Chemistry Reference
In-Depth Information
tion of phosgene, the mixture was stirred at room temperature for 45 min, heated
to the boiling point, and filtered under slightly reduced pressure while still hot.
The triethylamine hydrochloride cake was washed on the filter with warm (60
C)
benzene (3
25 mL). The combined filtrate and washings were transferred to a
500-mL round-bottomed flask and concentrated to dryness in a rotary evaporator at
low temperature and pressure. The dry residue was gently boiled with anhydrous
benzene (75 mL), and the mixture was again filtered while still hot. The triethyl-
amine hydrochloride cake was washed with cold benzene (2
5 mL), and the
combined filtrate and washings were left to stand at 20
C for 2-3 h. The crystal-
line product was collected on a filter, washed with cold anhydrous benzene (2
4
mL), and dried in vacuo. The yield of nicotinic anhydride 1371, mp 122-125
C,
was 6.25 g (68%). The combined filtrate and washings were concentrated to dry-
ness in a rotary evaporator. The residue was gently boiled with 175 mL of a mixture
of benzene and cyclohexane (2:3), and a small amount of insoluble material was
removed by filtration of the hot mixture. The filtrate was stored at 5
C for 18 h;
the crystalline deposit obtained was collected, washed with 3 mL of a cold benzene/
cyclohexane mixture, and dried in vacuo. An additional 2.4 g (25%) of colorless
product; mp 122-123
C, was thus obtained. The total yield of nicotinic anhydride
1371 was 8.05-8.65 g (87-93%).
The formation of symmetric anhydrides from the corresponding carboxylic acids
and triphosgene has also been reported [1042].
O
O
O
O
O
(CCl
3
O)
2
CO
NEt
3
R
O
Cl
Et
3
NH
+
Cl
+
R
H
R
O
R
O
1373
RO
t
3
1374
1372
The triethylamine salt of a carboxylic acid, prepared by the reaction of triethyl-
amine and a carboxylic acid 1372, undergoes reaction with one-sixth of an equiva-
lent of triphosgene to give an equimolar mixture of the carboxylate and the pre-
dicted intermediate acyl chloroformate 1373 [1042]. Nucleophilic displacement of
the chloroformate function by the carboxylate affords the desired anhydride 1374,
with concomitant formation of triethylammonium chloride as a precipitate and
carbon dioxide gas. The reaction reaches completion in minutes. The solvents of
choice have been THF or ethyl acetate, and no evidence for the formation of diacyl
carbonates as potential by-products of the reaction has been found. The reaction
has been used to prepare the anhydrides from both electron-rich and electron-
deficient carboxylic acids (see below) [1042].
This triphosgene-mediated reaction for the synthesis of anhydrides has a num-
ber of advantages over the existing methods, in that the reaction is carried out un-
der neutral conditions and does not use highly toxic or allergenic (as with carbo-
diimides) reagents. Furthermore, no elaborate apparatus is needed for this one-pot
reaction, which proceeds conveniently to completion in minutes at ice-water tem-
perature.
