Reaction with POCI3: A Topical Tip from OPRD Barcelona

Gwydion Churchill form AZ described the reaction of the pyrimidone shown below with phosphorus oxychloride to generate the chlorocompound.  I was particularly intrigued where he commented that in their hands the reaction failed to reach completion, instead stopping at the ‘dichlorophosphate ester’ shown in the scheme below.  The solution to this problem was to add about 10-15% water to the mixture which would react with excess phosphorus oxychloride in the mixture releasing chloride ion which then helped complete the conversion.  I found this particularly interesting, as to me at least, it would be counter-intuitive to add water which might simply hydrolyse the intermediate back to the pyrimidone.

The message:  keep an open mind on the chemistry and always be prepared to challenge your thinking!