Substituent effects acid-catalyzed hydration

Protoporphyrin and its derivatives, because of their labile vinyl substituents, are susceptible to acid-catalyzed hydration. For this reason aqueous solutions should be avoided in the preparation of protoporphyrin dimethyl ester from protohemin, and subsequent reinsertion of the iron. Thus the direct esterification of protohemin under basic conditions appears to be the method of choice. More stable porphyrins such as H2oep are most conveniently prepared by the direct insertion of iron(lll) ion using the iron(III) chloride method5 the resultant Fe(IIl) (oep)Cl can be separated directly from the reaction medium as shining purple crystals. However, this method fails to give successful results with protoporphyrin derivatives. In general, the iron (II) sulfate method is the mildest and should be used for all prophyrins unless one is certain that the more rapid alternatives [boiling DMF with iron(II) chloride, or preferably the more stable iron(II) perchlorate] will have no ill effect on the peripheral substituents. 

The reactivity of carbon-carbon double bonds toward acid-catalyzed addition of water is greatly increased by ERG substituents. The reaction of vinyl ethers with water in acidic solution is an example that has been carefully studied. With these reactants, the initial addition products are unstable hemiacetals that decompose to a ketone and alcohol. Nevertheless, the protonation step is rate determining, and the kinetic results pertain to this step. The mechanistic features are similar to those for hydration of simple alkenes. Proton transfer is rate determining, as demonstrated by general acid catalysis and solvent isotope effect data. ... 

Only a sparse amount of material has been published on this topic. Chlorination of 2,4,6-trimethyl-l,3,5-trioxane provided a mixture of chloroaldehydes which could be treated with concentrated sulfuric acid to yield 2,4,6-tri(chloromethyl)-l,3,5-trithiane 168 <1992CL171>. The corresponding dichlorination reaction catalyzed by SbCls at 80 °C (via the previously mentioned chloroaldehyde and hydrolysis to the hydrate) finally yielded the dichloro analog 167 (Scheme 44) <1993SC1289>. Actually, it is chlorination of 1,3,5-trioxane substituents via open-chain reactants that is the process in effect. 

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