The Lab Notes

Here, we bring you the latest trends, in-depth analyses, and practical tips from the world of industrial chemistry and chemical engineering.

Process Chemistry Articles

Oxazoles are relatively common heterocyclic rings, but are not always the easiest rings to prepare by de novo synthesis.  Two recent papers describe new methods for the preparation of these compounds1,2. In the first paper1, a heterogeneous gold catalyst (MCM-41-Ph3PAuNTf2) is used prepare oxazoles from an acetylene, a nitrile with the oxygen atom coming from…

Process Chemistry Articles

Francis Arnold and her group have published a series of papers using modified Cytochrome P450 enzymes to cyclopropanate olefins with diazo esters1.  More recently they have used a related system to create chiral carbon-silicon bonds2. P.S. Coelho, E.M. Brustad, A. Kannan, and F.H. Arnold et al, Science, 2013, 339, 307-310; Z.J. Wang, H. Ranata, N.E.…

Process Chemistry Articles

There have been a number of papers on the subject of how to specify regulatory starting materials, with a bench marking exercise carried out by the IQ Consortium1.  Now a sub-group has published a risk assessment tool to evaluate potential regulatory starting materials2, particularly in early development. For any proposed RSM a score is built…

Process Chemistry Articles

Flow chemistry is big news at the moment, but one of the issues from a scale up perspective has been carrying out some of the process hazard analysis, and in particular reaction calorimetry.  If reactants are unstable either thermally or chemically is it possible to get meaningful results from a conventional reaction calorimeter?  A recent…

Process Chemistry Articles

Photochemistry has to me always seemed to be an area whose potential for industrial manufacture has never been realized. I may be biased (I did my PhD on photochemistry from 1967-1970) but I feel the tremendous synthetic potential of photoreactions has not been exploited enough.  One of the reasons is that scale up of batch…

Topical tips

Considering the environmental footprint of a typical pharmaceutical / agrochemical process, 60-80% arises from the use of solvents.  Good solvent selection and use - can be the biggest positive hit on improving the sustainability of a process. The timely identification of an optimum chemical route can save you time and money.  An efficient route, selected…

Process Chemistry Articles

This excellent paper from BMS describes a method for predicting the process mass intensity (PMI) for a given chemical step or for a whole synthesis, and thus provides a new way to compare synthetic routes even at the design stage. At the heart of this approach is an internal database of PMI scores for 15…

Topical tips

Permissible limits for impurities during clinical development has always been a grey area. Existing guidelines, specifically ICH Q3A only formally apply to marketed products.  How factors such as duration of clinical trials have never been effectively addressed.  A new paper looks in depth at how limits for impurities can be effectively linked to duration.  It…

Topical tips

Whereas process parameter risk quantification is conducted using mathematical calculations (Monte Carlo simulations) based on a process model, risk analysis is a semi-subjective methodology, of value for both early, as well as for late process development work. Herein we will focus on early process development, when little experimental information is available. In spite of its…

Process Chemistry Articles

In the past, the particle size of finished APIs was mostly controlled by processes such as milling and micronization, but this often creates fines and can lead to formulation issues for some compounds. More recently companies are trying to control the particle size of the product as part of the crystallisation process (not forgetting that…