Furan presentation

5 membered heterocyclic compound Furan. it is complete powerpoint presentation who want to learn from basics of heterocyclic chemistry. I have referred from various books and done my best so that view can get all they can without scroll many books. Kindly give your feedback after viewing powerpoint presentation

1. FURAN Submitted by Vayu Chaurasiya M.Sc Chemistry 4th Semester MS14CHM016 CHEMISTRY OF HETEROCYCLIC COMPOUNDS

2. Furan is a Heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen. The class of compounds containing such rings are also referred to as furans Physical Properties : It is colorless, flammable and highly volatile liquid. Melting point: -85.6°C Boiling Point: 31.3°C Soluble in alcohol, ether and acetone but slightly soluble in water Toxic and may be carcinogenic

3. Interesting Furan Containing Drugs Ranbezolid Anti-bacterial Drug Nifurzide Anti-Infective Drug Ranitidine (Zantac) H 2 histamine receptor antagonist Furaneol Perfume distilled from Strawberries

4. Synthesis of Furan 1. From Pentosans 2. From Oxidation of cis-but-2-ene-1,4-diol Pentosans are hydrolyzed to Xylose followed by dehydration and cyclization to give furfural

5. 3. From diacetosuccinic ester : When diacetosuccinic ester is heated with dilute sulphuric acid, 2,5-dimethylfuran-3,4-dicarboxylic acid is obtained. 4. From Alkynes 5. Ring opening of Epoxide in presence of Lewis acid BF3

6. Name Reactions for Furan Synthesis 6. Paal-Knorr Synthesis: The acid-catalyzed cyclization of 1,4-dicarbonyl compounds in presence of acid or lewis acid Mechanism :

7. 7. Feist– Benary synthesis It is Organic reaction between α-haloketones and β -dicarbonyl compounds to substituted furan compounds.This condensation reaction is catalyzed by base. Mechanism: This classical synthesis rests on an initial aldol condensation at the carbonyl carbon of a 2 - halo - arbonyl -component; ring closure is achieved via intramolecular displacement of halide by enolate oxygen.

8. Aromaticity of Furan The resonance energy of furan is 67 kJ (16 kcal)/mol. The oxygen within the cyclic structure can assume an sp2 hybridization. With sp2 , one of the two lone pairs occupies a pz orbital, allowing oxygen to contribute to the continuous loop of pz orbitals and maintains the ring’s flat shape. The other lone pair occupies an sp2 orbital, perpendicular to the pi electron cloud. This pair is not involved in the pi electron cloud. Furan also obeys Hückel’s rule (4n + 2 = 6 pi electrons, n = 1). Because furan has a continuous, closed loop of pz orbitals, planarity, and obeys Hückel’s rule, it is aromatic.

9. Chemical Properties of Furan It appears that structure ( I ), ( II ) and ( III ) are the main contributing structures since 2- (or 5-) substitution (with electrophile) occur more readily. (IV) and (V) would account for 3-substitution when the 2- and 5-positions are both occupied. Calculations of the bond lengths and comparison with the measured values show that (I) contributes about 85%, to the resonance hybrid. It is considerably more reactive than Benzene in electrophilic substitution reactions, due to the electron-donating effects of the oxygen heteroatom. Examination of the resonance contributors shows the increased electron density of the ring, leading to increased rates of electrophilic substitution. Furan behaves as resonance hybrid.

10. Reactions of Furan 1. Reactions of Protonated Furans The hydrolysis (or alcoholysis) of furans involves nucleophilic addition of water (or an alcohol) to an initially formed cation, giving rise to open - chain 1,4 -dicarbonyl compounds or derivatives

11. 2. Nitration 3. Sulphonation 4. Halogenation Furan reacts vigorously with chlorine and bromine at room temperature to give polyhalogenated products, but does not react at all with iodine.

12. If the bromination is conducted in an alcohol, trapping of the intermediate by C - 5 addition of the alcohol, then alcoholysis of C - 2 - bromide, produces 2,5 - dialkoxy - 2,5 - dihydrofurans, as mixtures of cis - and trans isomers; Hydrogenation of these species affords 2,5 - dialkoxy – tetrahydrofurans. The 2,5 - dialkoxy -2,5 - dihydrofurans are also useful for the synthesis of 2 - substituted furans, for example with benzenethiol or phenylsulfinic acid, 2 - sulfur - substituted furans are formed.

13. The reaction of furfural with excess halogen to produce mucobromic acid which reacts with formamide to provide a useful synthesis of 5 – bromopyrimidine. 5. Acylation: Carboxylic acid anhydrides or halides normally require the presence of a Lewis acid (often boron trifluoride) for Friedel – Crafts acylation of furans, trifluoroacetic anhydride will react alone

14. 6. Vilsmeier Haack Formylation 7. Alkylation 8. Alkenylation Intramolecular alkenylation at a furan α- or β- position by an alkyne occurs, with the formation of bicyclic derivatives, when promoted by mercury(II) acetate (or Hg(OAc)(OTf), generated in situ from mercuric acetate and scandium triflate)

15. 9. Mannich Reaction 10. Mercuration Mercuration takes place very readily with replacement of hydrogen, or carbon dioxide from an acid. 11. Reaction with Oxidizing agents

16. 12. Achmatowicz Reaction It is an organic synthesis in which a furan is converted to a dihydropyran. Furfuryl alcohol is reacted with bromine in methanol to 2,5-dimethoxy-2,5-dihydrofuran which rearranges to the dihydropyran with dilute sulphuric acid followed by alcohol protection with methyl orthoformate and boron trifluoride and ketone reduction with sodium borohydride. 13. Reaction with Nucleophilic reagents Simple furans do not react with nucleophiles by addition or by substitution. Nitro substituents activate the displacement of halogen

17. 14. Direct Ring C – H Metallation Lithium diisopropylamide can effect C - 2 - deprotonation of 3 - halofurans. With furoic acid and two equivalents of lithium diisopropylamide, selective formation of the 5 - lithio lithium 2 - carboxylate takes place, whereas n - butyllithium, via ortho - assistance, produces the 3 - lithio lithium 2 – carboxylate.

18. 15. Reaction with Reducing Agents 16. Diels-Alder Reaction Furan serves as a diene in Diels-Alder reactions with electron-deficient dienophiles such as ethyl (E)-3-nitroacrylate. The reaction product is a mixture of isomers with preference for the endo isomer:

19. 17. Paterno-Buchi reaction The cycloaddition of diaryl ketones and some aldehydes across the furan 2,3 - double bond proceeds regioselectively to afford oxetano - dihydrofurans, proton - catalyzed cleavage of the acetal linkage in which produces 3 - substituted furans.

20. Synthesis of Furaneol Furaneol is a natural flavour principle, isolated from pineapple and strawberry, and used in the food and beverage industries

21. Synthesis of Ranitidine Ranitidine is one of the most commercially successful medicines ever developed; it is used for the treatment of stomach ulcers and has been synthesized from furfuryl alcohol.