Chemistry Reference
In-Depth Information
formate is used, the reaction time is decreased to ca. 5 h and the yield is increased to
90-95%.
Organic acid chlorides have been prepared with diphosgene in the presence of
DMF as a catalyst [1017].
Typical procedure. Octanoyl chloride [1017]:
Diphosgene (108.8 g) was added to a
mixture of octanoic acid (144.2 g) and DMF (1.5 L) at 70
C. The mixture was left
to stand for 1 h, and then nitrogen was bubbled through it for 30 min at 100
Cto
give 96.9% of octanoyl chloride (purity 99.99%). Benzoyl chloride and terephthaloyl
chloride were similarly prepared.
4.4.2.4
Triphosgene
Alkyl vinyl ethers have been converted into acid chlorides with triphosgene or di-
phosgene [1018].
m-Toluic acid 1344 has been converted into m-toluyl chloride 1345 with triphos-
gene [1019]. Triphosgene offers several advantages over thionyl chloride, giving
a cleaner reaction without the formation of SO
2
or dark-colored impurities. The
synthesis is the first stage in the preparation of N,N-diethyl-m-toluamide (Deet)
1346, the active ingredient in many commercial insect repellents.
H
3
C
COOH
H
3
C
COCl
(CCl
3
O)
2
CO
DMF, CH
2
Cl
2
1344
1345
H
3
C
CONEt
2
2 HNEt
2
+
H
2
NEt
2
Cl
0 °C
1346
Typical procedure. m-Toluyl chloride 1345 with triphosgene [1019]:
A micro-reflux
condenser, a CaCl
2
drying tube, a micro-Claisen head, and a 3-mL conical vial
containing a spin vane were oven-dried. They were then left to cool to room tem-
perature in a desiccator. The vial was charged with pure m-toluic acid (136 mg, 1.00
mmol) and dichloromethane (0.50 mL) and the mixture was stirred until the solid
had dissolved. To this solution were added triphosgene (100 mg, 0.34 mmol) and
one drop of dry dimethylformamide. The vial was fitted with the Claisen head. The
opening above the vial was capped and the condenser (fitted with the drying tube)
was attached at the other opening. A piece of Tygon tubing was used to connect the
drying tube to a small, inverted glass funnel placed just under the surface of a 10%
NaOH solution in a beaker to neutralize the HCl generated during the preparation
of m-toluyl chloride. The solution was heated to reflux in a sand bath for 1 h.
Bubbles of CO
2
and HCl could be observed in the gas trap shortly after the reaction
had begun. The acid chloride was not isolated, but was reacted in situ with diethyl-
amine to give N,N-diethyl-m-toluamide (Deet) in an average overall yield of 51%.
