Preparation of N,N-Diethyl-meta-toluamide
Introduction:
The purpose of this lab is to synthesize N,N-diethyl-m-toluamide through a two step
process involving the preparation of m-toluoyl chloride by heating m-toluic acid with excess
thionyl chloride followed by treating the acid chloride with diethylamine in aquous sodium
hydroxide to yield N,N-diethyl-m-toluamide.
Amides are often prepared by treating carboxylic acid derivatives with a primary or
secondary amine. In this experiment, Acid Chloride is used as the “derivative”;
And it is treated with diethyl amine which via nucleophilic acyl substitution yields the
product, N,N-diethyl-m-toluamide;
Various methods are used to accomplish these three steps; preparation of the acid
chloride, synthesis of the nucleophile (diethylamine), and nucleophilic acyl substitution of the
acid chloride.
Preparation of the acid chloride will be done under reflux, diethylamine is then
added to the acid chloride via separatory addition and after the reaction is complete, column
chromatography will be used for purification.
Column chromatography is based on a principle of separating a mixture into its different
components between two phases. This is accomplished by the column having a stationary
phase (alumina) which is fixed in place and a mobile phase (hexane) which is a solvent and is
able to carry the different components through the stationary phase. The stationary phase acts
as a “brake” holding back specific components while other components elute more rapidly.
To then analyze the product in solution, H NMR spectrometry is used. An NMR
spectrometer is essentially a large magnet that generates a magnetic field that varies as the
nuclei change spin states, this is change is then converted into peaks on a graph. From these
peaks it is possible to identify fragments of the compound being analyzed by looking at the
splitting of signals, how downfield a signal is, determining its integration, and piece together all
fragments to yield an image of a product.
Physical Properties:
Discussion:
The purpose of this experiment is to synthesize N,N-Diethyl-meta-toluamide. Amides are
usually prepared by using a carboxylic acid derivative as a starting material, and treating this
carboxylic acid derivative with a secondary or primary amine;
Yielding an amide. This reaction is a nucleophilic acyl substitution reaction where with
amine acts as the nucleophile and attacks the carbonyl carbon to form the amide;
The first step in the experiment is the preparation of the Acid chloride to be used for
the reaction with diethylamine, m-Toluoyl Chloride. The first step in the synthesis of the acid
chloride is to ensure that all glassware is thoroughly dried to prevent unwanted side reactions.
The setup is for an addition under reflux where approximately 4.037g of m-toluic acid was
weighed out and placed into a reaction flask along with a stir bar. About 2.6 ml of thionyl
chloride was then added to this reaction flask and the mixture was then stirred gently under
reflux for 20 minutes. After refluxing the solution is then cooled in an ice bath.
The next step in the process is to form the nucleophile which is in this case diethylamine.
To accomplish this, approximately 47 ml of a 3.0M aqueous solution of Sodium Hydroxide was
placed into an Erlenmeyer flask and cooled in an ice bath. Diethylamine hydrochloride is easier
to handle and will not protonate easily which is why there is the chlorine. 2.767 g of diethylamine
hydrochloride was then weighed out and added to the Sodium Hydroxide in small portions
with stirring. With each addition to the NaOH solution, the amine salt is being converted into
diethylamine. 0.105 g of sodium lauryl sulfate is then added.
The final step in the reaction is the nucleophilic acyl substitution between diethylamine
and m-toluoyl chloride. The diethylamine previous prepared is transferred to the seperatory
addition funnel which is connected to the reaction vessel containing the m-toluoyl chloride. The
reaction begins once the diethylamine is added dropwise to the reaction vessel , the reaction
mixture is then heated using a steam bath to yield a precipitate.
Once the reaction is complete, the next step is separation. The reaction mixture is
transferred to a seperatory funnel and extracted with three 20 ml portions of diethyl ether, 30 ml
of HCL and then 30 ml of aqueous sodium chloride. This solution is then dried over anhydrous
magnesium sulfate and evaporated yielding the crude product.
Column chromatography is then used in this experiment to purify the crude product. To
accomplish this, a column is obtained, stuffed with a small amount of cotton, and then sand is
even placed over the cotton followed by alumina (stationary phase) and sand again. Hexane
(mobile phase) is then added to the column and eluted. Crude deet is added along with more
hexane. The first 10 ml of eluant is discarded and the following 30 to 40 ml is filtered. The
product is then evaporated and collected.
For analysis, the product was placed in an nmr tube and analyzed. The spectrum
showed the presence of key fragments such as the signal at roughly 7.2 ppm which is a signal
for benzene. Another fragment at 3.4 ppm indicates the presence of and sp3 alkyl halide which
is not the carbonyl fragment of the product but rather an impurity from a reactant. However the
signal from 2.30 coupled with the signal from 3.4 ppm can indicate the presence of the carbonyl
amide group. The signal at 1.20 ppm closely resembles the literature nmr of the diethylamine so
it is possible to conclude that this is in fact that particular fragment.
Conclusion:
The synthesis of N,N-Diethyl-meta-toluamide is a 2 step process where an acid chloride
is prepared, and then is treated with an amine and undergoes nucleophilic acyl substitution to
yield the desired product. To perform this reaction methods such as mixing and heating under
reflux, and column chromatography for purification are utilized. To then identify the compound in
solution, an H NMR analysis was performed and concluded the experiment.