Trichloroisocyanuric Acid as an Efficient Reagent for the Synthesis of Phosphoroamidates via Atherton–Todd Reaction under Base-Free Conditions

Abstract

A simple, efficient, and novel method is developed for the synthesis of phosphoroamidates via an Atherton–Todd coupling reaction of amines with dialkyl H-phosphite using trichloroisocyanuric acid as an efficient and safe reagent. Treatment of amines with dialkyl H-phosphite and trichloroisocyanuric acid under base-free conditions gives phosphoroamidates in moderate to good yields. The reaction proceeded effectively to afford the corresponding phosphoroamidates via a dehydrogenative coupling of H-phosphonates with amines. This method is easy, rapid, and good-yielding for the synthesis of phosphoroamidates.

Opening up the Toolbox: Synthesis and Mechanisms of Phosphoramidates

“…A one-pot synthesis of P-Ns was reported by Gupta et al ( Scheme 6 a) [ 97 ]. According to the authors, the chlorination of (RO) 2 P(O)H (R = Me, Et, Pr, i -Pr; 3 eq.)…”

“…The mechanisms of P-N formation from Gupta et al [ 97 ] and Kaboudin et al [ 98 ] suggest that the dialkyl H-phosphonate ((RO) 2 P(O)H, R = alkyl) reacts with trichloroisocyanuric acid ( t CiC-A) to form the intermediate (RO) 2 P(O)Cl ( d ACP; R = alkyl) and 1,3,5-triazinane-2,4,6-trione ( t A t O) ( Scheme 22 ). Following, a nucleophilic substitution between the d ACP and the amine result in the P-N with HCl as the major by-product.…”

ZnCl2-mediated stereo- and chemoselective synthesis of vinylphosphonates

“…22 However, to the best of our knowledge, there are only a few reports on the reaction with methylphosphonates as nucleophilic species in the presence of TiCl 4 / N-methylmorpholine and (i-PrO) 3 TiCl/NaH. 23,24 We recently reported a double hydrophosphonylation of nitriles in the presence of ZnCl 2 /Et 3 N. 25 In continuation of our efforts in developing new synthetic methods for organophosphorous compounds, [26][27][28][29][30][31][32][33] we decided to study the vinylphosphonate-forming reaction using a Lewis acid/base combination. Herein we report an efficient and practical method via the Knoevenagel condensation reaction of carbonyl compounds with cyanomethylphosphonates to yield (E)vinylphosphonates.…”

“…In continuation of our efforts in developing new synthetic methods for organophosphorous compounds, 26–33 we decided to study the vinylphosphonate-forming reaction using a Lewis acid/base combination. Herein we report an efficient and practical method via the Knoevenagel condensation reaction of carbonyl compounds with cyanomethylphosphonates to yield ( E )-vinylphosphonates.…”

Experimental study on the microreactor-assisted synthesis of phosphinic chlorides with varying steric hindrance

“…Our attention was focused on the synthesis of reactive pentavalent tetracoordinated organophosphorus chlorides t BuRP(O)Cl from easy accessible secondary phosphine oxides (SPOs). It is known that SPOs, phosphonates and phosphinates are rearranged to their corresponding acid chlorides by treatment with different chlorinating agents (CCl4 [19][20] , CCl4/base [21] , CHCl3/base [22] , CuCl2 [23] , PhICl2 [24] , Cl2 [25] , oxalyl chloride [26] , chloramines [27] , TCICA [28] , NCS [29] . Among the previously mentioned compounds, CCl4 appears to be the most convenient and available reagent (CAUTION: hepatotoxic!).…”