REMP latest

29 September 2008 - metathesis

A recent addition to the ever growing family of olefin metathesis concepts is ring expansion metathesis polymerization or REMP for short. Discovered in 2002 in the Grubbs (who else) group (Bielawski et al. 2007 DOI), this polymerization requires a cyclic monomer cyclooctaene and a type of Hoveyda-Grubbs Catalyst fitted with a molecular tether. This tether makes sure that new monomer joins the ring and prevents ordinary linear polymerization.

The catalyst is regenerated in an intramolecular chain transfer step. The end result is a cyclic macromolecule and simply hydrogenation affords cyclic polyethylene. COD also does the trick (Bielawski et al. 2007 DOI) but a tenacious contaminant (4-vinylcyclohexene) spoils the fun by causing linear polymerization. The triene cyclododecatriene (CDT) can be obtained sufficiently pure to go cyclic all the way.

The catalyst itself was first prepared by the Fürstner group (Fürstner et al. 2001DOI) by metathesis of the ligands:

Cyclic polymers are nothing new but this particular method for making them is appealing. One tried and tested way is to have a suitable telechelic polymer to join ends but this requires extremely dilute conditions. Another method is back-biting in polycondensation reaction.

Cyclic polymers can have physical properties very different from their linear counterparts as they do not have interfering end-groups among other characteristics. In the case of cyclic polyethylene it is found thin films have a larger contact angle for water. Cyclic PE also melts at a higher temperature (attributed to lower entropic disorder) and in fact a mix of both tend to phase separate. Cyclic PE also has a lower hydrodynamic volume which can be deduced from simple SEC. The case of cyclic CDT is an illustration that cyclic polymers in general have lower viscosity as well.

The methodology has since then been employed with other monomers but not necessarily with a tethered Grubbs catalyst, again forcing dilute reaction conditions. It was used in the synthesis of a special type of salen ligand (Zheng et al. 2007 DOI) and it was investigated as alkane metathesis (Ahuja et al. 2008DOI) with cyclooctane (forming a wild bunch of products).

A study on cyclic polytetrahydrofuran (Tezuka et al. 2008DOI) synthesised from THF reveals a distinct spherulite pattern and a slow spherulite growth rate.

In a most recent contribution, the Grubbs group have spent some effort optimizing their tethered Ru catalyst ((Boydston et al. 2008DOI): saturate the NHC ligand and increase tether size.

Mercury(IV) shelved

26 September 2008 - updated 6 November

In a recent commentary in the Journal of Chemical Education (Link) W.B. Jensen questions certain claims made by Wang et al. in their 2007 publication on the detection of the elusive molecule mercury(IV) fluoride (DOI). Also in 2008 Rooms et al. report they were unable to repeat a similar feat (DOI). About time to shelve mercury(IV).

The Chemical & Engineering News had reported enthusiastically on the Wang publication (Link) and for a good reason. For HgF4 to exist, the mercury ion requires a +4 oxidation state with a breached d10 subshell configuration. This in turn means that mercury would move from the select group of post-transition metals to the group of transition metals the reason being simply that transition metals are defined as having partially filled d-subshells.

The Wang group did not isolate the compound but observed it indirectly. After irradiating a mixture of elemental fluorine and mercury in an neon matrix at 4 degrees Kelvin they found evidence for its existence by an specific IR absorption band that persisted all the way up to 12 K. In an argon matrix the IR band was especially weak but detectable up to 25 K.

Jensen now argues that given its surroundings , HgF4 is only kinetically stable and when given a chance would immediately react to form polymeric HgF2. In the new Hoffmann/Schleyer and Schaefer doctrine (see earlier post) the molecule would be fleeting at best but not viable.

Finally, JF Rooms was unable to find evidence for HgF4 in his argon matrix up to 10 K, a finding he presents as in agreement with the Wang result (which clearly it is not). Intriguingly although this group has apparently been searching for years for HgF4 in argon the article fails to explain why they did not switch to neon.

Update November 6: It is also curtains drawn for a mercury(III) compound postulated in 1976 by Deming et al (DOI), at least according to Hrobarik et al in 2008 (DOI). In silico evidence suggests oxidation of a Hg(cyclam)2+ species removes an electron not from mercury but from the cyclam ligand (until now assumed redox-innocent):

John F. Rooms, Antony V. Wilson, Ian Harvey, Adam J. Bridgeman, Nigel A. Young (2008). Mercury–fluorine interactions: a matrix isolation investigation of Hg⋯F2, HgF2 and HgF4 in argon matrices Physical Chemistry Chemical Physics, 10 (31) DOI: 10.1039/b805608k

Richard L. Deming, A. L. Allred, Alan R. Dahl, Albert W. Herlinger, Mark O. Kestner (1976). Tripositive mercury. Low temperature electrochemical oxidation of 1,4,8,11-tetraazacyclotetradecanemercury(II) tetrafluoroborate
Journal of the American Chemical Society, 98 (14), 4132-4137 DOI: 10.1021/ja00430a020

Organocatalytic Aldol latest

24 September 2008

Please store to memory: from now on an intramolecular Aldol reaction is called an aldolization or aldolisation if you insist on British English. A recent venture by the List group (DOI) combining aldolization with organocatalysis (see also the Hajos-Parrish reaction) produces both enantiomers of celery ketone with a epiquinine or quinidine based catalyst. Not necessarily new chemistry but altogether a nice display of symmetry. As in related carvone both enantiomers vary wildly in percieved smell.

The melamine milk scandal

21 September 2008 The chemistry - updated 3 Oct.

Making news headlines this week the 2008 baby milk scandal similarly themes as the 2007 pet food recalls and part of a larger topic of poor Chinese business practises. In this scandal, milk has been found to be deliberately spiked with the compound melamine as a result of which many infants have become ill and some even tragically died. Chinese farmers dilute milk they sell to processing plants for an additional profit and as milk is primarily tested for nitrogen content, the farmers make up for the loss of nitrogen by adding a very nitrogen-rich compound to the milk which is melamine.

The journalists are very brief on the chemical details but trying to get some chemical background information is not that easy and certainly the scientific literature is not very helpfull (my library does not exactly subscribe to such journals as journal of food protection or journal of diary science). So with the combined power of search engines, wikipedia and some educated guesses this is a milk / melamine update.

The nitrogen content of milk is made up of casein protein and whey protein both of which give the nutritional value. Non-protein nitrogen sources are ammonia, urea, creatine, creatinine, uric acid, orotic acid, peptides, hippuric acid and several amino acids. A typical milk sample will contain 87% water, true protein (TP) 3% , crude protein (CP) 3.10% and casein 2.6% link. These figures are surprisingly stable regardless of cow brand or cow nationality.

The melamine contamination scandal concerns both regular milk and milk powder. One liquid milk sample was found to contain 8.4 milligrams of melamine per kg Link. With a crude protein content of 3.1% per kilogram milk, it is theoretically possible to disguise up to 40% dilution with an added 3 gram of melamine which is also the maximum solubility of melamine in water.

The Kjeldahl method is very indiscriminate and simply tests for all nitrogen present. Crude protein (CP) is the Kjeldahl N multiplied by 6.38 and includes protein and non-protein sources. Apparently the Kjeldal method is is the only method used in Chinese quality labs and that's where all the trouble started. At least two methods exist that specifically target TP and not used by the Chinese: Udy dye colorimetry and infrared reflectance.

The Udy dye (Udy is the name of the company selling the method) (Link) is the
azo dye Acid Orange 12 and a close cousin of methyl orange which specifically binds to protein causing it to precipitate. The remaining azo dye is then determined by colorimetry. The website states the method will discriminate against any non-protein source but it would be interesting to examine if it interacts with melamine.

Another option is examination of melamine content directly, preferably by one cheap and simple method that can also be used those people affected the worst. A very old method published in 1954 is simple paper chromatography (J.E. Milks DOI (eluent BuOH/EtOH/water 4:1:1 staining with dimethylaminobenzaldehyde) but that method cannot be very sensitive. The US FDA has a protocol ased on GC-MS for the quantification of melamine, ammeline, ammelide and cyanuric Acid link. Other methods based exist based on LC-MS. On the other side of the technology spectrum (and lot easier to use than any MS technique), at least two companies supply tests based on enzyme-linked immunosorbent assay ELISA: Romer labs link and Abraxis link. All these methods have been developed in response of the pet food scandal but not necessarily optimized for milk. There is much ado about molecular sensors in the scientific literature but surprisingly melamine is not a target.

Even if Chinese milk quality control will eventually catch up with melamine the nagging question remains why the Chinese milk plants apparently did not simple test for water content of milk supplies coming into the plant. Measuring water content is easy and although drying out seems straightforward (as anyone who left pan of milk on the stove for too long a can attest to)
freezing point depression appears to be the preferred method Link . The addition of 10% water to milk will universally reduce the freezing point of the mixture from -0.510°C to 0.459°C. And even if the plant did not check water content in the laboratory beforehand the manager would be surprised to find much less milk powder production than he had bargained for.

Update (25 September 2008). Reuters report that poor quality cow feed (causing low nitrogen content) is at the heart of the problem (Link). Also cited local costs for testing for melamine in milk: 145 US dollars.
Correction: Changed calorimetry to colorimetry (many thanks to vigilant reader).
Correction: taking 3.1% crude protein and 3 g/L solubility it is possible to dilute up to 40% (again thanks to reader comment)

Water is the medium

15 September 2008 - Really?

In 2007 Donna Blackmond co-authored a critical article on the use of water as reaction solvent in organocatalysis (DOI). Generally hailed as a contribution to green chemistry, after all what can be more environmentally friendly than water, Blackmond argues that organic reactions carried out in water generally require a lot of organic solvent during work up just to isolate the organic product (extraction). Alternatives such as stripping require a lot of energy. The water residue in any case is contaminated by organics and cannot just be discharged to a waste-water treatment plant. Although the criticism was targeted specifically at organocatalysis it is also relevant for a lot of research conducted in water-mediated organic reactions in general. This research is available today in great abundance and it would be interesting to examine if the researchers have taken Blackmonds points to heart. Be prepared to be 50% disappointed.

The reports listed below are all recent, all carry the phrase "in water" somewhere in the title and all advocate the use of water as environmentally friendly. This does not imply homogeneous systems and should also not be confused with an on water reaction.

The workup procedure in a reported water-borne Hiyama coupling by Chen et al. (DOI) involves a non-quantified amount of organic hexane or ethyl acetate.

On the upside though the water-phase including the palladium can be recycled at least 4 times!.
Marqués-López et al (DOI) report on a Strecker reaction in water without any catalyst that does require ethyl acetate extraction.

Shen et al. (DOI) also present a Strecker reaction in water (published just days after the one above) this time catalysed by Indium(III) chloride:

The method also requires extraction (this time with a lot of diethyl ether) but luckily a solvent free reaction is thrown in to save the day.

Next up Teimouri et al. (DOI) in a Knoevenagel condensation / cycloaddition multicomponent reaction and no complaints here because the ultimate reaction product (a 1-amino furan) simply precipitates from the water medium:

except for one by Marqués-López, none of the reports listed above actually cite Blackmond when they could and should have. In that respect the Blackmond message has not yet sunk in.