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Phosphonohydrazines were prepared in good yield from corresponding arylamines by a one-pot reaction through diazotization with an organic nitrite and treatment with a trialkyl phosphite. The trialkyl phosphite is postulated to function as a nucleophile as well as a reducing agent.
Arylamines react readily with inorganic nitrite in acid to form diazonium compounds, which can be transformed to halides and other derivatives through the Sandmeyer reaction.1 The reaction of aryl amines with organic nitrite is reported to form a series of diazo compounds as shown in Scheme 1. The formation and reaction of diazoamino compound 1 have been established and carefully investigated; whereas the formation of diazo intermediates 2 and 3 has not been fully established.2–9 The formation of aryl radical intermediates from the decomposition of these diazo intermediates has been utilized in aryl-aryl coupling reactions.5–9 The aryl radical intermediates were also implicated in the conversion of aryl amines to aryl halides in the presence of organic nitrite as an alternative method to the Sandmeyer reaction.4,10,11 In Meerwein and related reactions, cupric chloride was proposed to catalyze the direct decomposition of aryldiazonium to from aryl radicals in the arylation of α,β-unsaturated carbonyl compounds.12,13
We are interested in the synthesis of arylphosphonate esters. Dialkylphosphite has been reported to react with alkenes to form phosphonate and phosphite radical from the homo-cleavage of the P–H bond was proposed as the reactive intermediate.14 We thus sought to prepare aryl phosponate esters through radical coupling of the phosphite radical and aryl radicals derived from arylamines as depicted in Scheme 1. However, aryl-phosphorus coupling did not occur when arylamine was treated with alkyl nitrite in the presence of dialkyl or trialkyl phosphite. When trialkyl phosphite was used, phosphonohydrazines 4 were formed in good yield instead (Scheme 2). In this Letter, we report the one-pot reaction of arylamines with isoamyl nitrite in the presence of triisopropyl phosphite to form phosphonohydrazines in good yield.
Phosphonohydrazines have been proposed as potential candidates for novel insecticides.15 Simple phosphonohydrazines (without aryl groups) were synthesized by the reaction of monochlorophosphonate and hydrazine.16–18 In a special case, 2,4-dinitrophenylated phosphonohydrazine has been isolated as a rearranged product from the reaction of bis(2,4-dinitrophenyl) phosphate with hydrazine.19 This reaction therefore presented a convenient method for the preparation of phosphoryl derivatives of aromatic hydrazines.
The reaction was conveniently carried out in one pot and works with mild electron-donating and electron-withdrawing substituting groups on the aromatic ring as shown in Table 1.20 Arylamines with strong electron-withdrawing or electron-donating groups such as nitro and methoxy groups, respectively, did not react very well. It may be difficult to form intermediates such as 3 from arylamines with strong electron-withdrawing groups. On the other hand, the reaction of diazo intermediates with phosphite (first step in the proposed mechanism shown in Scheme 3) may not proceed well when strong electron-donating group is present.
The reaction progress was monitored by thin-layer chromatography (TLC). In most cases, the reaction was completed in three hours. However, reactions run overnight did not seem to decrease the yield. The products were characterized using NMR and HRMS and the yields were found to be generally moderate to very good (Table 1).20
The mechanism of the reaction is still under investigation. However, it is conceivable that the reaction involves nucleophilic attack by phosphite on intermediate such as 3 to form phosphonium intermediate 5 as shown in Scheme 3. Elimination of the isopropyl group leads to the formation of the phosphorus-oxygen double bond in phosphonodiazo intermediate 6. Subsequent reduction of the diazo moiety in 6 by phosphite generates the final product 4. Phosphites are known to be excellent reducing agents and the reduction of N–N bonds in diaziridinones and N–O bonds in nitro compounds has been reported.21–23 Further mechanistic investigation is currently under way and focuses on the characterization of reaction intermediates.
In summary, arylamines can be converted to aromatic phosphonohydrazines in good yield by reacting with organic nitrite in the presence of trialkyl phosphite. The reaction is likely to involve diazo intermediates formed by the reaction of arylamines and alkyl nitrite. Trialkyl phosphite is postulated to be the nucleophile as well as reducing agent. Considering the convenient and efficient one-pot nature of the reaction, this mechanistically interesting transformation represents an excellent method for the preparation of some aromatic phosphonohydrazines.
This investigation was supported by the National Institutes of Health, Grant SC1 GM095419 (W.W.), Departmental Summer Research Fellowship and CSUPERB Presidents’ Commission Scholarship (D.J.B.), National Institutes of Health MARC (M.L.M.) and RISE (J.R.G.) Scholarships. We thank Dr. Robert Yen for obtaining the mass spectra. The Mass Spectrometry Facility was funded by the National Science Foundation (CHE-1228656). The NMR facility was funded by the National Science Foundation (DUE-9451624 and DBI 0521342). We also thank Professor Ihsan Erden for helpful discussions and Sam Weick for technical assistance.
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