,4,3-c1>bis<1>benzopyran-6,7-dione (5248-12-4) → coumarin (91-64-5)

Conditions	Yield
With 2,4,6-triphenylpyrylium tetrafluoroborate In acetonitrile at 25℃; for 0.333333h; Quantum yield; Mechanism; Irradiation;	96%
With 5-ethyl-1,3-dimethyl-8-(trifluoromethyl)alloxazinium perchlorate In acetonitrile at 20℃; for 0.5h; Catalytic behavior; Reagent/catalyst; Time; Irradiation; Inert atmosphere; Schlenk technique;	92%
With trifluorormethanesulfonic acid; riboflavine tetraacetate In acetonitrile at 20℃; for 0.166667h; Reagent/catalyst; Solvent; Irradiation; Schlenk technique; Inert atmosphere;	90%
In 1,4-dioxane for 0.266667h; Product distribution; Ambient temperature; Irradiation; correlation between photochemical fission and chemical structure;	25 % Chromat.
UV-irradiation;

ethyl 3-(2-methoxyphenyl)acrylate (33877-05-3) → coumarin (91-64-5)

Conditions	Yield
With boron tribromide In dichloromethane at 50℃; for 5h; Inert atmosphere;	96%

3,4-dibromochroman-2-one → coumarin (91-64-5)

Conditions	Yield
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; sodium carbonate In dimethyl sulfoxide at 20℃; for 1.5h; Inert atmosphere; Irradiation;	96%

C6H4(CH2CH2C(O)O) (119-84-6) → coumarin (91-64-5)

Conditions	Yield
With dimethyl cis-but-2-ene-1,4-dioate at 200℃;	95%
Stage #1: C6H4(CH2CH2C(O)O) With di-n-butylboryl trifluoromethanesulfonate; N-ethyl-N,N-diisopropylamine In fluorobenzene; dichloromethane Stage #2: With dichloro( 1,5-cyclooctadiene)platinum(ll); diallylcarbonate; silver trifluoroacetate In fluorobenzene; dichloromethane at 20℃; for 24h; Sealed tube; chemoselective reaction;	67%
With N,N’-di-tert-butylthiadiaziridine-1,1-dioxide; triphenylphosphine; copper(l) chloride at 65℃; for 20h; Inert atmosphere;	60%

(E)-3-(2-Hydroxy-phenyl)-N-[2-(4-hydroxy-phenyl)-ethyl]-acrylamide → tyrosamine (51-67-2) + coumarin (91-64-5)

Conditions	Yield
With acetic acid In methanol for 2h; Ambient temperature; Irradiation; other N-subsituted amides of o-hydroxy-trans-cinnamic acid;	A 95% B 100 % Spectr.

2-oxo-2H-chromene-3-carboxylic acid (531-81-7) → coumarin (91-64-5)

Conditions	Yield
With pyridine for 5h; Heating;	95%
With acetic acid; silver carbonate In 2,4-dichlorophenoxyacetic acid dimethylamine at 100℃; for 16h;	63%
With copper(l) iodide; triethylamine In dimethyl sulfoxide at 120℃; under 760.051 Torr; for 20h; Inert atmosphere; Schlenk technique;	57%
With bromobenzene; silver carbonate; palladium dichloride In dimethyl sulfoxide at 120℃; for 5h;
With dipotassium peroxodisulfate; silver(I) trifluoromethanethiolate; potassium carbonate In water; dimethyl sulfoxide at 110℃; for 24h; Solvent; Inert atmosphere; Sealed tube;	33 %Spectr.

(E)-ethyl 2-hydroxycinnamate (3943-94-0, 17041-46-2, 6236-62-0) → coumarin (91-64-5)

Conditions	Yield
With tris[2-phenylpyridinato-C2,N]iridium(III) In acetonitrile at 20℃; for 24h; Sealed tube; Inert atmosphere; Irradiation;	94%
With tributylphosphine In methanol at 70℃; for 20h; Solvent; Reagent/catalyst; Inert atmosphere;	82%
With palladium on activated charcoal In dimethyl amine at 140℃; Sealed tube; Inert atmosphere;	78%
In benzene for 1h; Irradiation;	95 % Turnov.
With toluene-4-sulfonic acid In poly(methyl methacrylate) for 0.075h; Quantum yield; Reagent/catalyst; UV-irradiation; Darkness;

Propiolic acid (471-25-0) + phenol (108-95-2) → coumarin (91-64-5)

Conditions	Yield
With ytterbium(III) trifluoromethanesulfonate hydrate at 80℃; for 0.0333333h; Reagent/catalyst; Microwave irradiation;	93%
With trifluoroacetic acid In chlorobenzene at 100℃; for 1h; Inert atmosphere;	76%
With trifluorormethanesulfonic acid In chlorobenzene at 100℃; for 2h;	76%

Acrylic acid ((E)-2-propenyl)-phenyl ester (151597-71-6) → coumarin (91-64-5)

Conditions	Yield
Stage #1: Acrylic acid ((E)-2-propenyl)-phenyl ester With titanium(IV) isopropylate In dichloromethane for 1h; Heating; Stage #2: tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane for 4h; ring closing metathesis; Heating;	93%

phenyl prop-2-ynoate (60998-71-2) → coumarin (91-64-5)

Conditions	Yield
With Echavarren's catalyst In dichloromethane at 18℃; for 1h;	93%
With gold(III) chloride; silver trifluoromethanesulfonate In 1,2-dichloro-ethane at 50℃;	84%

2-(1,1,1,1,1-pentacarbonyl-1-chroma)-2H-1-benzopyran → coumarin (91-64-5)

Conditions	Yield
With pyridine N-oxide In dichloromethane at 23℃; for 3h;	93%

S-phenyl hydrogen thiomalonate (4279-77-0) + salicylaldehyde (90-02-8) → coumarin (91-64-5)

Conditions	Yield
With triethylamine; benzylamine In chloroform at 55℃; for 6h; Reagent/catalyst; Solvent;	93%

4-chloro-2H-1-benzopyran-2-one (17831-88-8) → coumarin (91-64-5) + 4,4'-bis-(2H-chromen-2-one) (118545-81-6)

Conditions	Yield
With bis[2-(diphenylphosphino)phenyl] ether; potassium iodide; zinc; bis(triphenylphosphine)nickel(II) chloride In 1,4-dioxane at 130℃; for 0.5h; Ullmann-type reaction; microwave irradiation;	A n/a B 92%

(3R*,4R*)-3,4-dibromo-3,4-dihydrocoumarin → coumarin (91-64-5)

Conditions	Yield
With tris(2,2'-bipyridyl)ruthenium dichloride; 1,5-dimethoxynaphthalene; ascorbic acid In methanol; water for 5h; Inert atmosphere; Irradiation;	92%

3-((4-fluorophenyl)thio)-3-oxopropanoic acid (957770-83-1) + salicylaldehyde (90-02-8) → coumarin (91-64-5)

Conditions	Yield
With triethylamine; benzylamine In chloroform at 55℃; for 4h; Reagent/catalyst; Solvent;	92%

n-butyl thiomalonate (19754-56-4) + salicylaldehyde (90-02-8) → coumarin (91-64-5)

Conditions	Yield
With triethylamine; benzylamine In chloroform at 55℃; for 6h; Reagent/catalyst; Solvent;	92%

acetic anhydride (108-24-7) + salicylaldehyde (90-02-8) → coumarin (91-64-5)

Conditions	Yield
With polyphosphoric acid In N,N-dimethyl-formamide at 145℃; for 3h; Temperature; Solvent; Concentration; Time; Inert atmosphere;	91%
With polyphosphoric acid In N,N-dimethyl-formamide at 145℃; for 3h; Temperature; Inert atmosphere;	91%
With cesium acetate at 150 - 160℃; for 8h;	79%

salicylaldehyde (90-02-8) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → (E)-ethyl 2-hydroxycinnamate (3943-94-0, 17041-46-2, 6236-62-0) + coumarin (91-64-5)

Conditions	Yield
In toluene Heating;	A 91% B 4%
In xylene for 4h; Heating;	A 83% B 10%
for 4h; Heating;	A 82.8% B 9.6%

7-(1-Phenyl-1H-tetrazol-5-yloxy)-chromen-2-one (77924-22-2) → 1-phenyl-5-hydroxytetrazole (5097-82-5) + coumarin (91-64-5) + C6H4(CH2CH2C(O)O) (119-84-6)

Conditions	Yield
With sodium hypophosphite; palladium on activated charcoal In ethanol; water; benzene for 0.916667h; Heating;	A n/a B 91% C n/a
With sodium hypophosphite; palladium on activated charcoal In ethanol; benzene for 55h; Mechanism; Heating;	A n/a B 91% C n/a

3,4-dibromo-3,4-dihydrocoumarin (42974-18-5) → coumarin (91-64-5)

Conditions	Yield
With sodium tetrahydroborate; nickel dichloride In methanol at 20℃; for 0.25h;	90%
With sodium sulfide; Aliquat 336 In water; benzene for 1h; Ambient temperature;	88%
With N,N,N,N,-tetramethylethylenediamine; sexithiophene In N,N-dimethyl-formamide for 2h; Inert atmosphere; Irradiation;	88%
In methanol at 20℃; for 6h; Irradiation;	65%

3,4,5,6,7,8-hexahydro-chromen-2-one (700-82-3) + diethyl Fumarate (623-91-6) → coumarin (91-64-5)

Conditions	Yield
palladium-carbon	90%

salicylaldehyde (90-02-8) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → coumarin (91-64-5)

Conditions	Yield
With N,N-diethylaniline at 210 - 215℃; for 4h;	89.2%
With N,N-diethylaniline In xylene for 4h; Heating;	89%

coumarin (91-64-5) → 2-thiocoumarin (3986-98-9)

Conditions	Yield
With tetraphosphorus decasulfide In 5,5-dimethyl-1,3-cyclohexadiene for 12h; Inert atmosphere; Reflux;	100%
With Lawessons reagent for 0.05h; microwave irradiation;	98%
With bis(tricyclohexyltin)sulfide; boron trichloride for 7h; Heating;	94%

coumarin (91-64-5) → 6-nitrocoumarin (2725-81-7)

Conditions	Yield
With sulfuric acid; nitric acid	100%
Stage #1: coumarin With sulfuric acid at 4℃; for 0.166667h; Stage #2: With guanidine nitrate	98%
With ammonium cerium(IV) nitrate; acetic acid at 20℃; for 2h;	92%

coumarin (91-64-5) → C6H4(CH2CH2C(O)O) (119-84-6)

Conditions	Yield
With formic acid; palladium In methanol; water Ambient temperature;	100%
With hydrogen; W-2 Raney nickel In ethyl acetate for 0.833333h; Ambient temperature; Irradiation;	100%
With hydrogen; palladium on activated charcoal In acetic acid under 760.051 Torr; for 12h;	99%

decacarbonyl-1κ(4)C,2κ(3)C,3κ(3)C-μ-hydrido-2:3κ(2)H-μ-hydroxy-2:3κ(2)O-trisosmium-(3 Os-Os) + coumarin (91-64-5) → Os3(CO)10(μ-H)(μ-OH)*coumarin

Conditions	Yield
In hexane ligand was added to hexane soln. of Os-cluster in Schlenk tube, stirred for 100 min at room temp. under N2; solvent was removed under reduced pressure, recrystd. from CH2Cl2/hexaneat -5°C; elem. anal.;	99%

coumarin (91-64-5) → coumarin-d6 (116295-83-1)

Conditions	Yield
With 10% Pt/activated carbon; water-d2 In cyclohexane; isopropyl alcohol at 80℃; for 24h; Inert atmosphere;	99%

1-ethoxy-1-(tert-butyldimethylsilyloxy)ethene (42201-84-3) + coumarin (91-64-5) + cyclohexanone (108-94-1) → ethyl 2-(3-(1-((tert-butyldimethylsilyl)oxy)cyclohexyl)-2-oxochroman-4-yl)acetate

Conditions	Yield
Stage #1: 1-ethoxy-1-(tert-butyldimethylsilyloxy)ethene; coumarin With C18H14F18O15S6 In dichloromethane at -78℃; for 0.5h; Inert atmosphere; Stage #2: cyclohexanone In dichloromethane at -78℃; for 0.5h; Reagent/catalyst; Inert atmosphere;	99%

coumarin (91-64-5) + salicylic acid (69-72-7) → 2H,6H-pyrano<3,2-b>xanthene-2,6-dione

Conditions	Yield
With ytterbium(III) trifluoromethanesulfonate nonohydrate In neat (no solvent) for 0.0833333h; Milling; Microwave irradiation;	98%

6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (4721-98-6) + coumarin (91-64-5) → (10RS,15aRS)-2,3-dimethoxy-9,10-dihydro-5H-10,15a methanobenzo[7,8][1,3]oxazocino[2,3-a]isoquinolin-8(6H)-one

Conditions	Yield
With sodium carbonate In water at 80℃; for 16h; Solvent; Temperature; Reagent/catalyst; stereoselective reaction;	98%

2-Methylbenzophenone (131-58-8) + coumarin (91-64-5) → 7-hydroxy-7-phenyl-6a,7,12,12a-tetrahydro-6H-naphtho[2,3-c]chromen-6-one

Conditions	Yield
In toluene at 25℃; for 0.583333h; Concentration; Solvent; Time; Inert atmosphere; UV-irradiation; Flow reactor; diastereoselective reaction;	98%

diphenyl diselenide (1666-13-3) + coumarin (91-64-5) → 3-(phenylselanyl)-2H-chromen-2-one

Conditions	Yield
With trimethylsilylazide; bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 0.5h; Solvent; Reagent/catalyst;	98%
With bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 1h; Reagent/catalyst; Solvent; regioselective reaction;	95%

bis(2-methylphenyl) diselenide (69447-36-5) + coumarin (91-64-5) → 3-(o-tolylselanyl)-2H-chromen-2-one

Conditions	Yield
With bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 1.5h; regioselective reaction;	98%

1,2-bis(3-fluorophenyl)diselane (63930-16-5) + coumarin (91-64-5) → 3-((3-fluorophenyl)selanyl)-2H-chromen-2-one

Conditions	Yield
With bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 2h; regioselective reaction;	98%

di-p-tolyl diselenide (21856-94-0) + coumarin (91-64-5) → 3-(p-tolylselanyl)-2H-chromen-2-one

Conditions	Yield
With bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 1h; regioselective reaction;	98%

2,3-Dimethyl-2-butene (563-79-1) + coumarin (91-64-5) → 1,1,2,2-tetramethyl-2,2adihydro-1H-cyclobuta[c]chromen-3(8bH)-one (7305-18-2)

Conditions	Yield
With aluminum tri-bromide In dichloromethane; 1,2-dibromomethane at 20℃; for 5h; Inert atmosphere; Irradiation;	97%

coumarin (91-64-5) + phenylboronic acid (98-80-6) → 4-phenylcoumarin (15185-05-4)

Conditions	Yield
With 5-Nitro-1,10-phenanthroline; oxygen; palladium diacetate In N,N-dimethyl-formamide at 80℃; for 24h; Heck reaction; chemoselective reaction;	97%
With 1,10-Phenanthroline; oxygen In N,N-dimethyl-formamide at 100℃; for 24h; Catalytic behavior; Solvent; Suzuki Coupling; Sealed tube; regioselective reaction;	87%
With 1,10-Phenanthroline; oxygen; palladium diacetate In N,N-dimethyl-formamide at 100℃; for 24h; Sealed tube;	82%
With 5-Nitro-1,10-phenanthroline; oxygen; palladium diacetate In N,N-dimethyl-formamide at 80℃; for 12h; Schlenk technique; Sealed tube;	60%
Stage #1: coumarin With 1,10-Phenanthroline; oxygen; palladium diacetate In acetonitrile for 0.0833333h; Heck type reaction; Stage #2: phenylboronic acid In N,N-dimethyl-formamide at 100℃; Heck type reaction; regioselective reaction;	14%

1-ethoxy-1-(tert-butyldimethylsilyloxy)ethene (42201-84-3) + coumarin (91-64-5) + acetone (67-64-1) → ethyl 2-(3-(2-((tert-butyldimethylsilyl)oxy)propan-2-yl)-2-oxochroman-4-yl)acetate

Conditions	Yield
Stage #1: 1-ethoxy-1-(tert-butyldimethylsilyloxy)ethene; coumarin With C18H14F18O15S6 In dichloromethane at -78℃; for 0.5h; Inert atmosphere; Stage #2: acetone In dichloromethane at -78℃; for 0.5h; Inert atmosphere;	97%

N,N-dimethyl acetamide (127-19-5) + coumarin (91-64-5) → N-methyl-N-((2-oxo-2H-chromen-3-yl)methyl)acetamide

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; di-tert-butyl peroxide at 120℃; for 6h;	97%
With di-tert-butyl peroxide; potassium iodide at 120℃; for 20h; Sealed tube;	77%

ethanol (64-17-5) + coumarin (91-64-5) → ethyl 3-(2-hydroxyphenyl)propanoate (20921-04-4)

Conditions	Yield
With (BQ‑NCOP)IrHCl; sodium t-butanolate at 60℃; for 8h; Inert atmosphere; Schlenk technique; Sealed tube; chemoselective reaction;	97%

1,9-dimethyl-3,4-dihydro-β-carboline (91806-16-5) + coumarin (91-64-5) → (5RS,15bRS)-15-methyl-5,6,9,10-tetrahydro-5,15b-methanobenzo[7',8'][1,3]oxazocino-[3',2':1,2]pyrido[3,4-b]indol-7(15H)-one

Conditions	Yield
With sodium carbonate In water at 80℃; for 20h; stereoselective reaction;	97%

sodium 2,2,2-trifluoroacetate (2923-18-4) + coumarin (91-64-5) → 3-((trifluoromethyl)thio)-2H-chromen-2-one

Conditions	Yield
With iron(III) chloride; sulfur In ethanol at 60℃; for 2h; Sealed tube;	97%

1,2-bis(4-bromophenyl)diselenide (20541-48-4) + coumarin (91-64-5) → 3-((4-bromophenyl)selanyl)-2H-chromen-2-one

Conditions	Yield
With bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 1.5h;	97%
With bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 1.5h; regioselective reaction;	97%

Upstream product

• 67-56-1 methanol 
• 614-60-8 o-Coumaric acid 
• 6236-69-7 methyl 2-hydroxycinnamate 
• 17831-88-8 4-chloro-2H-1-benzopyran-2-one 
• 531-81-7 2-oxo-2H-chromene-3-carboxylic acid 
• 64-17-5 ethanol 
• 3943-94-0 (E)-ethyl 2-hydroxycinnamate 
• 16189-10-9 (E)-3-<2-(acetyloxy)phenyl>-2-propenoic acid 
• 5663-67-2 2-acetoxybenzaldehyde 
• 127-09-3 sodium acetate 
• 2631-82-5 3-carboxy-2-hydroxy-cinnamic acid 
• 132593-85-2 2,4-bis-(2-hydroxy-phenyl)-cyclobutane-1,3-dicarboxylic acid 
• 3116-83-4 sodium salicylate 
• 108-24-7 acetic anhydride 

Downstream Products

• 100914-87-2 4-phenylsulfanyl-chroman-2-one 
• 109407-38-7 [4-(2-oxo-2H-chromen-3-yl)-phenyl]-arsonic acid 
• 2513-25-9 2,2-dimethyl-2H-chromene 
• 17235-14-2 (Z)-4-(o-hydroxyphenyl)-2-methylbut-3-en-2-ol 
• 107274-41-9 2-butoxy-cis-cinnamic acid 
• 495-79-4 cis-o-hydroxycinnamic acid 
• 73923-83-8 (2-hydroxy-phenyl)-succinic acid 
• 3943-94-0 (E)-ethyl 2-hydroxycinnamate 
• 2555-25-1 3-(4-nitrophenyl)coumarin 
• 82381-23-5 3-ethyl-1c-(2-hydroxy-phenyl)-penten-⁽¹⁾-ol-⁽³⁾ 
• 6236-69-7 methyl 2-hydroxycinnamate 
• 955-10-2 3-phenylcumarin 
• 10465-91-5 3-(4-chlorophenyl)-2H-chromen-2-one 
• 100976-16-7 3-(2-hydroxy-phenyl)-1-(2-oxo-cyclohexyl)-propenone 

Relevant articles and documents

Two-photon-induced cycloreversion reaction of coumarin photodimers

Photochemical reactions induced by two-photon-absorption processes offer several advantages over common one-photon initiated photoreactions, e.g., three-dimensional spatial control. We present the photocleavage reaction of coumarin photodimers via a two-photon process using pulsed frequency-doubled Nd:YAG-laser light. The two-photon-induced cycloreversion reaction leads selectively to the cleavage of the coumarin photodimers resulting in the formation of monomeric coumarin molecules. The two-photon cross section of the coumarin photodimer was determined to be of 1.6×10-52 cm4 s photon-1. The presented reaction is of interest, e.g., for the photo-triggered release of chemicals in areas which cannot be directly optically addressed due to cover layers which have a high absorption at the single-photon-absorption wavelength.

Visible-light-driven, photoredox-catalyzed cascade of ortho-hydroxycinnamic esters to access 3-fluoroalkylated coumarins

A general and straightforward protocol for di-/perfluoroalkylation of ortho-hydroxycinnamic esters via a photoredox-catalyzed cascade was developed to access a variety of 3-fluoroalkylated coumarins. This method was characterized by all-in-one synthetic design, simplified operation, mild reaction conditions, and broad substrate scope. Moreover, a sequential one-pot procedure starting from commercially available salicylaldehyde was also successfully realized to synthesize 3-fluoroalkylated coumarins.

The Copper-Catalyzed Reaction of 2-(1-Hydroxyprop-2-yn-1-yl)phenols with Sulfonyl Azides Leading to C3-Unsubstituted N-Sulfonyl-2-iminocoumarins

An operationally simple synthesis of Z-configured and C3-unsubstituted N-sulfonyl-2-iminocoumarins (e.g., 8a) that proceeds under mild conditions is achieved by reacting 2-(1-hydroxyprop-2-yn-1-yl)phenols (e.g., 6a) with sulfonyl azides (e.g., 7a). The cascade process involved likely starts with a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. This is followed by ring-opening of the resulting metalated triazole (with accompanying loss of nitrogen), reaction of the ensuing ketenimine with the pendant phenolic hydroxyl group, and finally dehydration of the (Z)-N-(4-hydroxychroman-2-ylidene)sulfonamide so formed.

Quantification of free coumarin and its liberation from glucosylated precursors by stable isotope dilution assays based on liquid chromatography-tandem mass spectrometry detection

A stable isotope dilution assay for the quantification of free coumarin and glucosylated coumarin precursors has been developed using [13C 2]-coumarin as the internal standard. The doubly labeled coumarin was synthesized by reacting [13C2]-acetic anhydride with salicylic aldehyde and characterized by means of mass spectrometry and nuclear magnetic resonance (NMR) experiments. The specifity of liquid chromatography-tandem mass spectrometry enabled unequivocal determination and sensitive quantitation of the odorant. Because of the very simple extraction procedure, free coumarin could be analyzed within 1h. For quantification of total coumarin, the odorant was liberated from its precursors by an incubation with hydrochloric acid or β-glucosidase. In analyses of breakfast cereals, the intra-assay coefficient of variation was 9.9% (n = 5) for total coumarin. When coumarin was added to butter cookies at a level of 10 μg/kg, a recovery of 94.1% was found. Further addition studies revealed a detection limit of 2.9 μg/kg and a quantification limit of 8.6 μg/kg. Application of the stable isotope dilution assay to several plants, foods, and essential oils revealed high contents in cassia products and those foods in which cassia has been used as an ingredient. In contrast to this, Ceylon cinnamon contained much less coumarin. The odorant was also quantified in woodruff, clover seeds, and the essential oils of lavender, citron, and chamomile. Only trace amounts were detected in carrots and the essential oils of peppermint and dill, whereas in bilberries, black raspberries, and Angelica roots, coumarin was below detectable levels. In Ceylon cinnamon and cassia, the odorant occurred mainly in its free form, whereas in fenugreek seeds and woodruff, 68 and 88% of the total coumarin content was liberated from glucosylated precursors, respectively.

Cyclobutane-cleavage of anti-head-to-head coumarin and quinolinone homo- and cross-dimers via single- and two-photon-absorption photochemistry

The light-driven cleavage of cyclobutane containing systems via [2 + 2] cycloreversion, such as di-coumarin, is an important yet poorly investigated photochemical reaction. Its applications can be found in smart crosslinking polymers or light-activated drug release. We report the increased cleavage efficiencies of the coumarins lactam analog quinolinone for single-photon as well as two-photon-absorption experiments. To investigate the structure-function relationship of the molecular substitution pattern and its influence on the photoactivity, a coumarin-quinolinone cross-dimer was synthesized and investigated towards its cleavage efficiencies in single-photon as well as two-photon photocleavage. The cross-dimer shows a lower cleavage efficiency than both homo-dimers. The presented results are of interest, e.g., for applications utilizing highly efficient cleavage reactions in symmetric or asymmetric molecular frameworks.

Photocatalytic Oxidative [2+2] Cycloelimination Reactions with Flavinium Salts: Mechanistic Study and Influence of the Catalyst Structure

Flavinium salts are frequently used in organocatalysis but their application in photoredox catalysis has not been systematically investigated to date. We synthesized a series of 5-ethyl-1,3-dimethylalloxazinium salts with different substituents in the positions 7 and 8 and investigated their application in light-dependent oxidative cycloelimination of cyclobutanes. Detailed mechanistic investigations with a coumarin dimer as a model substrate reveal that the reaction preferentially occurs via the triplet-born radical pair after electron transfer from the substrate to the triplet state of an alloxazinium salt. The very photostable 7,8-dimethoxy derivative is a superior catalyst with a sufficiently high oxidation power (E=2.26 V) allowing the conversion of various cyclobutanes (with Eox up to 2.05 V) in high yields. Even compounds such as all-trans dimethyl 3,4-bis(4-methoxyphenyl)cyclobutane-1,2-dicarboxylate can be converted, whose opening requires a high activation energy due to a missing pre-activation caused by bulky adjacent substituents in cis-position.

Design, synthesis, and antifungal evaluation of novel coumarin-pyrrole hybrids

A series of coumarin derivatives bearing a pyrrole scaffold were designed, prepared, and assessed for their in vitro antifungal activities against six phytopathogenic fungi. The antifungal activity screening results suggest that some synthesized hybrids exhibited potential fungicidal activities against the tested fungi. In particular, compounds 6j, 6k, 6o, 6p, and 6r displayed significant antifungal effects against Rhizoctorzia solani, and possessed EC50 values of 3.94, 7.75, 6.38, 6.25, and 7.67 μg/ mL, respectively. The above activities are more potent than the commercialized fungicide Boscalid (11.52 μg/mL) and Osthole (9.79 μg/mL). These results provide a significant reference for further rational design of coumarin-based fungicides.

Gold(I)-Catalyzed Intramolecular Hydroarylation of Phenol-Derived Propiolates and Certain Related Ethers as a Route to Selectively Functionalized Coumarins and 2 H-Chromenes

Methods are reported for the efficient assembly of a series of phenol-derived propiolates, including the parent system 56, and their Au(I)-catalyzed cyclization (intramolecular hydroarylation) to give the corresponding coumarins (e.g., 1). Simple syntheses of natural products such as ayapin (144) and scoparone (145) have been realized by such means, and the first of these subject to single-crystal X-ray analysis. A related process is described for the conversion of propargyl ethers such as 156 into the isomeric 2H-chromene precocene I (159), a naturally occurring inhibitor of juvenile hormone biosynthesis.

Exploiting a silver-bismuth hybrid material as heterogeneous noble metal catalyst for decarboxylations and decarboxylative deuterations of carboxylic acids under batch and continuous flow conditions

Herein, we report novel catalytic methodologies for protodecarboxylations and decarboxylative deuterations of carboxylic acids utilizing a silver-containing hybrid material as a heterogeneous noble metal catalyst. After an initial batch method development, a chemically intensified continuous flow process was established in a simple packed-bed system which enabled gram-scale protodecarboxlyations without detectable structural degradation of the catalyst. The scope and applicability of the batch and flow processes were demonstrated through decarboxylations of a diverse set of aromatic carboxylic acids. Catalytic decarboxylative deuterations were achieved on the basis of the reaction conditions developed for the protodecarboxylations using D2O as a readily available deuterium source.

Preparation method of photoresponse phase change material

The invention relates to the field of phase change materials, in particular to a preparation method of a photoresponse phase change material, and provides the preparation method of the photoresponse phase change material, the structural formula of the prepared phase change material is shown as a formula I, and the photoresponse phase change material has the advantages of cheap and easily availableraw materials, simple process, mild reaction conditions and suitability for large-scale production.