Coumarines & Chromones 1.pptx

slides

1. Coumarines & Chromones Presented by: Hadeel Fawzi Hammad &Nesma Emad

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 CO 2 . 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. Occurance : 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.