Chemistry Reference
In-Depth Information
General procedure. Methyl 3,5-dimethoxybenzoate 1312 (R
¼
3,5-dimethoxyphenyl,
R
0
¼
Me) [1043]:
A mixture of 3,5-dimethoxybenzoic acid (3.32 g, 18.22 mmol)
and methanol (5.90 mL, 145.8 mmol), was cooled to
10
C in an ice-salt
bath. A solution of triphosgene (1.98 g, 20.00 mmol) in dichloromethane (5 mL)
was then added dropwise. The resulting mixture was warmed to 40
C and stirred
for 2 h. Excess solvent was then removed in vacuo, leaving a white residue. The
solid was neutralized with 5% aq. NaOH solution, and the two-phase system was
extracted with ethyl acetate (2
5to
50 mL). The combined organic phases were dried
(Na
2
SO
4
), and removal of the solvent under reduced pressure gave the product.
The crude solid consisted only of the pure ester.
4.5
Dehydration Reactions
This section differs from the preceding sections in that during the dehydration re-
action no part of phosgene is transferred to the reaction partner; in the other three
typical reactions of phosgene (chlorocarbonylation, carbonylation, chlorination),
parts of it are transferred to another molecule. Herein, the formal dehydration
product, a symmetrical acid anhydride, is not presented, since the true intermediate
in the phosgenation of a carboxylic acid is the acid chloride (having similar reac-
tivity). We prefer to classify the process as chlorination rather than a dehydration
by phosgene or phosgene equivalents. Reviews on dehydration reactions can be
found under the relevant functional groups, such as cyanides, isocyanides, and
carbodiimides. A general overview on dehydration reactions in the context of mild
chemical methods is given in [1044].
4.5.1
Cyanides
The preparation of cyanides by dehydration is best accomplished from aldoximes
(standard method) rather than from carboxamides, because the former require
milder reaction conditions. However, carboxamides, as carboxylic acid derivatives,
are more easily accessible. Phosgene has been applied in the dehydration of car-
boxamides rather than of aldoximes.
Dehydration of carboxamides 1377, for example with phosgene, can be envis-
aged as involving nucleophilic attack of the electron-rich carbonyl function of the
carboxamide group on the strongly activated carbonyl function of phosgene form-
ing an azaanhydride of chlorocarbonic acid 1378. This high-energy species then sta-
bilizes by decomposition, driven by the good leaving group ability of the chloride
anion and by the formation of the low-energy, small, stable molecule CO
2
, thereby
affording cyanides 1379.
An analogous mechanism can be given for the dehydration of aldoximes 1380
with phosgene.
