[1449-17-8] · C6H4ClO3P · 1,2-Phenylene Phosphorochloridate · (MW 190.52)
Physical Data: bp 120 °C/9 mmHg; 91 °C/0.9 mmHg.
Solubility: sol most organic solvents; react with alcohols.
Form Supplied in: liquid; commercially available.
Analysis of Reagent Purity: FT-IR.11
Preparative Methods: reaction of Catechol with Phosphorus(V) Chloride gives the intermediate (2) which on warming with Acetic Anhydride decomposes giving acetyl chloride and 1,2-phenylene phosphorochloridate (1) in 88% yield (eq 1).1
Purification: redistil under reduced pressure.
Handling, Storage, and Precautions: will keep indefinitely in a sealed tube. Harmful and irritant; moisture sensitive. Incompatible with alcohols and water.4 Use in a fume hood.
1,2-Phenylene phosphorochloridate is a convenient and efficient phosphorylating agent. Reaction with primary alcohols in the presence of base (Pyridine) gives the phosphate ester (3). This is readily hydrolysed to the o-hydroxyphenyl ester (4), which on treatment with Bromine in neutral aqueous buffer gives the monophosphate ester (5) in good yield (eq 2).2,5
Adams' catalyst6 has been used as an alternative to bromine in the last step and the use of other oxidative conditions involving periodic acid and Lead(IV) Acetate has also been reported.3 Unsaturated alcohols are not compatible with some of the reaction conditions used to cleave (4).
The reagent is particularly useful for the phosphorylation of nucleotides (eq 3).3 Reaction of (1) with 2´,3´-O-isopropylidene ribonucleosides (6) is carried out at room temperature in the presence of 2,6-Lutidine for 3 hours. Addition of water hydrolyses the intermediate phosphotriesters and gives the 5´-o-hydroxyphenyl phosphates (7) in good yields. This functionality is stable to the acidic conditions required for removal of the isopropylidene group and subsequent treatment with an excess of bromine water gives the 5´-phosphates (8) as the sole nucleotide products. For example, with B = adenine, the overall yield for the sequence was 78%.3 Phosphorylation of a 2´-deoxyribonucleotide using this procedure was successful.3
The reaction of 3-trifluoromethylphenylhydrazine with (1) gives the ring-opened monohydrazide (9) in 66% yield (eq 4).7
Reaction of (1) with 1,2-diols, 2-hydroxy acids, or 2-keto acids leads to the formation of spirophosphoranes (10) which are in equilibrium with the phosphotriesters (11) (eq 5).8 The use of (1) in the synthesis of a hexacovalent phosphate ester has also been reported.9
Reaction of (1) with a range of aryl Grignard reagents leads to the formation of o-hydroxyphenyl phosphinates (12) (eq 6).10
King's College London, UK