N,N'-(1,2-Phenylene)-bis[4-(azidomethyl)benzamide]

Abstract

The synthesis of N,N''-(1,2-phenylene)-bis[4-(azidomethyl)benzamide] (2) by direct nucleophilic disubstitution of the suitable dihalogen precursor 1 with NaN3 is reported. The structure of the title compound was fully characterized by FT-IR, 1H NMR, 13C NMR, EI-MS, elemental analysis and melting point determination.

Full text

Molbank 2010, M707; doi:10.3390/M707
molbank
ISSN 1422-8599
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Short Note
N,N'-(1,2-Phenylene)-bis[4-(azidomethyl)benzamide]
Jürgen Bachl 1 and David D. Díaz 1,2,*
1 Institut für Organische Chemie, Universität Regensburg, Universitätsstr. 31, 93040 Regensburg,
Germany
2 ICMA, CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
* Author to whom correspondence should be addressed;
E-Mail: David.Diaz@chemie.uni-regensburg.de
Received: 8 October 2010 / Accepted: 16 November 2010 / Published: 18 November 2010
Abstract: The synthesis of N,N''-(1,2-phenylene)-bis[4-(azidomethyl)benzamide] (2) by
direct nucleophilic disubstitution of the suitable dihalogen precursor 1 with NaN3 is
reported. The structure of the title compound was fully characterized by FT-IR, 1H NMR,
13C NMR, EI-MS, elemental analysis and melting point determination.
Keywords: o-phenylenediamine; azide; benzamide; nucleophilic substitution
Organic azides (R-N3) are an important class of energy-rich and versatile intermediates for organic
synthesis [1] that have drawn great interest since the late 19th century [2]. They currently engage a key
interdisciplinary position at the interfaces between chemistry, biomedicine and materials science [3].
The industrial interest in these compounds derives from their use as precursors for the synthesis of
amines [3,4], nitrenes [5], heterocycles such as triazoles and tetrazoles [3,6], as latent amino groups in
the synthesis of natural products [3], as detonators [7], blowing agents for polymeric foams [3], and
functional groups in pharmaceuticals as illustrated by azidonucleosides in the AIDS treatment [8] and
their bioconjugation via Staudinger ligation [9]. Moreover, in the last decade organic azides have
emerged as a key component of the powerful ‘click’ chemistry [10]. In particular, polyvalent azides are
valued cross-linking agents and monomers in materials science [11,12].
Herein, we report the synthesis of N,N'-(1,2-phenylene)-bis[4-(azidomethyl)benzamide] (2). This
compound represents a versatile building block for the synthesis of a library of 3,1,5-
benzoxadiazepines with potential bioactivities that could lead to potential new drug candidates [13].
The preparation of 2 was carried out by double nucleophilic substitution of the suitable dihalogen
OPEN ACCESS

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precursor 1 with NaN3 in DMSO at 100 °C for 24 h (Scheme 1). Dihalogen precursor 1 was prepared
by double nucleophilic addition of o-phenylenediamine on 4-(chloromethyl)benzoyl chloride as
reported previously [14].
Scheme 1.
Experimental Section
General
1H and 13C NMR spectra were recorded at 25 °C on a Bruker Avance 300 spectrometer in CDCl3 as
solvent, and chemical shifts are reported relative to Me4Si (

= 0) [15]. The low-resolution mass
spectrum was obtained by using a Varian MAT 311A spectrometer. Elemental analysis was performed
on a Heraeus Mikro-Rapid analyzer. The infrared spectrum was recorded using a Diamond ATR
(attenuated total reflection) accessory (Golden Gate) on a Bio-Rad Excalibur FTS 3000 MX
spectrophotometer. The melting point (mp) was measured in a Büchi 510 and is uncorrected. Thin-
layer chromatography was carried out on Merck aluminium sheets coated with silica gel
60 F254. Compounds were visualized by use of 254 nm UV light and/or iodine as staining reagent. All
solvents were of p.a. grade or purified by standard techniques [16]. Anhydrous sodium sulfate was
used for drying solutions.
Safety Note
Although the title compound was found to be a stable solid (C/N = 2.75) at room temperature,
highly energy-rich organic azides (C/N < 1) should never be isolated and they should be stored away
from sources of heat, light, pressure, and shock. Azide-containing reaction mixtures should not be
concentrated through rotary evaporation or distillation.
Synthesis of N,N'-(1,2-phenylene)-bis[4-(azidomethyl)benzamide] (2)
To a 50 mL round-bottomed flask equipped with a stirring bar and condenser were added N,N'-(1,2-
phenylene)-bis[4-(chloromethyl)benzamide] (1) (500 mg, 1.21 mmol), sodium azide (236 mg,
3.63 mmol), and DMSO (10 mL). The mixture was heated at 100 °C for 24 h, cooled, and water
(30 mL) and brine (10 mL) were added. The mixture was extracted five times with EtOAc, and the
combined organic phases were washed with brine, dried (Na2SO4), filtered, and concentrated. The final

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traces of solvent were removed under vacuum to yield 2 (417 mg, 81%) as a white solid: TLC Rf
(AcOEt/hexane 1:1) 0.44; m.p. = 116–118 °C; 1H NMR (300 MHz, CDCl3) /ppm = 4.46 (s, 2H),
6.84–6.47 (m, 1H), 7.34–7.26 (m, 1H), 7.48 (d, J = 8.4 Hz, 2H), 8.04 (d, J = 8.3 Hz, 2H), 9.61 (s, 1H);
13C NMR (75 MHz, CDCl3) /ppm = 54.28, 125.88, 126.17, 128.29, 128.32, 130.58, 133.30, 139.68,
166.06; FT-IR (ATR) max (cm-1) 3225 (N-H stretching), 2086 (N3 asymmetric stretching), 1646 (C=O
stretching, amide I band), 1505 (N-H bending, amide II band), 1252 (N3 symmetric stretching); MS
(ESI) m/z 427 [MH+]. Elemental analysis calculated for C22H18N8O2: C, 61.96; H, 4.25; N, 26.28;
found: C, 62.09; H, 4.69; N, 26.89.
Acknowledgements
D.D.D. thanks the Alexander von Humboldt Foundation for a research fellowship for experienced
researchers.
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