Phosphoryl anion reactions

Acyl-phosphates can participate in so-called in-line phosphoryl transfer reactions, and depending on reaction conditions, acyl-phosphate compounds can form a metaphosphate anion ... 

Suelter90 has classified enzymes that are activated by monovalent cations into two groups. One involves the catalysis of phosphoryl-transfer reactions and the other a variety of elimination and/or hydrolytic reactions in which a keto-enol tautomer can be invoked as an intermediate. The M+ cation is then required to stabilize the enolate anion. It is still not possible to verify this hypothesis, but it seems unlikely in view of the comments above. 

Although phosphate monoesters chiral by virtue of oxygen isotope substitutions cannot be used in stereochemical studies of phosphate monoester hydrolysis (since there are only three stable isotopes of oxygen), they have been used profitably in studies of phosphoryl transfer reactions relevant to the question of the intermediacy of monomeric metaphosphate anion in phosphoryl transfer reactions (see Section III,A). The laboratories of Knowles and Lowe have reported general methods for the synthesis of phosphate monoesters chiral by virtue of oxygen isotope substitution, and these syntheses are summarized in this section. 

In summary, Cullis and Lowe have demonstrated that the generation of stable thiometaphosphate in solution is possible. The next section describes analogous studies on probing for the existence of free metaphosphate anion, since it is this intermediate that has potential significance in enzyme-catalyzed phosphoryl transfer reactions. 

A very clever three-phase test for the detection of metaphosphate intermediates in phosphoryl transfer reactions has been described by Rebek and coworkers (44). The basis of this test is the use of two polymers suspended in solution. The donor polymer contains a potential precursor to metaphosphate anion, e.g., an acyl phosphate or a phosphoramidate, and the recipient polymer contains an acceptor nucleophile, e.g., an amine. After reaction and physical separation of the polymers, the recipient polymer is analyzed for covalently bound phosphate. Since very few of the phosphoryl groups to be transferred will be on the surface of the donor polymer, detection of significant transfer to the recipient polymer provides evidence for a diffusible intermediate, i.e., free metaphosphate anion. Significant transfer did occur in dioxane or acetonitrile suspensions of the polymers, thereby providing evidence for an intermediate. However, this test for diffusible and, therefore, relatively stable metaphosphate anion is compromised by the choice of solvent. Both dioxane and acetonitrile can provide unshared electron pairs for the highly electrophilic metaphosphate anion such that the actual species that migrates from the donor polymer to the recipient polymer may be a complex between metaphosphate anion and the solvent. Such a role for solvent has been investigated stereochemically, the results of which will be described later in this section. 

Sn2 Nucleophilicity of (CH30)2P0. To determine the intrinsic SN2 kinetic nucleophilicity of (CH30)2P0, we investigated the reactions of the anion with the series of CH3X molecules listed in Table V. The rates of these reactions vary from modest with the most reactive CH3I molecules to slow with CH3Br to no observed reaction with CH3C1. From the results, we conclude that the phosphoryl anion is kinetically a poor nucleophile in SN2 displacement reactions. 

The phosphoryl anion is an ambident species and the calculated AHf values (19) of the tautomers (CH30)2P(=0)CH3 ( — 210.2 kcal/mol) and (CH30)3P ( — 167.6 kcal/mol) differ by 43 kcal/mol. Whether methyl transfer occurs to phosphorus of the anion (thermodynamic control) where a large intrinsic barrier exists or at oxygen under kinetic control with a smaller intrinsic barrier is not clear at this time a much lower reaction exothermicity exists in this latter mode. 

Reactions Involving Electron Transfer. To model the first step in the SRN1 mechanism of electron transfer from the anion to the neutral substrate, we examined the reactions of the phosphoryl anion with the XCF3 molecules where X = I, Br, or Cl ... 

The ambident phosphoryl anion (MeO)2PO is a weak nucleophile in the gas phase further, the neutral products in its reactions with MeX (X = Cl, Br and I) remain uncertain. Methyl transfer to PO would result in (Me0)2P(0)Me while methyl transfer to O would result in (MeO)3P. 

Homer-Wadsworth-Emmons reaction remained unimportant as a preparative route owing to the low reactivity of (136) (Pommer, 1960) toward phosphoryl anions. 

The carboxylic acids (332) and (333) are retinoids lacking a terminal ring system. The carbon skeletons of the two compounds were built in accordance with the (Ci8 + C2) method via Reformatsky reactions (Augustyn et al., 1971). The aldehyde (334) was synthesized using a PO-stabilized phosphoryl anion in conventional reaction steps (Crouch, 1982). 

Many enzymes that mediate phosphoryl transfer from ATP are thought to do so via the formation of a phosphorylated imidazole residue of histidine (Scheme 49). Spontaneous reactions of amines with ATP are legendarily slow, but now a systematic study, involving trapping of the phosphorylated amine with F , has shown that amines (pyridines, imidazoles) react with ATP 30-100-fold faster than do water or alcohols. To complicate the interpretation of the results, it was found that the rate constant for the reaction of F with ATP tetraanion is similar to rate constants for reaction of uncharged amine and oxygen nucleophiles, thus dispelling the myth that reactions of ATP and other phosphoryl anions with anionic nucleophiles are prevented by electrostatic repulsion in aqueous solution. ... 

Orthophosphates can be converted to polyphosphates, such as adenosine triphosphate, where they have new properties of an anionic substance with a relatively high charge. This allows the polyphosphate to sequester cations as calcium and magnesium yielding locally very high concentrations of these ions at reaction sites while the concentration of a total system can be very dilute. This can happen while the molecule is entering into reactions such as phosphorylations. These reactions are critical to metabolism and photosynthesis. 

The development of monoalkyl phosphate as a low-skin-irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste- and liquid-type skin cleansers, and also on phosphorylation reactions from the viewpoint of industrial production [26]. The preparation and industrial applications of phosphate esters as anionic surfactants were discussed [27]. 

The development of monoalkyl phosphate as a low skin irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste and liquid-type skin cleansers, and also phosphorylation reactions from the viewpoint of industrial production [26]. Amine salts of acrylate ester polymers, which are physiologically acceptable and useful as surfactants, are prepared by transesterification of alkyl acrylate polymers with 4-morpholinethanol or the alkanolamines and fatty alcohols or alkoxylated alkylphenols, and neutralizing with carboxylic or phosphoric acid. The polymer salt was used as an emulsifying agent for oils and waxes [70]. Preparation of pharmaceutical liposomes with surfactants derived from phosphoric acid is described in [279]. Lipid bilayer vesicles comprise an anionic or zwitterionic surfactant which when dispersed in H20 at a temperature above the phase transition temperature is in a micellar phase and a second lipid which is a single-chain fatty acid, fatty acid ester, or fatty alcohol which is in an emulsion phase, and cholesterol or a derivative. 

Chlorodiphenylphosphine 488 reacts with a-sulphinyl carbanions to give a-sulphinylphosphines 489 which undergo ready isomerization to a-sulphenylphosphine oxides 4W (equation 295). The report of Almog and Weissman that a-sulphinyl carbanions react with phosphorochloridates 491 to give a-phosphoryl sulphoxides 492 calls for correction (equation 296). Actually, the phosphorylation occurs at the oxygen atom of the ambident dimsyl anion, and is followed by the Pummerer-type reaction affording diethylphosphoric acid and tetraethyl pyrophosphate among other products . ... 

Doubts have recently been expressed regarding the validity of the metaphosphate pathway for hydrolysis of the monoanion of 2,4-dinitrophenyl phosphate (111) 70,71,72) since the basicity of the 2,4-dinitrophenolate group is insufficient to produce a zwitterion corresponding to 106 or even a proton transfer via intermediates of type 103 or 105 (pKa values in water 4.07 for 2,4-dinitrophenol, 1.0 and 4.6 for 2,4-dinitrophenyl phosphate). Instead, hydrolysis and phosphorylation reactions of the anion 111 are formulated via oxyphosphorane intermediates according to 114. 

When monomeric metaphosphate anion POf (102) is generated form the phos-phonate dianion 170 in the presence of the hindered base 2,2,6,6-tetramethylpiper-idine, it undergoes reaction with added carbonyl compounds147), Thus, it phosphoryl-ates acetophenone to yield the enol phosphate, whereas in the presence of acetophenone and aniline the Schiff base is formed from both compounds, probably by way of the intermediate C6H5—C(CH3) (OPO e) ( NH2C6HS). This reactivity pattern closely resembles that of monomeric methyl metaphosphate 151 (see Sect. 4.4.2). 

The clearest example of rapid turnover of a functional micelle is a reaction of a micellized gem-diol. Attack of the anion of the gem-diol gives an acetylated or phosphorylated intermediate which rapidly breaks down regenerating the catalytic gem-diol (Scheme 8) (Menger and Whitesell, 1985). 

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