Shahsavari-Fard & Sardarian
General Procedure for the Reaction in Solvent
(Method A)
corresponding nitriles was conducted in toluene as solvent and
in solvent-free conditions (Scheme 1).
For each reaction, the amide (1 mmol) and toluene (1 ml)
According to the mechanism proposed in Scheme 1,
primary amide (1) is in equilibrium with imidic acid (2) which
could react with diethyl chlorophosphate to form the
corresponding diethyl phosphate (3). Then the intermediate
releases diethyl hydrogen phosphoric acid to produce nitriles
subsequently. As it is shown in Table 1, good to excellent
yields were obtained over dehydration of amides to nitriles in
toluene as solvent (method A); however, the yields of alkyl
amides were lower than those of aryl amides. All the nitriles
were separated from the reaction mixture by neutralization of
the produced acid, (EtO)2PO(OH), with aqueous solution of
sodium hydroxide (5%) followed by extraction with ether.
Evaporation of ether and column chromatography produced
the pure nitriles. The nitriles could also be purified by a short
column without neutralization of the produced acid.
Additionally, we studied the effect of solvent-free
conditions (method B) on the formation of nitriles from the
corresponding primary amides. The results are shown in Table
1. It appears that by omitting the solvent there is a slight
improvement in the yields of the reactions; however, there is
no noticeable effect on the rate of the reactions.
We compared our findings with a recently reported
protocol [19], where ethyl dichlorophosphate was used as a
dehydrating agent, whose results are shown in Table 2.
According to these data, although the yields are comparable,
diethyl chlorophosphate has several striking economical and
environmental advantages over ethyl dichlorophosphate: a)
cheaper reagent, b) less moisture sensitive, c) shorter reaction
time, d) no use of toxic solvents such as CH2Cl2, c) using just
stoichiometric ratio of amid to dehydrating agent (1:1), and e)
no need to use base.
was charged into a 5 ml double-necked round-bottom flask
equipped with a magnetic stirrer and condenser. The mixture
was heated to reflux and diethyl chlorophosphate (1 mmol)
was added. The reaction was heated for 5-20 min and then the
reaction mixture was cooled to room temperature. The crude
mixture was neutralized by 10 ml aqueous solution of sodium
hydroxide (5%) and was extracted by diethyl ether (2 × 10
ml). Drying the combined ethereal layer by anhydrous sodium
sulphate and then filtration and evaporation of the solvent
gave the crude product, which was purified by short column of
silica gel with n-hexane and ethyl acetate (9:1-1:1) to give the
pure product.
General Procedure for the Solvent-Free Condition
(Method B)
For each reaction, the amide (1 mmol) was charged into a
5 ml double-necked round-bottom flask equipped with a
magnetic stirrer and condenser. Then the mixture was heated
at 120 °C and diethyl chlorophosphate (1 mmol) was added.
The reaction was heated for 5-25 min and then the reaction
mixture was cooled to room temperature. The mixture was
extracted by diethyl ether (2 ×10 ml). The combined ethereal
layer was allowed to dry by anhydrous sodium sulphate and
then filtration and evaporation of the solvent gave the crude
product, which was purified by short column of silica gel with
n-hexane and ethyl acetate (9:1-1:1) to give the pure product.
RESULTS AND DISCUSSION
Dehydration of a series of aryl and alkyl amides to the
PO(OEt)2
O
O
OH
(EtO)2POCl
- HCl
R
C
N
R
NH2
R
NH
R
NH
4
1
2
3
R= alkyl, aryl
Scheme 1
205
Shahsavari-Fard
