Heterocycic compound Thiophene

This PPT contains informations about five membered heterocyclic compound with one hetero atom.i.e.Sulphur.

1. Heterocyclic compound - Thiophene Lecture by S.Mathivanan.,M.Pharm Asst professor Pharmacy

2. History of Thiophene Viktor Meyer   was a   German   chemist  and significant contributor to both  organic  and  inorganic chemistry . He is best known for inventing an apparatus for determining vapour densities, the  Viktor Meyer apparatus , and for discovering  thiophene , a  heterocyclic compound . In 1882 Victor Meyer discovered thiophene as contaminant in benzene. It was observed that  isatin  (an  indole ) forms a blue  dye  if it is mixed with   sulfuric acid  and crude benzene. The formation of the blue indophenin had long been believed to be a reaction of benzene itself.  Viktor Meyer  was able to isolate thiophene as the actual substance responsible for this reaction.

3. Thiophene Thiophene and its derivatives exist in petroleum or coal. Thiophene is taken from the word ‘ theion ’ , the Greek word for sulfur, and another Greek word ‘ phaino ’ which means shinning. Thiophene structure can be found in certain natural products and is also incorporated in several pharmacologically active compounds.

4. Properties of Thiophene At room temperature, thiophene is a toxic , flammable and colourless liquid with a mildly pleasant odor reminiscent of benzene . The molecular mass of thiophene is 84.14 16 g/mol , density is 1.051 g/ml and Melting Point is -38 °C . It is insoluble in water but soluble in most of the organic solvents including alcohol and ether. The "electron pairs" on sulfur are significantly delocalized in the π electron system, due to this it behaves extremely reactive benzene derivative.

5. BIOISOSTERISM (Benzene vs Thiophene ) Like benzene, thiophene forms an azeotrope with ethanol. The similarity between the physicochemical properties of benzene and thiophene is striking. For example, the boiling point of benzene is 81.1 ˚ C and that of thiophene is 84.4 ˚ C (at 760mm Hg) and therefore, thiophene and benzene is a well known example of bioisosterism . It can be easily sulfonated , nitrated, halogenated, acylated , but cannot be alkylated and oxidized.

6. Chemical properties

7. Aromaticity of Thiphene

8. Synthesis of Thiophene Acetonyl acetone 2,5-Dimethyl thiophene

9. 180°C

10. Commercial synthesis

11. Reactions of Thiophene

12. Electrophillic substitution reaction 2-Nitrothiophene 2,5-Dinitrothiophene 2-chlorothiophene (2-Thienyl chloride) 2,5-Dibromothiophene 2-Iodothiophene 2-Thiophene-sulfonic acid Methy 2-thienyl ketone (2-Acetyl thiophene ) 2-Thienyl chloride (2-chloromethyl thiophene ) 2-acetoxy mercury thiophene

13. Reduction [O] Tetramethylene sulphone

14. Reaction with organolithium

15. Vilsmeier Haack reaction This reaction can be applied to active aromatic compounds (such as amines and phenols) Involves the formylation of an aromatic ring with a di -substituted formamide and Phosphorus o xyxhloride . Thiophene is more reactive than benzene. It can be formylated and forms Thiophene carbaldehyde

16. Diels alder reaction

17. Medicinal value of Thiophene Thiophene with its 6π electrons aromaticity and sterically similar to benzene derivatives may well exhibits similar activities ( B ioisosterism ). At the same time presence of heteroatom in thiophene may alter its metabolic fate , thus thiophene derivatives may have less toxic effects and/or better therapeutic profile. Thiophene is used in two principal ways. The most interesting chemically is the use of thiophene either as central rings or as a part of fused ring system

18. Medicinal importance of Thiophene Thiophene moiety have attracted great attention in medicinal field due to its diversified biological activities such as: A nti-microbial activity , A nti-fungal activity , A ntitubercular activity, A nti-oxidant activity , L ocal anaesthetic activity, 5-HT1A receptor antagonist , Thiophenes and their derivatives are important class of compounds. 5-HT6 receptor antagonist, Anti-inflammatory, Analgesic, Anticancer , Anti- convulsant , Anti-allergy , P hosphodiesterase -IV inhibitors.

19. Medicinal uses of some Thiophene derivatives

20. Suprofen : NSAID – Analgesic and antipyretic Tienilic acid : Loop diuretics and also has uric acid lowering property

21. Pyrantel : Used to treat and prevent the occurrence of intenstinal parasits in small animal pets

22. Thank you.. Ellarum safe ah irunga .. Byee .!!