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It’s hard to look back and not wonder what we’ve lost.  Organic chemistry is not immune to fickle trends and fashion, and more than one darling of yesteryear lies forgotten in the dusty pages of Tet. Lett. [1].  While I’ve no desire to go back to preparing platonic solids, there’s a few tricks I feel happier to have up my sleeves.

1) Ethylene dibromide/1,2-Dibromoethane is a Grignard Entrainer/Initiator

Grignard reactions are notoriously finicky, which is why they are a standard feature in second-year organic chemistry labs.  The key lies in initiating the reactions.  Exposure to oxygen leaves a thin film of magnesium oxide on the surface of the metal, which weak bromides are unable to pierce.

Ethylene bromide is far stronger than your average electrophile, and will rapidly clear the magnesium oxide.  The product is ethylene gas, allowing both a clear sign that the grignard is proceeding and ensuring that no new grignard reagents are added to the system.

2) Toluenesulfonyl Chloride Purification (original unavailable)

TsCl is one of those chemicals that no organic lab will ever be without, in large part due to the fact that someone bought 250 g over a decade ago.  Unfortunately, by now what’s left in the bottle has at least partially decomposed to TsOH and HCl.

The cost of regenerating TsOH may be greater than a fresh bottle, but all is not lost.  Simply dissolve the entire bottle in about 2.5 mL chloroform per gram of material, then dilute five-fold in petroleum ether.  Filter off the resulting impurities, remove any fine impurities with activated carbon, and concentrate off the solvent.  The resulting “fine white crystals of analytically pure tosyl chloride, m.p. 67.5-68.5 [degC]” can go back in the bottle, while the TsOH collected during the first filtration can be kept elsewhere for future use.

2b) Potassium tert-Butoxide Purification

A reagent of 1001 uses, KOtBu rapidly hydrolyzes in air to form potassium hydroxide and butanol.  Unfortunately this process has no effect on the appearance of the off-white powder, and it can be almost impossible to tell if bottle has gone off.  While not mentioned in Fieser and Fieser [2], here’s a neat trick for purifying the mixture:

Dissolve the powder in a small amount of dry tetrahydrofuran.  While potassium t-butoxide has magnificent solubility in THF (25 g/100 mL, according to Fieser and Fieser), potassium hydroxide is so inert it can be used as a drying agent.  After filtration of the KOH the solvent can be removed under stringent anhydrous conditions (perhaps an Ar stream), or an aliquot can be mixed with water and titrated to determine the effective KOtBu concentration for a stock solution.

3) Sodium Azide and Iodine

Here’s a nice use for an old reagent.  Thiols and thioketones catalyze the reaction of sodium azide and iodine, and the liberated nitrogen can be used as a spot test to detect sulfur compounds.

4) Tetramethylguanidinium Azide

Nucleophilic substitution with sodium azide followed by palladium reduction is a beautiful way to convert alkyl halides to primary amines, but unfortunately sodium azide has very poor solubility in non-polar solvents.  The usual solution is to use dimethylformamide and/or water, but this reagent makes for a nice acetonitrile-soluble alternative [3].  The corresponding halide salt is insoluble in diethyl ether, and can be crashed out following completion of the reaction.

5) The DABCO-Bromine Complex

DABCO binds to bromine quite strongly, and the resulting DABCO-Bromine complexes are good oxidizing agents for the conversion of sulfides to sulfones.  Interestingly, this seems to have been rediscovered some 40 years later, with a recent publication in Tet. Lett. on alcohol oxidations.

6) Lithium Dimethylcuprate (Gilman’s Reagent)

I’m hesitant to call this reagent “forgotten”, but it is less well known than I would expect.  Effectively a soft carbanion, lithium alkyl cuprates replace good leaving groups with inversion of stereochemistry, convert acyl chlorides to the corresponding ketones, and add 1-4 to enones.  As an added bonus, these organocopper compounds will also reduce disubstituted alkynes to cis-alkenes.

7) Dimethylsulfoxide and Acetic Anhydride

This combination somewhat surprisingly converts secondary alcohols to ketones.

8) Zinc Dust and Dimethylformamide

Zinc causes rapid bromine elimination, converting alkyl bromides to alkenes.  This effect is so strong that it will even break aromaticity, converting o-xylene to a (rather unstable) tetraene.

Zinc Dust9) Formic Acid Cleaves Many Protecting Groups

The go-to conditions for cleavage of hindered acid-labile protecting groups is HCl in MeOH, but occasionally that just isn’t strong enough.  Pure formic acid has a bit more kick, and will remove carbamates and acetals (and presumably silyl ethers) much more readily.

10) The Vilsmeier Reagent (Dimethylformamide-Thionyl Chloride)

Ever wonder why chlorinating reactions work so well with a little DMF in the flask?  Thionyl chloride, oxalyl chloride, phosphorus pentachloride and phosgene all react with dimethylformamide to form a charged chloroforminium species through elimination of SO2.

Chloroforminium PreparationThis compound has been isolated (pdf), and is a (relatively) mild chlorinating reagent, reacting with alcohols and carboxylic acids to give alkyl chlorides and acyl chlorides, respectively.  It also formylates electron rich aromatic rings, via the Vilmeier-Haack reaction.


[1] Pre-Elsevier’s purchase, of course.

[2] Or Purification of Laboratory Chemicals, oddly enough.

[3] Fieser suggests chloroform as a solvent for the azide substitution reaction, which isn’t something I would ever recommend.

Edited to add schemes and Vilsmeier link.

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