Enough of the blog-syn bashing. See Arr Oh, I think this is a fantastic website and you and your colleagues are doing an excellent service to the synthetic community by not only scutinizing these reactions, but also in teaching students how to conduct research (and how reactions are really run – no I am not going to freshly prepare/purify my IBX(or insert any other finicky reagent) for every reaction. If that is the only way to get your procedure to work then its not really that useful.
Can’t wait for the next post!!
I guess the onus is on YOU to explain how you can’t reproduce a reaction that others already have. Perhaps you should write to the german group in the Org. Lett. and ask them too how they were able to reproduce Nicolaou’s reaction.
Perhaps it is an impurity in the IBX that is doing it? The procedure that uses catalytic IBX to do benzylic oxidation uses Oxone as the stoichiometric oxidant so why don’t you try adding a little Oxone to your reaction. Maybe you’ll actually solve a problem and add something useful to the literature with your little anonymous blog instead of casting doubt with a weekend of work on reactions that are already working in other people’s hands.
josef: The dangerous step in the preparation of Dess-Martin is the acylation step. Making IBX is super easy and safe using the oxone prep.
Solid IBX decomposes violently when heated, so when doing this reaction on a reasonable scale, make sure your stirring is really efficient (mechanical if need be), and carefully monitor the reaction temperature. Of course, make sure there’s a shield between you and the reaction.
There’s nothing tedious about any of it… it just poses a very substantial safety risk.
@3 Observer: My bet would be on bromide/bromate impurities from the old IBX prep using KBrO3 as oxidant. Br radical is a perfectly able agent for this transformation. (Heating aryl bromides in DMSO produces aldehydes.)
Well I’ve used IBX for making an enone and it saved the day. I’ve seen Evans, Jacobsen, Corey, and dozens of other groups use it in total synthesis.
Given that there is a report of someone using this to do benzylic oxidation it seems like an issue of IBX quality.
The epoxides of several polycyclic aromatic hydrocarbons have been prepared by the use of a large excess of oxidant in a biphasic Oxone-ketone system under neutral conditions, as shown for the oxidation of phenanthrene (eq 11). However, the use of isolated dioxirane solutions is more efficient for the synthesis of reactive epoxides, since hydrolysis of the product is avoided., A number of unstable epoxides of various types have been produced in a similar manner, as discussed for and .
Finally, Oxone is the stoichiometric oxidant in interesting modifications of the widely studied metal porphyrin oxidations, where it has obvious advantages over some of the other oxidants commonly used. The potential of this method is illustrated by the epoxidation reaction in eq 13. In this conversion, only 1.4 mol % of the robust catalyst
Equally remarkable is the epoxidation of the methylenecyclopropane derivatives indicated in eq 8, given the propensity of the products to rearrange to the isomeric cyclobutanones.The epoxidation of conjugated double bonds also proceeds smoothly with the Oxone-acetone system, as illustrated by eq 9. The conversion of water-insoluble enones can be accomplished with this method using CHCl as a cosolvent and a quaternary ammonium salt as a phase-transfer catalyst.
For example, aqueous Oxone selectively oxidizes sulfides to sulfones even in highly functionalized molecules, as illustrated in eq 22. Sulfones can also be prepared by a convenient two-phase system consisting of a mixture of solid Oxone, clay, and a solution of the sulfide in an inert solvent.The partial oxidation of sulfides to sulfoxides has been accomplished in a few cases by careful control of the reaction stoichiometry and conditions. A biphasic procedure for sulfoxide formation from diaryl sulfides is shown in eq 23. However, a more attractive and versatile procedure uses a solid Oxone-wet alumina reagent with a solution of the sulfide. This method permits control of the reaction to form either the sulfoxide or the sulfone simply by adjusting the amount of oxidant and the reaction temperature, as illustrated in eq 24.
Rapidly stirred heterogeneous mixtures of liquid alkenes and aqueous Oxone solutions buffered with NaHCO also produce epoxides, as shown in eq 6.An in situ method for epoxidations with dimethyldioxirane using buffered aqueous acetone solutions of Oxone has been widely applied. The epoxidation of 1-dodecene is particularly impressive in view of the difficulty generally encountered in the epoxidation of relatively unreactive terminal alkenes (eq 7). A biphasic procedure using benzene as a cosolvent and a phase-transfer agent was utilized in this case.
There are some fantastic reagents out there, some scare the hell out of me, others are scary and cool at the same time. I once made about 20g of solid vinyl-lithium (very flammable in air), that was a lot of fun but I did not for one second lose my respect for it
There was a accident in my lab recently caused by someone who used a procedure that they hadn’t been taught. It could’ve been very seriously (ie. death) but they got away with minor cuts.
It got me thinking about not only reagents but also procedures which can be more dangerous than their individual components.
I was wondering if anyone knows any good websites that contains real world information on how to use dangerous reagents and teaching for procedures.
Dylan’s tenderbutton blog has listed some great procedures (ie. the large scale LiAlH4 rxn) but there should be some others.
Back in the 1960-70s when I was a young chemist in the lab, the oldtimers bemoaned the increasing emphasis on lab safety and all these worries about carcinogens etc. Mind you, being still young and immortal, we were still able to be standing at the hood with a burning cigarette hanging from our lips and shaking the sep funnel while we did the ether extractions. Carbon tet or benzene?…available in half-gallon glass bottles in every lab.
The dangers of dimethyl sulfate were known, fortunately, although this didn’t stop me from using bottles of it although always in the hood and with gloves on my hands. Speaking of alkylating agents, one of my favorites was triethyloxonium tetrafluoroborate (one of the Meerwein salts), made by the reaction of (gasp!) epichlorohydrin, ether, and BF3 etherate in a nice dry glove bag (see for details). Unrelated, but one that still causes me to think about its effects on my body, was all the work I did making and using chromyl chloride.
All of the lab exposure we had pales by comparison with the dangers that many plant workers in the chemical process industry were exposed to.