2. Chromones
Coumarines
The word chromones is derived from the Greek
word chroma, meaning “color”, chromone
derivatives exhibit a broad variation of colors.
It is an isomer of coumarin
Coumarins are phenolic substances composed
of fused benzene and α-pyrone rings.
Structure
3. Occurance
Chromones
Coumarines
Chromones are naturally occurring phenolic
Phytochemicals compounds are well-known for their
health-promoting properties, because of their potential
as anti-oxidants
To date, thousands of chromone derivatives, including
chromone glycosides have been discovered both from
natural and synthetic origin.
Many plant genera are rich sources of chromones
including Aloe, Aquilaria, Cassia,
Hypericum and Polygonum Several genera of fungi,
such as Aspergillus and Penicillium
produce bioactive chromones
Coumarin is a natural volatile active compound
found in many plants. For example, coumarin
was first isolated from tonka bean . It was
subsequently identified in a large number of
plants belonging to many different families. Its
better known occurrences are in cassia,
lavender, and balsam of Peru. the main source
of coumarin in the diet is cinnamon
4. Synthesis
Chromones
Coumarines
Most synthesis required harsh acidic conditions
as the final step . On the other hand, synthesis
utilizing basic conditions to affect ring closure.
Recently, microwave heating has also been used
to affect ring cyclization
1) From Phenol (Pechmann condensation)
Coumarin is formed by reaction of phenol
with malic acid in the presence of
concentrated sulfuric acid.
5. Synthesis
Chromones
Coumarines
1- Acid as catalyst in chromone ring closure
Phosphorus oxychloride as a catalyst
This catalyst is most widely used in the
chromone ring closure . 6-hydroxy-4-
chromone-3-carbaldehydes were easily
prepared by the reaction of 2,5-dihydroxy-
acetophenone with DMF in POCl3 solution
2) From Salicylaldehyde
2.1 ) Perkin Reaction
In this reaction coumarin is formed by reaction
of salicylaldehyde with acetic anhydride in the
presence of sodium acetate as a catalyst,
through the intermediary of cis-o-
acetoxycinnamic acid.
6. Synthesis
Chromones
Coumarines
2- Base as catalyst in chromone ring closure
Pyridine as a catalyst
This method of using pyridine as a catalyst
was more suitable to acyl phenols and
chloroacetyl carboxylic acid esters in the
chromone ring closure.
2) From Salicylaldehyde
2.1 ) Perkin Reaction
In this reaction coumarin is formed by reaction
of salicylaldehyde with acetic anhydride in the
presence of sodium acetate as a catalyst,
through the intermediary of cis-o-
acetoxycinnamic acid.
7. Synthesis
Chromones
Coumarines
3- Chromone ring closure under the
microwave irradiation
An eco-friendly direct solvent-free
synthesis of functionalized flavones under
microwave irradiation
prepared from the corresponding ethyl
benzoyl acetates and phloroglucinol for 2–
12 min of irradiation
2.2) Knoevenagel Reaction
Synthesis of coumarin by this reaction involves the
condensation of salicylaldehyde with acetic acid
derivatives containing an active methylene group
such as cyanoacetic acid. Ammonia or organic bases
are used as catalysts. coumarin 3-carboxylic acid is
obtained by hydrolysis of the cyano group removal of
the carboxylic group in the 3-position by heating to
290◦C.
8. (2) Rhodanines
Synthesis
Chromones
Coumarines
4-Recent Synthetic methods of chromones
A highly efficient and selective palladium-
catalyzed ligand-free cyclocarbonylation
reaction of o-iodophenols with terminal
acetylenes under atmospheric CO pressure
affords diversified chromones in very good
yields. The use of a phosphonium salt ionic
liquid as the reaction medium enhances the
efficiency of the cyclocarbonylation reaction
3) From o-Cresol
The hydroxyl group of o-cresol is first protected by a
carbonate group and the methyl group is converted
into a benzal chloride intermediate by dichlorination.
The α,α-dichlorocresyl ester then reacts with acetic
anhydride in the presence of a metal catalyst such as
cobalt oxide to yield o-acetylsalicylaldehyde, acetyl
chloride, and CO2. Ring closure of o-
acetylsalicylaldehyde with acetic anhydride gives
coumarin and acetic acid.
9. Separation of amixture of chromones and
coumarins
• To a mixture of chromone and coumarin was added a solution of
sodium ethoxide in ethanol, whereby the 2- and 4-pyranone rings
were opened to give phenolic diketone and carboxylic acid,
respectively. The carboxylic acid was recyclized by acid at 18°C to
yield coumarin, while the β-ketoester was extracted with aqueous
sodium hydroxide and cyclized to the chromone in the presence of
acid
10. Occur
ance:
Reactions
Chromones
Coumarines
The 3-chlorochromones have been prepared in
excellent yield by selective monochlorination of
2-methylchromones and chromone-2-
carbaldehydes using aqueous sodium
hypochlorite and acetic acid
Reagents: i) NaOCl, AcOH; ii) Se02, xylene.
1) Reduction
Coumarin is reduced to o-hydroxycinnamyl alcohol
by reaction with lithium aluminum hydride.
11. Synthesis:
• Rhodanine and its derivatives can be directly prepared via the
reaction of thioureas and thioglycolic acid in one step catalyzed by
protic acid in good yields.
Occurance
:
Reactions
Chromones
Coumarines
2) Hydrogenation
Hydrogenation of coumarin gives several different
products depending on experimental conditions.
For example; Hydrogenation with a Raney nickel
catalyst under moderate conditions yields 3,4-
dihydrocoumarin.
12. Synthesis:
And also can be directly prepared via the three-component coupling of
carbon disulfide, primary amines, and acetylenic esters under neutral
conditions in water
Occurance
:
Reactions
Chromones
Coumarines
While continued hydrogenation especially at higher
temperatures leads to the formation of the
saturated octahydrocoumarin.
13. Reactions:
• Knoevenagel condensation of aldehydes or ketones with
compounds containing an active methylene group in the
presence of bases, resulting in the formation of ethylene
derivatives
Occurance
:
Reactions
Chromones
Coumarines
3) Halogenation
Coumarin reacts with bromine under moderate
conditions to give 3,4-dibromocoumarin.
3-Chlorocoumarin is formed by reaction with
chlorine in dichloroethane or without solvent.
14. Reactions:
• The condensation take place in ammonium hydroxide-ethyl alcohol
medium containig ammonium chloride.
Occurance
:
Reactions
Chromones
Coumarines
4) Oxidation
Coumarin is oxidized by the action of the Fenton’s
reagent and converted into 7-hydroxycoumarin.
15. Reactions:
• Synthesis of 3- carboxyethylrhodanine by the
reactions of carbonyl compounds with
various alcohols, hydrogen chloride gas, and
the resultant esters purified by vacuum-
distillation.
• The esters were condensed with
benzaldehyde, and with isatin in glacial acetic
acid.
Occurance
:
Reactions
Chromones
Coumarines
5) Sulfonation
Fuming sulfuric acid reacts with coumarin to give
coumarin-6-sulfonic acid at moderate temperature.
16. Applications:
• A rhodanine-based chemosensor RDV proved to be a practical sensor to
water sample analysis and cell imaging.
• Antiviral, anticancer, antimicrobial, and drug discovery.
• In drug discovery, rhodanines are special heterocyclic structure. Their derivatives
possess strong anti-bacterial activity and some of them have shown potent activity
against multidrug-resistant pathogens, both under in vitro and in vivo conditions. To
treat multi-drug resistant pathogens, the development of novel potent drugs, with
superior anti-bacterial efficacy, is most important. One of the promising paths is the
design and development of new rhodanine.
Occurance
:
Reactions
Chromones
Coumarines
6) Nitration
Fuming nitric acid forms 6-nitrocoumarin.
17. Applications:
• A rhodanine-based chemosensor RDV proved to be a practical sensor to
water sample analysis and cell imaging.
• Antiviral, anticancer, antimicrobial, and drug discovery.
• In drug discovery, rhodanines are special heterocyclic structure. Their derivatives
possess strong anti-bacterial activity and some of them have shown potent activity
against multidrug-resistant pathogens, both under in vitro and in vivo conditions. To
treat multi-drug resistant pathogens, the development of novel potent drugs, with
superior anti-bacterial efficacy, is most important. One of the promising paths is the
design and development of new rhodanine.
Occurance
:
Applications
Chromones
Coumarines
The bicyclic chromone fragment has been classified
as a structure in drug discovery, due to its use in a
wide variety of pharmacological propreties such as
Anticancer
anti-HIV
antibacterial
anti-inflammatory
• Because of its unique sweet note and stability,
coumarin has long been recognized as an
important raw material in the fragrance industry.
• It is widely used in hand soaps, detergents,
lotions, and perfumes at concentrations usually
extending from 0.01 to 0.8%.
18. Applications:
• A rhodanine-based chemosensor RDV proved to be a practical sensor to
water sample analysis and cell imaging.
• Antiviral, anticancer, antimicrobial, and drug discovery.
• In drug discovery, rhodanines are special heterocyclic structure. Their derivatives
possess strong anti-bacterial activity and some of them have shown potent activity
against multidrug-resistant pathogens, both under in vitro and in vivo conditions. To
treat multi-drug resistant pathogens, the development of novel potent drugs, with
superior anti-bacterial efficacy, is most important. One of the promising paths is the
design and development of new rhodanine.
Occurance
:
Applications
Chromones
Coumarines
• It is used as an odor enhancer to achieve a long
lasting effect when combined with natural
essential oils such as lavender, citrus, rosemary.
• Coumarin and some of its derivatives have been
tested in pharmacology for treatment of
schizophrenia, or of microcirculation disorders
and also for treatment of high protein edemas in
animals.
