1H, 13C and 15N NMR spectroscopy and tautomerism of nitrobenzotriazoles

Article abstract of DOI:10.1002/mrc.2366

Benzotriazole nitro derivatives were prepared by nitration of the corresponding benzotriazoles and by methylation or cyclization of appropriate nitro-1,2-phenylenediamines. Structures and tautomerism of the nitrobenzotriazoles were studied by multinuclear ¹H, ¹³C, ¹⁵N, and ²D NMR spectroscopy and quantum chemistry. Copyright

Full text of DOI:10.1002/mrc.2366

Research Article
Received: 29 July 2008
Revised: 28 September 2008
Accepted: 3 October 2008
Published online in Wiley Interscience: 28 November 2008
(www.interscience.com) DOI 10.1002/mrc.2366
1H, 13C and 15N NMR spectroscopy
and tautomerism of nitrobenzotriazoles
Lyudmila I. Larinaa∗ and Viktor Milatab
Benzotriazole nitro derivatives were prepared by nitration of the corresponding benzotriazoles and by methylation or
cyclization of appropriate nitro-1,2-phenylenediamines. Structures and tautomerism of the nitrobenzotriazoles were studied
by multinuclear 1H, 13C, 15N, and 2D NMR spectroscopy and quantum chemistry. Copyright ꢀ 2008 John Wiley & Sons, Ltd.
c
Keywords: 4-,5-,6-,7-nitrobenzotriazoles; nitration; tautomeric equilibria; structure; 1H,13C and 15N NMR; B3LYP/6-311G∗∗
Introduction
Benzotriazoles hold a special position in the chemistry of
heterocycles. During the last years interest in the chemistry
of benzazoles and, in particular, nitrobenzotriazoles has been
increasing.[1–8] Their unique properties and specific biological
activity attract much attention of research chemists all over
the world. Nitro derivatives of benzotriazoles have found wide
applications in various branches of medicine, technology, and
chemistry as ionic liquids, synthones for nanocompounds, and
intermediates for organic synthesis.[2,7,8]
Prototropictransformationsofalmostallbenzazolesinsolutions
Scheme 2. The formation of diazocompounds in photolysis of benzotria-
zole.
proceed so quickly on the NMR time scale that varying the solution
temperatures does not cause changes in the spectra.[9–14] In all
cases the time-averaged signals are observed in the spectra.
Speculation about the existence of tautomeric forms of
benzotriazole in solution and in gas-phase has persisted over
a long period of time (Scheme 1).[15–20]
the positions 2 and 3 (repulsion energy equals 6.5 kcal/mol).[18] For
the quinoid-like tautomer, this type of interaction is impossible. In
solution, the equilibrium is shifted toward the tautomer A, which
can be explained by better solvation of more polar 1H-form (µ =
4.3 D) as compared to 2H-tautomer (µ = 0.38 D).[18]
It has been found that benzotriazole in gas-phase is stable as
2H-tautomer (B), while it exists as 1H-tautomer (A) in solution and
in the solid state.[18,21–30] According to ion-cyclotron resonance
data, B is thermodynamically more favorable in the gas-phase
than A by 4 kcal/mol whereas a calculated value (ab initio, MP2/6-
31G∗∗) is 2.5 kcal/mol.[18] Practically, the position of the tautomeric
equilibrium in solution does not depend on the value of pKa of the
solvent used (acetone, methanol, chloroform, DMSO).[22]
−−−ꢀ
Analysis of the IR spectra of benzotriazole in argon and nitrogen
matrices (12–14 K) indicates that the ratio of tautomers [1H] :
[2H] is ∼1.6 : 1 (gas-phase, 315 K).[31] These results correlate well
with the data on the band forms ν(NH) in gas-phase spectra of
benzotriazole (1.4 : 1). Photolysis of benzotriazole made it possible
to reveal formation of diazo compounds[31] (Scheme 2):
The shift of the tautomeric equilibrium A
B (Scheme 1) is
The intensity ratio of the ν(NH) band (3486 cm−1) of tautomer
A and the pair of bands (3460 and 3452 cm−1) of tautomer B after
2 min of photolysis becomes equal to 1.2 : 1. This indicates the
phototransformation of the tautomer A (Scheme 2). Assignment
of the IR bands has been carried out on the basis of ab initio
calculations using B3LYP/6-31G∗ set.[31]
ꢁ−−−
caused by two factors, namely benzene ring aromaticity and
mutual repulsion of unshared electron pairs of neighboring
pyridine nitrogen atoms of the tautomer.[30] The aromaticity of 1H-
benzotriazole is higher than that of its quinoid-like 2H-tautomer.
In the case of the 1H-form, a high destabilizing effect is due to
mutual repulsion of unshared electron pairs of nitrogen atoms at
∗
Correspondence to: Lyudmila I. Larina, A. E. Favorsky Irkutsk Institute of
Chemistry, Siberian Branch, Russian Academy of Sciences, 664033, Russian
Federation, Irkutsk. E-mail: larina@irrioch.irk.ru
a
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy
of Sciences, 664033, Russian Federation, Irkutsk
b
Department of Organic Chemistry, Slovak University of Technology,
Radlinskeho 9, SK-812 37 Bratislava, Slovak Republic
Scheme 1. Tautomeric equilibrium in benzotriazole.
c
Magn. Reson. Chem. 2009, 47, 142–148
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Copyright ꢀ 2008 John Wiley & Sons, Ltd.

NMR spectroscopy and tautomerism of nitrobenzotriazoles
Scheme 5. The possible structures of 4(7)-nitrobenzotriazole (1a) and
N-oxy-7-nitrobenzotriazole.
−−−−ꢀ
ꢁ−−−−
Scheme 3. Tautomeric equilibrium of benzotriazole N-oxide
hydroxybenzotriazole.
1-
methylbenzotriazole (3b), and their model compounds benzo-
triazole and 1-methyl- and 2-methylbenzotriazole by means of
multinuclear one- and two-dimensional 1H, 13C and15N NMR spec-
troscopy (Scheme 4):
−−−ꢀ
The benzotriazole N-oxide
1-hydroxybenzotriazole equi-
ꢁ−−−
librium, investigated by photoelectron spectroscopy, proved the
presence of the only 1-hydroxybenzotriazole in the gas-phase
(Scheme 3).[32]
1
The H, 13C and 15N NMR chemical shifts (ppm) and coupling
According to 15N NMR spectroscopy the content of
the N-hydroxy tautomer in both equilibrium mixtures, N-
constants J(1H–1H) and J(13C–1H) (Hz) of benzotriazoles 1, 2 and
3 are presented in the Tables 1, 2 and 3.
It should be noted that, unlike methylated analogs such as 2
and 3, nitrobenzotriazoles 1 exist in tautomeric equilibria. The
introduction of the nitro group into the benzotriazole ring leads
to significant changes of chemical shifts.
The 13C and 15N NMR spectra of 4(7)- and 5(6)-
nitrobenzotriazoles (1a and 1b, respectively) show signal broad-
ening caused by prototropic exchange. The prototropic exchange
in 5(6)-nitrobenzotriazole (1b) did not allow detection of the N-1
and N-3 signals in the 15N NMR spectrum (Table 3). In the 15N NMR
spectra of 1-methylsubstituted benzotriazoles 2 (no tautomerism)
it was possible to identify all three 15N signals of the benzotriazole
skeleton.
1-hydroxybenzotriazole[33] and N-oxide
1-
−−−ꢀ
ꢁ−−−
−−−ꢀ
oxide
ꢁ−−−
hydroxybenzimidazole,[34] is significantly higher than that of the
N-oxide form and is proportional to the pKa value of the sol-
vent employed. The latter is in good accordance with electron
spectroscopy data.[34]
Quantum-chemical studies of the nitration of benzazoles have
shown that the more stable 1H- tautomer of benzimidazole is ni-
trated at the position 6, and the cations of 1,3-H-benzimidazolium
and 1-methyl-3-H-benzimidazolium are nitrated at positions 5 and
6; this is in good agreement with the experiment. These results in-
dicate the importance of the protonated benzimidazolium cations
on the nitration.[6]
Thus, we have carried out the quantum-chemical calculations
(B3LYP/6-311G+) to determine the 15N chemical shifts of the
nitrobenzotriazole tautomers of 1a and 1b as well as their N-
methyl substituted nitrobenzotriazoles (Table 4). It should be
noted that the results of the B3LYP/6-311G+ calculations correlate
satisfactorily to the experimental data.
On going from the benzenoid (2) to the quinoid-like structure
3 (2-methyl-substituted), the position of 15N signals changes
significantly: N-1 is deshielded whereas N-2 is shielded by
approximately 100 ppm, and N-3 is shielded by ca 20 ppm.
(Table 3). The nitro group position at the heterocyclic phenylene
fragmentdoesnotinfluencemuchthe15Nshifts(lessthan10 ppm).
The 15N chemical shift values of the N-1, N-2 atoms in N-
unsubstituted benzotriazoles (1) and their 1-methylated analogs
(2) are nearly coincident (Table 3). This provides good basis to
assume that nitrobenzotriazoles 1 exist as an equilibrium mixture:
Results and Discussion
We have studied the electronic structures of 4(7)-nitro-
(1a) and 5(6)-nitrobenzotriazole (1b), 4-nitro-1-methyl- (2a),
5-nitro-1-methyl- (2b), 6-nitro-1-methyl- (2c), and 7-nitro-1-
methylbenzotriazole (2d), 4-nitro-2-methyl- (3a) and 5-nitro-2-
−−−ꢀ
ꢁ−−−
−−−ꢀ
ꢁ−−−
1-NH
3-NH i.e. A
C
but not
−−−ꢀ
ꢁ−−−
−−−ꢀ
ꢁ−−−
1-NH
3-NH i.e. A
B
Moreover, the calculated 15N chemical shift values of nitroben-
zotriazoles (1) are practically coincident with calculated and some
experimental (N-2, N-3, NO2) values of 1-methylated nitrobenzo-
triazoles (2) (Table 3 and 4).
Thus, the experimental and calculated screening constant
values indicate that N-unsubstituted benzotriazoles (1) undergo a
−−−ꢀ
−−−ꢀ
prototropic exchange 1
3, but not 1
2. The position
ꢁ−−−
ꢁ−−−
of a nitro group at the phenylene fragment of benzimidazole cycle
does not influence the tautomeric equilibrium significantly and
has some impact only on screening constants of magnetic active
Scheme 4. Chemical structures of nitrobenzotriazoles (1) and their
methylated derivatives (2 and3).
c
Magn. Reson. Chem. 2009, 47, 142–148
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L. I. Larina and V. Milata
Table 1. 1H NMR chemical shifts and coupling constants (J) of nitrobenzotriazoles (1) and their 1-methyl- (2) and 2-methyl derivatives (3) (DMSO-d6)
δ1H (ppm) and J (Hz)
Position
NO2
NH
N–CH3
Compound
No
H-4
H-5
H-6
H-7
Benzotriazole (BT)a
13.0
7.98
7.47
7.47
7.98
16.3b
15.2c
12.0d
8.32 dd
3J = 8.1
4J = 0.8
7.39 dd
3J = 8.1
3J = 8.1
8.16 dd
3J = 8.1
4J = 0.8
4
4(7)
5(6)
1a
1b
–
9
8
N
5
3
2
N
O2N
1
6
N
8.97 dd
4J = 1.7
5J = 0.6
8.32 dd
3J = 9.1
4J = 1.7
8.11 d
3J = 9.1
5J = 0.6
7
H
16.0
–
1-Methylbenzotriazolea (1-MeBT)
4
4.36
7.92
7.27
7.32
7.36
7.77 dd
3J = 8.3
3J = 7.7
8.29 d
3J = 7.7
8.35 d
3J = 8.3
2a
2b
4.41 s
–
9.00 dd
4J = 2.0
5J = 0.6
8.39 dd
3J = 9.2
4J = 2.0
8.09 dd
3J = 9.2
5J = 0.6
4
5
4.39 s
–
9
8
N
5
3
2
N
O2N
1
6
N
8.19 dd
3J = 9.1
4J = 1.8
7.54 dd
3J = 8.2
3J = 7.8
7
8.25 d
3J = 9.1
8.89 d
4J = 1.8
Me
6
7
2c
4.44 s
4.44 s
–
8.30 dd
3J = 7.8
4J = 0.9
8.44 dd
3J = 8.2
4J = 0.9
2d
–
8.39 dd
3J = 8.2
4J = 1.8
7.63 dd
3J = 8.2
3J = 7.5
8.38 dd
3J = 7.5
4J = 1.8
4
5
3a
3b
4.61 s
4.64 s
–
3
N
2
4
9
8
5
N
Me
O2N
6
N
7
1
8.88 dd
4J = 2.0
5J = 0.8
8.26 dd
3J = 9.3
4J = 2.0
8.21 dd
3J = 9.3
5J = 0.8
–
2-Methylbenzotriazolea (2-MeBT)
4.57
7.93
7.38
7.38
7.93
a from Ref. [35].
+27 ◦C.
+80 ◦C.
b
+50 ◦C.
c
d
nuclei of the heterocycle. So, 15N NMR spectroscopy along with
quantum-chemical calculations is the convenient approach in the
examination of tautomeric processes.
problem.[35,36,38] Structuralinvestigationby15NNMRspectroscopy
is convenient and a unique approach in the examination of
tautomerism problems in azoles. Furthermore, the shielding of
15N nuclei on going from the benzenoid to the quinoid-like
structure can be a test for the determination of the structure
of nitrogen-containing heterocycles. However, in studying the
electronic structure of aromatic heteroatom compounds by NMR
spectroscopy it should be kept in mind that even minor variations
in tautomeric equilibrium constants, molecular conformations,
temperature or solvents can change the shielding of the nuclei
markedly, and this is not always in line with the electron
redistribution. So, 15N NMR spectroscopy provides one of the most
In addition, the broad NH-signal (16 ppm) in the 1H NMR
spectrum of 4(7)-nitrobenzotriazole undergoes a 4 ppm low-
frequ◦ency shift (12 ppm) when the sample temperature rises to
+80 C. (Table 1). This may indicate the presence of an N–O... H–N
hydrogenbondandtheexistenceofa7-nitrotautomer(Scheme5).
The realization of an analogous structure N-oxy-7-
nitrobenzotriazole has been reported in the literature.[33]
The tautomerism and isomerism of benzotriazoles (and azoles)
make the structure analysis of such compounds a difficult
c
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NMR spectroscopy and tautomerism of nitrobenzotriazoles
Table 2. 13C NMR (ppm) chemical shifts and coupling constants J(13C–1H) (Hz) of nitrobenzotriazoles (1) and their 1-methyl- (2) and 2-methyl
derivatives (3) (DMSO-d6)
δ
13 C (ppm) and J (Hz)
Position
NO2
No
C-4
C-5
C-6
C-7
C-8
C-9
N-Me
BTa
115.1
125.7
125.7
115.1
138.1
138.1
123.74
126.88
1J = 168.2
3J = 7.0
146.59
3J = 7.0
123.67
1J = 168.0
1J = 168.1
126.92
br sb
133.03
3J = 7.4
1a
1b
4(7)
5(6)
3J = 8.0
2J = 2.7
114.11
1J = 175.3
3J = 8.1
120.90
1J = 171.3
3J = 4.4
144.55
3J = 4.4
113.70
1J = 171.3
138.93
br sb
140.15
br sb
1-MeBTc
119.3
123.4
126.8
108.8
133.1
145.5
36.6
121.52
1J = 168.7
3J = 8.4
118.83
1J = 171.7
3J = 8.4
137.86
3J = 8.4
126.78
1J = 168.2
135.86
3J = 6.4
137.41
3J = 10.0
2a
4
34.98
2J = 2.4
115.67
1J = 172.9
3J = 4.7
121.34
1J = 169.5
3J = 4.4
147.20
3J = 9.6
2J = 4.8
143.89
mc
111.26
1J = 172.9
135.69
3J = 5.4
143.66
md
2b
2c
5
6
34.26
35.02
118.60
1J = 170.7
3J = 4.4
108.64
1J = 175.8
3J = 4.4
120.21
1J = 171.2
132.79
md
146.17
md
125.25
1J = 169.0
3J = 8.4
2J = 2.4
126.96
1J = 169.0
3J = 8.0
123.62
1J = 169.0
148.55
3J = 10.0
125.54
3J = 7.6
134.87
3J = 7.6
2d
7
39.19
49.19
2-MeBTc
117.5
125.9
125.9
117.5
144.3
144.3
124.11
1J = 167.8
3J = 7.6
125.84
1J = 167.8
3J = 7.6
145.77
3J = 10.5
125.01
1J = 167.8
137.01
3J = 9.4
136.92
3J = 7.8
3a
3b
4
5
44.40
43.80
2J = 2.1
115.37
1J = 173.4
3J = 4.2
120.12
1J = 170.2
3J = 4.8
145.83
3J = 9.5
119.01
1J = 171.5
142.24
3J = 5.7
136.51
3J = 9.1
a from Ref. [35].
b broad signal.
c from Refs [15,35].
d multiplet.
powerful tools for the identification of structures and tautomeric
forms of nitrogen-containing heterocycles.
(NOESY), whereas the 13C and 15N NMR signal assignment was
made on the basis of 2D NMR methods, HSQC-GP and HMBC-GP
1H–13C, HSQC-GP and HMBC-GP 1H–15N, and also of the
data reported in Refs [9,35–38], respectively. Two-dimensional
inverse-1H-detected heteronuclear-shift-correlation spectra were
obtained with standard pulse sequences.[39] HMBC spectra were
recorded with an acquisition time of 0.2 s, a spectral width of
6000 Hz, 1024 points in the 1H dimension and 17 and 20 kHz
spectral widths for 15N and 13C dimensions, 512 increments and,
aiming at long-range coupling constants of 5 and 10 Hz for 15N
and 13C, respectively, with a relaxation delay of 2 s.
Experimental
1H, 13C and 15N NMR spectra of studied compounds were recorded
in DMSO-d6 at room temperature on Bruker DPX-400 and AV-
400 spectrometers (400.13, 100.61 and 40.56 MHz, respectively).
1H, 13C and15N chemical shifts (δ in ppm) were measured with
accuracy of 0.01, 0.05 and 0.1 ppm, respectively, and referred to
TMS (1H, 13C) and nitromethane (15N). 1H, 1H, 13C, 1H and 15N,
1H coupling constants (J in Hz) are accurate to 0.1 Hz. Some
The B3LYP/6-311G+ calculations were carried out with using
1
1H signals were assigned using H–1H two-dimensional spectra
Gaussian-98 program.[40]
c
Magn. Reson. Chem. 2009, 47, 142–148
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L. I. Larina and V. Milata
Table 3. 15N NMR (ppm) chemical shifts of nitrobenzotriazoles (1) and their 1-methyl- (2) and 2-methyl derivatives (3) (DMSO-d6)
15N (ppm)
δ
Position
NO2
No
N-1
N-2
N-3
NO2
–
BTa
−96.7
−171.0 (or −169.0)b
–
7.5
8.4c
5.4c
−96.7
1a
1b
4(7)
5(6)
−169.0 (or −171.0)b
−11.4
−8.4
–
–
1-MeBTa
−161.8
−0.9
8.3
−40.8
−42.3
−32.3
−38.2
−38.2
−62.5
−59.8
−58.3
2a
2b
2c
2d
4
5
6
7
−153.7
−10.8
−8.2
−8.2
−11.0
–
−155.8
12.9
−152.4
14.7
−156.6
10.7
2-MeBTa
−62.5
−117.0
−106.0
−102.7
3a
3b
4
5
−56.5
−11.3
−9.5
−52.3
a δ15N from Refs [35–37].
b broad signals and may be reversed.
c broad signal.
Table 4. Calculated (B3LYP/6-311G+) 15N NMR chemical shifts of nitrobenzotriazolesa
δ
15N, ppm
Position
Compound
No
NO2
NO2
N-1
N-2
N-3
4
1a
4
−14.9
−233.2
−234.6
−228.6
−230.0
−226.2
−225.0
−93.4
−99.5
−11.0
−14.7
−2.6
−63.3
N
9
8
5
3
2 N
O2N
1
6
N
1b
5
4
−13.2
−54.1
7
H
N
N
2a
−14.5
−12.7
−12.8
−11.8
−14.3
−12.4
−68.6
−58.5
−71.1
−67.4
−98.8
−89.0
N
O2N
2b
2c
5
6
−6.0
5.6
Me
2d
3a
3b
7
4
5
−3.5
−156.1
−153.7
N
N
N
Me
O2N
4a
4b
4
5
−15.1
−13.0
−99.0
−171.9
−169.7
−98.7
−89.1
N
N
H
O2N
N
−105.1
a Chemical shifts were referenced to nitromethane.
Synthesis
1-methylbenzotriazole)[47] and 3-nitro-1,2-phenylenediamine
(unambiguous alternative synthesis of 4(7)-nitrobenzotriazole).[48]
The target nitrobenzotriazoles were prepared by nitration of ben-
zotriazole (4(7)-nitrobenzotriazole)[41] and 1-methylbenzotriazole
(4-nitro-1-methylbenzotriazole),[41] methylation of 4(7)-nitro-
benzotriazole (4-nitro-2-methylbenzotriazole),[42] 5(6)-nitro-
benzotriazole (5-nitro-2-methylbenzotriazole)[43,44] and 6-nitro-
1-methylbenzotriazole[43,44] or cyclization of 4-nitro-1,2-
phenylenediamine (5(6)-nitrobenzotriazole),[45] 6-nitro-1-N-
4(7)-Nitrobenzotriazole (1a)
Benzotriazole (90 g, 0.75 mol) is dissolved in small parts in
concentrated sulfuric acid (300 ml, 96%). Nitric acid (54 ml, 65%, at
30 ◦C) is added dropwise to the cooled solution. After adding the
whole amount of acid the reaction mixture is heated to 60 ◦C for
1 h and poured onto cold water (3 l). The light yellow precipitate
methyl-1,2-phenylenediamine
(7-nitro-1-methylbenzotri-
azole),[46] 4-nitro−1 − N-methyl-1,2-phenylenediamine (5-nitro-
c
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NMR spectroscopy and tautomerism of nitrobenzotriazoles
is filtered, dried and recrystallized fro◦m acetic acid (or ◦acetone,
ethanol). Yield 114 g (92.7%), m.p. 229 C (m.p. 228–229 C).[41]
5-Nitro-2-methylbenzotriazole (3b)
Methylation of 5(6)-nitrobenzotriazole has been carried out
according to Ref. [43] with 20.25 g yield (93%). The obtained
product is recrystallized with charcoal from acetone to yield
product with m.p. 185 ◦C.
5(6)-Nitrobenzotriazole (1b)
A solution of sodium nitrite (21 g, 0.3 mol) in water (60 ml) is slowly
added dropwise to a suspension of 4-nitro-1,2-phenylenediamine
(46 g,0.3 mol)inglacialaceticacid(72 ml)andcoldwater(3l)under
vigorous mechanical stirring. The hot mixture is neutralized with
ammonia solution (5%) and cooled. The product separates and is
filtered, washed with cold water (500 ml) and dried at 80 ◦C. The
product is recrystallized with charcoal fr◦om acetic acid (or acetone,
ethanol). Yield 45.1 g (91.7%), m.p. 211 C (m.p. 209 ◦C).[45]
Acknowledgements
The authors thank the Russian Foundation for Basic Research
(Grant No. 08-03-00021), Slovak grant agency VEGA 1/0225/08
and Science and Technology Assistance Agency under contract
No. APVT-0055-07 for financial support.
4-Nitro-1-methylbenzotriazole (2a)
References
Nitric acid (7 ml, 65%) is added dropwise to 1-methylbenzotriazole
(13.3 g) dissolved slowly in concentrated sulfuric acid (40 ml, 96%)
and cooled to 0 ◦C under stirring. The reaction mixture is heated to
60–65 ◦C for 30 min and 100 ◦C for the next 30 min. After cooling
to room temperature the reaction mixture is poured into ice-water
(400 ml), the precipitate is filtered, washed with cold water to
neutral washings and recrystallized from ethanol to obtain the
product (12.0 g) with m.p. 203 ◦C.[41]
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