Paul Wyman

Base catalysed phosphate diester hydrolysis

The rate of attack of hydroxide on dialkyl phosphate diesters is far slower than previously estimated, allowing us to estimate the stability of the diester link in DNA and showing that ethylene phosphate is 1011 fold more reactive towards attack by hydroxide than an acyclic diester (1000 fold more than previously estimated).

Improved synthesis of phosphorus-containing styrenic monomers

Several dialkyl-p-vinylbenzyl phosphonates, for use in making fire-retardant styrenic and acrylic polymers, have been synthesised by reaction of p-vinylbenzyl chloride with various dialkyl phosphonates using the Michaelis-Becker reaction. This reaction is shown to have several benefits over the conventional Arbuzov methodology. Principal amongst these are that the Michaelis-Becker reaction proceeds rapidly at room temperature, or below, to give high yields of products requiring little or no purification, thus avoiding the heating necessary in the Arbuzov procedure, which can lead to premature thermal polymerization of the vinyl reactants and products. The Michaelis-Becker procedure is also shown to give ready access to higher dialkyl-p-vinylbenzyl phosphonates that would be difficult to obtain by the Arbuzov procedure.

Phosphate diester hydrolysis within a highly reactive dinuclear cobalt(III) complex. Ligand effect on reactivity, transition state and dissociation

The hydrolysis of methyl aryl phosphate diesters coordinated to a dinuclear Co(III) complex ([Co2(tame)2(OH)2{O2P(OAr)(OMe)}]3+; tame = 1,1,1-tris(aminomethyl)ethane; 2) has been studied in aqueous solution at 25 °C. Hydrolysis of the phosphate diester is base catalysed and occurs 30 to 60 fold faster than in analogous complexes where tame is replaced by 1,4,7-triazacyclononane (tacn) (1). The second order rate constants for base catalysed hydrolysis of 2 are highly sensitive to the basicity of the aryloxy leaving group with βlg = −1.29 ± 0.03. This leaving group dependence is similar to that of 1 (βlg = −1.38 ± 0.01), showing that the ligand affects reactivity without greatly altering the transition state at phosphorus. The slight decrease in βlg is consistent with previous rationalisations of this high sensitivity. Dimethyl phosphate coordinated to both types of complex (3, tame; 4, tacn) only dissociates from the complex, with no hydrolysis. Base catalysed dissociation is slower with tame (3 20 fold slower than 4) but the pH independent reaction is faster (3 10 fold faster than 4). These data suggest that the reactivity and turnover properties of these dinuclear complexes may be tuned rationally and independently.

The reaction of 1-aryl- and 1-pyridyl-1,2,3,4-tetrahydroisoquinolin-3-ones with dimethylcarbamoyl chloride: the preparation of amidines, isoquinolines and N-carbamoylated products

1-(Halogenophenyl)-1,2,3,4-tetrahydroisoquinolin-3-ones, such as 3, react with neat dimethylcarbamoyl chloride at 95–165 °C to give high yields of the corresponding N,N-dimethylamidines; higher temperatures favoured N-carbamoylation. At 155 °C the related 1-(3-pyridyl)-1,2,3,4-tetrahydroisoquinolin-3-ones 6–8, 10 and 11 gave lower yields of amidine, with those lactams not bearing an electron-releasing substituent on the benzo ring (6–8) giving medium to good yields of 1-(3-pyridyl)isoquinolines. In contrast, treatment of the corresponding 1-(4-pyridyl)-1,2,3,4-tetrahydroisoquinolin- 3-one 12 with neat dimethylcarbamoyl chloride at temperatures between 125 °C and reflux gave none of the corresponding amidine. At high temperature the N-carbamoylated product 30 predominated, whereas at 125 °C, 3-(N,N-dimethylcarbamoyloxy)-1-(4-pyridyl)isoquinoline 37 was the major product.