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Newsletter Issue 59 August 2016

Scientific Updates' What's New in Process ChemistryScientific Update
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Chemical Development and Scale Up


Dr Claire Francis

We are delighted to announce our course 'Chemical Development & Scale Up in the Fine Chemical and Pharmaceutical Industries' has been approved by the Royal Society of Chemistry for the purposes of continuing professional development. If you are a Member of the Royal Society of Chemistry - you can apply for a discount to attend this course.

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Pot Economy and One Pot Synthesis


Dr Trevor Laird

An interesting review article from Prof Yujiro Hayashi of the University of Tohoku in Japan discusses the characteristics and limitations of one-pot synthetic approaches to complex molecules (Chemical Science, 2016, 7,866). He gives many examples, mostly from his own work on organocatalysis using nitro-olefins.

Use of Bromine and Bromo-Organic Compounds in Organic Synthesis


Dr Trevor Laird

A long (220 pages) and incredibly detailed review has appeared which covers
everything you need to know about bromine and bromination.

Additive Effects on Asymmetric Catalysis


Dr Trevor Laird

Process chemists are always trying to squeeze a few extra % yield from a reaction or improve the quality of the product, particularly enantiomeric purity. A new review from a group of Chinese academics gives some hints as to how this can be achieved, by looking at additive effects in asymmetric catalysis.


Miyaura Borylation


Dr Will Watson

At the recent 'Scale Up of Chemical Processes Conference' in Baveno, Italy, Charles Papageorgiu of Eisai described the optimization of a borylation process to prepare boronic acid ML-826 (see Scheme 1)

Scheme 1 July2016

Scheme 1: Preparation of boronic acid ML-826

Problems with Waste Streams


Dr Will Watson

At the recent 'Scale Up of Chemical Processes Conference' in Baveno, Italy, Wim Dermaut from Agfa presented some case studies where problems have occurred as a result of reactive chemicals present in waste streams. In the first case study a drum containing a waste stream including  diethylhydroxylamine exploded. The most likely cause was caustic present in the empty drum which initially raised the temperature of the waste to a temperature that interaction with Zn led to the runaway reaction (the waste drum was galvanized).

Solvent Effects


Dr Will Watson

At the recent 'Scale Up of Chemical Processes Conference' in Baveno, Italy, John Snoonian of Sunovion discussed the development and scale up of a manufacturing route to make a 5HT4 partial agonist containing a 1,2,4-oxadiazole ring. During route scouting studies on the synthesis of the benzopyrazole an interesting solvent effect was observed – see Scheme 2. As the ketone was the desired product this was manufactured via ortho-metalation of 1,2-difluorobenzene followed by reaction with isobutyryl chloride.

Scheme 2 July2016

A More Holistic Solvent Selection Tool


Dr Will Watson

Louis Diorazio and co-workers at AstraZeneca recently published an article entitled “Toward a More Holistic Framework for Solvent Selection”, which describes the development of a solvent selection tool. Most solvent guides concentrate on Health and Environmental aspects of solvents, but where this new solvent selection tool differs is that it takes in to account issues that affect the success (conversion, selectivity and so on) of the reaction.

Solvent Mapping


Dr Will Watson

Another paper on the theme of solvents, is from Paul Murray working with the University College London and concerns the use of solvent maps and design of experiments (DoE). IN DoE solvent is usually considered to be a discrete or categorical variable, but by applying principle components analysis one can generate solvent maps so that solvent maps can be generated and this allows solvents to be considered as continuous variables albeit in a quantized form. This idea is not new but this paper makes available a new 3 dimensional solvent map with 136 solvents included.

Updated Solvent Guide and Solvent NMR Data


Dr Will Watson

GSK were one of the first companies to publish a solvent selection guide and they have updated this gradually over the years, with the latest version of their guide being published just recently in Green Chemistry1. The new guide contains 44 more solvents taking the total number of solvents covered to 154.

An Alternative to NMP, DMF and DMAc


Dr Will Watson

A recent paper from the University of York Green Chemistry Centre of excellence and Eastman Chemical proposes a new solvent, n-butylpyrrolidinone (NBP), as a replacement for common dipolar aprotics such as DMF, DMAc, and NMP which are under severe pressure from legislation such as REACH, and the updated TSCA regulations in the USA. The big advantage of NBP is that it is non-reproductively toxic, non-mutagenic, and also inherently biodegradable, however it is more acutely toxic (LD50 rat oral 300-2000 mg/kg) than NMP (~4000 mg/kg). Physically it is similar to NMP and other dipolar aprotics as can be seen in Figure 1.

Volatility vs polarity for solventsJuly2016

Just for Fun...


Dr Will Watson

What does 2 + 2 make?

The mathematician will say 4

The chemist will say between 3.95 and 4.05

The lawyer will want to know what their fee will be for providing the information

The accountant will say the answer is 4, but I’m sure you can manage with 1.6

The engineer will say the answer is 4 but just to be on the safe side let’s say 16.

 

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