Dialkyl chlorophosphates

The purified tetraethyl pyrophosphate is a colorless, odorless, water-soluble, hygroscopic liquid (24, 4 )- It possesses a very high acute toxicity (28), exceeding that of parathion, and is rapidly absorbed through the skin. There is no spray-residue problem, however, for tetraethyl pyrophosphate hydrolyzes even in the absence of alkali to nontoxic diethyl phosphoric acid. Hall and Jacobson (24) and Toy (47) have measured its rate of hydrolysis, which is a first-order reaction. Its half-life at 25° C. is 6.8 hours and at 38° C. is 3.3 hours. Coates (10) determined the over-all velocity constant at 25° C. k = 160 [OH-] + 1.6 X 10 3 min.-1 Toy (47) has described an elegant method for preparing this ester as well as other tetraalkyl pyrophosphates, based upon the controlled hydrolysis of 2 moles of dialkyl chlorophosphate ... 

Symmetric dialkylphosphoryl-S -alkanediyldiisothioureas have been prepared by reaction of diisothiourea derivatives with dialkyl chlorophosphate (Scheme 71).164... 

The addition of any one of several dialkyl chlorophosphates to an arylalkyne-derived vinyl zirconocene in the presence of catalytic amounts of CuBr in THF leads to the corresponding vinyl phosphonate in high yields (78—92% see, for example, Scheme 4.38) [25]. Here, alkyl-substituted acetylenic starting materials do not react beyond the initial hydrozirconation stage. Vinyl phosphonates may be readily converted to acyloins by oxidation to the diol followed by base-induced cleavage. 

When reacted with trialkyl phosphite in benzene for 1 hr, dialkyl magnates (364, X = F) gave a mixture of amino(trifluoromethyl)methylene-malonates (365) (20% yields), dialkyl trifluoromethyl(substituted amino)-methylenemalonates (366) (40-45% yields), and dialkyl chlorophosphate (-20%) (86ZOB805). The reactions of dialkyl malonates (364, X = F, Cl) and triphenylphosphine in the presence of triethylamine in diethyl ether for 1 hr gave trihalomethyl(substituted amino)methylenemalonates (367) in 87-95% yields. The treatment of a solution of dialkyl trifluoromethyl-(substituted amino)methylenemalonates (366, R1 = Et) in benzene with aqueous hydrochloric acid gave amino(trifluoromethyl)methylene-malonates (368) in 82-84% yields (86ZOB805) (Scheme 32). 

Reaction of isoquinoline and potassium cyanide with dialkyl ehlorothiophosphates - and dialkyl chlorophosphates gives rise to compounds of the type 72a (X = S or O). 

Two methods have been presented for the phosphonation of poly(bro-moaryloxyphosphazenes), viz. via sodium dialkyl phosphite as reagent or via a treatment with Bu Li in combination with dialkyl chlorophosphate. The reactions are visualized by the product formation of (206) and (208) from (205) and (207), respectively. Polyphosphazenes with diphenyl phosphonate groups (209) have been synthesized by the reaction of the bromophenoxy substituted polymer (207) with Bu Li followed by a rapid addition of diphenyl chlorophosphate in thf. Only 50% of the available bromophenoxy groups are converted to diphenyl phosphonate esters groups. ... 

The parent dialkyl ethynylphosphonate was first prepared in 1960 by the addition of stoichiometric ethynylmagnesium bromide to the appropriate dialkyl chlorophosphates in THF. ° The product was isolated in low yield (12-25%), presumably because of side reactions involving the relatively acidic alkynyl proton. The yields can be increased slightly (25-35%) by the use of (toxic) dialkyl fluorophosphates. Despite advances in developing methodologies for the elaboration of dialkyl... 

Diethyl 1-lithio-l-chloromethylphosphonate also reacts with dialkyl chlorophosphates in THF at low temperature to give the corresponding symmetric and disymmetric chloromethylenediphos-phonates in moderate to good yields (51-81%). ... 

Other procedures for the synthesis of P-ketophosphonates based on the use of a phosphorus electrophile have been explored. For example, the reaction of dialkyl chlorophosphates with the dilithium derivatives of a-bromo ketones has been described,but the yields of isolated products remain modest. The Lewis acid-catalyzed reaction of oc-hydroxy ketones with dialkyl chlorophosphites constitutes an efficient synthesis of P-ketophosphonates in high yields (92-96%, Scheme 7.42). This reaction is of special value for the preparation of oc-fully substituted P-keto-phosphonates. ... 

An attractive procedure for the preparation of 2-oxo-m-(alkoxycarbonyl)alkylphosphonatcs involves the C-phosphonylation of p-keto ester dianions with dialkyl chlorophosphate (45-67%) or C-phosphirylation of the monoanion of substituted dioxinones with diethyl chlorophosphite followed by oxidation ... 

The paper reporting the reaction of isoquinoline and potassium cyanide with dialkyl chlorophosphates and dialkyl chlorothiophosphates to give products of the type 114 has now appeared. These compounds can be alkylated in the same manner as a normal Reissert compound, and hydrolysis of the alkylation product gives 1-methylisoquinoline. A phthalazine analog (115) has also been prepared. ... 

Dialkyl chlorophosphates are occasionally used in place of the trialkyl esters aniline was thus monoalkylated in 95% yield at 240-245°.847... 

Dialkyl chlorophosphates. TeCL 11 verts dialkyl and trialkyl phosphites into... 

Dialkyl chlorophosphates. TeCU is an efficient chlorinating agent that converts dialkyl and trialkyl phosphites into chlorophosphates at room temperature. 

The use of oxirane together with Na2HP03 to prepare (2-hydroxyethyl)phosphonic acid as its disodium salt is of historical interest. Other poorly exploited, yet interesting and potentially valuable, reactions include the combination of a trialkyl phosphite and dialkyl chlorophosphate with an oxirane to yield O-phosphorylated derivatives of (2-hydrox-yalkyl)phosphonic diesters (reaction 10)" and, following the initial reaction of an a,j8-unsaturated ketone with a phosphorus(III) triester to give the cyclic phosphorane 272, the subsequent further reaction of the latter with an aldehyde followed by hydrolysis (reaction 11)" Dialkyl acetyl phosphites are reported to react with oxirane through anionic intermediate species with the formation, albeit in low yields, of dialkyl (2-acetyloxyethyl)phos-phonates hydrolysable with concentrated HCl, to give (2-hydroxyethyl)phosphonic acid ... 

Trialkyl phosphites have been converted to dialkyl chlorophosphates (32) in a mild and efficient way by tellurium tetrachloride. Tris(dimethylamino)phosphine abstracts iodine from 1-iodoperfluoroalkanes to give metal-free perfluoroalkyl anions which have basic but poor nucleophilic properties. The bicyclic phosphite (33) with chlorine gave a sole product (34) resulting from opening of the five-membered and not the seven-membered ring. ... 

Kaushik and co-workers have made use of TCCA as an effective reagent for the rapid conversion of dialkyl phosphites to their corresponding dialkyl chlorophosphates under mild conditions. The authors have confirmed that TCCA detoxifies completely sulfur mustard, a potential chemical warfare agent <2005TL5293>. 

This reaction was first reported by Atherton and Todd et al. in 1945T It is a transformation of dialkylphosphite into dialkyl chlorophosphate in the presence of carbon tetrachloride and a base (usually tertiary amine, secondary amine, or primary amine). Therefore, it is generally known as the Atherton-Todd reaction. In general, the formed dialkyl chlorophosphate is too reactive to be isolated, which further reacts with alcohol or amine to give phosphate or phosphoramidate. Only a few dialkyl chlorophosphates have been separated so far. ... 

The Atherton-Todd reaction is an interaction of dialkyl phosphonates with chlorocarbons in the presence of a base (see Appendix) [80]. This is a route for the oxidation of dialkyl H-phosphonates to the highly reactive dialkyl chlorophosphates, which are usually not isolated, but rather used in situ under mild conditions [81]. 

Within this reaction cycle, dialkyl H-phosphonate and carbon tetrachloride react to form dialkyl chlorophosphate and chloroform as the final products of the Atherton-Todd reaction. A simple equilibrium shift (without salt formation) toward the dialkyl phosphite tautomer in step 1 [82] or formation of pentacoordinated phosphorane intermediates in step 2 [84,85] has also been discussed. It has been shown that the rate of this reaction depends on the strength of the applied base [86]. Amines are the most commonly used bases under Atherton-Todd conditions [80-85]. The validity of the deprotonation step in the above mechanism in the case of the base being an amine is, however, questionable, since it has been established that amines are alkylated and not protonated at the nitrogen by dialkyl phosphonates. It has been shown, however, [87] that in the case of basic activation with amines, which are the most commonly used bases, the phosphite intermediates are formed according to a different and more complex pathway (see Section 3.8.1). This pathway includes alkylation of the amine and formation of a monoalkyl H-phosphonate salt. 

In this new scheme, the initial step is the reaction of the amine with dialkyl H-phosphonate to form the corresponding monoalkyl phosphonium salt. The subsequent three steps form the catalytic cycle that leads to product formation. The anion of the monoalkyl H-phosphonate, acting as a base, first deprotonates the dialkyl H-phosphonate to generate the reactive diaUcyl phosphite anion. In the subsequent step, which is the same as in the originally proposed mechanism of that reaction, dialkyl chlorophosphate is formed along... 

Dialkyl chlorophosphates, except via the Atherton-Todd reaction, are also formed in the reaction between dialkyl H-phosphonates and copper dichloride in tetrachloromethane... 

Dialkyl chlorophosphates are formed by the interaction of dialkyl H-phosphonates and trichloracetic acid in the presence of triethylamine [100]. 

The so-formed dialkyl chlorophosphates are reported to undergo reduction with sodium borohydride, yielding back dialkyl H-phosphonates (see Appendix) [103]. 

Synthetic application. The synthetic applications of the Atherton-Todd reaction include preparation of diatkyl amidophosphates and di- or trialkyl phosphates by in situ condensation of the intermediately formed dialkyl chlorophosphates with N-H or 0-H containing substrates. Thus, when the reaction takes place in an excess of the basic compounds (primary or secondary amines), dialkyl phosphoramides are formed as final products [81],... 

The reaction of dialkyl chlorophosphates with 1,3-aminopropanol mainly furnished derivatives of the N-phosphorylation-y-hydroxypropylamide of dialkylphosphoric acid (5 = 9.0 ppm for R = Et 5 = 11.0 ppm for t-Pr) [105], The final product is stable and does not undergo isomerization resulting in the formation of corresponding phosphates, as in the case of the P-hydroxyethylamides of dialkylphosphates. This result indicates that the regioselectivity of this substitution (N-H versus O— H) correlates with the acidity of the corresponding protons. 

For the preparation of multiply phosphorus bridged systems, we studied the pyrolytic behavior of calixarene dialkyl phosphate ester derivatives. These compounds are useful intermediates for the OH-depletion of the calixarenes [15, 16] and for the preparation of aminocalixarenes [17]. These esters can be prepared by treatment of the calixarenes with a dialkyl chlorophosphate in the presence of base [18]. In the case of 1, under mild conditions, the distal (i.e, 1,3-) bis(diethyl phosphate ester) derivative is obtained (2a) while under more drastic conditions (CH2Cl2/aq NaOH, phase transfer catalysis) the tetraphosphate 2b is formed [15a]. Calixarene mono diisopropyl phosphate ester and l,2-bis(diisopropyl phosphate ester) derivatives (2c and 2d) were prepared by mono- or dideprotonation by LDA of the monospirodienone derivative 3 followed by treatment with the corresponding dialkyl chlorophosphate [15e, 17b]. Aromatization of the spirodienone products was achieved by heating or by their treatment with HBr yielding the dialkylphos-phate esters derivatives 2c and 2d [15e, 17b]. 

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