Beta-functionalization of alpha, gamma-Dinitro compounds: synthetic and mechanistic studies

Abstract

Bromination of 2,4-dinitropentane in the presence of methanolic sodium methoxide leads to the formation of 2,4-dibromo-3-methoxy-2,4-dinitropentane as the major product. Thus, during the course of bromination, a α,γ-dinitro compound has been functionalized at the position between the two nitro groups. This observation has led to development of a new general reaction best carried out on 2,4-dibromo-2,4-dinitropentane as the starting material. A series of sodium alkoxides including sodium methoxide, sodium ethoxide, sodium npropoxide, and sodium 1-phenylmethoxide react with 2,4-dibromo-2,4-dinitropentane to give 2,4-dibromo-3-alkoxy-2,4-dinitropentane derivatives (each as 2 to 3 diastereomers) in 75-90% yield. 2-Bromo-2,4-dinitropent-3-ene (mainly the E-isomer) has been isolated from these reactions and shown to be an intermediate in product formation. Sodium alkoxides also react with E-2-bromo-2,4-dinitropent-3-ene to give 2,4-dibromo-3-alkoxy-2,4-dinitropentane derivatives in 30-75% yield. Furthermore, sodium iso-propoxide affords 2,4-dibromo-3-(1-methylethoxy)-2,4-dinitropentane in 30% yield under these conditions but fails to give the product directly from 2,4-dibromo-2,4-dinitropentane. Sodium azide can be used to prepare 3-azido-2,4-dibromo-2,4-dinitropentane either directly from 2,4-dibromo-2,4-dinitropentane (32% yield) or from E-4-bromo-2,4-dinitropentene (39% yield). Monodebromination of 2,4-dibromo-3-methoxy-2,4-dinitropentane and 2,4-dibromo-3-ethoxy-2,4-dinitropentane was carried out in 81% and 93% yield respectively, using acetic acid and sodium iodide. 3-Methoxy-2,4-dinitropentanewas obtainin 89% yield from the reaction of sodium methoxideand 2,4-dibromo-2,4-dinitropentane followed by work-up with a methanolic solution of acetic acid and sodium iodide. Treatment of 2,4-dibromo-3-methoxy-2,4-dinitropentane and 2,4-dibromo-3-ethoxy-2,4-dinitropentane with potassium acetate / iodine in DMSO, conditions previously shown to furnish trans-1,2-dinitrocyclopropane derivatives, gave 4,5-dihydro-5-methoxy-3,4-dimethyl-4-nitroisoxazoleN-oxide and 4,5-dihydro-5-ethoxy-3,4-dimethyl-4-nitroisoxazole N-oxide respectively, in 25-35% yield. A mechanistic rationalization of this outcome is presented.%%%%Ph.D., Chemistry – Drexel University, 2012