67846-69-9Relevant academic research and scientific papers
On the origins of enhanced reacivity of five-mambered cyclic phosphat esters. The relative contributions of enthalpic and entropic factors
Kluger, Ronald,Taylor, Scott D.
, p. 6669 - 6671 (2007/10/02)
The hydrolysis of five-membered cyclic phosphate and phosphonate esters is about 106-fold more rapid than the hydrolysis of related acyclic esters. The origin of the enhanced reactivity of the cyclic esters has been ascribed to enthalpic factors, associated with ground-state strain, and to entropic factors, associated with optimal orbital orientations. The temperature dependence of the rates of alkaline hydrolysis of ethyl and methyl esters of ethylene phosphate and of ethyl and methyl esters of propylphostonate have been determined. The enthalpies of activation for the cyclic esters are much less than those for the corresponding acyclic esters while differences in entropies of activation are dependent on the nature of the alkyl substituent, varying from than 1 cal mol-11 deg-1 (eu) for the methyl esters to about 8 eu for the ethyl esters. The data in the present study indicate that the report of an unusually low entropy of activation (17 eu less than the acyclic analogue) for the hydrolysis of the cyclic phosphonate ester, ethyl propylphostonate (Aksnes, G.; Bergesen, K. Acta Chem. Scand. 1966 50, 2508) is in error and thus cannot support assumptions that the high reactivity of cyclic esters is due primarily to entropic effects. The acceleration of the rate of hydrolysis of cyclic phosphate esters is therefore due to enthalpic factors, consistent with interpretations based on ring strain.
A REAFFIRMATION OF STEREOELECTRONIC CONTROL IN THE ALKALINE HYDROLYSIS OF METHYL AND ETHYL ETHYLENE PHOSPHATE
Gorenstein, David G.,Chang, Andrew,Yang, Ji-Charng
, p. 469 - 478 (2007/10/02)
A reinvestigation of the product distribution in the hydrolysis of ethyl and methyl ethylene phosphates has confirmed our earlier suggestion (Taira et al., J.Org.Chem., 1984, 4531) that the stereoelectronic effect is an important factor in these reactions.In contrast to the claims of Kluger and Thatcher (J.Am.Chem.Soc., 1985, 107, 6006; J.Org.Chem., 1986, 51, 207), the increase in exocyclic cleavage product, methanol, with increasing strong base is shown to arise from an artifactual side-reaction in the base catalyzed hydrolysis of methyl ethylene phosphate.The initial product of endocyclic cleavage, methyl hydroxyethyl phosphate, reacts with a second molecule of methyl ethylene phosphate to yield a "triester" dimer which subsequently releases methanol to yield a "diester" dimer.Although a small amount of exocyclic cleavage product is observed in strong alkali (2 - 4percent +/- 1.5percent for methyl ethylene phosphate and .5percent +/-1.5percent for ethyl ethylene phosphate) the proportion does not vary with alkali when the hydrolysis reaction is run under dilute conditions to minimize the dimerization reaction.Even these small proportions of exocyclic cleavage are still completely consistent with arguments regarding stereoelectronic control in these reactions.
Stereoelectronic Effects in the Hydrolysis of Ethyl and Methyl Ethylene Phosphates
Taira, Kazunari,Fanni, Tahsin,Gorenstein, David G.
, p. 4531 - 4536 (2007/10/02)
Ethyl and methyl ethylene phosphates 1 are shown to hydrolyze with complete endocyclic cleavage between pH 8 and 15 to yield ethyl and methyl 2-hydroxyethyl phosphates 3, respectively.A much slower reaction involving recyclization of the methyl hydroxyethyl phosphate 3 to form ethylene phosphate 4, which undergoes rapid further hydrolysis to 2-hydroxyethyl phosphate 5, is conveniently monitored by 31P NMR.The strained cyclic five-membered ring phosphate triester 1 reacts 108- to 1012-fold faster than its strain-free initial diester product 3 via a common phosphorane intermediate/transition state 2.When 1 is hydrolyzed in H218O, only mono 18O-labeled ester 3 is formed but no doubly 18O-labeled 3 is detected.All reactions proceed with complete P-O cleavage as monitored by 18O isotope shifts on the 31P signals of the products.These results are consistent with the stereoelectronic effect, and a mechanism involving a hexacoordinate phosphorus intermediate can be ruled out.
