SYNTHESIS Traube Synthesis , + Introduces one carbon fragment to bridge the nitrogen atoms o1 C5 & C6 carbons of pyrimidine + Introduction of amino group by nitrosation & ammonium sulfide reduction followed by ring closure with formic acid o1 chlorocarbonic ester OH OH OH OH i wy _HONO La. (He)25 rr cicoor rc l q l ‘OH A A HOW ~N* NH ‘ee now? NH> Woon? N # We Pratip KR Chashan SYNTHESIS é) Traube SynthesisThe Traube synthesis of purine involves several key steps, which | will explain in detail: Formation of Formamidine: The synthesis begins with the condensation of formic acid (HCOOH) with cyanamide (NH_2CN) in the presence of a catalyst such as hydrochloric acid (HCI) or sulfuric acid (H_2SO_4). This reaction forms a compound called formamidine, which contains the amidine functional group (-C(=NH)-NH_2). Cyclization to Glyoxalylurea: i} The fermamidine molecule then undergoes cyclization to form glyoxalylurea. Cyclization occurs through the reaction of the amidine group with the carbonyl group of formamidine, resulting in the formation of a six-membered ring. 3. Alkylation to Aminoimidazole: Glyoxalylurea is alkylated with an alkyl! halide, typically methyl iodide (CH_3)), in the presence of a base such as sodium hydroxide (NaOH). Alkylation takes place at the nitrogen atom adjacent to the carbonyl group, resulting in the formation of Elarlatelinilce r-rel [om 4. Condensation with Carbon Dioxide: The aminoimidazole molecule reacts with carbon dioxide (CO_2) to form a compound known as aminoimidazole carboxamide. This reaction involves the nucleophilic attack of the nitrogen atom in aminoimidazole on the carbon dioxide molecule.4. Condensation with Carbon Dioxide: The amingimidazole molecule reacts with carbon dioxide (CO_2) to form a compound known as aminoimidazole carboxamide. This reaction involves the nucleophilic attack of the nitrogen atom in aminoimidazole on the carbon dioxide molecule. gr . Dehydration and Rearrangement: Aminoimidazole carboxamide undergoes dehydration and rearrangement in the presence of strong sulfuric acid (H_2S0_4). This step leads to the formation of an isomer called 4-aminopyrazol-5-one. 6. Cyclization to Form Purine: The final step of the Traube synthesis involves the cyclization of 4-aminopyrazol-5-one to form purine. This cyclization occurs by the rearrangement of atoms within the molecule, resulting in the formation of the characteristic purine ring system. Overall, the Traube synthesis provides a synthetic pathway for the construction of the purine ring system through a series of chemical transformations, starting from simple precursors such as formic acid and cyanamide. While the Traube synthesis is a classic method, modern synthetic approaches have been developed that offer more efficient and practical routes for the synthesis of purine and its derivatives.