Generation of oxodiazonium ions 4.* Nitramine O-alkyl derivatives in the synthesis of benzotetrazine-1,3-dioxides

Article abstract of DOI:10.1007/s11172-011-0312-7

A new method for the synthesis of benzotetrazine-1,3-dioxides was developed from the 2-(tert-butyl-NNO-azoxy)-N-nitroaniline O-alkyl derivatives upon the action of strong acids (H₂SO₄, MeSO₃H, CF ₃CO₂H) or BF3·Et₂O. A mechanism suggested for these reactions includes transformation of the N=N(O)OR group (R = Me, Pri) to the oxodiazonium ion (N=N=O)⁺, which intramolecularly reacts with the neighboring tert-butyl-NNO-azoxy group, furnishing the tetrazine-1,3-dioxide ring.

Full text of DOI:10.1007/s11172-011-0312-7

Russian Chemical Bulletin, International Edition, Vol. 60, No. 10, pp. 2051—2056, October, 2011
2051
Generation of oxodiazonium ions
4.* Nitramine Oꢀalkyl derivatives in the synthesis of benzotetrazineꢀ1,3ꢀdioxides
M. S. Klenov, A. M. Churakov, Yu. A. Strelenko, and V. A. Tartakovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: churakov@ioc.ac.ru
A new method for the synthesis of benzotetrazineꢀ1,3ꢀdioxides was developed from the
2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀNꢀnitroaniline Oꢀalkyl derivatives upon the action of strong acids
(H2SO4, MeSO3H, CF3CO2H) or BF3•Et2O. A mechanism suggested for these reactions
includes transformation of the N=N(O)OR group (R = Me, Pri) to the oxodiazonium ion
(N=N=O)+, which intramolecularly reacts with the neighboring tertꢀbutylꢀNNOꢀazoxy group,
furnishing the tetrazineꢀ1,3ꢀdioxide ring.
Key words: 1,2,3,4ꢀtetrazineꢀ1,3ꢀdioxides, azoxy compounds, nitramines, oxodiazonium
ion, 1H, 13C, 14N NMR spectroscopy.
Earlier, we have developed approaches to the synthesis
of benzotetrazineꢀ1,3ꢀdioxides (BTDO) by the reaction of
2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀNꢀnitroanilines with nitratꢀ
ing2,3 (N2O5, NO2BF4), phosphorylating4 (P4O10, PCl5),
or acylating5 (Ac2O/H2SO4) agents. A mechanism sugꢀ
gested for these processes includes formation of the interꢀ
mediates A by the reaction of the nitramine group with the
nitrating, phosphorylating, or acylating agents, transforꢀ
mation of these intermediates to oxodiazonium ion, and
the reaction of the latter with the neighboring azoxy group
(Scheme 1). The intermediates A are extremely reactive
and attempts to detect them failed.
Recently,6 we have developed a method for the prepaꢀ
ration of furazanocinnolinꢀ5ꢀoxide 1 by the reaction of
3ꢀ[methoxy(oxido)diazenyl]ꢀ4ꢀphenylfurazane (2) with
acids or BF3•Et2O (Scheme 2). These reactions presumꢀ
Scheme 1
XOH = HNO3, AcOH,
Scheme 2
* For part 3, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2014—2019, October, 2011.
1066ꢀ5285/11/6010ꢀ2051 © 2011 Springer Science+Business Media, Inc.

2052
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Klenov et al.
Scheme 3
R1= R2 = H (a), R1 = H, R2 = Br (b), R1 = R2 = Br (c)
ably include formation of the intermediate B from the
N=N(O)OMe group, then converting to the oxodiazoꢀ
nium ion C, which is further involved into the intramolecꢀ
ular aromatic electrophilic substitution reaction (SEAr)
with the phenyl group.
The main goal of the present work is to study a possiꢀ
bility of cyclization of the 2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀNꢀ
nitroaniline Oꢀalkyl derivatives to BTDO upon the action
of strong acids or BF3•Et2O. OꢀMethyl derivatives of unꢀ
substituted and bromoꢀsubstituted 2ꢀ(tertꢀbutylꢀNNOꢀ
azoxy)ꢀNꢀnitroanilines, as well as Oꢀisopropyl derivative
of 5ꢀbromoꢀ2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀNꢀnitroaniline,
have been chosen as model compounds.
Synthesis of the starting compounds. Methylation of
nitramines 3a—c (see Ref. 5) with diazomethane in diꢀ
ethyl ether at 20 °C leads to the high yields of the mixtures
of Oꢀ and Nꢀmethyl derivatives 4a—c and 5a—c in the
ratio close to 1 : 1 (Scheme 3, Table 1), which were sepaꢀ
rated by preparative TLC. According to the 1H NMR specꢀ
troscopic data, the Oꢀmethyl compounds 4a—c are mixꢀ
tures of two geometric isomers at the methoxy(oxido)ꢀ
diazenyl group (see Table 1). Similarly to the Oꢀmethylated
nitramines,7 the major isomer of compounds 4a—c can be
assigned the Eꢀconfiguration.
silver salts of nitramines with secondary and tertiary alkyl
halides (for example, PriBr, 1ꢀbromoadamantane)8,9 exꢀ
clusively leads to the products of Oꢀalkylation.
We carried out alkylation of the Agꢀsalt of nitramine
3b with isopropyl bromide in MeCN and Et2O (Scheme 4,
Table 2). The reaction with a tenꢀfold excess of PriBr in
MeCN at 20 °C takes 24 days and leads to a mixture of
Oꢀ and Nꢀisopropyl compounds 4d and 5d in the ratio ~5 : 1,
which were separated by preparative TLC. The reaction in
Et2O is slower (35 days), but leads to the formation of only
Oꢀalkylated product 4d (the yield was 71%) virtually as
a single geometric isomer. Like with Oꢀalkylated nitrꢀ
amines,7 the N=N(O)OPri group in compound 4d can be
assigned the Eꢀconfiguration.
Scheme 4
A serious disadvantage in the preparation of the Oꢀmethyl
compounds 4a—c from nitramines by the reaction with
diazomethane is the formation of considerable (to 50%,
see Table 1) amounts of the side Nꢀmethyl compounds
5a—c. At the same time, it is known that alkylation of the
i. 1) AgNO3/NH4OH; 2) PriBr (10 equiv.)
The structures of 2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀNꢀnitroꢀ
aniline Oꢀalkyl derivatives 4a—c and Nꢀmethyl compounds
Table 1. The reaction of nitramines 3a—c with diazomethane
Nitrꢀ
amine 3
Ratioa
4 : 5
(mol)
Ratio
(E)ꢀ4 : (Z)ꢀ4
(%)
Yield (%)b
Table 2. The synthesis of Oꢀ and Nꢀisopropyl compounds 4d and
5d from nitramine 3b
4
5
3a
3b
3c
1.1 : 1
1 : 1
1 : 1
96 : 4
93 : 7
97 : 3
48
35
42
47
48
51
Entry
Solvent
Reaction
time/days
Yield (%)*
4d
5d
a The molar ratios of products 4a—c and 5a—c were determined
from the 1H NMR spectra.
b The yields were calculated on the isolated product. The conꢀ
version of 3a—c was quantitative.
1
2
MeCN
Et2O
24
35
64
71
12
—
* The yields were calculated on the isolated product.

Oxodiazonium ion
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2053
5a—c were confirmed by the 1H, 13C, and 14N NMR specꢀ
tra. The full assignment of signals in the 13C NMR spectra
of these compounds was performed using the 1H—13C
twoꢀdimensional NMR spectra (HMBC and HSQC).
Synthesis of BTDO 6a—c by the reaction of Oꢀalkyl
compounds 4a—c with acids or BF3•Et2O. It was found
that Oꢀmethyl compounds 4a—c in the solutions of conꢀ
centrated acids are transformed into BTDO 6a—c in virꢀ
tually quantitative yields (Scheme 5, Table 3). The rate of
cyclization strongly depends on the acid strengths. Thus,
in H2SO4 (Ho = –11.9410), compound 4a is completely
consumed within 5 min (the TLC data), in the weaker
MeSO3H (Ho = –7.7411), within 10 min, whereas in
CF3COOH (Ho = –2.7112), the reaction reaches completion
within 2 h. Similar tendency is observed in the case of the ring
closure in compounds 4b,c with the cyclization being the
slowest in the case of dibromoꢀsubstituted compound 4c,
which can be explained by the steric effect of the Br atom
in the orthoꢀposition to the tertꢀbutylꢀNNOꢀazoxy group.
In contrast to Oꢀmethyl derivatives 4a—c, the Oꢀisoꢀ
propyl compound 4d upon the action of H2SO4 and
MeSO3H leads to BTDO 6b in only 6—10% yield (the
1H NMR spectroscopic data), with the reaction mixture
containing several unidentified products (the TLC and
1H NMR spectroscopic data). Apparently, this is caused
by involvement of the isopropyl group into the reaction.
At the same time, the Oꢀisopropyl compound 4d is quantiꢀ
tatively converted to the corresponding tetrazineꢀ1,3ꢀdiꢀ
oxide 6b in the solution of weaker CF3COOH, with the
rate of the reaction in this case being higher than that in
the case of Oꢀmethyl derivatives 4a—c (see Table 3).
A Lewis acid, for example BF3•OEt2, can also be used
for the transformation of Oꢀalkyl compounds 4a—d into
BTDO 6a—c (see Scheme 5 and Table 3). For compounds
4a,b and 4d, the cyclization reaction in the solution of
BF3•OEt2 takes approximately the same time (45—50 min)
and leads to BTDO 6a,b in quantitative yields. However,
for the sterically hindered 4c the process comes to comꢀ
pletion only for 7 h, and the target product 6c was obꢀ
tained in 83% yield.
Scheme 5
Suggested scheme for the generation of the oxodiazoniꢀ
um ion from Oꢀalkyl compounds 4a—d upon the action of
acids or BF3•Et2O. Earlier,6 we have carried out quantum
chemical calculations for the reaction of 3ꢀ[methoxyꢀ
(oxido)diazenyl]ꢀ4ꢀphenylfurazane 2 with H2SO4 (see
Scheme 2), which showed that in the course of the reacꢀ
tion, formation of the complex B takes place with its further
unactivated decomposition to the oxodiazonium ion C
i. H+ or BF3•OEt
R1 = R2 = H, R3 = Me (a); R1 = H, R2 = Br, R3 = Me (b);
R
1 = R2 = Br, R3 = Me (c); R1 = H, R2 = Br, R3 = Pri (d)
Table 3. The synthesis of BTDO 6a—c from Oꢀalkyl compounds 4a—d
Entry
OꢀAlkyl
compound
Acid
T/°Ca
Reaction
time
BTDO
Yield of BTDO
(%)b
(concentration (%))
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4b
4b
4b
4b
4c
4c
4c
4c
4d
4d
4d
4d
H2SO4 (93)
0→20
20
20
20
0→20
20
20
20
0→20
20
20
05 min
10 min
02h
50 min
10 min
30 min
01.5 h
45 min
10 min
01 h
02 days
07 h
05 min
10 min
30 min
50 min
6a
6a
6a
6a
6b
6b
6b
6b
6c
6c
6c
6c
6b
6b
6b
6b
99
99
99
99
98
96
99
97
97
89
98
83
10c
6c
СH3SO3H (100)
CF3COOH (100)
BF3•Et2O (100)
H2SO4 (93)
СH3SO3H (100)
CF3COOH (100)
BF3•Et2O (100)
H2SO4 (93)
СH3SO3H (100)
CF3COOH (100)
BF3•Et2O (100)
H2SO4 (93)
СH3SO3H (100)
CF3COOH (100)
BF3•Et2O (100)
9
10
11
12
13
14
15
16
20
20
20
20
98
98
20
a The reaction temperature.
b The yields of BTDO 6a—c were determined from the 1H NMR spectra. The conversion of compounds 4a—c was quantitative.
c The yields of BTDO 6b were determined from the 1H NMR spectra. The conversion of compound 4d was quantitative.
Unidentified products were additionally found in the mixture with BTDO 6b.

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Klenov et al.
micrOTOF II instrument with electrospray ionization (ESI).13
For the fragments containing bromine atoms, only peaks of ions
containing 79Br isotopes are given. Reaction progress and purity
of compounds were monitored by thinꢀlayer chromatography
(Silufol UVꢀ254 and Merck 60 F254). Silica gel was used for
preparative thinꢀlayer chromatography. 2ꢀ(tertꢀButylꢀNNOꢀ
azoxy)ꢀNꢀnitroaniline,5 2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀ5ꢀbromoꢀNꢀ
nitroaniline,5 2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀ3,5ꢀdibromoꢀNꢀnitroꢀ
aniline,5 and solution of diazomethane in diethyl ether14 were
obtained according to the known procedures.
and the molecule of methanol. Formation of the oxodiazꢀ
onium ion D from compounds 4a—d can occur according
to the similar mechanism, which includes protonation with
the formation of the kinetically unstable intermediate E
and its dissociation (Scheme 6).
Scheme 6
Reaction of 2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀNꢀnitroanilines (3a—c)
with diazomethane (general procedure). A solution of diazoꢀ
methane in Et2O (3 mL), obtained from NꢀmethylꢀNꢀnitrosourea
(0.2 g), was added dropwise to a stirred solution of nitramine
3a—c (0.33 mmol) in Et2O (5 mL) at 20 °C until evolution of the gas
and pale yellow coloring of the solution stopped. Then, the solꢀ
vent was evaporated in vacuo. The molar ratios of the Oꢀalkylꢀ
ated 4a—c and Nꢀalkylated 5a—c products were determined by
1H NMR spectroscopy. The products 4b and 5b were separated
by preparative TLC on silica gel (light petroleum—AcOEt (20 : 1,
then 10 : 1)). The products 4a and 5a, as well as 4c and 5c, were sepꢀ
arated by preparative TLC on silica gel (light petroleum—AcOEt
(20 : 1)). The yields of products 4a—c and 5a—c are given
in Table 1.
2ꢀ(tertꢀButylꢀNNOꢀazoxy)[methoxy(oxido)diazenyl]benzene
(4a). A mixture of Eꢀ and Zꢀisomers at the methoxy(oxido)ꢀ
diazenyl group in the ratio 96 : 4. Oil. MS (ESI), m/z: 253.1298
[M + H]+; calculated for C11H16N4O3, [M + H]+: m/z 253.1295.
MS (EI), m/z: 191 [M – MeONO]+. IR (KBr), ν/cm–1: 1280 s,
1316 s, 1360 m, 1392 w, 1456 s, 1488 s, 1560 s, 1604 w. 14N NMR
(CDCl3) δ: –52 (N→O, Δν
= 130 Hz); –57 (N(O)OMe,
1/2
Δν = 250 Hz). 1H NMR of the major isomer (E) (CDCl3),
1/2
δ: 1.46 (s, 9 H, 3 Me); 4.07 (s, 3 H, OMe); 7.37 (dd, 1 H, H(4),
J = 8.0 Hz, J = 7.7 Hz); 7.48 (dd, 1 H, H(5), J = 8.0 Hz,
J = 7.7 Hz); 7.60 (d, 1 H, H(6), J = 8.0 Hz); 7.72 (d, 1 H, H(3),
J = 8.0 Hz). 13C NMR of the major isomer (E) (CDCl3), δ: 27.0
(CMe3); 59.9 (OMe); 61.1 (CMe3); 124.9 (C(6)); 125.7 (C(3));
129.7 (C(4)); 131.8 (C(5)); 136.7 (C(1)); 145.1 (br.s, C(2)). The
HMBC and HSQC experiments were used for the assignment of
the signals in the spectrum. 1H NMR of the minor isomer (Z)
(CDCl3), δ: 1.43 (s, 9 H, 3 Me); 3.88 (s, 3 H, OMe); the other
signals overlap with the signals of the Eꢀisomer. 13C NMR
(CDCl3), δ (there are given some signals, which presumably are
related to the minor Zꢀisomer and do not overlap with the signals
of the major Eꢀisomer): 27.1 (CMe3); 125.2 (C(6)); 128.7 (C(4));
132.1 (C(5)).
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀNꢀmethylꢀNꢀnitroaniline (5a),
m.p. 34—36 °C. MS (ESI), m/z: 275.1122 [M + Na]+, calculatꢀ
ed for C11H16N4O3, [M+Na]+: m/z 275.1115. MS (EI), m/z:
176. IR (KBr), ν/cm–1: 1304 s, 1360 w, 1392 w, 1420 w, 1440 w,
1456 w, 1480 m, 1516 s, 1588 w, 1604 w. 1H NMR (CDCl3),
δ: 1.43 (s, 9 H, 3 Me); 3.68 (s, 3 H, NMe); 7.35 (dd, 1 H, H(6),
J = 7.9 Hz, J = 1.1 Hz); 7.52—7.57 (m, 2 H, H(4) and H(5));
7.91 (dd, 1 H, H(3), J = 7.7 Hz, J = 1.1 Hz). 13C NMR (CDCl3),
δ: 26.8 (Me); 42.9 (NMe); 61.4 (CMe3); 126.7 (C(3)); 130.1
(C(6)); 131.8 (C(4)); 132.9 (C(5)); 134.3 (C(1)); 146.7 (br.s,
C(2)). The HMBC and HSQC experiments were used for the
assignment of the signals in the spectrum. 14N NMR (CDCl3),
δ: –31 (N—NO2, Δν1/2 = 30 Hz); –53 (N→O, Δν1/2 = 70 Hz).
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀ5ꢀbromo[methoxy(oxido)diazenꢀ
yl]benzene (4b). A mixture of Eꢀ and Zꢀisomers at the methꢀ
Generation of the cation D from the Oꢀalkyl comꢀ
pound upon the action of BF3•Et2O can occur similarly
via formation of the intermediate complex F (see Scheme 6).
In conclusion, in the present work we developed a new
method for the synthesis of benzotetrazineꢀ1,3ꢀdioxides
from Oꢀalkyl derivatives of 2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀNꢀ
nitroanilines upon the action of acids or BF3•Et2O.
Experimental
1
H NMR spectra were recorded on Bruker AMꢀ300 and
Bruker DRX 500 spectrometers (300.13 and 500.13 MHz, reꢀ
spectively). 13C and 14N NMR spectra were recorded on a Bruker
DRX 500 spectrometer (125.76 and 36.14 MHz, respectively)).
Chemical shifts are given relatively Me4Si (1H, 13C) or MeNO2
(
14N, external standard, the highꢀfield chemical shifts are negaꢀ
tive). IR spectra were recorded on a Specord Mꢀ80 spectrometer
in KBr pellets or for neat layers on clear NaCl plates. Mass
spectra were recorded on a Kratos MSꢀ300 instrument (EI,
70 eV). High resolution mass spectra were recorded on a Bruker

Oxodiazonium ion
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2055
oxy(oxido)diazenyl group in the ratio 93 : 7 after recrystallizaꢀ
tion from light petroleum gave a mixture of Eꢀ and Zꢀisomers in
the ratio 98 : 2. M.p. 27—29 °C (from light petroleum). MS (ESI),
m/z: 331.0392 [M + H]+; calculated for C11H15N4O3Br, [M + H]+:
m/z 331.0400. MS (EI), m/z: 269 [M – MeONO]+. IR (neat),
ν/cm–1: 1275 m, 1313 m, 1361 w, 1392 w, 1454 m, 1476 s, 1553 s,
1595 w. 14N NMR (CDCl3), δ: –54 (N→O and N(O)OMe,
1H NMR (CDCl3), δ: 1.44 (s, 9 H, 3 Me); 3.61 (s, 3 H, NMe);
7.53 (d, 1 H, H(6), J = 1.9 Hz); 7.92 (d, 1 H, H(4), J = 1.9 Hz).
13C NMR (CDCl3), δ: 25.2 (CMe3); 41.4 (NMe); 60.8 (CMe3);
117.4 (C(3)); 123.1 (C(5)); 131.2 (C(6)); 134.6 (C(1)); 137.7
(C(4)); 145.2 (br.s, C(2)). The HMBC and HSQC experiments
and calculations by the additive scheme15 were used for the asꢀ
signment of the signals in the spectrum. 14N NMR (CDCl3), δ:
–32 (N—NO2, Δν1/2 = 30 Hz); –59 (N→O, Δν1/2 = 170 Hz).
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀ5ꢀbromo[(E)ꢀisopropoxy(oxido)ꢀ
diazenyl]benzene (4d) and 2ꢀ(tertꢀbutylꢀNNOꢀazoxy)ꢀ5ꢀbromoꢀ
NꢀisopropylꢀNꢀnitroaniline (5d). Concentrated aqueous NH3
(0.1 mL) was added in one portion to a suspension of nitramine 3b
(0.26 g, 0.82 mmol) in DI water (3 mL), followed by a dropwise
addition of a solution of AgNO3 (0.14 g, 0.82 mmol) in DI water
(0.5 mL). A white precipitate that formed was filtered off, washed
with DI water (3 mL), EtOH (2 mL), dried for 12 h in a vacuum
desiccator over P2O5 to obtain Agꢀsalt of nitramine 3b (260 mg,
75%). The Agꢀsalt that obtained was further used without addiꢀ
tional purification.
A. Isopropyl bromide (0.22 mL, 2.4 mmol) was added in one
portion to a solution of Agꢀsalt of nitramine 3b (0.1 g, 0.24 mmol)
in anhydrous MeCN (3 mL) at 20 °C under argon. The reaction
mixture was kept for 3 weeks at 20 °C, a precipitate was filtered
off, washed with MeCN (2 mL), the filtrates were combined, the
solvent was evaporated in vacuo. The residue was separated by
preparative TLC (light petroleum—AcOEt (20 : 1)) to obtain
Oꢀisopropyl compound 4d (54 mg, 64%) as a light yellow oil and
Nꢀisopropyl compound 5d (10 mg, 12%) as a light yellow oil,
as well.
B. Isopropyl bromide (0.11 mL, 1.2 mmol) was added in one
portion to a suspension of thoroughly powdered Agꢀsalt of nitrꢀ
amine 3b (50 mg, 0.12 mmol) in anhydrous Et2O (2 mL) at 20 °C
under argon. The reaction mixture was stirred for 1 month at
20 °C, then applied on the layer of silica gel (h = 1 cm, d = 2
cm), eluted with the light petroleum—AcOEt solvent mixture
(20 : 1, 50 mL), the eluate was concentrated in vacuo. The
Oꢀisopropyl compound 4d was purified by preparative TLC (light
petroleum—AcOEt (20 : 1, then 10 : 1)) to obtained Oꢀisopropyl
compound 4d (30 mg, 71%) as a light yellow oil.
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀ5ꢀbromo[(E)ꢀisopropoxy(oxido)ꢀ
diazenyl]benzene (4d). MS (ESI), m/z: 359.0719 [M + H]+; calꢀ
culated for C13H19N4O3Br, [M + H]+: m/z 359.0713. MS (EI),
m/z: 269 [M – PriONO]+. IR (neat), ν/cm–1: 1272 m, 1316 m,
1360 w, 1388 w, 1448 m, 1476 s, 1540 s, 1596 w. 1H NMR
(CDCl3), δ: 1.39 (d, 6 H, OCHMe2, J = 6.3 Hz); 1.44 (s, 9 H,
CMe3); 5.25 (sept, 1 H, OCHMe2, J = 6.3 Hz); 7.49 (dd, 1 H,
H(4), J = 8.6 Hz, J = 2.1 Hz); 7.62 (d, 1 H, H(3), J = 8.6 Hz);
7.74 (d, 1 H, H(6), J = 2.1 Hz). 13C NMR (CDCl3), δ: 20.4
(OCHMe2); 25.6 (CMe3); 59.8 (CMe3); 76.1 (OCHMe2); 123.8
(C(5)); 125.7 (C(3)); 126.8 (C(6)); 130.9 (C(4)); 136.6 (C(1));
142.6 (br.s, C(2)). The HMBC and HSQC experiments and calꢀ
culations by the additive scheme15 were used for the assignment
of the signals in the spectrum. 14N NMR (CDCl3), δ: –53 (N→O
and N(O)OPri, Δν1/2 = 170 Hz).
Δν = 140 Hz). 1H NMR of the major isomer (E) (CDCl3),
1/2
δ: 1.44 (s, 9 H, 3 Me); 4.09 (s, 3 H, OMe); 7.51 (dd, 1 H, H(4),
J = 8.6 Hz, J = 2.1 Hz); 7.63 (d, 1 H, H(3), J = 8.6 Hz); 7.77
(d, 1 H, H(6), J = 2.1 Hz). 13C NMR of the major isomer (E)
(CDCl3), δ: 25.5 (CMe3); 58.6 (OMe); 59.9 (CMe3); 123.8
(C(5)); 125.6 (C(3)); 126.6 (C(6)); 131.1 (C(4)); 136.3 (C(1));
142.6 (br.s, C(2)). The HMBC and HSQC experiments and calꢀ
culations by the additive scheme15 were used for the assignment
of the signals in the spectrum. 1H NMR of the minor isomer (Z)
(CDCl3), δ: 1.42 (s, 9 H, 3 Me); 3.91 (s, 3 H, OMe); the other
signals overlap with the signals of Eꢀisomer. 13C NMR (CDCl3),
δ (there are given some signals, which presumably are related
to the minor Zꢀisomer and do not overlap with the signals of
the major Eꢀisomer): 25.6 (CMe3); 124.1 (C(5)); 126.7 (C(6));
130.3 (C(4)).
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀ5ꢀbromoꢀNꢀmethylꢀNꢀnitroaniline
(5b), oil. MS (ESI), m/z: 331.0399 [M + H]+; calculated for
C11H15N4O3Br, [M + H]+: m/z 331.0400. MS (EI), m/z: 254. IR
(neat), ν/cm–1: 1296 s, 1364 m, 1396 w, 1428 w, 1452 w, 1484 m,
1540 s, 1576 w, 1596 w. 1H NMR (CDCl3), δ: 1.41 (s, 9 H,
3 Me); 3.67 (s, 3 H, NMe); 7.52 (d, 1 H, H(6), J = 2.1 Hz); 7.67
(dd, 1 H, H(4), J = 8.7 Hz, J = 2.1 Hz); 7.84 (d, 1 H, H(3),
J = 8.7 Hz). 13C NMR (CDCl3), δ: 25.4 (CMe3); 41.4 (NMe);
60.2 (CMe3); 124.6 (C(5)); 126.6 (C(3)); 131.8 (C(6));
133.3 (C(4)); 133.9 (C(1)); 144.2 (br.s, C(2)). The HMBC and
HSQC experiments and calculations by the additive scheme15
were used for the assignment of the signals in the spectrum.
14N NMR (CDCl3), δ: –32 (N—NO2, Δν
(N→O, Δν1/2 = 90 Hz).
= 30 Hz); –55
1/2
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀ3,5ꢀdibromo[methoxy(oxido)ꢀ
diazenyl]benzene (4c). A mixture of Eꢀ and Zꢀisomers at the
methoxy(oxido)diazenyl group in the ratio 97 : 3. M.p. 94—97 °C.
MS (ESI), m/z: 430.9310 [M
+
Na]+; calculated for
C11H14N4O3Br2, [M + Na]+: m/z 430.9325. MS (EI), m/z: 347
[M – MeONO]+. IR (KBr), ν/cm–1: 1320 m, 1364 w, 1388 w,
1436 m, 1468 w, 1500 m, 1548 s, 1580 m. 14N NMR (CDCl3),
δ: –57 (N→O and N(O)OMe, Δν1/2 = 240 Hz). 1H NMR of the
major isomer (E) (CDCl3), δ: 1.50 (s, 9 H, 3 Me); 4.07 (s, 3 H,
OMe); 7.74 (d, 1 H, H(4), J = 1.9 Hz); 8.36 (d, 1 H, H(6),
J = 1.9 Hz). 13C NMR of the major isomer (E) (CDCl3), δ: 25.6
(CMe3); 58.7 (OMe); 60.7 (CMe3); 116.6 (C(3)); 122.7 (C(5));
124.4 (C(6)); 135.0 (C(4)); 136.5 (C(1)); 143.3 (br.s, C(2)). The
HMBC and HSQC experiments and calculations by the additive
scheme15 were used for the assignment of the signals in the specꢀ
trum. 1H NMR of the minor isomer (Z) (CDCl3), δ: 1.44 (s, 9 H,
3 Me); 3.96 (s, 3 H, OMe); the rest of the signals overlap with
the signals of Eꢀisomer. 13C the minor isomer (Z) (CDCl3),
δ: 25.4 (CMe3); the other signals overlap with the signals of
Eꢀisomer.
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀ5ꢀbromoꢀNꢀisopropylꢀNꢀnitroꢀ
aniline (5d). MS (ESI), m/z: 397.0287 [M + K]+; calculated for
C13H19N4O3Br, [M + K]+: m/z 397.0272. MS (EI), m/z: 312
[M – NO2]+. IR (neat), ν/cm–1: 1256 m, 1280 s, 1300 s, 1364 m,
1388 w, 1452 m, 1484 s, 1540 s, 1572 m, 1592 w. 1H NMR
(CDCl3), δ: 1.41 (s, 9 H, CMe3); 1.48 (d, 6 H, NCHMe2,
J = 6.5 Hz); 4.87 (sept, 1 H, OCHMe2, J = 6.5 Hz); 7.41 (d, 1 H,
2ꢀ(tertꢀButylꢀNNOꢀazoxy)ꢀ3,5ꢀdibromoꢀNꢀmethylꢀNꢀnitroꢀ
aniline (5c), m.p. 112—115 °C. MS (ESI), m/z: 430.9316
[M + Na]+; calculated for C11H14N4O3Br2, [M + Na]+: m/z
430.9325. MS (EI), m/z: 332. IR (KBr), ν/cm–1: 1284 s, 1316 m,
1364 w, 1404 w, 1428 m, 1452 m, 1488 m, 1544 s, 1584 w.

2056
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Klenov et al.
H(6), J = 2.1 Hz); 7.71 (dd, 1 H, H(4), J = 8.7 Hz, J = 2.1 Hz);
7.87 (d, 1 H, H(3), J = 8.7 Hz). 14N NMR (CDCl3), δ: –33
(N—NO2, Δν1/2 = 30 Hz); –55 (N→O, Δν1/2 = 100 Hz).
Synthesis of BTDO 6a—c from Oꢀalkyl compounds 4a—d (genꢀ
eral procedure). A. An acid (0.5 mL) (see Table 3) was added in
one portion to Oꢀalkyl compound 4a—d (0.015 mmol) with vigꢀ
orous stirring at 20 °C.* The reaction mixture was kept at 20 °C
for the time indicated in Table 3, then poured into water with ice
(3 mL),** followed by extraction with CH2Cl2 (3×2 mL). The
organic extracts were combined, washed with brine (1 mL), dried
with MgSO4, and concentrated in vacuo. The yields of BTDO
6a—c were determined from the 1H NMR spectroscopic data
(see Table 3).
B. Boron trifluoride diethyl etherate (0.5 mL) was added in
one portion to Oꢀalkyl compound 4a—d (0.015 mmol) at 20 °C
under dry argon. The reaction mixture was kept at 20 °C for the
time indicated in Table 3 and then diluted with CH2Cl2 (3 mL)
and H2O (2 mL). The mixture was neutralized with NaHCO3 to
pH 7, followed by separation of the organic layer. The aqueous
layer was extracted with CH2Cl2 (3 mL). The organic extracts
were combined, washed with brine (1 mL), dried with MgSO4,
and concentrated in vacuo. The yield of BTDO 6a—c were deꢀ
termined by 1H NMR spectroscopy (see Table 3).
2. A. M. Churakov, S. L. Ioffe, V. A. Tartakovsky, Mendeleev
Commun., 1991, 1, 101.
3. A. M. Churakov, O. Yu. Smirnov, S. L. Ioffe, Yu. A. Strelenꢀ
ko, V. A. Tartakovsky, Eur. J. Org. Chem., 2002, 2342.
4. A. E. Frumkin, A. M. Churakov, Yu. A. Strelenko, V. A.
Tartakovsky, Izv. Akad. Nauk, Ser. Khim., 2000, 480 [Russ.
Chem. Bull., Int. Ed., 2000, 49, 482].
5. M. S. Klenov, V. P. Zelenov, A. M. Churakov, Yu. A. Streꢀ
lenko, V. A. Tartakovsky, Izv. Akad. Nauk, Ser. Khim., 2011,
2003 [Russ. Chem. Bull., Int. Ed., 2011, 60, 2040].
6. M. S. Klenov, M. O. Ratnikov, A. M. Churakov, V. N. Solꢀ
kan, Yu. A. Strelenko, V. A. Tartakovsky, Izv. Akad. Nauk,
Ser. Khim., 2011, 523 [Russ. Chem. Bull., Int. Ed., 2011,
60, 536].
7. V. N. Yandovskii, B. V. Gidaspov, I. V. Tselinskii, Usp. Khim.,
1980, 49, 461 [Russ. Chem. Rev. (Engl. Transl.), 1980,
49, 237].
8. S. L. Ioffe, A. S. Shashkov, A. L. Blyumenfel´d, L. M.
Leont´eva, L. M. Makarenekova, O. B. Belkina, V. A. Tarꢀ
takovsky, Izv. Akad. Nauk SSSR, Ser. Khim., 1976, 25, 2547
[Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1976,
25, 2371].
9. O. A. Luk´yanov, N. I. Shlykova, V. A. Tartakovsky, Izv.
Akad. Nauk, Ser. Khim., 1994, 1775 [Russ. Chem. Bull.
(Engl. Transl.), 1994, 43, 1680].
Physicochemical and spectral data for compounds 6a—c
agrees with those given in the literature.3
10. A. J. Gordon, R. A. Ford, The Chemist´s Companion, John
Wiley and Sons, New York, 1972, p. 80.
11. I. S. Kislina, S. G. Sysoeva, Izv. Akad. Nauk, Ser. Khim.,
1999, 1940 [Russ. Chem. Bull. (Engl. Transl.), 1999, 48, 1916].
12. U. A. Spitzer, T. W. Toone, R. Stewart, Can. J. Chem., 1976,
54, 440.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00752)
and the Ministry of Education and Science of the Russian
Federation (State Contract No. 02.740.11.0258).
13. P. A. Belyakov, V. I. Kadentsev, A. O. Chizhov, N. G. Koloꢀ
tyrkina, A. S. Shashkov, V. P. Ananikov, Mendeleev Comꢀ
mun., 2010, 20, 125.
References
14. F. Arndt, in Organic Syntheses, Vol. 15, Wiley, New York,
1935, p. 3.
15. D. E. Ewing, Org. Magn. Reson., 1979, 12, 499.
1. V. P. Zelenov, A. A. Voronin, A. M. Churakov, M. S. Klenꢀ
ov, Yu. A. Strelenko, V. A. Tartakovsky, Izv. Akad. Nauk,
Ser. Khim., 2011, 2009 [Russ. Chem. Bull., Int. Ed., 2011, 60,
2046].
* For the reaction with H2SO4, an acid, preliminary cooled to 0 °C,
was added to the Oꢀalkyl compound 4a—c, and then the temperꢀ
ature was raised to 20 °C over the time indicated in Table 3.
** For the reaction in CF3COOH, the reaction mixture was concenꢀ
trated, and the residue was analyzed by 1H NMR spectroscopy.
Received March 31, 2011