Esters Phosphate triester

Phosphate triesters (18) are iatermediates ia both the phosphotriester and phosphoramidite methods, and under appropriate conditions for deprotection of the bases and cleavage of the support, can be obtained directiy by usiag these approaches. The ethyl and isopropyl esters have been obtained directiy by usiag the phosphoramidite method because these are stable duting the normal deprotection procedure (62). By changing the oxidizing agent to Sg, both amidate and triester thiolates can be obtained. 

II RO—P—OR phosphate ester (phosphate) (ortho)phosphoric acid, mono-, di-, and triesters exist... 

The use of a lipophilic zinc(II) macrocycle complex, 1-hexadecyl-1,4,7,10-tetraazacyclododecane, to catalyze hydrolysis of lipophilic esters, both phosphate and carboxy (425), links this Section to the previous Section. Here, and in studies of the catalysis of hydrolysis of 4-nitrophenyl acetate by the Zn2+ and Co2+ complexes of tris(4,5-di-n-propyl-2 -imidazolyl)phosphine (426) and of a phosphate triester, a phos-phonate diester, and O-isopropyl methylfluorophosphonate (Sarin) by [Cu(A(A(A/,-trimethyl-A/,-tetradecylethylenediamine)l (427), various micellar effects have been brought into play. Catalysis of carboxylic ester hydrolysis is more effectively catalyzed by A"-methylimidazole-functionalized gold nanoparticles than by micellar catalysis (428). Other reports on mechanisms of metal-assisted carboxy ester hydrolyses deal with copper(II) (429), zinc(II) (430,431), and palladium(II) (432). 

Various esterases exist in mammalian tissues, hydrolyzing different types of esters. They have been classified as type A, B, or C on the basis of activity toward phosphate triesters. A-esterases, which include arylesterases, are not inhibited by phosphotriesters and will metabolize them by hydrolysis. Paraoxonase is a type A esterase (an organophosphatase). B-esterases are inhibited by paraoxon and have a serine group in the active site (see chap. 7). Within this group are carboxylesterases, cholinesterases, and arylamidases. C-esterases are also not inhibited by paraoxon, and the preferred substrates are acetyl esters, hence these are acetylesterases. Carboxythioesters are also hydrolyzed by esterases. Other enzymes such as trypsin and chymotrypsin may also hydrolyze certain carboxyl esters. 

The first term, representing acid-"catalyzed" hydrolysis, is important in reactions of carboxylic acid esters but is relatively unimportant in loss of phosphate triesters and is totally absent for the halogenated alkanes and alkenes. Alkaline hydrolysis, the mechanism indicated by the third term in Equation (2), dominates degradation of pentachloroethane and 1,1,2,2-tetrachloroethane, even at pH 7. Carbon tetrachloride, TCA, 2,2-dichloropropane, and other "gem" haloalkanes hydrolyze only by the neutral mechanism (Fells and Molewyn-Hughes, 1958 Molewyn-Hughes, 1953). Monohaloalkanes show alkaline hydrolysis only in basic solutions as concentrated as 0.01-1.0 molar OH- (Mabey and Mill, 1978). In fact, the terms in Equation(2) can be even more complex both elimination and substitution pathways can operate, leading to different products, and a true unimolecular process can result from initial bond breaking in the reactant molecule. 

Substitutionally inert Co(m) or Ir(m) complexes have been used to measure directly the effect of Lewis acid activation on the hydrolysis of an amide [35-37], a nitrile [38] and a phosphate triester [39] (Figure 6.4). The p/C, of the cobalt-bound water molecule in 5 is 6.6 [40], Thus the upper limit for the rate-acceleration due to Lewis acid activation with this metal in the hydrolysis of esters, amides, nitriles and phosphates should be close to 109-fold. Although the observed rate accelerations for the hydrolysis reac-... 

They are a versatile surfactant type, with some properties analogous to those of ether sulphates. Unlike sulphate (which is a sulphuric acid mono alkyl ester), phosphate can form di- and triester, giving a wider range of structures and, with them, the ability to tailor the product to a greater number of application areas. 

The phosphorus-based nerve gases and insecticides act by deactivating acetylcholinesterase. Note that all of these compounds have a good leaving group on the phosphorus. They react readily with the nucleophilic hydroxy group of the enzyme to form a phosphate triester in a reaction that is very similar, both in its mechanism and its product, to the reaction of an acyl chloride with an alcohol to form an ester ... 

In the case of phosphates, the triesters are most susceptible to nucleophilic attack and hence the base-catalyzed reaction generally predominates in the pH-rate profile of these esters. Phosphate diesters, with the exception of small ring cyclic ones, are relatively unreactive in neutral... 

A mild and efficient deprotection of phosphate triesters involves nucleophilic attack by weakly basic nucleophiles such as iodide, thiolate and amines at the O-C bond with synchronous expulsion of a phosphate diester as the leaving group [Scheme 7.6]. The reaction is especially useful for the deprotection of methyl, benzyl and allyl phosphates as in Scheme 7.8 shown below. An analogous reaction occurs with carboxylic esters but the conditions required are more stringent because the carboxylate anion is a poorer leaving group (see section 6.3.1),... 

The 4-nitrohenzyl group, used in the synthesis of phosphorylated serine, is introduced by the phosphoramidite method and can he cleaved with TFMSA/MTB/tn-cresol/l,2-ethanedithiol/TFA, 4h, 0°C to rt. A-Methylmorpholine at 80°C also cleaves a 4-nitrohenzyl phosphate triester. This ester is more acid stable than the benzyl ester. ... 

This seemingly small isotope effect must be compared to the isotope effect measured for the hydrolysis of the dibenzyl ester precursor to the isotopically labeled monoester [phosphate triesters can only hydrolyze by an Sn2(P) mechanism], 1.0070 -I- 0.0038, for proper interpretation. The fact that the hydrolysis of the monoester has a larger isotope effect was interpreted as demonstrating that substantial cleavage of the phosphate ester bond occurs in the transition state this is in accord with the expectation based on an Sn 1(P) mechanism. 

Data for a series of phosphate monoester dianions and phosphate triesters indicate a similar dependence of the P-OR bond length on the pK of ROH. In phosphate salts, this bond seems to be about twice as sensitive to the nature of OR as in the esters. Thus, both in acetals and phosphates, stabilization of the incipient electron deficient center is important in influencing the scissile bond distance and its sensitivity to the nature of the leaving group. 

Phosphoric and sulfuric acid derivatives possess crucial properties that allow them to uniquely fill their many roles in biochemistry. Phosphoric acid may be esterified to form a monoester, diester, or triester (Figure 1). Sulfuric acid may be esterified at one or two positions, to form a monoester or a diester. Sulfate diesters are highly reactive, and have not been found in nature nor do phosphate triesters occur naturally. The hydrolysis of both phosphate and sulfate esters are thermodynamically favorable, but nucleophiles are repelled by the negative charge of the ionized forms. The resulting kinetic stability of phosphate monoesters and diesters, and of sulfate monoesters, is a major factor in their suitability for biological roles. For example, the half-life for hydrolysis of alkyl phosphate dianions by water is approximately 1.1 X 10 years k=2 x 10 s ) at 25°C. Such species... 

Coenzyme A analogs are best synthesized by a combined chemical and enzymatic method. Pantothenic acid was first converted to the thiophenol ester and then the terminal OH group was phosphorylated via the dimethyl phosphate triester. Thiol exchange with ethanedithiol gave the a-thiol—phosphate. This compound was first enzymatically combined with ATP and then phosphorylated at 3-OH (Scheme 7.3.8). A wide range of CoA analogs is thus accessible (Martin and Drueckhammer, 1992). 

Synonyms 2-Ethylhexanol phosphate 2-Ethyl-1-hexanol phosphate 2-Ethylhexanol, phosphate triester 1 -Hexanol, 2-ethyl-, phosphate Octyl phosphate Phosphoric acid, tris (2-ethylhe) l) ester TOF TOP Triethylhexyl phosphate Tri (2-ethylhexyl) phosphate Tris (2-ethylhexyl) phosphate ClassiTtcation Phosphoric acid ester Empirical C2,H5,0,P Formula [CH,(CH2),CH(C2H5)CH20]3P0... 

EthyM-hexanol ester with diphenyl phosphate. See Diphenyl octyl phosphate 2-Ethyl-1-hexanol hydrogen phosphate. See,Di (2-ethylhexyl) phosphate 2-Ethyl-1-hexanol, hydrogen sulfate, sodium salt. See Sodium 2-ethylhexyl sulfate 2-Ethylhexanol phosphate. See Trioctyl phosphate 2-Ethylhexyl phosphate 2-Ethyl-1-hexanol phosphate 2-Ethylhexanol, phosphate triester. See Trioctyl phosphate 2-Ethyl-1-hexanol silicate. See Tetrakis (2-ethylhexoxy) silane... 

CAS 78-42-2 EINECS/ELINCS 201-116-6 Synonyms 2-Ethylhexanol phosphate 2-Ethyl-1-hexanol phosphate 2-Ethyl hexanol, phosphate triester 1-Hexanol, 2-ethyl-, phosphate Octyl phosphate Phosphoric acid, tris (2-ethylhexyl) ester TOP TOP Triethylhexyl phosphate Tri (2-ethylhexyl) phosphate Tris (2-ethylhexyl) phosphate Classification Phosphoric acid ester Empirical C24H51O4P Formula [CH3(CH2)3CH(C2Hs)CH20]3P0 Properties Colorless to pale yel. clear liq. si. sharp odor sol. in alcohol, acetone, ether, min. oil, gasoline pract. insol. in water m.w. 434.72 dens. 0.924 (26 C) vapor pressure 1.9 mm Hg (20 C) f.p. -90 C (sets to glass) pour pt. -74 C b.p. 190-233 C (dec.) flash pt.(OC) 207 C ref. index 1.4440 anionic... 

Phosphate triesters. Phosphorous oxychloride can be reacted with various aliphatic and aromatic alcohols and phenols to yield phosphate triesters. Commercially, the trioctyl (from 2-EH) and triphenyl (from phenol) phosphates are often seen. Mixed esters are frequently encountered as well. Phosphate esters are considered to be both secondary plasticizers as well as flame retardants. 

The reactions in cationic micellar media between the a-nucleophile salicylhydroxa-mate anion (SHA ) and p-nitrophenyl benzoate (PNPB), tris(3-nitrophenyl) phosphate (TRIS), and bis(2,4-dinitrophenyl) phosphate (BDNPP) were examined kinetically. SHA was incorporated into CTAB micelles and accelerated dephosphorylation of TRIS over the pH range 6.7—11.4. At 1.0 mM SHA in CTAB, the nucleophilicity of SHA followed the order of reactivity, PNPB (C=0, carboxylate ester) > TRIS (phosphate triester) > BDNPP (phosphate diester) monoanionic SHA and dianionic SHA are the reactive species. The critical micelle concentration of CTAB decreased and the fractional ionization constant, a, increased with an increase in the concentration of SHA . ... 

Mechanistic Generalizations. Substitution reactions at phosphate esters can occur by three limiting mechanisms (Fig. 2) a dissociative, Sn 1-type two-step mechanism, designated Dn + An in the lUPAC nomenclature (2) an associative, two-step mechanism (An -I- Dn) and a concerted mechanism (AnDn) with no intermediate. In the Dn -I- An mechanism, a stable PO3 ion (metaphosphate) is formed that is attacked by a nucleophile in a subsequent step. The An -I- Dn mechanism is an addition-elimination pathway in which a stable pentacoordinate intermediate, called a phosphorane, is formed. Some reactions of phosphate triesters and diesters follow this mechanism, and such a mechanism has been speculated to occur in phosphatases. In the concerted AnDn... 

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