Kinetics and mechanism of the hydrolysis of a (5,6)-spirophosphorane. Thermodynamics of the hydrolysis of cyclic five-membered and six-membered phosphonium ions

Abstract

Can. J. Chem. 69, 2064. The cyclic five-membered phosphonium ion 26 (2-(2'-hydroxyethoxy)-2-pheny1-1,3,2-dioxaphospholan-2-ylium) derived from ring-opening of the (5,5)-spirophosphorane 16 (5-phenyl-l,4,6,9-tetraoxa-5-phosphaspiro[4.4]nonane) has been observed in neat CF3S03H and at >85% H2SO4. The cation undergoes hydrolysis in the latter solutions, and an extrapolation has been carried out to obtain an estimate for reactivity in 100% water. Hydrolysis rate constants for phenyltrialkoxyphosphonium ions in water are lo7, lo0, and 5 x s-I for cyclic five-membered, cyclic six-membered, and acyclic derivatives respectively; these show an excellent correlation with rate constants for a similar series of phosphate esters. An investigation of the hydrolysis of the (5,6)-spirophosphorane 5 (5-phenyl-8,8-dimethyl-1,4,6,1O-tetraoxa-5-phosphaspiro[4,5]decane) provides a clue as to the origins of these rate differences. This phosphorane can in principle hydrolyze via two isomeric cyclic phosphonium ions, the six-membered 14 and the five-membered 15. The former is thermodynamically more stable, being the only cation observed under equilibrating conditions of strong acid. However, the hydrolysis of the spirophosphorane, as well as the hydrolysis of fully formed 14, channels through the cyclic five-membered 15. A thermodynamic breakdown reveals that the 9.5 kcal mol-I difference in activation free energy for the hydrolysis of five-and six-membered cyclic phosphonium ions is due to a combination of a higher free energy (2.5-4.5 kcal mol-') for the five-membered cation, and a lower free energy (7-5 kcal mol-l) for the pentacoordinate transition state with the five-membered ring. This analysis also shows that a ($6)-spirophosphorane is 6 8 kcal mol-I more stable than a (6,6)-spirophosphorane. Thus, a five-membered ring has a significant stabilizing effect on a pentacoordinated phosphorus structure. The accelerated hydrolysis of cyclic phosphonium ions and phosphate esters with five-membered rings is caused by a combination of this stabilizing effect in the transition state and a destabilizing effect in the ground state associated with ring strain.Key words: phosphorane, hydrolysis, phosphate, phosphonium. Une attribution thermodynamique rCvtle que la diffkrence de 9,5 kcal mol-' qui existe entre Cnergies libres d'activation pour les hydrolyses des ions phosphonium cycliques i cinq et i six chafnons est due 2 une combinaison d'une tnergie libre plus deve'e (2,5-4,5 kcal mol-') pour le cation a cinq chainons et une Cnergie libre plus faible (7-5 kcal mol-') pour 1'Ctat de transition pentacoordine du cycle i cinq chainons. Cette analyse permet aussi de montrer qu'un (5,6)-spirophosphorane est de 6 8 kcal mol-' plus stable qu'un (6,6)-spirophosphorane. Un cycle i cinq chainons a donc comme effet de stabiliser une structure phosphorte pentacoordinbe. L'hydrolyse plus rapide des ions phosphonium cycliques et des esters de l'acide phosphorique comportant des cycles B cinq chainons est causCe par une combinaison de cet effet stabilisan...

Ketalization of phosphonium ions by 1,4-dioxane: Selective detection of the chemical warfare agent simulant DMMP in mixtures using ion/molecule reactions

“…The CID spectrum of the 1,3,2-dioxaphospholanium ion (137 Th) in Figure 2 illustrates that it fragments exclusively back to give CH 3 P(O)OCH 3 ϩ (93 Th). Correspondingly, in solution, 1,3,2-dioxaphospholanes are often hydrolyzed or photolyzed back to the initial phosphonium ions [21,40]. This provides additional evidence for the structure of the 1,3,2-dioxaphospholanium ion (137 Th).…”

Kinetics and Mechanisms for the Cleavage and Isomerization of the Phosphodiester Bonds of RNA by Brønsted Acids and Bases

“…Evidence for the importance of both the ring strain , and stereoelectronic effect ,, has been presented. Recent quantum chemical calculations attribute the rate acceleration to different solvation of the transition states formed from cyclic and acyclic substrates. ,,, Studies with a (5,6)-spirophosphorane suggest that the ring strain is not, at least completely, relieved on going from a five-membered cyclic phosphate to a phosphorane: the Gibbs free energy of a five-membered cyclic phosphonium ion ( 27 ) still is 10−20 kJ mol -1 higher than, for example, that of its six-membered counterpart ( 28 ) …”

“…62,65,74,136 Studies with a (5,6)-spirophosphorane suggest that the ring strain is not, at least completely, relieved on going from a five-membered cyclic phosphate to a phosphorane: the Gibbs free energy of a five-membered cyclic phosphonium ion (27) still is 10-20 kJ mol -1 higher than, for example, that of its six-membered counterpart (28). 137 2′,3′-Cyclic phosphates (4) are hydrolyzed about 1 order of magnitude faster than ethylene phosphate (12), 43,138 the reaction being enthalpically more favored. 139,140 Whether this increased instability results from extra ring strain that results from fusion of the five-membered phosphodiester ring with the ribofuranose ring and is released on going to the pentacoordinated intermediate remains an open question.…”

Reaction Kinetics of Oxyphosphoranes with Model Compounds of Nucleosides

“…Furthermore, as compared to the 1,3-diol, the 1,2-diol was a much more favorable substrate for the ester exchange on 1. The great reactivity difference must be due to the driving force for the five-five membered spirooxyphosphorane than the corresponding five-six membered one, since a fivemembered ring has a significant stabilizing effect on a pentacoordinated phosphorus structure (16). Consequently, the ribonucleotides with 2Ј-OH showed much greater reactivity than 2Ј-deoxyribonucleotides when the phosphorus was the reaction center.…”