Uses
Hexahydropyridazine Dihydrochloride is a useful reagent for organic synthesis and other chemical processes. It is used as a reagent in the synthesis of completely hydrogenated dipiperidazino tetrazine, tetrazepine and tetrazone derivatives.
Synthesis
The general procedure for the synthesis of hexahydropyridazine hydrochloride from 1,4-dibromobutane was as follows: 7.6 g of NaH (60% w/w dispersed in mineral oil, 0.19 mol, 2.2 eq.) was added to a 1-liter, three-necked, round-bottomed flask equipped with a magnetic stir bar, a dosing funnel, and nitrogen protection. NaH was washed three times with hexane, followed by the addition of 350 mL of anhydrous DMF. the reaction mixture was cooled to 0 °C via an ice bath, and then 20 g of tert-butylhydrazinium formate (0.086 mol, 1 eq.) dissolved in 50 mL of anhydrous DMF was added slowly and dropwise via the charging funnel. After the dropwise addition was completed, the reaction mixture was allowed to warm slowly to room temperature and stirring was continued for 30 minutes. Subsequently, 10.27 mL of 1,4-dibromobutane (0.086 mol, 1 eq.) was added in a single addition at room temperature and the reaction mixture was stirred overnight. Upon completion of the reaction, the reaction was quenched with water until no gas escaped and then the mixture was partitioned between ether and water. The phases were separated and the organic phase was washed twice with water. The ether layer was concentrated under vacuum. The residue was dissolved in 300 ml of dioxane solution in 4N HCl, followed by the addition of 300 ml of diethyl ether. The mixture was stirred at room temperature for 1 hour, during which time a white solid precipitated. The white solid (13.7 g, 100% yield) was isolated by filtration and dried under vacuum. The product was characterized by 1H NMR (400 MHz, DMSO-D6) with chemical shifts δppm 1.6 (m, 4H), 3.0 (m, 4H).
