Schotten-Bauman condensation

The Schotten-Bauman condensation produces polyanhydrides with moderate molecular weights by a dehydrochlorination reaction between a diacid chloride and a dicarboxylic acid. The polymerization takes place by reacting the monomers for 1 hr at room temperature, and it can be conducted via solution or interfacial methods. Solvents that are used in solution polymerization include dichloromethane, chloroform, benzene, and ethyl ether. The degree of polymerization obtained with this method is approximately 20-30. Lower molecular weight products are obtained for less reactive monomers such as isophthaloyl chloride. 

In one synthetic approach (Veld 1990, 1992), alanine is first converted to the bromo derivative via the reaction of the diazonium salt of the amine with hydrogen bromide. In the next step the acid functionality is activated by converting it to the acid chloride using thionyl chloride. The activated acid is condensed with a protected a-amino acid to yield the dipeptide intermediate which is then cyclized by heating in presence of Celite (ion exchange resin) to yield the final product. However, the overall yield of this reaction is fairly low. A more elegant approach is shown in Scheme 5. In this approach, an a-amino acid wth a protected side chain (e.g., e-Z-lysine) is reacted with 2-bromo-propionyl bromide under Schotten-Bauman condidons (Fischer 1908) to yield the intermediate 5a, which is then cyclized under basic conditions to the depsipeptide 5b. 

Prominent among these efforts are ones using the classical Schotten-Bauman [403-408] method, condensing aromatic acid chloride with aromatic hydroxyl in the presence of an organic base to create an ester group ... 

---