The Synthesis of Large Cyclic Molecules

In order to circumvent the unwanted intermolecular reactions that are usually observed, syntheses are often performed under conditions of moderate to very great dilution. Under these circumstances, the intramolecular reaction becomes more likely than the intermolecular process. It is more likely for the reactive end of a molecule to encounter the other end of the same molecule as opposed to the reactive site of another molecule. In extreme cases, milligrams of reactants are dissolved in litres of solvent. This places extreme constraints upon the purities of reactants and solvents and also upon the quantities of products which may reasonably be obtained. A further synthetic problem is associated with the observation that many of the reactive precursors are water sensitive it is very difficult to completely exclude water from a reaction vessel, and many of the solvents used are hygroscopic. Think about a high dilution reaction with 0.1 mmol of a hydrolytically unstable compound in one litre of solvent. It would only require 1.8 mg of water to completely destroy the reactant. This corresponds to 0.0002 % (w/v) of water in the solvent  

If there are potential donor atoms within the reactant and/or product molecules then it is possible to use a different methodology for the synthesis of cyclic compounds. 

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