Written By: Mark Redlich, Ph.D.

I want to take a break from the heady, cutting-edge content that we normally blog about and hopefully open up a little more to your input.  As you may or may not be aware, Sigma-Aldrich has recently released a series of solutions of commonly used lab reagents that in their neat form are generally not fun to handle – they’re difficult to weigh out, sticky, or noxious – our list of currently available solutions is below.  We are working on more solutions based on our own experience with difficult to handle reagents, but I thought it might be a good idea to see if you have any suggestions – think of this as a “Please Bother Us” ChemBlog.

So, are there any reagents that are frequently used in your lab, which are a pain to handle, but might be viable as a solution?

Currently available solutions:
436267 Di-tert-butyl dicarbonate, 1M in THF
703753 Di-tert-butyl dicarbonate, 2M in THF
703737 Di-tert-butyl dicarbonate, 2M in dichloromethane
703745 Di-tert-butyl dicarbonate, 2M in ethyl acetate
706442 (S)-(-)-a,a-Diphenyl-2-pyrrolidinemethanol trimethylsilyl ether, 0.05M in toluene
706450 (R)-(+)-a,a-Diphenyl-2-pyrrolidinemethanol trimethylsilyl ether, 0.05M in toluene
705284 1,1'-Carbonyldiimidazole, 0.4M in dichloromethane
704083 Triflic anhydride, 1M in dichloromethane
704091 Tributyltin hydride 1M in cyclohexane
291048 Iodine monochloride, 1M in dichloromethane
708496 Acetyl chloride, 1M in dichloromethane

Written by Dr. Sharbil J. Firsan

Raines and co-workers have prepared and investigated a series of phosphinothiols for their ability to mediate the traceless Staudinger ligation in water, and to be integrated with expressed protein ligation.  Of the three phophinothiols (1–3) that were tested, 1 and 2 gave disappointing results in good part due to their poor water solubility and the protonation of the nitrogen atom in their iminophosphorane intermediate in aqueous media.
Phosphinothiol 3 trihydrochloride is a water soluble, air-stable, odor-free, and easy-to-handle white solid, which mediates the rapid Staudinger ligation of equimolar amounts of azide and phosphine reagents in aqueous media at room temperature,  leading to >80% yields in solutions with pH ≥ 7.5.  It also undergoes transthioesterification with a thioester intermediate generated by recombinant DNA technology to produce a protein phosphinothioester that is poised to undergo the Staudinger ligation.

Tam, A.; Soellner, M. B.; Raines, R. T. J. Am. Chem. Soc. 2007, 129, 11421.

Written by: Dr. Sharbil J. Firsan

Myers and Raines have recently disclosed the “deimidogenation” of azides as a mild and convenient method for the synthesis of diazo compounds, which, while being versatile intermediates in organic synthesis, are a challenging class of compounds to prepare and isolate.  The current approach utilizes a phosphine-mediated conversion of azides into alkyl acyl triazenes in wet THF.  The triazenes then undergo a base-catalyzed fragmentation in situ to generate the diazo compounds in high yields, with phosphinyl-tethered primary amides as byproducts.

Myers, E. L.; Raines, R. T.  Angew. Chem., Int. Ed. 2009, 48, 2359.

While amide coupling is one of the most common reactions in organic synthesis, the development of methods that are general for all substrates is still warranted. In addition, preactivation of an acid is routinly required, either in situ or in a two-step process. Researchers at Pfizer developed a useful method utilizing sub-stoichiometric quantities of DBU in the mild conversion of alkyl cyanoacetates to the corresponding amides, which was proposed to proceed through a mechanism by which DBU behaves as a nucleophilic catalyst, activating the acid. The method is relatively general, generated the amidation product when a variety of amines and alkyl cyanoacetates were employed, and the only byproduct generated is the corresponding alcohol derived from the alkyl cyanoacetate.

Price, K.E.; Larrivee-Aboussafy, C.; Lillie, B. M.; McLaughlin, R. W.; Mustakis, J; Hettenbach, K.W.; Hawkins, J. M.; Vaidyanathan, R. Org. Lett. ASAP.