Hydrolysis and Exchange in Esters of Phosphoric Acid^1a,b

The Preparation and Hydrolysis of Alkyl Hydrogen Methylphosphonates

“…The rates of hydrolysis of a series of esters were determined (Table 11) and the relative rates of hydrolysis a t 130.5' calculated to be methyl, 1.06; ethyl, 1.00; isopropyl, 40; neopentyl, 1.20. The order of reactivity is very close to that observed in the hydrolysis of the diesters (13) and it suggests t h a t the main mechanism involves C-0 fission, which has been suggested for the phosphate diesters (3,4). T h e acid catalysis also suggests C-0 fission since the hydrolysis of phenyl esters which cannot undergo C -4 fission is not acid catalyzed (17).…”

“…Although the hydrolysis of secondary phosphate esters (I) has been extensively studied (1)(2)(3)(4), the hydrolysis of phosphonate monoesters (11) has received little attention (5, G), although several esters, mainly those of aromatic phosphonic acids, have been prepared by various means (7)(8)(9)(10)(11)(12). The phosphonate monoesters are similar to phosphate diesters, being hydrolyzed in strongly acid solution, very stable a t neutral pH's, and very slowly hydrolyzed in alkaline solutions (3, 4).…”

“…Studies on the phosphonate diesters (13,14) have shown that, just as with the phosphate triesters (15, lG), hydrolysis of one ester group proceeds with P-0 fission in alkali and C-0 fission in acid solution. I t was, therefore, of some interest t o study accurately the rates of solvolysis of a series of phosphonate inonoesters and see if the results corroborate the mechanisms postulated for dialkyl phosphates (3,4). Preliminary experiments showed that the hydrolysis of phosphonate monoesters was too slow for accurate nleasuren~ent in alkaline or neutral solution and detailed measurements were, therefore, only made in acid solution.…”

Self-Splicing and Enzymatic Activity of an Intervening Sequence RNA from Tetrahymena

“…Arrows designate the P-O bond that undergoes cleavage. Above line, data for dimethyl phosphate and ethylene phosphate from Kumamoto et al (1956) and Haake and Westheimer (1961). Below line, hydrolysis of RNA (left) uncatalyzed and (right) catalyzed by the catalytic center of the Tetrahymena IVS.…”

Mechanisms Related to Enzyme Catalysis

“…Such is not the fact; 2',3'-cyclic phosphates of cytidine and uridine are rapidly hydrolyzed either enzymically or by dilute alkali (34, 35), and experiment has shown that five-membered cyclic phosphates usually hydrolyze at an extremely rapid rate. For example (105), potassium ethylene phosphate hydrolyzes in alkali about lo7 times as fast as potassium dimethyl phosphate does; since most of the reaction of dimethyl phosphate (39,72) with alkali occurs at carbon, the rate difference for attack at phosphorus is about lO*-fold. This extraordinarily fast rate is, however, restricted t o the five-membered rings; six-membered cyclic phosphates hydrolyze at a normal (99) rate.…”