The Catalytic Reaction of 1,1,2,3 Propanetetracarboxylic acid with HOI and H₂O₂

HOI and H₂O₂

A mixture of (R and S) isocitric acid, both of which are useful for the generation of citric acid (US4056567 V. Lamberti,E. Gutierrez), were prepared by the halogenation of 1,1,2,3 Propanetetracarboxylic acid (PTCA) (US4022803 E. Gutierrez, V.Lamberti) and both chemical processes were patented in 1977 at Lever Brothers (now Unilever). Although the preferred halogens at that time were chlorine and bromine, no attempts were made to patent iodine a much more expensive halogen. Around 1978 I decided to use iodine but via a catalytic route. It is known that when iodine is dissolved in water iodine disproportionation to HOI and iodide occur:

Using the method of US4022803 patent mentioned above catalytic amounts of iodine either in the form of pure iodine or iodide were used. Iodine dissolved in water at a pH of about 5-7 generates HOI which halogenates the PTCA to produce the iodo compound IPTCA. Under the reaction conditions this iodo compound cyclizes to a mixture of (R,S) isocitric acids via an Sn2 reaction (carboxylate group kicks out iodide) with subsequent loss of carbon dioxide via decarboxylation. The iodide generated in turn is oxidized back to HOI by 30% hydrogen peroxide, which reacts with more PTCA according to the following reaction scheme:

Since iodide can be converted to iodine using hydrogen peroxide, the use of iodide as a way of generating iodine is the alternative way of running this reaction. Both achieved the desired end. It should be noted that the dimethyl(hydroxy malonyl) succinic acid gamma lactone (DHMSAL) ( i.e. diester of the lactone of carboxylated isocitrate) has been prepared in (US4146543 E. Gutierrez) where no loss of carbon dioxide occurs. Consequently, the decarboxylation step most probably occurs after the Sn2 step:

A Resemblance to the Oscillating Clock Reaction

The reaction using HOI/H₂O₂/PTCA looks quite similar to the known Briggs-Rauscher clock reaction. While there are similarities, the oscillating reaction uses, in addition, iodate and manganese sulfate. The overall reaction scheme for the clock reaction is:

which can be broken down into a series of equations

There are two key process ocurring. One is a non radical process where the iodine is consumed by the malonic acid in the presence of iodate and a radical process involving manganese and free radical intermediates which converts hydrogen peroxide and iodate to free iodine and oxygen. It is quite an involved process as opposed to the catalytic iodination of PTCA, which undergoes Sn2 elimination of iodide and reoxidation of iodide back to HOI with no buildup of iodine as in the clock reaction.

Why not patent this process? At the time 1978-79 the lawyers were writing up the patent disclosure, but, unfortunately, the business end decided to abruptly terminate the project whereby all worked ceased. However, the details of the work (written in lab notebooks) were archived and saved for posterity.

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