Aqueous hydrotope solution

Khadilkar and Madyar have developed a large scale continuous synthesis of Hantzsch l,4-dihydropyridine-3,5-dicarboxylates in aqueous hydrotope solution, using a modified domestic microwave oven [81]. The authors used novel reusable aqueous hydrotope solution as a safe alternative to inflammable organic solutions, in a microwave cavity, for synthesis of commercially important calcium blockers such as nifedipine, nitrendipine, and a variety of other 1,4-dihydropyridines (DHP) (Scheme 10.38). Nitrendipine (R = 3-N02, R = Me) has been obtained in 94% yield (50 g) after 24 min by microwave irradiation of the reaction mixture (final temperature 86 °C) at a flow rate of 100 mL min. The reaction mixture was circulated through the microwave cavity in four cycles of 6 min each a 2-min gap between each cycle was imposed to avoid excessive heating. 

Hydrotopy is the phenomenon by which otherwise water-insoluble compounds can be solubilized in the aqueous solution of some compounds, e. g. arene sulfonates. These compounds, known as hydrotopes, are readily water-soluble. The aqueous concentrated solutions (20 to 50%) of the hydrotopes can significantly increase the water solubility of many water-insoluble compounds. 

The authors used for the first time aromatic hydrotope solution system such as 50% sodium p-toluene sulfonate aqueous solution (NaPTSA), 40% sodium cumene sulfonate aqueous solution (NaCuS), and 20% sodium p-xy-lene sulfonate (NaXS) aqueous solution to perform Hantzsch ester synthesis. 

In Section 4.3.3 the use of hydrotropes for intensifying multiphase reactions and making them more selective was covered. The key advantage of an aqueous solution of a hydrotrope is that the solute can be recovered by diluting the aqueous solution, after extraction, to a hydrotope concentration below the critical hydrotrope concentration, when a major part of the product will separate out. The diluted solution can then be reconcentrated at reduced pressure to the original concentration for recycle. Thus a number of products of commercial value, such as phenyl ethyl alcohol, can be recovered (Friberg et al 1996 Gaikar and Phatak, 1999). 

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