BASF's highly pure intermediate avoids side reactions

Huenig's base is currently involved in the synthesis of more than 40 different active pharmaceutical ingredients (APIs), used in medicines such as analgesics, antihypertensives, antibiotics and antidepressants.

The intermediate operates as a so-called proton scavenger helping to avoid unwanted side reactions because it does not react with the product.

A proton scavenger is a compound capable of reacting with free protons and not producing a new species of catalyst or, if it does produce a new species of catalyst, that catalyst is substantially inactive when compared to the original catalyst system.

The reason EDIPA does not react with the product is because of its molecular structure, making it non-nucleophilic by virtue of sterical hindrance.

This prevents nucleophilic reactions of the SN2 type which are typical for non sterically hindered bases such as ethyl amine and sodium methylate.

"Huenig's base is one of the cheapest non nucleophilic proton scavengers available,"​ BASF spokesman Klaus-Peter Rieser told In-PharmaTechnologist.com​.

"Resins are widely used in research but are too expensive for industrial scale applications, as are a number of structural variations of non-nucleophilic proton scavengers, most of which are of limited availability too."​

Other compounds in this class include t-Butylamine, Triethylamine and Diazabicycloundecene (DBU), which BASF markets.

EDIPAA is manufactured in BASF's Ludwigshafen site, where chemical synthesis and purification are both carried out in multipurpose plants belonging to the company's Intermediates division.

The chemical reaction of the starting materials diisopropylamine and acetaldehyde is, according to BASF, environmentally more benign and thus more sustainable than alternative processes.

This means significantly less waste materials are produced and these pose no problems for incineration in modern residue incineration plants.