Chemistry Reference
In-Depth Information
in dry dioxane or THF (freshly distilled from Na or Na/K benzophenone) (50 mL).
1,8-Bis(dimethylamino)naphthalene (Proton Sponge
TM
; one equivalent per equiva-
lent of carboxylic acid) was then added to the homogeneous acid solution and the
resulting mixture was stirred for 15-30 min at room temperature. If necessary, the
mixture was warmed to 50
C to aid dissolution. DPPA (one equivalent per equiv-
alent of Proton Sponge
TM
) was then added by means of a syringe. The mixture was
gradually heated to reflux temperature and kept under reflux for 6 h. It was then
allowed to cool to room temperature, before storing at
2
C overnight to precipi-
tate the ammonium phosphate salt. The cold mixture was quickly frit-filtered,
washing with anhydrous diethyl ether or diethyl ether/ethyl acetate (1:1, v/v). The
filtrate was then partly concentrated and the residual liquid was vacuum distilled
(short-path Vigreux column distillation apparatus, 0.20 mmHg) to yield the iso-
cyanate product as a clear, colorless liquid, which was characterized by IR,
1
H
NMR, and
13
C NMR.
This method allows the preparation of aromatic and aliphatic monoisocyanates
in moderate yields and with very high purities. Of the di- and tricarboxylic acids
evaluated, only hexamethylene diisocyanate was successfully synthesized.
4.3.1.3
Alkyl and Alkenyl Isocyanates
Phosgene as carbonylation reagent
Methyl 2-isocyanato-3-phenylpropenoate 365 is obtained in 68% yield by perrhenate-
catalyzed decomposition of methyl 2-azido-3-phenylpropionate 364 in the presence
of phosgene [257]. This reaction resulted in a higher yield compared to the same
reaction employing diphosgene (instead of phosgene), which afforded the product
in just 53% yield [257].
COCl
2
[NaReO
4
]
hydroquinone
EtOAc, 80°C
N
3
CO
2
Me
OCN
CO
2
Me
- N
2
, - HCl
364
68 %
365
Typical procedure. Methyl 2-isocyanato-3-phenylpropenoate 365 [257]:
At 80
C, phos-
gene (for a safe source, see Chapter 7) was passed into a solution of ammonium
perrhenate (1 mol%) in ethyl acetate (10 mL) saturated with HCl, until the solution
was saturated. A solution of 364 (4.1 g, 20.0 mmol) and hydrochinone (50 mg) in
ethyl acetate (10 mL) was then added dropwise, while the mixture was cooled to
65
C. More phosgene was then passed in, until reaction was complete (monitored
by IR spectroscopy). The mixture was filtered at room temperature, the filtrate was
concentrated, and the residue was distilled in vacuo to afford 2.77 g (68%) of 365.
Author's remark: Note! Excess phosgene has to be passed into a vessel filled with
ethanol to make it harmless, and thereby HCl gas is evolved (see Chapter 7).
