The Lab Notes

Aryl- and heteroaryl- diazonium tetrafluoroborate salts, prepared by diazotization of an aniline in the presence of HBF4, are unique in that in many cases they are sufficiently stable to isolate. Thermal decomposition of these salts at elevated temperatures results in fluoro-dediazoniation and formation of the corresponding aryl or heteroaryl fluoride- the Balz-Schiemann reaction.1a,bRadiolabelled 18F compounds…

Raltegravir (free base) Selective N- v’s O- alkylation of an amide can be challenging and somewhat unpredictable- the outcome being highly dependent on the structure of the substrate. A good example of this is the N-methylated pyrimidone intermediate (5) en route to Merck’s antiretroviral drug Raltegravir.1 Direct methylation of amide (4) (Figure 1) using MeI gives significant…

Lithium (Li, Element 3) Lithium, first member of the group 1 alkali metals, was discovered in 1817 by Johan August Arfwedson. It’s been around since the dawn of (astronomical) time- both stable isotopes, Li6 and Li7, being among a small handful of elements created in the Big Bang.1Terrestrially its highly abundant in seawater (up to…

Figure 1: Suzuki-Miyaura Coupling   It’s a reaction that most organic chemists have run at some stage in their careers and is almost certainly in the running for the most widely used C-C bond forming reaction. First reported in 1979, the Suzuki-Miyaura cross-coupling between an organoboron nucleophile and an aryl halide electrophile is still ubiquitous in…

Vanadium (V, Element 23) Vanadium, a group 5 transition metal, discovered in 1801 by Andres Manuel del Rio, occurs naturally as a component of vanadinite (Pb5(VO4)3Cl), one of the main industrial ores used as a source of the metal. Over 60 ores are known, with 70-80 thousand tonnes of ore mined globally each year, producing…

Heterocyclic phosphonium salts- powerful intermediates for pyridine coupling:- I’ve always had a keen interest in phosphorus chemistry and have followed the work of the McNally group at Colorado state on heterocyclic phosphonium salts closely. In late 2016 a paper describing synthesis and application of the so called HetPhos salts for C4 (or C2) functionalisation of…

Figure 1 I guess to qualify as a reagent of the month the material has to fulfil certain criteria and commercial availability, though not essential, is very desirable. N-((Methylsulfonyl)oxy)acetimiodyl chloride (henceforth known, at least by me, as Fier’s reagent) is now available to buy from Sigma Aldrich (CAS: 1433887-06-9). The compound is an air and…

Gin is rapidly becoming the nations favourite tipple. Its undergone a modern renaissance with familiar trade names such as Gordon’s, Plymouth and London and multiple artisan distilleries appearing country-wide. It’s even drawn synthetic organic chemists out of the lab and into the refineries. This week at our 5th Winter Process Chemistry Conference in Manchester UK…

Figure: 1 The idea of using transition metal chemistry in a cellular setting might at first seem counterintuitive- biological conditions are challenging with respect to stability, efficiency and catalyst (not to mention patient) poisoning. Having said that many important intracellular processes are modulated by transition metals complexed in metalloproteins, with functions including storage and transport…

At the Scientific Update OPRD conference in Milan earlier this month, Xiaohu Deng from Kura Oncology discussed a pyrimidine-derived diazo intermediate that exists predominantly in the tautomeric ‘tetrazole’ form at equilibrium in solution.[1] The compound was shown as a putative retrosynthetic building block for synthesis of a J&J P2X7 antagonist (Figure 1).[2] I’d not come…