Reaction of N-Nitro-benzotriazole with nucleophiles

Article abstract of DOI:10.1080/00397910903353754

N-Nitro-benzotriazole 1 reacts with various C-nucleophiles 2 in tetrahydrofuran at room temperature to afford o-nitramidophenylazo-compounds 3a-f and o-nitramidophenyl hydrazones 3g-l, respectively. Reaction of 1 with sodium azide in aqueous acetonitrile gives a reactive 2-azidophenylnitramide intermediate 4 which is trapped by Cu-catalyzed 1,3-dipolar cycloadition with phenyl acetylene to afford 1-o-nitramidophenyl-4-phenyl-1,2,3-triazole 5. Reaction of 1 with trimethylsilylcyanide affords 3-amino-benzo[e][1,2,4]triazine 6. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903353754

This article was downloaded by: [North Carolina State University]
On: 19 April 2013, At: 22:54
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Reaction of N-Nitro-benzotriazole with
Nucleophiles
Moritz Uhde a & Thomas Ziegler a
a Institute of Organic Chemistry, University of Tuebingen, Tuebingen,
Germany
Version of record first published: 13 Sep 2010.
To cite this article: Moritz Uhde & Thomas Ziegler (2010): Reaction of N-Nitro-benzotriazole with
Nucleophiles, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 40:20, 3046-3057
To link to this article: http://dx.doi.org/10.1080/00397910903353754
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 40: 3046–3057, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903353754
REACTION OF N-NITRO-BENZOTRIAZOLE
WITH NUCLEOPHILES
Moritz Uhde and Thomas Ziegler
Institute of Organic Chemistry, University of Tuebingen, Tuebingen, Germany
N-Nitro-benzotriazole 1 reacts with various C-nucleophiles 2 in tetrahydrofuran at room
temperature to afford o-nitramidophenylazo-compounds 3a–f and o-nitramidophenyl hydra-
zones 3g–l, respectively. Reaction of 1 with sodium azide in aqueous acetonitrile gives
a reactive 2-azidophenylnitramide intermediate 4 which is trapped by Cu-catalyzed
1,3-dipolar cycloadition with phenyl acetylene to afford 1-o-nitramidophenyl-4-
phenyl-1,2,3-triazole 5. Reaction of
benzo[e][1,2,4]triazine 6.
1 with trimethylsilylcyanide affords 3-amino-
Keywords: Azo compounds; benzotriazole; hydrazones; ring opening; tetrazine
INTRODUCTION
Benzotriazole is a widely used activating auxiliary for numerous condensation
reactions.[1–6] Benzotriazole is a stable, inexpensive, and biologically innocuous com-
pound that is usually stable under a wide variety of reaction conditions. More drastic
conditions, however, may result in the cleavage of the triazole ring in benzotriazole.
For example, in the classical Graebe–Ullmann reaction, 1-phenylbenzotriazole
affords carbazole upon pyrolysis[7,8] or photolysis.[9,10] Other ring-cleavage reactions
of benzotriazoles are known to occur upon treatment of benzotriazoles with
Grignard reagents affording phenylenediamines in low to medium yields.[11–13]
Katritzky et al. described domino reactions of some benzotriazole derivatives that
proceeded via a ring-opening=ring-closure sequence to afford 1,2,4-triazolo[1.5-
a]quinoxaline[14] and benzo[c]tetrazolo[1.5-e]triazepine.[15] Recently, we decribed
a novel ring-opening reaction of 1-nonafluorobutanesulfonyl-1H-benzotriazole
(Nf-Bt) upon reaction with soft nucleophiles, affording azo compounds. Specifically,
treatment of Nf-Bt with phenolates and naphtholates gave o- and p-hydroxy-
substituted phenylazo- and naphthylazo-anilines in excellent yields.[16–20] Likewise,
CH-acidic compounds reacted with Nf-Bt to afford hydrazones in excellent yield
in a new variant of the Japp–Klingemann reaction.[21] Similarly, Wittig reagents
reacted with Nf-Bt to afford phenylazomethylene-triphenylphosphoranes and
Received August 25, 2009.
Address correspondence to Thomas Ziegler, Institute of Organic Chemistry, University of
Tuebingen, Germany, Auf der Morgenstelle 18, D-72076 Tuebingen, Germany. E-mail: thomas.ziegler@
uni-tuebingen.de
3046

REACTION OF N-NITRO-BENZOTRIAZOLE WITH NUCLEOPHILES
3047
bis-phenylazomethylene-triphenylphosphoranes,[22] enamines reacted with Nf-Bt
and 1-cyano-benzotriazole to give o-nonafluorobutanesulfonamido-phenylazo-
enamines, 4H-pyridazines, and imidazo[1,2-b][1,2,4]triazines,[23,24] silylenolether
reacted with Nf-Bt to afford hydrazones,[25] and secondary amines reacted with
1,10-sulfonyl-bisbenzotriazole to give o-sulfamidotriazobenzenes.[26] Here, we report
on the reaction of N-nitrobenzotriazole (1) with C-nucleophiles.
RESULTS AND DISCUSSION
1-Nitro-1,2,3-benzotriazole 1 is a stable, crystalline, and nonexplosive com-
pound that melts without decomposition at 74 ꢀC. It can be easily prepared from
1-chloro-1,2,3-benzotriazole with trimethylphosphite–silver nitrate complex[27] or
by simple nitration of benzotriazole with nitric acid in acetic acid.[28] The latter
procedure affords 1 in 90% yield when fuming nitric acid is used. So far, 1-nitroben-
zotriazole 1 has only been reacted with secondary amines to give triazenes[29] and
with indolizines to give o-(nitroamino)phenylazo-indolizines.[30]
Scheme 1 summarizes the reactions of 1-nitrobenzotriazole 1 with phenolates
and naphtholates 2a–f to give azo compounds 3a–f. All reactions were performed in
Scheme 1. Reaction of 1-nitrobenzotriazole with phenols and naphthols.

3048
M. UHDE AND T. ZIEGLER
tetrahydrofuran (THF) as the solvent at room temperature. Compared to the corre-
sponding reactions of phenolates and naphtholates with Nf-Bt,[16] 1-nitrobenzotriazole
1 reacts significantly more slowly (1–6 h versus 24h). There is also no indication that 1
reacts through its possible 2-diazonitroimin form.[16,29] Similarly, the reaction of 1 with
phenol 2a affords a mixture of the p-azobenzene 3a (41%) and the o-azobenzene 3a0
(22%), whereas Nf-Bt gave exclusively one isomer depending on the solvent.[16] Like-
wise, m-chlorophenol 2f also results in a mixture of the corresponding o- and p-azoben-
zenes 3f and 3f0. The assignment of the o- and p-isomers 3a,a0 and 3f,f0 through
their NMR spectra is unambiguous. In both p-isomers 3a and 3f, the protons of the
aromatic OH groups resonate at 5.20 and 5.46ppm, respectively, whereas the ones
of the o-isomers resonate at 11.79 and 12.02 ppm, respectively. Similarly, the protons
of the aromatic OH group of compound 3d resonate at 5.07ppm, and those of
compounds 3b, 3c, and 3e resonate at 11.22–13.86 ppm, indicating that the
downfield-shifted protons form strong hydrogen bonds with the azo groups. There is
no indication in the NMR spectra for the presence of an azo-hydrazo-tautomeric
equilibrium, as was observed for reactions products of 1 with secondary amines.[29]
Scheme 2 summarizes the reactions of 1-nitrobenzotriazole 1 with various
CH-acidic compounds 2g–n under similar conditions (THF, 25 ꢀC) to give hydra-
zones 3g–l. Once again, 1 reacts with CH-acidic compounds significantly more
slowly than Nf-Bt.[21] Ethyl nitroacetate 2 m and nitromethane 2n do not react with
1. Likewise, enolethers and enamines do not react with 1 or result in complex reac-
tion mixtures, showing the reduced reactivity of 1 compared to Nf-Bt. All hydra-
zones 3g–l show 1H NMR signals for the hydrazone NH group at 11–15 ppm,
indicative that no azo-tautomer is present. The hydrazones formed from 1 and 2g
are obtained as an inseparable 64:36 E=Z-isomeric mixture of 3g0 and 3g isolated
in quantitative yield. All other hydrazones 3h–l show the Z configuration, which is
evident from the downfield shift of the NH-groups as a result of hydrogen bonds
to the neighboring carbonyl group.
Treatment of 1 with trimethylsilylazide and tetrabutylammonium fluoride
in toluene proceeds smoothly to afford o-azidonitraniline 4 after elimination of
nitrogen (Scheme 3). The sodium salt of 4 was previously obtained by reacting 1 with
NaN3 in ethanol and is likely to proceed via pentazene and pentazole A.[31] Azide 4 is
a very sensitive compound that could not be isolated in pure form without extensive
decomposition. Therefore, crude 4 was directly converted into triazole 5 by a
Cu(I)-catalyzed click reaction with phenylacetylene. The purification of 5 appeared
to rather difficult, though, because many by-products were formed.
1-Nitrobenzotriazole 1 also reacts with trimethylsilylcyanide (TMSCN) and
tetrabutylammonium fluoride in toluene to afford 3-amino-benzo[e][1,2,4]triazine 6
in 62% yield (Scheme 4). Although the mechanism for the formation of 6 remains
enigmatic, it is likely that the sequence starts with a nucleophilic attack of cyanide
on 1 followed by ring-closure of intermediate B to afford intermediate benzotriazine
C. The latter is finally reduced to give 6. Most likely, the hypervalent trimethyl
cyanofluorosilicate which initially forms from TMSCN and tetrabutylammonium
fluoride reduces intermediate C by cleaving off O2N-CN, which in turn quickly
decomposes to N2 and CO.[32] This is supported by the fact that 2 mol equivalents
of TMSCN are needed to drive the reaction to completion. An equimolar amount
of TMSCN results in a turnover of only 50%.

REACTION OF N-NITRO-BENZOTRIAZOLE WITH NUCLEOPHILES
3049
Scheme 2. Reaction of 1-nitrobenzotriazole with CH-acidic compounds.
Scheme 3. Reaction of 1-nitrobenzotriazole with TMS-azide and phenyl acetylene.

3050
M. UHDE AND T. ZIEGLER
Scheme 4. Reaction of 1-nitrobenzotriazole with TMS-cyanide.
EXPERIMENTAL
All reagents were commercially obtained at the best quality and used without
further purification. Organic solutions were concentrated by rotary evaporation at
less than 45 ꢀC. Reactions were carried out under anhydrous conditions in dry, freshly
distilled solvents. Yields refer to chromatographically and spectroscopically
(1H NMR,13C NMR, mass, elemental analysis) homogeneous materials. Analytical
thin-layer chromatography (TLC) was performed on glass plates precoated with
0.25-mm-thick Macherey & Nagel Polygram silica gel=UV254 with ultraviolet
(UV) light as the visualizing agent. Silica gel 60 (particle size 0.040–0.063 mm) was
used for flash chromatography. Mass spectra (MS) were recorded with a Bruker Apex
II Fourier transform (FT)–ion cyclotron resonance (ICR) (fast atom bombardment,
FAB) instrument. NMR spectra were recorded on a Bruker Advance 400 spec-
1
trometer (at 400 MHz for H and at 100.2 MHz for 13C NMR spectra) and on a
Bruker 250 spectrometer (at 250 MHz for 1H and at 62.9 MHz for 13C NMR spectra),
calibrated using CDCl3 as an internal reference. The following abbreviations were
used to explain the multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; m, multi-
plet; br, broad; Pn, phenol; Ph, phenyl; and arom, aromatic protons or carbons.
Melting points were determined on a Buchi B-540 instrument and are uncorrected.
¨
Elemental analysis was performed on Hekatech Euro EA 3000 analyzer.
1-Nitro-1H-1,2,3-benzotriazole (1)
1H-Benzotriazole (5.0 g, 42.0 mmol) was dissolved in acetic acid (40 ml) and
cooled to 0 ꢀC, and fuming nitric acid (>99.5%, 2 ml) was added with stirring. After
stirring the solution for 30 min, acetic anhydride (6 ml) was added, and stirring was
continued for another 30 min. The clear solution was poured into ice water, and the
precipitated crude 1 was collected by filtration. Chromatography of the crude 1 with
toluene gave pure 1 (6.2 g, 90%). Mp 74 ꢀC; lit.[28] mp 74 ꢀC.
General Experimental Procedure for the Addition of Phenols
and Naphthols
NaH (0.32 g of a 60% suspension in mineral oil, 7.9 mmol) was added under Ar
with stirring at 20 ꢀC to a solution of 1 (1.0 g, 6.1 mmol) and the respective phenol
or naphthol 2a–f or CH-acidic compound 2g–n (7.3 mmol) in THF (50 ml). The
resulting solution was stirred at 20 ꢀC until TLC revealed completion (4–24 h). Ethyl
acetate (100 ml), water (50 ml), and concentrated hydrochloric acid (2 ml) were
added, and stirring was continued until the aqueous phase turned colorless. The

REACTION OF N-NITRO-BENZOTRIAZOLE WITH NUCLEOPHILES
3051
organic phase was separated, dried with Na2SO4, filtered, and concentrated.
Chromatography of the residue with petroleum ether=ethyl acetate 4:1 þ 1% acetic
acid afforded azo compounds 3a–f or hydrazones 3g–l. Crystalline compounds were
recrystallized.
(E)-N-(2-((4-Hydroxyphenyl)diazenyl)phenyl)nitramide (3a)
Phenol (2a) (0.69 g) gave 3a (0.65 g, 41%), orange crystals, mp 140–141 ꢀC
(petroleum ether=Essigester 9:1); FAB-MS: m=z ¼ 259.1 [M þ H]þ; nmax, nm
1
(e, molꢁ1 cm3 cmꢁ1): 357.9 (57965); H NMR (400 MHz, CDCl3): d ¼ 5.20 (1H, s,
OH), 6.91–6.95 (2H, m, HPn), 7.30–7.34 (1H, m, Harom), 7.47–7.51 (1H, m, Harom),
7.81–7.86 (3H, m, Harom=Pn), 8.08–8.10 (1H, m, Harom), 12.32 (1H, s, NH); 13C
NMR (62,9 MHz, CDCl3): d ¼ 115.99 (2C, CPn), 125.27 (2C, CPn), 116.42, 128.11,
130.98 (3C, Carom=Pn), 129.69, 132.73, 145.60, 146.58 (4C, Carom), 161.54 (C-OH).
Anal. calcd. for C12H10N4O3 (258.08): C, 55.81; H, 3.90; N, 21.70. Found: C,
56.03; H, 3.87; N, 21.89.
(E)-N-(2-((2-Hydroxyphenyl)diazenyl)phenyl)nitramide (3a’)
Phenol (2a) (0.69 g) gave 3a0 (0.35 g, 22%), orange crystals, mp 106–107 ꢀC
(petroleum ether=ethyl acetate 9:1); FAB-MS: m=z ¼ 259.1 [M þ H]þ; nmax, nm (e,
molꢁ1 cm3 cmꢁ1) 324.05 (24655), 379.99 (13545); 1H NMR (400 MHz, CDCl3):
d ¼ 6.99–7.07 (2H, m, Harom), 7.34–7.43 (2H, m, Harom), 7.49–7.53 (1H, m, Harom),
7.81–7.84 (2H, m, Harom), 8.04–8.06 (1H, d, Harom), 11.79 (1H, s, OH), 12.89 (1H,
s, NH); 13C NMR (62.9 MHz, CDCl3): d ¼ 118.54, 120.64, 123.65, 127.37, 127.61,
131.60, 131.94, 134.72 (8C, Carom), 130.02, 136.80, 138.05 (3C, Carom), 152.96
(C-OH). Anal. calcd. for C12H10N4O3 (258.08): C, 55.81; H, 3.90; N, 21.70. Found:
C, 55.98; H, 3.95; N, 21.14.
(E)-N-(2-((2-Hydroxynaphthalene-1-yl)diazenyl)phenyl)nitramide (3b)
Freshly recrystallized b-naphthol (2b) (0.88 g) gave 3b (1.85 g, 98%), deep red
crystals, mp 148–150 ꢀC (n-hexane=acetone 9:1); FAB-MS: m=z ¼ 309.1 [M þ H]þ;
n
max, nm (e, molꢁ1 cm3 cmꢁ1): 306.46 (11100), 477.99 (19500); 1H NMR
(400 MHz, DMSO-d6): d ¼ 6.83–8.86 (1H, m, Harom), 7.41–7.50 (3H, m, Harom),
7.58–7.66 (2H, m, Harom), 7.74–7.77 (1H, m, Harom), 7.94–7.97 (1H, m, Harom),
8.16–8.18 (1H, d, Harom), 8.49–8.52 (1H, m, Harom), 13.86 (1H, s, OH), 15.95 (1H,
s, NH); 13C NMR (100.6 MHz, DMSO-d6): d ¼ 116.59, 121.56, 124.62, 126.52,
127.41, 127.96, 130.42, 130.83, 132.49, 141.53 (10C, Carom), 125.72, 127.96, 129.09,
129.41, 140.80 (5C, Carom), 172.78 (1C, C-OH). Anal. calcd. for C16H12N4O3
(308.09): C, 62.33; H, 3.92; N, 18.17. Found: C, 62.34; H, 3.98; N, 18.10.
(E)-N-(2-((1-Hydroxynaphthalene-2-yl)diazenyl)phenyl)nitramide (3c)
Freshly sublimated a-naphthol (2c) (1.05 g) gave 3c (1.86 g, 98%), deep red
crystals, mp 110.5–111.5 ꢀC (ethyl acetate=petroleum ether 1:4); FAB-MS: m=
z ¼ 309.0 [M þ H]þ; nmax, nm (e, molꢁ1 cm3 cmꢁ1): 288.86 (19264), 361.06 (10632),

3052
M. UHDE AND T. ZIEGLER
495.60 (16647); 1H NMR (400 MHz, DMSO-d6): d ¼ 7.22–7.25 (1H, d, Harom),
7.32–7.34 (1H, d, Harom), 7.41–7.45 (1H, m, Harom), 7.49–7.63 (3H, m, Harom), 7.70–
7.78 (2H, m, Harom), 8.06–8.08 (1H, d, Harom), 8.32–8.34 (1H, d, Harom), 13.84 (1H, s,
OH), 14.78 (1H, s, NH); 13C NMR (100.6 MHz, DMSO-d6): d ¼ 116.42, 121.85,
124.44, 125.99, 126.84, 127.78, 128.04, 130.56, 132.44 (10C, Carom), 126.74, 128.66,
133.63, 136.65, 141.20 (5C, Carom), 170.52 (1C, C-OH). Anal. calcd. for
C16H12N4O3 (308.09): C, 62.33; H, 3.92; N, 18,17. Found: C, 62.32; H, 3.76; N,
17.72.
(E)-N-(2-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)phenyl)-
nitramide (3d)
2,6-Dimethylphenol (2d) (0.89 g) gave 3d (670 mg, 38%), yellow crystals, mp
129–129.5 ꢀC (petroleum ether=ethyl acetate 9:1); FAB-MS: m=z ¼ 287.1 [M þ H]þ;
n
max, nm (e, molꢁ1 cm3 cmꢁ1): 253.18 (28129), 367.60 (43028.5); 1H NMR
(400 MHz, CDCl3): d ¼ 2.30 (6H, s, 2CH3), 5.07 (1H, s, OH), 7.29–7.33 (1H, m,
Harom), 7.44–7.48 (1H, m, Harom), 7.56 (2H, s, HPn), 7.82–7.85 (1H, m, Harom),
8.08–8.11 (1H, m, Harom), 12.54 (1H, s, NH); 13C NMR (100.6 MHz, CDCl3):
d ¼ 15.92 (2C, CH3), 122.01, 122.40, 124.00, 126.56, 131.27 (6C, Carom), 123.94,
131.90, 139.07, 145.63 (5C, Carom), 156.23 (1C, C-OH); FT-ICR-MS calcd. for
C14H14N4O3: 309.09581 [M þNa]þ; found: 309.09582 [M þNa]þ (Dm ¼ 0.03 ppm).
(E)-N-(2-((2-Hydroxy-5-methoxyphenyl)diazenyl)phenyl)nitramide (3e)
p-Methoxyphenol (2e) (0.91 g) gave 3e (1.51 g, 86%), red crystals, mp
133.5–134.0 ꢀC (petroleum ether=ethyl acetate 4:1); FAB-MS: m=z ¼ 287.1
[M ꢁ H]–; nmax, nm (e, molꢁ1 cm3 cmꢁ1): 255.67 (19402), 324.84 (27969), 438.50
1
(11595); H NMR (250 MHz, CDCl3): d ¼ 3.82 (3H, s, CH3), 6.93–7.02 (2H, m,
HPn), 7.26–7.27 (1H, d, HPn), 7.38–7.42 (1H. m, Harom), 7.48–7.53 (1H, m, Harom),
7.79–7.82 (1H, m, Harom), 8.02–8.04 (1H, m, Harom), 11.22 (1H, s, OH), 12.65
(1H, s, NH); 13C NMR (100.6 MHz, DMSO-d6): d ¼ 55.40 (CH3), 102.47, 116.96,
119.24, 122.28, 128.04, 129.76, 131.76 (7C, Carom), 133.24, 138.89, 146.26, 150.49,
152.54 (5C, Carom). Anal. calcd. for C13H12N4O4 (288.09): C, 54.17; H, 4.20; N,
19.44. Found: C, 54.37; H, 4.10; N, 19.40.
(E)-N-(2-((2-Chloro-4-hydroxyphenyl)diazenyl)phenyl)nitramide (3f)
3-Chlorophenol (2f) (0.94 g) gave 3f (610 mg, 34%), yellow crystals, mp
152.0–152.5 ꢀC (petroleum ether=ethyl acetate 9:1); FAB-MS: m=z ¼ 293.1 [M þ H]þ;
1
n
max, nm (e, molꢁ1 cm3 cmꢁ1): 259.37 (14515), 362.21 (21039); H NMR (250 MHz,
CDCl3): d ¼ 5.46 (1H, s, OH), 6.77–6.81 (1H, m, HPn), 7.03–7.04 (1H, d, HPn),
7.31–7.38 (1H, m, Harom), 7.45–7.52 (1H, m, Harom), 7.71–7.74 (1H, d, HPn),
7.94–7.98 (1H, m, Harom), 8.16–8.20 (1H, m, Harom), 13.30 (1H, s, NH); 13C NMR
(100.6 MHz, DMSO-d6): d ¼ 115.55, 116.46, 116.52, 118.94, 127.93, 129.68, 131.69
(7C, Carom), 133.19, 137.10, 141.16, 146.39 (4C, Carom), 162.10 (1C, C-OH). Anal.
calcd. for C12H9ClN4O3 (292.04): C, 49.24; H, 3.10; N, 19.14. Found: C, 49.23; H,
3.00; N, 18.83.

REACTION OF N-NITRO-BENZOTRIAZOLE WITH NUCLEOPHILES
3053
(E)-N-(2-((4-Chloro-2-hydroxyphenyl)diazenyl)phenyl)nitramide (3f’)
3-Chlorophenol (2f) (0.94 g) gave 3f0 (120 mg, 7%), yellow crystals, mp
132.5–133.5 ꢀC (petroleum ether=ethyl acetate 9:1); FAB-MS: m=z ¼ 291.1 [M ꢁ
1
H]–; nmax, nm (e, molꢁ1 dm3 cmꢁ1): 331.19 (15552.5), 373.86 (12302.5); H NMR
(250 MHz, CDCl3): d ¼ 7.05–7.09 (2H, m, Harom), 7.42–7.49 (1H, m, Harom),
7.53–7.60 (1H, m, Harom), 7.79–7.87 (2H, m, Harom), 8.03–8.07 (1H, m, Harom),
12.02 (1H, s, OH), 12.61 (1H, s, NH); 13C NMR (62.9 MHz, CDCl3): d ¼ 118.83,
121.50, 124.16, 127.29, 127.78, 132.37, 132.64 (7C, Carom), 130.23, 135.71, 138.56,
140.67 (4C, Carom), 153.74 (1C, C-OH). FT-ICR-MS calcd. for (Cꢁ12H9ClN4O3):
315.02554 [M þNa]þ; found: 315.02541 [M þ Na]þ (Dm ¼ 0.41 ppm).
(Z)-Methyl 2-(2-(2-(Nitroamino)phenyl)hydrazono-3-oxobutanoate
(3g) and (E)-Methyl 2-(2-(2-(Nitroamino)phenyl)hydrazono-3-
oxobutanoate (3g’)
Methyl acetoacetate (2g) (0.85 g) gave a 64:36 mixture of 3g and 3g0 (1.7 g,
100%), yellow crystals; FAB-MS: m=z ¼ 279.0 [M ꢁ H]–; 1H NMR (400 MHz, CDCl3):
d ¼ 2.42 (1.9 H, s, CH3 3g0), 2.51 (1.1 H, s, CH3 3g), 3.80 (1.1 H, s, OCH3 3g), 3.81 (1.9
H, s, OCH3 3g0), 7.22–7.30 (1H, m, Harom), 7.37–7.40 (1H, m, Harom), 7.52–7.58 (1H,
m, Harom), 7.75–7.78 (1H, m, Harom), 12.31 (0.64 H, s, NHHydrazon 3g0), 13.65 (1H, s,
NH), 14.54 (0.36 H, s, NHhydrazon 3g); 13C NMR 3g (100.6 MHz, CDCl3): d ¼ 30.48
(1C, CH3), 51.98 (1C, OCH3), 115.80, 125.47, 127.85, 130.89 (4C, Carom), 123.26,
127.51, 138.48 (3C, 2Carom, C N), 164.36 (1C, COOCH3), 196.88 (1C, COCH3);
=
13C NMR 3g0 (100.6 MHz, CDCl3): d ¼ 26.47 (1C, CH3), 52.17 (1C, OCH3), 115.90,
124.55, 128.03, 130.78 (4C, Carom), 122.89, 129.45, 138.45 (3C, 2Carom, C N),
=
163.02 (1C, COOCH3), 193.40 (COCH3). Anal. calcd. for C11H12N4O5 (280.08): C,
47.14; H, 4.32; N, 19.99. Found: C, 47.43; H, 4.13; N, 20.24.
N-(2-(2-(2,4-Dioxopentane-3-yliden)hydrazinyl)phenyl)nitramide (3h)
Acetylacetone (2h) (0.73 g) gave 3h (1.56 g, 97%), orange crystals, mp
147.0–147.5 ꢀC (n-hexane=acetone 3:1); FAB-MS: m=z ¼ 263.1 [M ꢁ H]–; nmax, nm
(e, molꢁ1 dm3 cmꢁ1): 359.57 (63805); 1H NMR (400 MHz, DMSO-d6): d ¼ 2.56–
2.57 (6H, d, 2CH3), 7.34–7.38 (1H, m, Harom), 7.45–7.48 (1H, m, Harom),
7.62–7.66 (1H, m, Harom), 7.94–7.98 (1H, m, Harom), 13.77 (1H, s, NH), 14.47
(1H, s, NH); 13C NMR (100.6 MHz, DMSO-d6): d ¼ 26.49 (1C, CH3), 31.22 (1C,
CH3), 115.91, 125.49, 127.85, 130.94 (4C, Carom), 123.36, 134.47, 138.46 (3C, Carom
,
=
=
=
C N), 196.30 (1C, C O), 197.55 (1C, C O). Anal. calcd. for C11H12N4O4 (264.09):
C, 50.00; H, 4.58; N, 21.20. Found: C, 49.95; H, 4.43; N, 21.21.
Dimethyl 2-(2-(2-(Nitroamino)phenyl)hydrazono)malonate (3i)
Diethyl malonate (2i) (0.96 g) gave 3i (1.45 g, 80%), yellow crystþals, mp
129–130 ꢀC (ethyl acetate=n-hexane 1:4); FAB-MS: m=z ¼ 297.0 [M þ H] ; nmax
CDCl3): d ¼ 3.12 (3H, s, CH3), 3.13 (3H, s, CH3), 6.41–6.46 (1H, m, Harom),
,
nm (e, molꢁ1 cm3 cmꢁ1): 279.28 (19564), 416.32 (26750); 1H NMR (400 MHz,

3054
M. UHDE AND T. ZIEGLER
6.56–6.63 (2H, m, Harom), 6.85–6.87 (1H, m, Harom), 10.84 (1H, s, NH), 12.17 (1H, s,
NH); 13C NMR (100.6 MHz, CDCl3): d ¼ 52.51 (1C, CH3), 52.53 (1C, CH3), 117.67,
124.97, 126.95, 129.18 (4C, Carom), 119.56, 124.14, 134.01 (3C, Carom, C N), 162.55
=
=
=
(1C, C O), 163.39 (1C, C O). Anal. calcd. for C11H12N4O6 (296.08): C, 44.6; H,
4.08; N, 18.91. Found: C, 44.78; H, 4.08; N, 18.45.
N-(2-(2-(2,6-Dioxocyclohexylidene)hydrazinyl)phenyl)nitramide (3j)
1,3-Cyclohexandione (2j) (0.82 g) gave 3j (1.15 g, 69%), orange crystals, mp
(decomp.) 157–158 ꢀC (ethyl acetate=petroleum ether 1:9); FAB-MS: m=z ¼ 274.9
[M ꢁ H]–; nmax, nm (e, molꢁ1 cm3 cmꢁ1): 381.77 (29700); 1H NMR (400 MHz,
DMSO-d6): d ¼ 1.94–2.01 (2H, m, CH2), 2.60–2.63 (2H, t, CH2), 2.69–2.72 (2H, t,
CH2), 7.32–7.36 (1H, m, Harom), 7.41–7.43 (1H, m, Harom), 7.57–7.61 (1H, m, Harom),
7.84–7.86 (1H, m, Harom), 13.74 (1H, s, NH), 15.06 (1H, s, NH); 13C NMR
(62.9 MHz, DMSO-d6): d ¼ 17.61 (1C, CH2), 38.51 (1C, CH2), 38.58 (1C, CH2),
116.13, 126.36, 127.81, 131.03 (4C, Carom), 123.97, 132.82, 138.48 (3C, Carom
,
=
=
=
C N), 193.16 (1C, C O), 198.73 (1C, C O). Anal. calcd. for C12H12N4O4
(276.09): C, 52.17; H, 4.38; N, 20.28. Found: C, 52.40; H, 4.49; N, 20.39.
N-(2-(2-(2,2-Dimethyl-4,6-dioxo-1,3-dioxan-5-
ylidene)hydrazinyl)phenylnitramide (3k)
Butyllithium (1.46 ml of a 2.5 M solution in n-hexane, 3.7 mmol) was added
slowly under Ar with stirring at ꢁ30 ꢀC to a solution of Meldrum’s acid (2k)
(0.53 g, 3.7 mmol) in THF (50 ml). Stirring was continued for 30 min, and a solution
of 1 (0.5 g, 3.0 mmol) in THF (10 ml) was slowly added. The solution was warmed to
20 ꢀC and stirred until TLC revealed completion (4 h). Ethyl acetate (50 ml), water
(25 ml), and concentrated hydrochloric acid (2 ml) were added, and stirring was con-
tinued until the aqueous phase turned colorless. The organic phase was separated,
dried with Na2SO4, filtered, and concentrated. Chromatography of the residue with
chloroform=methanol 30:1 þ 1% acetic acid afforded 3k (210 mg, 0.68, 22%), yellow
crystals, mp 136.0–136.5 ꢀC (petroleum ether=ethyl acetate 4:1); FAB-MS: m=
z ¼ 307.1 [M ꢁ H]–; nmax, nm (e, molꢁ1 dm3 cmꢁ1): 366.94 (22165.5); 1H NMR
(250 MHz, DMSO-d6): d ¼ 1.76 (6H, s, 2CH3), 7.36–7.49 (2H, m, Harom), 7.57–
7.64 (1H, m, Harom), 7.79–7.83 (1H, m, Harom), 13.40 (1H, s, NH); 13C NMR
62.9 MHz, DMSO-d6): d ¼ 27.08 (2C, CH3), 116.66, 126.95, 127.89, 130.93 (4C,
Carom), 105.90, 115.02, 124.35, 137.46 [4C, Carom, C N, C(CH3)2], 158.25 (1C,
=
=
=
C O), 159.97 (1C, C O). FT-ICR-MS calcd. for (C12H12N4O6): 331.06491 [M
þNa]þ; found: 331.06489 [M þNa]þ (Dm ¼ 0.06 ppm).
(Z)-Ethyl 2-Cyano-2-(2-(2-(Nitroamino)phenyl)hydrazono)acetate (3l)
Ethyl cyanoacetate (2l) (0.83 g) gave 3l (0.77 g, 46%), yellow crystals, mp
153.5–154 ꢀC (EtOH); FAB-MS: m=z ¼ 276.1 [M ꢁ H]–; nmax, nm (e, molꢁ1
cm3 cmꢁ1): 275.05 (10235), 351.80 (21383); 1H NMR (400 MHz, DMSO-d6):
d ¼ 1.29–1.32 (3H, t, CH3), 4.30–4.35 (2H, q, CH2), 7.29–7.33 (1H, m, Harom),
7.40–7.42 (1H, m, Harom), 7.53–7.57 (1H, m, Harom), 7.69–7.71 (1H, m, Harom),

REACTION OF N-NITRO-BENZOTRIAZOLE WITH NUCLEOPHILES
3055
13.04 (1H, s, NH); 13C NMR (100.6 MHz, DMSO-d6): d ¼ 13.82 (1C, CH3), 62.45
(1C, CH2), 115.86, 125.82, 127.9, 130.96 (4C, Carom), 107.25, 115.27, 123.25,
137.61 (4C, Carom, C N, CN), 161.21 (C O). Anal. calcd. for C11H11N5O4
(277.08): C, 47.66; H, 4.00; N, 25.26. Found: C, 47.67; H, 3.98; N, 24.49.
=
=
1-Nitro-(2-azido-phenyl)amide (4)
A solution of tetrabutylammonium fluoride trihydrate (1.92 g, 6.1 mmol) in
˚
toluene (50 ml) was dried over molecular sieves (3 A) and slowly added over
30 min at 20 ꢀC under Ar to a stirred solution of trimethylsilyl azide (0.84 g,
7.32 mmol) and 1 (0.84 g, 7.32 mmol) in toluene (50 ml). Stirring was continued until
TLC revealed completion of the reaction (15 min). Toluene (100 ml), water (50 ml),
and conc. hydrochloric acid (2 ml) were added with stirring. The organic phase
was separated, dried with Na2SO4, filtered, and concentrated to give 4 in approxi-
mately 150 ml of toluene. This solution was directly used for the next step. An ana-
1
lytical sample was concentrated further for measuring the NMR spectra. H NMR
(400 MHz, DMSO-d6): d ¼ 6.89–6.94 (2H, m, Harom), 7.0–7.04 (1H, m, Harom),
7.35–7.37 (1H, m, Harom); 13C NMR (100.6 MHz, DMSO-d6): d ¼ 119.82, 123.11,
124.55, 124.69 (4C, Carom), 131.60, 142.04 (2C, Carom).
1-Nitro-[2-(4-phenyl-[1,2,3]triazole-1-yl)-phenyl]amide (5)
Phenylacetylene (0.62 g, 6.1 mmol), diisopropyl ethyl amine (3.1 ml,
18.3 mmol), and (EtO)3P-CuI (0.22 g, 0.61 mmol) were added at 20 ꢀC to
the described solution of 4 in toluene, and the solution was stirred for 16 h.
Concentration of the solution and chromatography (petroleum ether=ethyl acetate
1:1 containing 1% acetic acid) of the residue gave 5 (500 mg, 29%), mp 160–161 ꢀC
(n-hexane=ethyl acetate 9:1); FAB-MS: m=z ¼ 280.0 [M – H]–; nmax, nm (e, molꢁ1
1
dm3 cmꢁ1): 253.97 (31656); H NMR (250 MHz, DMSO-d6): d ¼ 7.35–7.42 (1H, m,
Harom), 7.47–7.53 (2H, m, Harom), 7.66–7.73 (3H, m, harom), 7.79–7.84 (1H, m,
Harom), 7.93–7.97 (2H, m, Harom), 8.99 (1H, s, CHtriazol), 13.79 (1H, s, NH); 13C
NMR (62.9 MHz, DMSO-d6): d ¼ 122.26 (1C, CHtriazol), 125.33, 129.00 (2C, CPh),
125.83, 128.23, 129.52, 130.27, 130.30 (5C, CPh=arom), 128.79, 130.13, 133.10 (3C,
CPh=arom), 146.59 (1C, Ctriazol). FT-ICR-MS calcd. for (C14H11N5O2): 304.08050
[M þ Na]þ; found: 304.080315 [M þ Na]þ (Dm ¼ 0.6 ppm).
3-Amino-1,2,4-benzo[e]triazine (6)
A solution of tetrabutylammonium fluoride trihydrate (1.92 g, 6.1 mmol) in
˚
MeCN (50 ml) was dried over molecular sieves (3 A) and slowly added over 30 min
at 20 ꢀC under Ar to a stirred solution of trimethylsilyl cyanide (0.61 g, 6.1 mmol)
and 1 (0.50 g, 3.05 mmol) in MeCN (50 ml). Stirring was continued until TLC
revealed completion of the reaction (15 min). Ethyl acetate (100 ml), water (50 ml),
and conc. hydrochloric acid (2 ml) were added with stirring. The organic phase
was separated, dried with Na2SO4, filtered, and concentrated. Chromatography
(petroleum ether=ethyl acetate 1:1 containing 1% acetic acid) of the residue gave 6
(280 mg, 62%), yellow crystals, mp 205–206 ꢀC (CHCl3), lit.[33] 205–208 ꢀC;

3056
M. UHDE AND T. ZIEGLER
FAB-MS: m=z ¼ 147.0 [M þ H]þ; 1H NMR (400 MHz, CDCl3): d ¼ 6.00 (2H, s,
NH2), 7.47–7.51 (1H, m, Harom), 7.59–7.61 (1H, d, Harom), 7.76–7.80 (1H, m, Harom),
8.28–8.31 (1H, m, Harom); 13C NMR (100.6 MHz, CDCl3): d ¼ 126.07, 126.14,
130.005, 136.22 (4C, Carom), 142.02, 143.52 (2C, Carom), 159.69 (1C, C-NH2).
Anal. calcd. for C7H6N4 (146.06): C, 57.38; H, 4.21; N, 38.26. Found: C, 57.53;
H, 4.14; N, 38.34.
ACKNOWLEDGMENTS
The authors thank K.-P. Zeller and G. Nicholson for performing the mass
spectra and K. Albert for performing the NMR spectra. This work is financially sup-
ported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
Industrie.
REFERENCES
1. Katritzki, A. R.; Manju, K.; Singh, S. K.; Meher, N. K. Benzotriazole-mediated amino-,
alkoxy- and alkylthio-alkylation. Tetrahedron 2005, 61, 2555–2581.
2. Katritzki, A. R.; Rogovoy, B. V. Benzotraizole: An ideal synthetic auxiliary. Chem. Eur.
J. 2003, 9, 4586–4593.
3. Katritzki, A. R.; Denisko, O. V. Designing efficient synthetic routes to polyfunctionality.
Pure Appl. Chem. 2000, 72, 1597–1603.
4. Donghi, M.; Habermann, J.; Ley, S. V. Benzotriazoles in solid-phase organic chemistry.
Chemtracts 2002, 15, 751–765.
5. Katritzki, A. R. The continuing magic of benzotriazole: An overview of some recent
advances in synthetic methodology. J. Heterocycl. Chem. 1999, 36, 1501–1522.
6. Katritzki, A. R.; Qi, M. Michael additions of benzotriazole-stabilized carbanions: A
review. Coll. Czech. Chem. Commun. 1998, 63, 599–613.
7. Graebe, C.; Ullmann, F. Ueber eine neue Carbazolsynthese. Liebigs Ann. 1896, 291,
16–17.
8. Ullmann, F. Studien in der Carbazolreihe. Liebigs Ann. 1904, 332, 82–104.
9. Mehta, L. K.; Parrick, J.; Payne, F. The elimination of an alkoxy group in the photo-
Graebe–Ullmann conversion of 1-(2,5-dialkoxyphenyl)triazolopyridined into carbolines,
and the preparation of a-, c- and d-carboline quinones. J. Chem. Soc., Perkin Trans. 1
1993, 1261–1267.
10. Burgess, E. M.; Carithers, R.; McCullagh, L. Photochemical decomposition of 1H-
1,2,3-triazole derivatives. J. Am. Chem. Soc. 1968, 90, 1923–1924.
11. Katritzky, A. R.; Rachwal, S.; Offerman, R. J.; Najzanek, Z.; Yagoub, A. K.; Zhang, Y.
Nucleophilic attack at heterocyclic nitrogen: Unusual reactivity of the benzotriazole
heterocyclic ring. Chem. Ber. 1990, 123, 1545–1552.
12. Katritzky, A. R.; Rachwal, S.; Rachwal, B. Reactions of 1-(a-alkoxyalkyl)- and 1-(a-
(aryloxy)alkyl)benzotriazoles with the Grignard reagents: A new and versatile method
for the preparation of ethers. J. Org. Chem. 1989, 54, 6022–6029.
13. Katritzky, A. R.; Hughes, C. V.; Rachwal, S. Chemistry of benzotriazoles:
Benzotriazol-1-ylmethylammonium salts’ synthesis and reactivity. J. Heterocycl. Chem.
1989, 26, 1579–1588.
14. Katritzky, A. R.; Huang, T.-B.; Denisko, O. V. A novel rearrangement to 1,2,4-
triazolo[1,5-a]quinoxalines. J. Org. Chem. 2002, 67, 3118–2119.

REACTION OF N-NITRO-BENZOTRIAZOLE WITH NUCLEOPHILES
3057
15. Katritzky, A. R.; Fan, W.-Q.; Greenhill, J. V. 4-(Benzotriazol-1-yl)-6H- benzo[c]tetrazolo[1,5-
e][1,2,5]triazepine, a new heterocyclic ring system formed by a novel benzotriazole ring
opening. J. Org. Chem. 1991, 56, 1299–1301.
´
16. Mico, X. A.; Ziegler, T.; Subramanian, L. R. A versatile direct approach to ortho-
substituted azobenzenes from benzotriazoles. Angew. Chem. 2004, 116, 1424–1427; Angew.
Chem., Int. Ed. Engl. 2004, 43, 1400–1403.
´
17. Mico, X. A.; Richter, M.; Schwarz, S.; Stra¨hle, J.; Ziegler, T.; Subramanian, L. R. Crystal
structure of nonafluoro-{N-[(E)-2-(4-hydroxyphenyl)diazenyl]-phenyl}-1-butanesulfona-
mide, C16H10F9N3O3S. Z. Kristallogr. NCS 2003, 218, 547–548.
´
18. Mico, X. A.; Richter, M.; Schwarz, S.; Stra¨hle, J.; Ziegler, T.; Subramanian, L. R. Crystal
structure of nonafluro-{N-[(E)-2-(2-hydroxyphenyl)diazenyl]-phenyl}-1-butanesulfona-
mide, C16H10F9N3O3S. Z. Kristallogr. NCS 2003, 218, 549–550.
´
19. Subramanian, L. R.; Mico, X. A.; Ziegler, T. Verfahren zur Herstellung von ortho- und
para-substitutierten aromatischen Azoverbindungen sowie anderer Azoverbindungen.
Ger. Offen. DE Patent 102004005316, 2005; Chem. Abstr. 143:268286.
´
20. Mico, X. A.; Vagin, S. I.; Subramanian, L. R.; Ziegler, T.; Hanack, M. New unsymmetri-
cal zinc–phthalocyanine conjugated with one azo-dye moiety: Synthesis via opening the
fused triazole ring and spectral properties. Eur. J. Org. Chem. 2005, 4328–4337.
21. Anwar, M. U.; Tragl, S.; Ziegler, T.; Subramanian, L. R. A resourceful access to
a-functionalized arylhydrazones. Synlett 2006, 627–629.
´
22. Mico, X. A.; Bombarelli, R. G.; Subramanian, L. R.; Ziegler, T. Ring opening reactions of
benzotriazoles with Wittig reagents. Tetrahedron Lett. 2006, 47, 7845–7848.
23. Uhde, M.; Anwar, M. U.; Ziegler, T. Reaction of N-nonaflyl and N-cyano-benzotriazoles
with enamines. Synth. Commun. 2008, 38, 881–888.
24. Ziegler, T.; Uhde, M.; Kirchmann, M. Crystal structure of nonafluorobutane-1-sulfonic acid
{2-[4-(4-diethyliminium-but-2-enylidene)-4H-pyridazin-1-yl]-phenyl-imide C22H21F9N4O2S.
Z. Kristallogr. NCS 2008, 223, 31–32.
25. Uhde, M.; Ziegler, T. Reaction of N-nonaflyl-benzotriazole with silylenolethers. Synthesis
2009, 1190–1194.
26. Katritzky, A. R.; Khelashvili, L.; Le, K. N. B.; Mohapatra, P. P.; Steel, P. J. Synthesis of
o-sulfamidotriazobenzenes from 1,10-sulfonylbis(benzotriazole). J. Org. Chem. 2007, 72,
5805–5808.
27. Ketari, R.; Foucaud, A. Synthesis of 4-bromo-1-nitropyrazoles and 1-nitrobenzotriazoles
(N-nitroazoles). Synthesis 1992, 844–846.
28. Cohen-Fernandes, P.; Habraken, C. L. Nitration of indazoles in the 3 position. J. Org.
Chem. 1971, 36, 3084–3086.
29. Habraken, C. L.; Erkelens, C.; Mellema, J. R.; Cohen-Fernandes, P. 1-Nitrobenzotriazole-
2-(nitroimino)diazobenzene isomerization: Formation of triazenes by azo coupling with
cyclic amines: Structure determination and dynamic NMR. J. Org. Chem. 1984, 49,
2197–2200.
30. Colonna, M.; Poloni, M. Electron-transfer processes: Reaction of electron-rich systems
with 1-nitrobenotriazoles. Gazz. Chim. Ital. 1988, 118, 673–674.
31. El-Shihi, T.; Herrmann, R. A practical synthesis of 2-azidophenylisocyanide. Z.
Naturforsch. B 1986, 41B, 132–133.
32. Korkin, A. A.; Leszczynski, J.; Bartlett, R. J. Theoretical ab initio study of CN2O2
structures: Prediction of nitryl cyanide as a high-energy molecule. J. Phys. Chem. 1996,
100, 19840–19846.
33. Gauthier, J.; Duceppe, J. S. Synthesis of novel imidazo[1,2-a][3,1]benzothiazines 4,
imidazo[1,2-a]-[1,2,4]benzotriazines 5, and 4H-imidazo[2,3-c]pyrido[2,3-e][1,4]oxazines 6.
J. Heterocycl. Chem. 1984, 21, 1081–1086.