Synthesis of 2-methyl-2-heaxanol

Abstract:
The preparation of 2-methyl-2-hexanol (40%) was carried out via the Grignard reaction between
butyl magnesium bromide and acetone in diethyl ether solvent media. Product was isolated from
reaction mixture two phase partitioning and fractional distillation, respectively.

Introduction:

The Grignard reactions dates as far back as 1900,where it was discovered by a French chemist
Victor Grignard2.The reaction initially entails making the Grignard reagent by reacting an alkyl
halide(1) with magnesium(2) to yield a organometallic compound(4) with a nucleophilic carbon.
Reaction is carried out under anhydrous conditions and in a ether solvent media which serves to
stabilise the Grignard reagent2, (scheme 1).

The organometallic compound is then reacted with a carbonyl compound (5) of choice to produce a
alcohol(6),scheme 2.

The importance of the Grignard reaction lies in that it allows one to easily synthesise
primary(7),secondary(8)and tertiary (9) alcohols from formyl aldehyde(10) ,aldehydes(11) and
ketones(12) in good yields(85-95%)2,(scheme 3)
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It virtually impossible to prepare Grignard reagents with compounds containing a acidic proton,
(i.e. compounds containing hydroxyl, amino, thiol and carboxyl groups) 2, as the Grignard reagent is
formed it then simply attacks the remaining acidic reagents. Grignard reagents are strong
necrophiles and Lewis bases so easily loose integrity in the presence of water (16) to form an alkane
(17), (scheme 4).

Grignard reagents have a wide variety of industrial applications which include synthesis of drugs
such as Naproxen® which is a antiinflammatory drug used for treatment of Gout, pain and fever3. ,

The aim of this experiment was to synthesise 2-methyl-2-hexanol (18) from reacting butyl
magnesium bromide (19) with acetone (18) under anhydrous conditions in a diethyl ether solvent.
The butyl magnesium bromide was prepared from magnesium (2) and 2-bromobutane (21),scheme
5.

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Preparation of 2-methl-2-hexanol (19) is a two step process,(scheme 6).First step entails preparing
the Grignard reagent, by reacting magnesium with 2-bromobutane leading to a polarity
inversion,(UPOLONG), and hence the production of a nucleophilic terminus carbon. Once the
Grignard has been prepare it is then reacted with its molar equivalent of acetone (20) to yield 2-
methyl-hexanol (19).

Results:

Preparation of butyl magnesium bromide

Reagents Used:
2-Bromo butane Magnesium
Volume (ml) : 10, 8 Mass (g) : 2,431
Density (g/ml) : 1,263 Molar mass (g/mol):24, 31
Molar mass (g/mol) :137, 02 Amount (mmol) :100
Amount (mmol) : 100
*Boiling temperature (oC) :101, 4

*correct at 760 torr

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Scheme 7 shows that 2-bromobutane reacts with magnesium in a 1:1 stoichiometric ratio, and hence
2-bromobutane is the limiting reagent in this reaction. The maximum amount of butyl magnesium
bromide that can be made is 100mmol.

% Yield was assumed to be 100% as all the magnesium was used up in the reaction.

Grignard reaction between butyl magnesium bromide and acetone

Butyl magnesium bromide Acetone

Molar mass (g/mol): 161, 33 Molar mass(g/mol): 58,08

Amount (mmol) : 100 Volume (ml) : 7,4
Mass (g) : 16, 1 Density (g/mol) : 0,79
Amount (mmol) : 100

Butyl magnesium bromide and acetone reacted in 1:1 stoichiometric ratio and so theoretical yield of
2-methyl-2-hexanol is 100mmol.

Yield = Actual amount of product synthesised / Theoretical amount expected x 100

= 40mmol/100mmol
= 40%

Discussion:

The preparation of 2-methyl-2-hexanol is a two step process using reagents 2-bromobutane,

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magensium and acetone. The initial step involved preparation of a nucleophilic butyl magnesium
bromide (19) from 2-bromobutane (21) and magnesium(2),scheme 9.The product (2-methyl-2-
hexanol) was obtained in a 40% yield and was found to be 145-155 C at a pressure of 57 torr, this
compares favourably with the literature1 value of 135-143 C.

Acetone (20) was added to the newly formed butyl magnesium bromide (19), the electrophonic
magnesium chelates with the electronegative oxygen whilst simultaneously the nucleophillic carbon
bonded to the magnesium attack the slightly positive acetone carbonyl carbon.This attack leads to
the formation of a unstable enol inermediate which is stabilised by the now positive MgBr (21).

Once the reaction has reached completion the reaction mixture is treated with (25% m/v) solution of
ammonium chloride (22). This serves two purposes,firstly it disturbs the enol-MgBr complex and
then it protonates the enol converying it into 2-methyl-2-hexanol (19).

Isolation of 2-methyl-2-hexanol
Once the product had been produced it was isolated from the reaction mixture by two phase
partionng and fractional distallation,respectively. Two phase partioning was carried out using a
seperatory funnel and extracting the organic componets of the mixture by washing with the reaction
solvent,(diethyl ether).After this the inorganic components of the ether mixture were removed by
washing the mixture with distilled water,10% (m/v) sodium carbonate solution and a saturated brine
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solution. Any remaining water in the resulting oraganic mixture was then removed by addition of
anhydrous magnesium sulfate.

Rotary vaporation removed excess diethyl ether solvent and other organic impurities.Fractional
distallation was then done at a pressure of 57 torres to isolate the 2-methyl-2-hexanol which boiled
off at a temeprature of 64-68 C.

The isolated product was at a very yield of 40%,which is not like the expected yield,this may be as
a result of the power failure that occurred whilst the experiment was in progress and so had to be
aborted due to lack of ventilation.This could have somehow affected the highly sensetive Grignard
reagent.

References:

1. L.M. Harwood and C.J Moody Instructors Manual to Accompany Experimental Organic
Chemistry, Principals and Practices. Blackwell scientific Publications.,1989.,447-449.

2. T.W. Solomons and C.B. Fryhle ,Organic Chemistry 8th Edition, John Wiley and
Sons,Danvers,2004,736-740

3. http://en.wikipedia.org/wiki/Ethylene _glycol

4. http://en.wikipedia.org