Pyridine and pyrimidine

THIS PRESENTATION COVER INTRODUCTION, STRUCTURE, AROMATICITY, RESONANCE, BASICITY, PHYSICAL PROPERTIES, SYNTHESIS, CHEMICAL PROPERTIES AND MEDICAL USES OF PYRIDINE AND PYRIMIDINE

1. 6 th MEMBERED HETEROCYCLIC COMPOUNDS CONTAINING ONE AND TWO HETERO ATOM BY- VISHAL SINGH SOLANKI IDEAL INSTITUTE OF PHARMACY, POSHERI, WADA, M.H.

2. INDEX PYRIDINE PYRIMIDINE

3. PYRIDINE

4. INTRODUCTION Pyridine is a  basic   heterocyclic   organic compound  with the  chemical formula   C 5 H 5 N . It is structurally related to  benzene , with one  methine group  (=CH−) replaced by a  nitrogen  atom. It is a highly flammable, weakly  alkaline , water-miscible liquid with a distinctive, unpleasant fish-like smell. Pyridine is colourless, but older or impure samples can appear yellow. The pyridine ring occurs in many important compounds, including  agrochemicals ,  pharmaceuticals , and  vitamins . Historically, pyridine was produced from coal tar. 

5. Structure of pyridine

6. AROMATICITY PYRIDINE FOLLOW HUCKLE RULE (4n+2 π e) PYRIDINE HAVE 6 π e PYRIDINE HAVE SP2 HYBRIDI zED ORBITAL IN EACH ATOM OF THE RING CYCLIC STRUCTURE

7. BASICITY OF PYRIDINE

8. RESONANCE The bond length and stability of Pyridine can be explained by the resonating structures. Electronegative atom N produces the deficiency of electron density in pyridine and ring carbon acquires increased electron density. Thus nitrogen atom in pyridine causes deactivation of the ring, contrary to pyrrole.

9. PHYSICAL PROPERTIES OF PYRIDINE Chemical formula C 5 H 5 N Molar mass 79.102 g·mol −1 Appearance Colourless liquid Odour Nauseating, fish-like Density 0.9819 g/ml Melting point −41.6 °C (−42.9 °F; 231.6 K) Boiling point 115.2 °C (239.4 °F; 388.3 K) Solubility in water Miscible Preferred IUPAC name Pyridine Other names Azine, Azinine , 1-Azacyclohexa-1,3,5-diene

10. SYNTHESIS OF PYRIDINE

11. 1. Hantzsch synthesis The Hantzsch synthesis is a four-component reaction between an aldehyde, two equivalents of a β- ketoester and ammonia, followed by oxidation to give a pyridine-3,5-dicarboxylate. Subsequent decarboxylation gives the corresponding pyridines.

12. MECHANISM

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17. 2. USING I,5 DIKETONE COMPOUNDS

18. CHEMICAL PROPERTIES OF PYRIDINE

19. APPLICATION OF PYRIDINE Pyridine is widely used as a versatile  solvent . It is important in industrial organic chemistry, both as a fundamental building block and as a solvent and reagent in organic synthesis. It is used as a solvent in Knoevenagel condensations. Pyridine-borane, C 5 H 5 NBH 3  ( m.p. 10–11°C), is a mild reducing agent with improved stability compared to sodium borohydride (NaBH 4 ) in protic solvents and improved solubility in aprotic organic solvents. Pyridine-sulphur trioxide, C 5 H 5 NSO 3  (mp - 175 °C), is a sulfonation agent used to convert alcohols to sulfonates, which in turn undergo C-O bond scission (break-up) upon reduction with hydride agents. It is a starting material in the synthesis of compounds used as intermediates in making insecticides, herbicides, pharmaceuticals, food flavorings ,  dyes ,  rubber  chemicals,  adhesives ,  paints ,  explosives , and disinfectants. It is used as a denaturant for antifreeze mixtures. It is sometimes used as a  ligand  in coordination chemistry.

20. PYRIMIDINE

21. INTRODUCTION TO PYRIMIDINE Pyrimidine is a simple aromatic ring composed of two nitrogen atoms and four carbon atoms, with hydrogen atoms attached to each carbon a six-membered ring. The carbon and nitrogen atoms are connected via alternating double and single bonds. This bond structure allows for resonance, or aromaticity, causing the ring to be very stable. The term pyrimidine is also used to refer to pyrimidine derivatives, most notably the three nitrogenous bases that, along with the two purines, are the building blocks of both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

22. Structure of pyrimidine

23. PHYSICAL PROPERTIES OF PYRIMMIDINE Chemical formula C 4 H 4 N 2 Molar mass 80.088 g mol −1 Density 1.016 g cm −3 Melting point 20 to 22 °C (68 to 72 °F; 293 to 295 K) Boiling point 123 to 124 °C (253 to 255 °F; 396 to 397 K) Solubility in water Miscible (25°C) Other names 1,3-Diazine, m -Diazine 1,3-Diazacyclohexa-1,3,5-triene state solid

24. AROMATICITY PYRIDIMINE FOLLOW HUCKLE RULE (4n+2 π e) PYRIMIDINE HAVE 6 π e PYRIMIDINE HAVE SP2 HYBRIDIZED ORBITAL IN EACH ATOM OF THE RING CYCLIC STRUCTURE

25. RESONANCE Pyrimidine shows aromatic properties because the resulting molecular orbital satisfies the Hackle’s rule (4n+2 rule). The nitrogen lone pair is not released into the aromatic system because it is perpendicular to the system. The nitrogen withdraws electrons by resonance, resulting in an electron-deficient ring system.

26. BASIC CHARACTER Pyrimidine is a weaker base than pyridine, because of electron withdrawing effect of the second nitrogen atom present in pyrimidine. Pyrimidine gets protonated in acidic medium. Presence of electron donating groups like alkyl, alkoxy enhance the basicity.

27. SYNTHESIS OF PYRIMIDINE

28. 1. BY USING 1,3 DICARBONYL COMPOUND COMBINING OF 1,3 DICARBONYL COMPOUND WITH N-C-N FRAGMENT SUCH AS AN UREA, AN AMIDINE OR A GUANIDINE.

29. EG.

30. 2. FROM ALKYL PYRIMIDINE

31. 3. FROM CHLORO PYRIMIDINE

32. CHEMICAL PROPERTIES OF PYRIMIDINE

33. ELECTROPHILIC ADDITION TO N

34. NUCLEOPHILIC SUBSTITUTION REACTIONS Pyrimidine easily undergoes nucleophilic substitution. Nucleophilic attack takes place at 2, 4 or 6th positions. Grignard & oregano lithium add to 4 position at reaction Metal – Halogen Exchange: Lithio - diazines are also accessible via halogen exchange with alkyl - lithiums , but very low temperatures must be used in order to avoid nucleophilic addition to the ring.

35. ELECTROPHILIC SUBSTITUTION REACTIONS Pyrimidine is less reactive than pyridine due to two electron withdrawing groups towards electrophilic substitution. However presence of electron donating groups on ring, electrophilic substitution is possible at 5th position (the least electron-deficient). Nitration, Sulphonation, Bromination , Formylation and azo coupling have been observed with substituted pyrimidines.

36. MEDICAL USES

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39. REFERENCE H. G. O. Alvim, E. N. da Silva Júnior and B. A. D. Neto, ORGANIC CHEMISTRY, RSC Adv. , 2014,  4 , 54282–54299. https://en.wikipedia.org/wiki/Pyrimidine#Synthesis https://www.slideshare.net/surajKumarGupta9/synthesis-of-pyrimidine-and-its-medical-application?qid=5f7091d1-a45b-4855-bd4e-aad69ebf4aed&v=&b=&from_search=28 https://www.slideshare.net/AZCPh/heterocyclic-compounds-organic-chemistry-b-pharm

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