Industrial Upscaling of DOPO-Based Phosphonamidates and Phosphonates Derivatives Using Cl2 Gas as a Chlorinating Agent

Abstract

Herein, we report the industrial synthesis procedure of phosphonamidate and phosphonate derivatives via an efficient and simple chlorination of 9,10-dihydro-9-oxa-10-phosphaphenanthren-10-oxide (DOPO) with Cl2 gas. The key step in the synthesis is the conversion of the P–H bond to P–Cl of DOPO by flowing Cl2 gas into a solution of DOPO in dichloromethane, affording the key intermediate 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-chloride (DOPO-Cl) compound which is industrially not available. DOPO-Cl was isolated, characterized, and used for this synthesis of DOPO-based phosphonamidates and phosphonates in relatively high yield by reaction with the corresponding amines and alcohols, respectively. The experimental results show that the chlorination reaction occurs in equimolar ratios of Cl2 gas to DOPO compound. Subsequently, the procedure developed in laboratory scale was industrially applied for synthesis of the 6,6′-(ethane-1,2-diylbis(azanediyl))bis(dibenzo[c,e][1,2]oxaphosphinine-6-oxide) (EDA-DOPO) compound and 6-((1-oxido-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octan-4-yl)methoxy)dibenzo[c,e][1,2]oxaphosphinine-6-oxide (DOPO-PEPA). All synthetic compounds thus obtainedwere characterized and found to be identical to the authentic laboratory scale products.