Notizen
132
Indeed, we found that under catalysis by CuBr and
KI, such a nucleophilic substitution proceeds in
DMF or propylene carbonate at 130 °C, but not in
other solvents often used for such reactions (HMPA,
DMPU, DMSO, N-methylpyrrolidone, tetramethyl-
urea, sulfolane, acetonitrile, 2-methylpyridine).
However, the conversions halide azide gave only low
yields (about 20%, even in the presence of large ex-
cesses of NaN3), as observed in similar cases [5]. In
addition, the separation of product and starting
material turned out to be very difficult. This method
was therefore abandoned.
Another approach uses benzotriazole as precur-
sor. A facile ring opening of 1-nitrobenzotriazole
with secondary amines, leading to imino-diazoben-
zene derivatives, has been reported [6]. As these
reactions proceed via diazonium cations, we tried the
reaction of substituted benzotriazoles with NaN3. On
mixing 1-nitrobenzotriazole and NaN3in the ratio 1:1
in ethanol at room temperature, a gentle evolution of
N2 occurs, indicating the formation of 2-azido-
nitroaniline salt:
A Practical Synthesis
of 2-Azidophenylisocyanide
Taha El-Shihi and Rudolf Herrmann*
Organisch-Chemisches Institut
der Technischen Universität München,
Lichtenbergstraße 4, D-8046 Garching, W-Germany
Z. Naturforsch. 41b, 132-133 (1986):
received August 14, 1985
2-Azidoaniline, Hofmann Degradation,
2-Azidophenylisocyanide, /3-Lactams
2-Azidophenylisocyanide is useful for the syn-
thesis of /3-lactams by four-component-condensa-
tion. Its preparation by various methods is com-
pared. The synthesis starting with 2-aminobenzoic
acid via Hofmann degradation of 2-aminobenz-
amide is the method of choice.
The four-component-condensation of a carbonyl
compound with a /3-amino acid and an isocyanide is a
method of high synthetic potential for the prepara-
tion of /3-Iactam antibiotics [1]. However, a carbon-
amide group is formed at the site where a carboxylic
acid is found in most /3-lactam antibiotics. The
cleavability of the amide group under conditions
which do not affect the /3-lactam, is therefore essen-
tial for applications of this technique.
Special isocyanides have been developed [2, 3]
which allow the amide/acid conversion via o-hy-
droxy or o-amino anilides under very mild condi-
tions. Among other isocyanides, 2-azidophenylisocy-
anide is a highly promising candidate [2]. Up to
now, it has been prepared via 2-azidoaniline using a
six-step procedure starting with 2-nitroaniline [2, 4].
The overall yield varies and does generally not ex-
ceed 16%.
CH0
Na
X = NH2
NHCHO
We therefore sought for a more viable synthesis of
this compound.
Schema 2
The most straigthforward approach is the nucleo-
philic replacement of a halogene by azide in a suit-
able precursor (e.g. 2-bromoformanilide), followed
by dehydration.
The presence of a azido group is confirmed by IR.
However, it was not possible to transform the nitro-
amino group to the free amine or the formamide.
1-Formylbenzotriazole, which would directly yield
2-azidoformanilide, does not react at all with NaN3.
Obviously, a formyl group is not sufficiently electron
withdrawing to promote the ring opening.
Finally, we checked the least expensive precursor,
2-aminobenzoic acid (anthranilic acid). Diazotation
and treatment with NaN3 gives 2-azidobenzoic acid
in 84% yield. This acid is converted via mixed an-
hydride to its amide which —without isolation — is
treated with aqueous NaOBr. The product of a nor-
mal Hofmann degradation, 2-azidoaniline, is isolated
in 45-49% yield. Formylation by mixed formic acid/
Schema
1
* Reprint requests to Dr. R. Herrmann.
Verlag der Zeitschrift für Naturforschung, D-7400 Tübingen
0340 - 5087/86/0100 - 0132/S 01.00/0
Unauthenticated
Download Date | 4/17/17 1:23 PM
El-Shihi
