A novel one-pot method for reductive conversion of azides to acyl amines with acetic anhydride and trimethyl chlorosilane

Article abstract of DOI:10.1055/s-1999-2673

A combination of acetic anhydride and chloro-trimethylsilane has been shown to effect the conversion of a variety of azides to the corresponding acetylated amines in excellent yields without affecting other functional groups such as ether, ester, halide etc.

Full text of DOI:10.1055/s-1999-2673

LETTER
553
A Novel One-pot Method for Reductive Conversion of Azides to Acyl Amines
with Acetic Anhydride and Trimethyl Chlorosilane
Apurba Barua, Ghanashyam Bez, Nabin C. Barua*
Natural Products Chemistry Division, Regional Research Laboratory, Jorhat-785006, Assam, India
Fax +91-(0376) 321158
Received 26 February 1999
action, the temperature of the reaction mixture was
Abstract : A combination of acetic anhydride and chloro-trimeth-
brought down to RT, quenched with cold water and ex-
ylsilane has been shown to effect the conversion of a variety of
tracted with dichloromethane. The dried extract on evap-
oration left a residue which was purified by preparative
TLC or by crystallization.
azides to the corresponding acetylated amines in excellent yields
without affecting other functional groups such as ether, ester, halide
etc.
Key words: azide, acyl amines, trimethyl chlorosilane, acetic anhy-
dride
It is evident from Table-1 that the methyl ether group in 2
and the ethyl ester function in 5 remained unaffected.
However, the phenolic hydroxyl group in 3 is converted
into its acetate. It is interesting to note that treatment of
anisyl azide with ClTMS and trifluoroacetic anhydride
gave trifluoroacetyl m-anisidine in 82% yield.
The reduction of azides to amines is of immense impor-
tance in organic synthesis as a general protocol for intro-
duction of an amino group and quite a number of excellent
methods are reported in the literature for bringing about
this transformation.1 Equally important is the protection
of amines as acetyl or other acyl derivatives albeit there
are only a few literature procedures2 for converting azides
directly to amides. Recently, Kotsuki et al.3 reported a
chemoselective procedure for conversion of azides to N-
(tert-butoxy carbonyl)amines in one step using Et3SiH
and di-tert-butyl dicarbonate in the presence of a catalytic
amount of 20% Degassa Pd(OH)2/C with moderate to ex-
cellent yields.
Table 1. Reductive acylation of azides to acyl amines with CITMS/
Ac2O.
We earlier reported that the combination of acetic anhy-
dride and chlorotrimethylsilane is an excellent reagent
system for cleaving a variety of methyl and methylthio-
methyl ethers to the corresponding acetates both in ali-
phatic and aromatic series.4 The same reagent system has
also been shown to be effective for converting a variety of
ketones into their corresponding enol acetates in good
yields.5 The naked acylonium ion, which is believed to be
formed on mixing acetic anhydride with chlorotrimethyl-
silane might be the reacting species in these transforma-
tions. We have recently observed that when azides are
treated with this reagent under reflux the corresponding
amides are formed in excellent yields. This observation
has been generalised through entries 1-14 in Table 1.
aAll the azides were prepared by following standard literature proce-
1
dures and characterised by IR, H NMR and MS before performing
the reactions. bAll the acyl amines were characterised by IR, 1H NMR,
MS and by direct comparison with authentic materials. cYields refers
to yields of pure isolated products.
Typical Procedure:
To a stirred solution of the azide (1 equiv) in a minimum
amount of acetic anhydride is added chlorotrimetylsilane
(1 equiv.). The reaction was refluxed for 0.5-1 hr while
monitoring the reaction on TLC. On completion of the re-
Synlett 1999, No. 5, 553–554 ISSN 0936-5214 © Thieme Stuttgart · New York

554
A. Barua et al.
LETTER
As for the mechanism of reaction no definit statement can
be made as yet. However, the most plausible mechanism
might involve initial attack of acylonium ion to electron
rich nitrogen atom of the azide with concomitant chloride
ion assisted nitrogen gas elimination and protonation from
the HCl associated with ClTMS to give the product as
shown in the following mechanism.
References and Notes
(1) a)Scrivens, E.F.V.; Turnbull, K. Chem.Rev.,1988, 88, 297 and
references cited therein. b) Samano, M.C.; Rabins, M.J.;
Tetrahedron Lett., 1991, 32, 6293 c) Poopeiko, N. E.; Protica,
T. I. and Mikhailopulo, I.A.; Synlett, 1991,342. d) Ranu, B.C.;
Sarkar, A.and Chakrabarty, R; J. Org. Chem.,1994, 59, 4114.
e) Corey, E.J.; Nicolaou, K.C.; Balanson, R.D.; Machida, Y.;
Synthesis, 1975, 590. f) Kirk, D.N.; Wilson, M.A.; J. Chem.
Soc. Chem.Commun., 1970, 64 g) Konodo,T.; Nakai, H.;
Goto, T.; Tetrahedron, 1973, 29, 1801. h) Rolla,E.; J. Org.
Chem., 1982, 47, 4327.
(2) a) Rosen, T.; Lico, I. M. and Chu, D.T.W.; J. Org. Chem.,
1988,1580. b) Garcia, J.; Urpi, F.and Vilarrasa, Tetrahedron
Lett., 1984, 25, 4841.
(3) Kotsuki, H; Ohishi, T and Araki, T. Tetrahedron Lett., 1997,
38, 2129.
(4) Barua, N C; Sharma, R P and Baruah, J N Tetrahedron Lett.,
1983, 24, 1189.
(5) Chowdhury, P K and Sharma, R P, Baruah, J N Tetrahedron
Lett.,1983, 24, 3383.
Thus we have demonstrated a straight forward one pot
procedure for conversion of azides to their corresponding
acylated amines in excellent yields in a easy-to-carryout
procedure.
Article Identifier:
1437-2096,E;1999,0,05,0553,0554,ftx,en;L02699ST.pdf
Acknowledgement
Authors are grateful to Director, RRL Jorhat for providing
facilities for this work. GB is grateful to CSIR for Senor
Resrarch Fellowship (SRF).
Synlett 1999, No. 5, 553–554 ISSN 0936-5214 © Thieme Stuttgart · New York