Otter
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Lucas' reagent mechanism
I just chlorinated isopropyl alcohol and distilled for myself a small quantity of isopropyl chloride, obviously I used Lucas' reagent, a solution of
ZnCl2 in aqueous HCl.
I've been trying to figure out the mechanism for this reaction (trawling the internet, looking in old notebooks), so I'd appreciate it if anyone could
verify what I'm thinking:
Zn2+ in HCl forms ligands with Cl- which are Zn 2+, ZnCl +, ZnCl2, ZnCl 3-, ZnCl4 2-. Ligands that haven't yet been saturated with chlorine bind to
the OH group on isopropyl alcohol to form something like Zn(Cl)n(OH) (2-n)-.
Cl- is supposed to do a SN1 substitution when the OH group is protonated by H+, making a H2O group whose pKa is quite large.
The effect of the Zn binding to the OH is to make the leaving group much more acidic, or a better leaving group. The acid is there to protonate this
leaving group. So this makes the reaction favor the SN2 mechanism more than SN1 or even the elimination reactions that might happen.
Am I right?
*Otter sniffs the puddle.*
*Licks a tiny bit of it up.*
*Pukes out dinner.*
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ThatchemistKid
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I always thought that the mechanism was something analogous to the blanc reaction
http://www.organic-chemistry.org/namedreactions/blanc-reacti...
but with protonation of the alcohol etc..as you suggested..
I think though it is an SN2 displacement not an SN1.
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byko3y
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There was almost no research on lucas reagent mechanism, so I'd say nobody knows exactly the mechanism of the reaction.
I've managed to find two articles:
A study of the Lucas test , J. Chem. Educ., 1991, 68 (8), p 704; doi: 10.1021/ed068p704
Ether Cleavage Re-Investigated. Elucidating the Mechanism of BBr3- Facilitated Demethylation of Aryl Methyl Ethers; Eur. J. Org. Chem., 2015, 34,
p. 7460-7467, download pdf
Briefly: raising amount of water in lucas reagent from 27% weight (made from 1 mole HCl 36% + 1 mole ZnCl2) to 36% leads to 40x slower positive test
with secondary alcohols; main nucleophile for ether cleavage with BBr3 is BBr4-, formed by taking bromide ion from
ether-BBrn complex.
There's a thread on this board about preparation of Lucas reagent "Easiest way to obtain Lucas Reagent?", and as you can see, ZnCl2 solution has ability to absorb HCl, as well as HCl-ZnCl2 solution readily absorbs
water (see "A Study of the Lucas Test").
Analogy with Blanc reaction is invalid. Why?
Synthesis and 5-HT2A Radioligand Receptor Binding Assays of DOMCl and DOMOM, Two Novel 5-HT2A Receptor Ligands
and
Blanc Chloromethylation - Comprehensive Organic Name Reactions and Reagents
Because Blanc reaction can be run without ZnCl2 with perfect yields of substituted benzyl chlorides, so the only role of ZnCl2 in this reaction is
Friedel-Crafts catalysis.
I'd say the mechanism of Lucas reagent reaction
- for primary alcohol is attack of ZnCl42- or ZnCl3-, as well as a simple Cl-, onto either ROH2+ or ROHZnCl+ (those
have similar properties and interconvert one into each other);
- for secondary alcohols also Sn1 reaction happens with water as leaving group and any form of chloride as nucleophile.
Lucas reagent made from 1:1 mole conc. HCl and ZnCl2 contains 3.5 moles of H2O, so water is always present in excess.
As you might know, one of the reasons why chloride is unreactive in protic solvent is shielding with hydrogen. Maybe something happens when water
content raises above 4 moles and chlorides become all completely shielded with water molecules.
By adding water actual speed of reaction is probably slowed by factor of 5-10, but excess of water leads to better solubility of alkyl halide, so much
more time is needed to see the positive result of the test.
There's a myth that HCl is present in undissociated form, that's why it is unreactive by itself. Obviously, pKa=-7 for HCl means it is completely
dissociated in water.
[Edited on 27-11-2015 by byko3y]
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