Phenol hydrogenation

30 November 2009 - catalysis

phenolhydrogenation
Cyclohexanone is industrially made by cyclohexane oxidation. it can also be made from cheaper phenol by hydrogenation but then spillover to cyclohexanol is just around the corner. In a recent Chinese publications this issue is tackled by combining a catalyst - palladium on carbon - with a Lewis acid - aluminium chloride in a phenol / scCO2 system (Liu et al. 2009 DOI). No cyclohexanol is formed and the authors offer a simple explanation. The Lewis acid is expected to activate the aromatic ring (just as in EAS) and palladium activates hydrogen. The carbon dioxide in addition to being a solvent speeds up the reaction even further by being a weak Lewis acid itself. Finally, By complexation with cyclohexanone the Lewis acid blocks the secondary reaction to the alcohol.

By one of those nice coincidences this article was dropped in the mailbox of one publisher the very same day (7 July 2009) another article also on cyclohexanone hydrogenation (Chatterjee et al. 2009 DOI) appeared online with another publisher. The solvent is again scCO2 and the catalyst is palladium embedded in mesoporous silica that is doped with sodium aluminate forming Pd/Al-MCM-41. At 50°C and 12GPa (H2 + CO2) the results are comparable. The presence of a Lewis acid is not appearant but the aluminium incorporated in the silica is creating acidic sites just the same.

It is easy being a global warming skeptic

22 November 2009 - Copenhagen

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It is about time this blog comes to the rescue of that little molecule called carbon dioxide. For the past millions of years it has helped trap heat in our atmosphere making life on earth possible but according to climate scientists mankind has been adding too much and now carbon dioxide is overheating the planet.

But it has never been easier being a global warming sceptic. This week a collection of email exchanges between global warming scientists were published that hackers had stolen from a university computer. From these exchanges a picture emerges that these scientists 1. may use statistical tricks in order to move data in the desired direction 2. may sweep data not fitting their models under the carpet and 3. may collude in smear campaign against scientists known to have a critical stand on climate change (see nytimes article).

And global temperature rise has come to a complete standstill anyway: for the past 10 years the planet has simply refused to heat up any further and global cooling is on the way. (see report in Der Spiegel or New Scientist). And how about those glaciers? The journal Science last week headlined No Sign Yet of Himalayan Meltdown, Indian Report Finds, the glaciers over there at least (contrary to many recent media reports) appear to be holding out despite global warming. According to climate scientist John Shroder cited in the Science article :The bottom line is that IPCC's Himalaya assessment got it horribly wrong (..) They were too quick to jump to conclusions on too little data. (DOI).

And how about those sunspots!. Solar activity varies over time and low activity as evidenced by low sunspot count corresponds to a relatively cool climate. The Little Ice Age in the 17 Th century is attributed to an extended solar slumber. Yet according to the IPPC (2007) solar activity today only accounts for 10% in the overall global warming. Nevertheless it is very tempting to connect the current global warming pause with the recent phenomenon of the missing sunspots. In a July 2009 article the NYTimes cites a NASA scientist on solar activity stating that it's been as dead as a doornail and in the beginning of 2009 there was a long lull of several months of virtually no activity, which had me worried (sunspot numbers here). The next solar maximum in 2013 is predicted to be the weakest since 1928.

But do not underestimate the IPPC. In their 2007 synthesis report they do not only assess radiative forcing components but also add an assessed level of scientific understanding (LOSU) for each component. And for carbon dioxide the LOSU value is high but for solar irradiance LOSU is low. So it is still possible for carbon dioxide to have it's name cleared if it is possible to steer research in the right direction although not before the upcoming Copenhagen 2009 summit.

The chromocapillary effect

20 November 2009 - Parlour games

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In another installment of that chemical parlour game we like to call "make it move" a French-Japanese team moves around droplets in the petri dish arena (Diguet et al. DOI). The droplet consists of oleic acid, the medium is water with dissolved in it a cationic photosensitive azobenzene trimethylammonium bromide surfactant. Illumination of the water surface with a precise wavelight (regular microscope) brings about a photochemical trans-cis isomerization of the azobenzene group resulting in a change in surface tension and hence autonomous motion - away from the illuminated area with light at 365nm and the reverse with light at 475 nm. By a two-color illumination setup the droplet can be moved around around at will, ideal for letter writing!

Novartis on Losartan

12 November 2009 - Patent literature

In the batch of latest patents (category C07 at espacenet.com) a novel method to synthesise tetrazoles by Novartis with some relevance to the production of the drug Losartan (EP2116548A1). Compared to the scientific literature where anything can be published and is published, a patent should be more relevant. A patent costs a lot of money to draw up and a scientific paper does not cost anything to have it published. As an added bonus, while the same scientific paper costs a lot of money to read (an expensive subscription to a scientific journal), the patent can be viewed for free.

The patent also has to really convince the patent office an invention is new (not known in the art) whereas with a scientific paper the peer-reviewers are fellow academic scientists and you can get away any variation that just was not tried before.

The Novartis patent in question is to the point: yes we know that tetrazoles can be made from nitriles and azides but ammonium azides are volatile with risk of explosion and organozinc azides are toxic with ecological concerns. So they have come up with dialkylboron and dialkylaluminium halides as an alternative which according to the claim has never been tried in cycloaddition with nitriles.

Diethyl aluminium chloride is reacted with sodium azide to (organic solvent soluble) diethylaluminium azide and this reagent reacts with a nitrile precursor to losartan. To keep the alcohol group preoccupied an excess of triethylaluminium is added first. The reaction is quenched with sodium nitrate , not reacting with the toluene solvent (another surprise according to the patent)

To be sure the patent also covers any tautomer of the tetrazole cycle as if you can isolate and sell them as unique compounds. Patent oddity.

The OCZnNNa cycle

05 November 2009 - Bimetallic bases

Breaking news in the field of chemistry dealing with otherwise unbreakable carbon-hydrogen bonds. The reaction: C-H activation, the substrate tetrahydrofuran (THF), the reagent: a so-called bimetallic base. Ordinary bases such as buLi can metallate the alpha hydrogen atom in THF but with subsequent ring-cleavage. Kennedy et al. now demonstrate that by adding a second metal to lithium and something else, lithiated THF can be stabilized or rather sedated (see title) (DOI).

Nitrogen cycle TMP is reacted with organosodium compound NaBu to TMPNa. The organozinc compound Zn(CH2SiMe3)2 is added next together with metal ligand TMEDA forming the actual reagent TMEDA(TMP)ZnR2. The molecular structure of the THF adduct contains a O-C-Zn-N-Na- cycle that looks odd and esoteric but makes sense. THF is stabilized by two metal chelating interactions (Zn-C and Na-O) and both metals in turn are stabilized by three nitrogen atoms. The complex is found to react predictably with common electrophile benzoyl chloride.



More bimetallic bases (Knochel base) in Grignards on lithium


Kennedy, A., Klett, J., Mulvey, R., & Wright, D. (2009). Synergic Sedation of Sensitive Anions: Alkali-Mediated Zincation of Cyclic Ethers and Ethene Science, 326 (5953), 706-708 DOI: 10.1126/science.1178165

The fate of adhumulone

02 November 2009 - Beer chemistry

Researchers at the Technical University of Munich and the University of Münster have identified several new chemicals in the complex brew we call beer (Intelmann et al. 2009 DOI). Adhumulone is one of several compounds present in hops and converts in a pinacol rearrangement to iso-adhumulone - a key bitter compound - as a cis and trans-isomer during beer processing. The bitter taste of beer (a quality) disappears over time - limiting shelf life - as the amount of trans humulones decreases (significantly the cis isomer is stable) and the German researchers now propose a new chemical pathway.

They purified a trans iso-adhumulone, stored an aqueous solution of it at pH 4 @ 40 °C for 6 days, separated the degradation products by reversed phase LC-MS and analysed components by NMR spectroscopy to arrive at a tricylocohumol as one of the main degradation products, the result of a Prins reaction. The researchers then went on to detect the compound in a sample of commercial aged beer and even found some time to establish bitter-taste threshold concentrations (poor volunteers) - still inconclusive as some tricycles are more bitter (but more harshly so) than their precursors.

Intelmann, D., Kummerlöwe, G., Haseleu, G., Desmer, N., Schulze, K., Fröhlich, R., Frank, O., Luy, B., & Hofmann, T. (2009). Structures of Storage-Induced Transformation Products of the Beer?s Bitter Principles, Revealed by Sophisticated NMR Spectroscopic and LC-MS Techniques Chemistry - A European Journal DOI: 10.1002/chem.200902058