Selective Reduction of an Aromatic Nitro Group to an Azoxy Unit in the Presence of an Aliphatic Nitro Group

Article abstract of DOI:10.1007/s00706-002-0549-9

Chemoselective reduction of 1-nitro-2-(2-nitro-2-methylpropyl)-benzene to 2,2′-di-(2-nitro-2-methylpropyl)-azoxybenzene was achieved with sodium borohydride in methanol in the presence of substoichiometric amounts of bismuth, whereas reduction with zinc in hydrochloric acid gave a mixture of the latter, 1-amino-2-(2-amino-2-methylpropyl)-benzene, and 3,3-dimethyl-3,4- dihydrocinnoline, and showed poor reproducibility. The crystal structure of the azoxybenzene was determined by single-crystal X-ray diffraction.

Full text of DOI:10.1007/s00706-002-0549-9

Monatshefte f€ur Chemie 134, 419–423 (2003)
DOI 10.1007/s00706-002-0549-9
Selective Reduction of an Aromatic
Nitro Group to an Azoxy Unit
in the Presence of an Aliphatic
Nitro Group
ꢀ
Ulrich Siemeling , Thomas Tu¨rk, Udo Vorfeld, and Heinrich Fink
Department of Physics, University of Kassel, D-34109 Kassel, Germany
Received August 26, 2002; accepted September 2, 2002
Published online February 3, 2003 # Springer-Verlag 2003
Summary. Chemoselective reduction of 1-nitro-2-(2-nitro-2-methylpropyl)-benzene to 2,20-di-(2-
nitro-2-methylpropyl)-azoxybenzene was achieved with sodium borohydride in methanol in the pres-
ence of substoichiometric amounts of bismuth, whereas reduction with zinc in hydrochloric acid gave
a mixture of the latter, 1-amino-2-(2-amino-2-methylpropyl)-benzene, and 3,3-dimethyl-3,4-dihydro-
cinnoline, and showed poor reproducibility. The crystal structure of the azoxybenzene was determined
by single-crystal X-ray diffraction.
Keywords. Azoxybenzene; Bismuth; Nitro compounds; Reductions; X-Ray structure determination.
Introduction
Aromatic azoxy compounds are of great current interest because of their phy-
siological activities and their use in liquid crystal systems [1]. The most
convenient method for their synthesis is the reduction of nitroarenes [1, 2]. How-
ever, this may also lead to hydroxylamines, hydrazines, azoarenes, and,
eventually, to anilines [3]. Not surprisingly, therefore, only very few methods
have been reported for the selective reduction of nitroarenes to azoxy com-
pounds [4]. The problem of chemoselectivity is further exacerbated by the
presence of functional groups which must remain intact during the reduction.
The most promising method appears to be the catalytic reduction with sodium
borohydride in the presence of bismuth which has been shown to tolerate ester
and nitrile functionalities [4]. A particularly challenging case is the selective
reduction of a nitroarene containing an aliphatic nitro group. We here report the
first example of such a transformation.
ꢀ
Corresponding author. E-mail: siemeling@uni-kassel.de

420
U. Siemeling et al.
Results and Discussion
1-Nitro-2-(2-nitro-2-methylpropyl)-benzene (1) [5] was reduced unselectively
with zinc in hydrochloric acid. The three products isolated were the aniline
Scheme 1. Synthesis of 2–4
Fig. 1. Molecular structure of 4 (non-centrosymmetric molecule). Selected bond lengths (pm) and
angles (ꢁ): N(1)–C(8) 154.4(2), N(2)–C(1) 143.7(2), N(3)–C(11) 143.7(2), N(4)–C(18) 153.7(2);
N(2)–N(3)–O(5) 127.85(14), N(2)–N(3)–C(11) 115.75(13), C(11)–N(3)–O(5) 116.13(14), C(1)–
N(2)–N(3) 116.52(14)

Selective Reduction of an Aromatic Nitro Group
421
2 [6], the cinnoline derivative 3 [7], and the desired azoxy compound 4
(Scheme 1). The reaction proved to be somewhat temperamental, giving vary-
ing yields of these compounds. Such poor reproducibility is not unusual for
heterogeneous reactions. The best result obtained with respect to the azoxy
species 4 was 12% of 2, 28% of 3 and 56% of 4. Tedious work-up involving
distillation and chromatography was necessary for separating this product mix-
ture. In contrast to this, reduction of 1 according to the protocol by Ren et al.
[7] (sodium borohydride in the presence of substoichiometric amounts of bis-
muth powder in methanol) gave 4 in 70% yield after simple recrystallisation
(Scheme 1).
The identity of the product was confirmed by a single-crystal X-ray structure
analysis. 4 adopts the (Z)-configuration (Fig. 1).
Two individual molecules are present whose bond parameters are almost iden-
tical. The asymmetric unit contains 1.5 molecules. Structural parameters are un-
exceptional and compare well to those obtained for related species such as
azoxybenzene [8] and 4,40-azoxydianisole [9]. The N–N distance is 126.9(2)
and 128.4(3) pm corresponding to a double bond. The azoxy N–O distance has
a value of 126.05(18) and 126.4(3) pm, which is slightly, but significantly, longer
than the N–O distances of the nitro groups which range from 121.99(19) to
122.48(19) pm.
Experimental
1
NMR: Bruker Avance DRX 500 (500.13 MHz, H, ext. TMS 125.04MHz, 13C, ext. TMS). MS: VG
Autospec (70 eV). Elemental analyses agreed favourably with the calculated values.
1-Amino-2-(2-amino-2-methylpropyl)-benzene (2), 3,3-Dimethyl-3,4-dihydrocinnoline
(3, C10H16N2) and 2,20-Di-(2-nitro-2-methylpropyl)-azoxybenzene (4, C20H24N4O5)
by Reduction of 1-Nitro-2-(2-nitro-2-methylpropyl)-benzene (1, C10H12N2O4)
with Zinc in Hydrochloric Acid
A mixture of 40cm3 6 N hydrochloric acid, 2.0 g 1 [5] (8.92 mmol) and 8.0 g Zn powder (122 mmol)
was heated to reflux for 1 h. The mixture was allowed to cool to room temperature. Undissolved Zn
was removed by decanting and washed with 20cm3 of water. After alkalisation by addition to an
excess of 2 N NaOH solution the mixture was extracted with 3Â 40 cm3 of diethyl ether. The combined
extracts were dried with Na2CO3. The solvent was removed in vacuo. 1-Amino-2-(2-amino-2-methyl-
propyl)-benzene (2) and 3,3-dimethyl-3,4-dihydrocinnoline (3) were distilled off at 0.1 Pa at a bath
temperature of 60ꢁC. The distillate was separated chromatographically using a silica gel column:
417 mg of 2 (28%) was eluted with CH2Cl2 and 165mg of 3 (12%) with ethyl acetate. Recrystallisation
of the distillation residue from ethanol afforded 2.01g of 4 (56%). In other runs the yield of 4 varied
and was as low as 10%.
2: The compounds was characterised by comparison with an authentic sample prepared by the
established route [6].
3: 1H NMR (CDCl3): ꢀ ¼ 1.33 (s, 6H, 2 Me), 2.51 (s, 2H, CH2), 7.04 (d, 1H, J ¼ 7.5 Hz, CH), 7.35
(t, 1H, J ¼ 7.5 Hz, CH), 7.42 (t, 1H, J ¼ 7.5 Hz, CH), 7.94 (d, 1H, J ¼ 7.5 Hz, CH) ppm; 13C NMR
(CDCl3): ꢀ ¼ 24.7 (Me), 31.9 (CH2), 60.4 (CMe2), 121.8 (ring C), 127.9 (ring C), 128.0 (ring C), 128.8
(ring C), 131.4 (ring C), 141.2 (ring C) ppm; EI-MS: m=z (%) ¼ 160 [Mþ ] (11), 132 [Mþ –N2] (40),
117 [Mþ –N2–Me].

422
U. Siemeling et al.
1
4: H NMR (CDCl3): ꢀ ¼ 1.51 (s, 6H, 2 Me), 1.53 (s, 6H, 2 Me), 3.42 (s, 2H, CH2), 3.63 (s, 2H,
CH2), 7.18 À 7.22 (m, 2H, 2 CH), 7.31 À 7.34 (m, 1H, CH), 7.38 À 7.44 (m, 3H, 3 CH), 7.66 À 7.86
(m, 1H, CH), 8.39 À 8.41 (m, 1H, CH) ppm; 13C NMR (CDCl3): ꢀ ¼ 25.5 (Me), 25.6 (Me), 40.6 (CH2),
41.3 (CH2), 88.7 (CMe2), 121.7 (ring C), 124.2 (ring C), 127.8 (ring C), 128.4 (ring C), 128.6 (ring C),
129.5 (ring C), 130.5 (ring C), 131.4 (ring C), 131.9 (ring C), 132.5 (ring C), 142.6 (ring C), 149.8
(ring C) ppm; CI-MS: m=z (%) ¼ 401 [Mþ þ 1] (2), 354 [Mþ –NO2].
2,20-Di(2-nitro-2-methylpropyl)azoxybenzene (4) by Reduction
of 1-Nitro-2-(2-nitro-2-methylpropyl)benzene (1) with Sodium Borohydride
in the Presence of Bismuth
1 [5] (1.12 g, 5.00mmol) was dissolved in 20cm3 of methanol under Ar. The stirred solution was cooled
to 0ꢁC with an ice bath. Bismuth powder (522mg, 2.50 mmol) was added, followed by 567 mg of
sodium borohydride (15.2 mmol). After 0.5h at room temperature the mixture was filtered. A small
amount of NaOH was added and stirring was continued for 4 h at room temperature in the air. Ice-cold
1 M HCl (100 cm3) was added and the mixture was stirred for 0.5 h. Crude 4 separated as a yellow solid
which was filtered off with suction, washed with water, dried in vacuo and recrystallised from methanol.
Yield 701 mg (70%). Spectroscopic data were identical to those described above. Single crystals for an
X-ray crystal structure determination were obtained by slow evaporation of a methanol solution.
X-Ray Crystallography
The crystal structure of 4 was determined at 100 K using a STOE IPDS II diffractometer with graphite-
˚
monochromated Mo-Kꢁ radiation (ꢂ ¼ 0.71073 A). Details of the structure determination are collected
in Table 1. Additional material to the structure determination can be obtained from the Cambridge
Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ (UK), Tel.: (þ 44)
1223=336-408, Fax: ( þ 44) 1223=336-033, E-mail: deposit@ccdc.cam.ac.uk, World Wide Web: http:==
www.ccdc.cam.ac.uk, referring to the deposition number CSD 192454. Atomic scattering factors were
taken from standard sources [10]. The program package used was SHELXL 97 [11].
Table 1. Crystal data and structure refinement parameters for 4
Formula
C20H24N4O5
400.43
Formula weight
Crystal system
Monoclinic
P21=n
Space group
a=nm
b=nm
1.55325(14)
1.24842(7)
1.63609(15)
111.059(6)
2.9607(4)
6
c=nm
ꢃ=ꢁ
V=nm3
Z
ꢄ=mmÀ 1
0.098
Crystal size=mm
Reflections collected=unique
R(int)
0.45Â0.35Â0.15
22329=6348
0.0447
Goodness-of-fit on F2
R1a [I>2ꢅ(I)], wR2b
P
0.977
0.0431, 0.1148
P
0:5
P
P
2
2
a
b
R1 ¼ kFoj À jFc k= jFoj; wR2 ¼ f ½wðFo2 À Fc2Þ Š= ½wðFo2Þ Šg

Selective Reduction of an Aromatic Nitro Group
423
Acknowledgments
This work was financially supported by the Fonds der Chemischen Industrie. J. Sandrock is thanked for
preparative support.
References
[1] Kabalka GW, Varma RS (1991) Reduction of Nitro and Nitroso Compounds. In: Trost BM,
Fleming I (eds) Comprehensive Organic Synthesis, vol 8, Pergamon, Oxford, p 363
[2] Lang-Fuhrmann S, Pawlenko S (1992) Diazen-N-oxide (Azoxy-Verbindungen). In: Klamann D
(ed) Methoden der organischen Chemie (Houben-Weyl), Bd E16d, Organische Stickstoff-
Verbindungen IV, Teil I, Thieme, Stuttgart, p 119
[3] Smith MB, March J (2001) March’s advanced organic chemistry, 5th ed, Wiley, New York
[4] Ren P, Pan S, Dong T, Wu S (1996) Synth Commun 26: 3903, and references cited therein
[5] Clark, JH, Miller JM, So K-H (1978) J Chem Soc, Perkin I: 941
€
[6] Siemeling U, Turk T, Schoeller WW, Redshaw C, Gibson VC (1998) Inorg Chem 37: 4738
[7] This compound has been previously prepared by a different route; however, spectroscopic data
have been unavailable: Wang SF, Mathew L, Warkentin J (1988) J Am Chem Soc 110: 7235
[8] Tsuji T, Takashima H, Takeuchi H, Egawa T, Konaka S (2000) J Mol Struct 554: 203
[9] Chebli C, Brisse F (1995) Acta Crystallogr C51: 1164
[10] Ibers JA, Hamilton WC (eds) (1974) International Tables for X-ray Crystallography, vol IV,
Kynoch Press, Birmingham
€
[11] Sheldrick GM (1997) SHELXL 97, University of Gottingen, Germany