Sciencemadness Discussion Board

Chlorobutanol assay mechanism i do not know

ANDLOS - 13-3-2010 at 11:13

I want to ask about the chemistry of this reaction for chlorobutanol assay

chlorobutanol +sodium hydroxide gives

2-hydroxy-2-methylpropanoic acid
i want to know the mechanism of this reaction

and the name of this reaction

smuv - 13-3-2010 at 12:11

It is a simple SN2 reaction where hydroxide displaces chloride. I am sure there is no formal name to it.

mech.gif - 5kB

ANDLOS - 13-3-2010 at 13:11

Thanks alot

Nicodem - 13-3-2010 at 14:56

ANDLOS, members here are not clairvoyant to read your mind, so make sure to be more precise. First of all, there are three stable isomers of chlorobutanol and then there is a pharmaceutical compound with the trivial name of "chlorobutanol" (a misnomer for 1,1,1-trichloro-2-methyl-2-propanol). Secondly, you need to provide the reference from which you got this. What do you think, that people are going to do a literature search just because you are too lazy to write down the reference? Well, I did search the literature and could only find one study on the reaction of Me2C(OH)CCl2Br and Me2C(OH)CBr2Cl with hydroxides and carbonates. So, provide the reference as discussion in its absence is fruitless!

Smuv, the reaction can not be an SN2 substitution like that because the sterics definitively prohibit the SN2 transition state. You can see that the steric hindrance is even worse than in neopentyl halides and these are the absolute borderline for SN2. In such a molecule only an intramolecular nucleophilic substitution could be possible, thus forming a dichloroepoxide intermediate (steps in the Corey-Link and the Bargellini reactions include this transformation). This should hydrolyse to alpha-hydroxyisobutyric acid trough ring opening by hydroxide, chloride elimination and hydrolysis. Yet, the CA abstract bellow claims alpha-halo-acids as products for two related systems, so things may not be that simple (for one thing, these can not form if the mechanism would be the SN2 depicted above). We'll see once ANDLOS cites a reference describing this reaction.
Quote:
The reaction of trihalo-tert-butanols with bases in ether and in aqueous and alcoholic media.
Saghatelyan, Sh. A.; Nalyan, M. V.; Sahakyan, L. A.; Shakhbatyan, A. L.
Khimicheskii Zhurnal Armenii, 53 (2000) 99-104.

CA 134: 41908

The reaction of Me2C(OH)X2Y (I; X = Br, Y = Cl; X = Cl, Y = Br) at -15 in ether in the presence of powd. potassium hydroxide results in the formation of mixed .alpha.-bromo- and .alpha.-chloroisobutyric acids in 1:1 and 1:3 molar ratios, resp., while I (X = Y = Br) is converted to .alpha.-bromoisobutyric acid. In aq. alk. medium at room temp. haloform cleavage takes place. In aq. potassium carbonate upon heating or in aq. potassium hydroxide at -5 gem-dibromochloro-tert-butanol is converted to a mixt. of .alpha.-chloro- and .alpha.-hydroxybutyric acids while I (X = Y = Br) is converted to .alpha.-hydroxyisobutyric acid. In alc. potassium hydroxide and potassium carbonate the trihalo-tert-butanols are converted to .alpha.-ethoxyisobutyric acid (50%), methacrylic acid (10-15%), and polymeric products.


[Edited on 14/3/2010 by Nicodem]