Chemistry Reference
In-Depth Information
found that pMZ-amino acids could be prepared directly from a number of amino
acids and p-methoxybenzyl chloroformate under the conditions of the Schotten-
Baumann reaction [388-390].
O
COCl
2
base
OH
O
l
MeO
MeO
544
545
R
O
R
H
2
NCOOH
O
H
COOH
NaOH, THF
0-5°C
MeO
546
Typical procedure. p-Methoxybenzyl carbamates of amino acids 546 [388]: The reagent
545 was prepared as follows: a solution of anisyl alcohol (12.4 mL, 0.1 mol) in dry
diethyl ether (100 mL) was added to a solution of phosgene (for a safe source, see
Chapter 7) (21 mL, 0.3 mol) in dry diethyl ether (100 mL) over a period of 10 min.
Then, a solution of dimethylaniline (12.7 mL, 0.1 mol) in dry diethyl ether (100
mL) was added dropwise over a period of 1 h and the resulting mixture was stirred
for 2 h at
5
C. After removal of the salt formed in the reaction by filtra-
tion, the filtrate was concentrated under reduced pressure below 0
C to leave an
oily residue. Twice more, dry diethyl ether (100 mL) was added and evaporation
was repeated to remove excess phosgene. The residue was immediately dissolved
in tetrahydrofuran (70 mL) to give a solution ready for use in the next reaction.
The solution of the chloroformate 545 was added in small portions over a period
of 10 min to a solution of the amino acid (0.05 mol) in 1 n sodium hydroxide (200
mL) (l-glutamic acid: 1.5 n sodium hydroxide) containing tetrahydrofuran (40 mL)
with vigorous stirring at 0-5
C. Stirring was continued for 2 h; then, the reaction
mixture was washed with diethyl ether (100 mL) and acidified by the addition of
solid citric acid. The product was extracted with ethyl acetate (500 mL). This layer
was washed with water, dried over anhydrous sodium sulfate, and concentrated in
vacuo; the residue, which was then crystallized from ethyl acetate/petroleum ether.
If the product did not crystallize at this stage, the residue was neutralized with a
calculated amount of dicyclohexylamine in diethyl ether and the pMZ-amino acid
was crystallized as the dicyclohexylammonium salt.
A simple method for o-azaxylylene synthesis by base-induced elimination of hy-
drogen chloride from carbamate derivatives (for example, 548), prepared with
phosgene, has been reported. These intermediates are readily trapped by p-
electron-rich alkenes, for example 549, to form hydroquinoline derivatives, 550
[391].
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