The Lucas Test

One of the reducing agents I used on a project last year (lithium tert-butoxyaluminohydride) was a hot reagent in the 1950’s and 60’s.  Before I left for grad school, I was gifted a whole bunch of mid-20^th century organic chemistry reference books.  I took a little time this weekend to peruse the work of our forefathers (that sounds incredibly hokey) in order to supplement the beginning stages of the construction of my dissertation.

Anyhow, I came across some interesting “named” chemistry that I’d never practically encountered: Lucas’ reagent.  Prior to the advent of TLC, qualitative analysis of reaction progress was typically accomplished by aliquot “testing.”  Think of this concept as the red cabbage experiment people (kids, in my case) do to determine acidity/basicity of common household chemicals (check out this video; he actually tests the acidity of salsa at 5:35 min).

Lucas’ reagent is simply ZnCl₂ in concentrated HCl, and it’s used to differentiate between primary, secondary or tertiary alcohols via S_N1 mechanism.  I’ve seen differences in the mechanistic details, but I imagine that the ZnCl₂ plays the critical role of cleaving the C-O bond by attaching to the oxygen.  With the carbocation exposed, the Cl^- in solution will form the new C-Cl bond (which is insoluble and turns the solution cloudy).  Keep in mind that carbocation stability is the driving force for this reaction.  Thus, tertiary alcohols form the precipitate almost immediately whereas it may take secondary alcohols a few minutes to behave (anywhere from 2-7 min).  As you might expect, the primary alcohols are more-or-less unreactive in this type of analysis.

There have been instances of improving the conditions of the Lucas test to get faster results (typically in identifying secondary alcohols).  Most notably, researchers at Albemarle patented a process whereby bubbling anhydrous HCl through an aqueous solution of ZnCl₂ containing menthol gave much faster results than the conventional Lucas test (US Patent # 5856597, WIPO Publication #: WO/1998/049100). 

Hope everyone’s having a great week thus far!

P.S. the chemical responsible for the qualitative color change in the red cabbage experiment is cyanidin or, more specifically, cyanidin-3-glucoside (C3G).  It’s recently been shown that C3G scavenges hydroxide and superoxide radicals (J. Biol. Chem. 2006, 281, 17359-17368) and thus is believed to be chemopreventative and chemotherapeutic in terms of cancer therapy.  But, since this is a chemistry-based blog, I’ll stray from the biology/biochemistry. 

Below is the general idea of the acid-base equilibrium for a generic cyanidin (the principle is still the same).  The middle structure is the compound you’d essentially get from an aqueous extraction of red cabbage.  Introducing an acid causes formation of an oxonium ion (balanced by an anion, of course), which causes the formation of a red color.  Removal of a proton from the neural species (i.e. in basic media) forms the “anhydrobase,” which (electronically) takes on a blue color. 

There’s an interesting experiment involving rose leaf extracts and pH: here