Diethyl ethylphosphonate, preparation

Diethyl methylphosphonate may be prepared similarly by refluxing one molar equivalent of triethyl phosphite with one mole of methyl iodide, but it is very difficult to separate the product from the small amount of diethyl ethylphosphonate that is formed simultaneously by the interaction of the phosphite with the ethyl iodide liberated in the reaction. The pure substance boils at 51°/1 mm., no 1.4117, dl5 1.050. 

Mixture with diethyl ethylphosphonate. For a preparation in pure form see Teulade, M.-P., Savignac, P., Aboujaoude, E. E. and Collignon. N. 

The allylsilanes are effective intennediates in the construction of various carbocyclic systems, and the Homer-Wadsworth-Emmons reaction appears to be well suited to prepare this class of compounds. Thus, diethyl 2-(trimethylsilyl)-l-(ethoxycarbonyl)ethylphosphonate reacts with aldehydes 5 ° and ketones under standard Homer-Wadsworth-Emmons reaction... 

In a one-pot synthesis of a-halo-a,p-unsaturatcd carboxylates from dialkyl l-(ethoxycarbo-nyl)methylphosphonate, the intermediate 1-chloro- and 1-bromo-l-(ethoxycarbonyl)methylphos-phonates were prepared by halogenation of sodium salt of dialkyl l-(ethoxycarbonyl)methylphos-phonates with NCS or NBS in THF at room temperature. Cupric chloride and cupric bromide have proved to be efficient reagents for the chlorination or bromination of sodium diethyl 1-(ethoxycarbonyl)ethylphosphonate in DMSO at room temperature in high yields (91%). ... 

There are a number of important methods worthy of merit for the synthesis of phosphorylglycines. Thus, electrophilic amination of diethyl l-(ethoxycarbonyl)methylphosphonate proceeds in one simple operation via the sodium salt in THF or DME. A variety of aminating agents are used with variable yields, such as 0-mesitylenesulfonylhydroxylamine (39 7%), chloramine (23-84%), and diphenyl (O-hydroxylamine)phosphine oxide (60%). Diethyl 1-ethoxycarbonyl- or l-(tert-butoxycarbonyl)methylphosphonate may also be efficiently transformed into oxime or diazo derivatives and then converted to an amine by a further reduction step. The oximes are prepared from EtONO via the sodium diethyl l-(tert-butoxycarbonyl)methylphosphonate (17% or 36%), from NOCl and diethyl l-(ethoxycarbonyl)methylphosphonate in the presence of tEtOljMg, Al-Hg, or Al(O7-Pr)3, 8 from NOCl and diethyl l-(methoxycarbonyl)ethylphosphonate, ° or from NOCl/ROH and diethyl l-tchlorocarbonyl)mclhy I phosphonate. ... 

Diethyl l-tert-butoxycarbonyl-l-diazomethylphosphonate is efficiently prepared in 81% yield from the sodium salt of diethyl l-(tert-butoxycarbonyl)methylphosphonate and tosyl azide in DME (Scheme 8.22). In the case of sodium and potassium salts of diethyl l-(methoxycarbonyl)eth-ylphosphonate, the desired azides are not formed. However, with alkoxymagnesium derivatives, the 1-azido-l-(methoxycarbonyl)ethylphosphonates are obtained in modest yields. Diazotation of diethyl 1-amino-l-(ethoxycarbonyl)methylphosphonate with n-PrONO in AcOH gives diethyl 1-ethoxycarbonyl-l-diazomethylphosphonate in 56-74% yields. ... 

Diethyl 2-(ethoxycarbonyl)ethylphosphonate has also been prepared from Mannich bases. For example, triethyl phosphite reacts with ethyl 3-(diethylamino)propionate at 170°C in the presence of AcOH to give diethyl 2-(ethoxycarbonyl)ethylphosphonate in 58% yield with elimination of diethylamine and AcOEt (Scheme 8.38). ... 

The diethyl 2-(ethoxycarbonyl)ethylphosphonate is prepared in 35% yield from sodium diethyl phosphite and ethyl 3-iodopropionate. -- Similarly, methyl 2,3-dibromopropionate reacts with sodium diethyl phosphite with fonnation of diethyl 2-(methoxycarbonyl)ethylphosphonate in low yield (15%). ° Most likely, these reactions occur via an elimination-addition process promoted by the sodium diethyl phosphite. Treatment of ethyl 3-bromobutyrate with sodium dibutyl phosphite in toluene at VO C affords dibutyl l-methyl-2-(ethoxycarbonyl)ethylphosphonate in 62% yield, ... 

Unquestionably, one of the most attractive synthetic methods for the preparation of dialkyl 2-(alkoxycarbonyl)ethylphosphonates involves the conjugate addition of a dialkyl phosphite to the carbon-carbon double bond of a,p-unsaturated carboxylates (Pudovik reaction, Scheme 8.44). In the presence of EtONa, diethyl phosphite reacts vigorously with acrylate in EtOH to give the Michael addition product in 84% yield. The reaction is applied with success to the synthesis of dialkyl 2-(alkoxycarbonyl)ethylphosphonates bearing a large variety of acyclic (symmetric - or disymmetric 30 or cyclic (symmetric or disynunetric ) substituents at phosphorus. 

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