IPOS are also actively involved in several research areas with the emphasis on projects that can provide a direct industrial benefit. Examples of projects we are currently involved with or plan to initiate in the near future include:

• Organic chemistry in liquid ammonia
• Asymmetric reductive animation.
• Counter current liquid/liquid flow processes.
• The safe use of hazardous reagents through in-situ generation.

Imine Transfer Hydrogenation and Asymmetric Reductive Amination:

This project involves the elucidation of the mechanism of the asymmetric transfer hydrogenation of imines using CATHyTM catalysts and the development of high yielding, catalytically efficient, highly selective procedures for the synthesis of a wide range of chiral amines on an industrial scale.

The improved mechanistic understanding will then be used to develop an efficient, industrially viable procedure for the asymmetric reductive amination of ketones.

This reaction was highlighted by the ACS GCI Pharmaceutical Roundtable* as one of the eight key “aspirational” reactions the pharmaceutical industry would like to be able to use if the technology was available.

Organic Chemistry in Liquid Ammonia

This project involves a detailed study of the suitability of liquid ammonia as a solvent for organic synthesis.

Currently dipolar aprotic solvents are used in ~10% of industrial processes however they are expensive, generally toxic and difficult to recycle due to their miscibility with water and usually have to be incinerated.

The properties of liquid ammonia are such that it is a promising green alternative to dipolar aprotic solvents as it is cheap and amenable to recycling. Although liquid ammonia has been known as a potential solvent for organic reactions for some time it is little used in modern organic synthesis and as such there is a large potential scope for the development of novel processes.

This project will assess the suitability of liquid ammonia as a solvent for a wide range of chemical reactions with particular focus on industrial processes. It is our aim to either sell or license the intellectual property generated and further develop the technology through industrial collaboration.

“Micronasties”

A number of useful gaseous intermediates for organic synthesis are difficult to access because of their inherent hazards, expense and the difficulty of feeding controlled quantities into the consuming reaction. Currently Industry would look for alternative synthetic methods rather than use some of these useful intermediates on a large scale.

It is proposed to develop laboratory scale continuous flow equipment to generate a number of such intermediates at a controllable rate from liquid or solutions of precursors.

Scale up of the apparatus for Industry would allow for these materials to be generated on site and reacted in-situ whilst maintaining a low inventory in the reactor. Target compounds in priority order for development, are

1. Cyanogen chloride.

2. Nitric oxide.

3. Nitrogen trioxide.

4. Chlorine .

5. Diazomethane .

6. Sulphur trioxide.

Counter-current liquid/liquid and liquid/solid flow processes

Phase transfer catalysed processes are widely used in industrial organic synthesis but rarely in flow reactors. Such processes show complex kinetics to which the main contributors are the partition behaviour of the reactive anion and the homogeneous kinetics in the reacting organic phase.

The kinetics commonly show product inhibition due to unfavourable partitioning of the displaced anion. In the case of a solid-liquid reaction, an additional problem is deposition of the displaced anion on the surface of the reactant solid.

These product inhibition problems should be substantially mitigated by use of countercurrent flow techniques, since the highest concentration of fresh inorganic reactant contacts the ‘end of reaction’ material. For liquid-liquid reactions equipment design is conventional.

New methodology based on modification of the Kuhni column will be used for liquid-solid reactions.