Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 1419–1420
Rapid Communication
Synthesis of N-sugar-substituted phthalimides and their
derivatives from sugar azides and phthalic anhydride
Su-Na Zhang, Zhong-Jun Li* and Meng-Shen Cai
Department of Chemical Biology, School of Pharmaceutical Sciences, National Laboratory of Natural and Biomimetic Drugs,
Peking University, Beijing 100083, China
Received 23 February 2004; accepted 30 March 2004
Abstract—N-Sugar-substituted phthalimides and tetrachlorophthalimide derivatives can be prepared in good yields under essen-
tially neutral conditions. Mixing a sugar azide, NaI, Me3SiCl, phthalic or substituted phthalic anhydride and tetrabutylammonium
iodide as catalyst in acetonitrile at rt or 60 °C, afforded 12 imides in 83–95% yields.
Ó 2004 Elsevier Ltd. All rights reserved.
Keywords: One-pot synthesis; Sugar azide; Phthalic anhydride; Phthalimides and their derivatives
The phthaloyl and tetrachlorophthaloyl groups are
common protecting groups for amines in organic syn-
thesis1 and are also important pharmacophores.2 Com-
mon methods for imide synthesis include dehydrative
condensation of an anhydride and amine at high tem-
perature,3 the acid-catalyzed cyclization of N-substi-
tuted amic acids4 and direct N-alkylation under
Mitsunobu conditions.5 The condensation of imino-
phosphoranes with phthaloyl dichloride, followed by
alkaline hydrolysis also affords phthalimides.6 Garcia
et al.7 have reported on condensation of iminophos-
phoranes with phthalic anhydride to give N-substituted
phthalimides. However, most of these routes have
problems when applied to a range of derivatives, espe-
cially when utilized to synthesize sugar imide deriva-
tives, where strongly basic or acidic conditions are often
unacceptable. An efficient and mild general synthetic
approach of sugar imides is thus desirable.
anhydride with a sugar azide and chlorotrimethylsilane–
sodium iodide in acetonitrile at room temperature or
at 60 °C to provide the corresponding sugar phthalimide
or tetrachlorophthalimide derivatives in high yields
(Fig. 1).
Typical procedure. To a solution of the sugar azide
(10 mmol) and anhydride (15 mmol) in dry MeCN
(150 mL), NaI (30 mmol) and Bu4NþIÀ (1 mmol) are
added and this solution is stirred at room temperature.
A solution of Me3SiCl (15 mmol) in dry MeCN (40 mL)
is then added dropwise under N2. The reaction is
monitored by TLC [petroleum (60–90 °C)–acetone], and
on completion of the reaction the mixture is taken up in
ether (100 mL), the solution washed with Na2S2O3, dried
(Na2SO4) and evaporated. The crude product is purified
by column chromatography [petroleum (60–90 °C)–
acetone] to afford a pure white solid product. The results
are summarized in Table 1.
Kamal and co-workers8;9 recently reported that the
reaction of an anhydride with an azide, with ‘in situ’
reduction through condensation with Me3SiCl–NaI,
gives the corresponding imide derivatives. Here, we
report a similar method, involving reaction of an
X
X
O
O
X
X
X
X
Me3SiCl, NaI
CH3CN, Bu4N+I-
rt or 60 oC
Sugar
N
Sugar-N3
O
+
O
O
X
X
X = H, Cl
X = H, Cl
Figure 1. Synthesis of N-sugar-substituted phthalimides from a sugar
azide and phthalic anhydride.
* Corresponding author. Tel.: +86-10-8280-1504; fax: +86-10-6236-
0008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.03.032
Zhang, Su-Na
