Schotten-Baumann reaction, selectivity

It is also interesting that in the Schotten-Baumann reaction (in which alcohols or amines are acylated in aqueous alkali) there is apparently a selectivity of the aromatic acyl halide for alcohol and amine molecules over water or hydroxide ions. The reason for this selectivity is not clear, but it is an example of the fact that the ease with which a reagent attacks a molecule does not always parallel its basicity (see also p. 112). 

Wu et al., reported syntheses of a series of novel azo polyelectrolytes, starting with a reactive precursor, poly(acryloyl chloride). The precursor polymer was functionalized by the Schotten-Baumann reaction with several aromatic azo compounds containing hydroxyl end groups. The degrees of functionalization were controlled by selecting suitable feed ratios between the azo reactants and poly(acryloyl chloride) The unreacted acyl chloride groups were hydrolyzed to obtain ionizable carboxylic acid structures. 

Aramides are prepared by polycondensation using the Schotten-Baumann reaction. This reaction, which uses the selected isomers of phthaloyl chloride and phenylenediamine (or its chlorohydrate), is carried out at low temperature (from 0°C to -40°C) in order to avoid side reactions it is carried out in an amide solution (dimethylacetamide, A-methylpyrrolidone, tetramethylurea, etc.) to which mineral salts are added. 

Carbamates are by far the most common type of amine protection used in solid-phase synthesis. Various types of carbamate have been developed that can be cleaved under mild reaction conditions on solid phase. Less well developed, however, are techniques that enable the protection of support-bound amines as carbamates. Protection of amino acids as carbamates (Boc or Fmoc) is usually performed in solution using aqueous base (Schotten-Baumann conditions). These conditions enable the selective protection of amines without simultaneous formation of imides or acylation of hydroxyl groups. Unfortunately, however, Schotten-Baumann conditions are not compatible with insoluble, hydrophobic supports. Other bases and solvents have to be used in order to prepare carbamates on, for example, cross-linked polystyrene, and more side reactions are generally observed than in aqueous solution. 

Preparation of para-acetylaminobenzensulfonyl chloride (PAS) was described in Example 7.2. Sulfonation of 2-aminothiazole is performed in aqueous medium under controlled addition of hydroxide according to the already-discussed Schotten-Baumann process. As the result, double-sulfonated amine is formed, which does not represent a serious technological issue since on heating with ammonia to the reaction pot, selective ammonolysis is achieved and one mole of sulfonamide obtained. This is a useful side product that on separation is recycled in the production of biologically active sulfonamides. The ammonium salt of the sulfathiazole precursor is submitted to hydrolysis of the A-acetyl group and sulfathiazole isolated by crystallization. 

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