The N-alkylation of 4-nitrobenzochalcogenadiazoles: Synthesis and theoretical approach

Article abstract of DOI:10.1016/j.molstruc.2019.06.091

A facile synthetic method for N-alkylated substituted benzochalcogenadiazoles is described. When treated with Meerwein salt, the 4-nitrobenzochalcogenadiazoles have undergone an N-alkylation to afford the expected salts as a mixture of two N1/N3 isomers in toluene. The regioselectivity of the alkylation reaction was then confirmed by spectroscopic data as well as theoretical calculations.

Full text of DOI:10.1016/j.molstruc.2019.06.091

Accepted Manuscript
The N-alkylation of 4-nitrobenzochalcogenadiazoles: Synthesis and theoretical
approach
Saida B. Salah, Rania Zaier, Sahbi Ayachi, Régis Goumont, Taoufik Boubaker
PII:
S0022-2860(19)30814-2
DOI:
https://doi.org/10.1016/j.molstruc.2019.06.091
MOLSTR 26733
Reference:
To appear in: Journal of Molecular Structure
Received Date: 4 May 2019
Revised Date: 24 June 2019
Accepted Date: 26 June 2019
Please cite this article as: S.B. Salah, R. Zaier, S. Ayachi, Ré. Goumont, T. Boubaker, The N-alkylation
of 4-nitrobenzochalcogenadiazoles: Synthesis and theoretical approach, Journal of Molecular Structure
(2019), doi: https://doi.org/10.1016/j.molstruc.2019.06.091.
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ACCEPTED MANUSCRIPT
The N-alkylation of 4-nitrobenzochalcogenadiazoles: Synthesis
and theoretical approach.
Saida B. Salaha,c , Rania Zaierb, Sahbi Ayachib, Régis Goumontc, Taoufik Boubakera,*
aLaboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité (LCHPNR), Faculté des Sciences de Monastir, Université de Monastir,
Avenue de l’Environnement 5019, Monastir, Tunisie
bLaboratoire de Physico-Chimie des Matériaux (LR01ES19), Faculté des Sciences de Monastir, Université de Monastir, Avenue de l’Environnement,
5019 Monastir, Tunisie.
cInstitut Lavoisier de Versailles, UMR 8180, Université de Versailles, 45, Avenue des Etats-Unis 78035, Versailles Cedex, France
Abstract
A facile synthetic method for N-alkylated substituted benzochalcogenadiazoles is described.
When treated with Meerwein salt, the 4-nitrobenzochalcogenadiazoles have undergone an N-
alkylation to afford the expected salts as a mixture of two N1/N3 isomers in toluene. The
regioselectivity of the alkylation reaction was then confirmed by spectroscopic data as well as
theoretical calculations.
Keywords: Benzochalcogenadiazoles, N-alkylation, DFT, Regioselectivity.
1. Introduction
Over recent decades, major advances have occurred in the field of electrophile-nucleophile
combinations owing to the discovery of electron-deficient heteroaromatic structures such as
nitrobenzotriazoles, nitrotetrazolopyridines, nitrobenzooxadiazoles and related 10-π electron
heterocycles [1-18]. Besides being of fundamental importance to chemistry [19], electrophilic
compounds, namely natural ones such as parthenolide, fosfomycin and serine, exert their biological
activities that range from antibiotic to antitumor effects which make them a privileged class of
compounds among pharmaceutical substances [20]. In this context, extensive efforts, that started in
the past, still continue to be made to synthesize electron-deficient species and increase their
electrophilic strength.
The concept of electrophilic activation was first proposed by Olah in the 1970s [21,22]. Since
these original studies, many examples of in situ generation of superelectrophiles have been
described in literature (e.g., acyliminium salts, ketoamides, imidazoles, and sulfonamides) [23-29].
The synthetic processes consists mainly in generating highly reactive cationic compounds by
coordinating basic centers with strong Lewis acids such as Al2Cl6 and SbCl5, or by protonating
these basic centers with superacids such as (HF/SBF5 and CF3SO3H) [19,30,31].

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On our part, our group paid a particular attention to the reactivity of heteroaromatic compounds
whose carboxylic ring is intrinsically very susceptible to nucleophilic attack [32-36]. Most
interestingly, we have proved that the introduction of a NO2 group at aromatic rings, enhances their
electrophilic reactivity by several orders of magnitude which makes them able to react with a
variety of nucleophiles [1,37]. We also recently optimized the alkylation of tetrazolopyridines
bearing electron withdrawing groups (NO2, CN, CO2Me and CF3). This synthetic way leads to a
new series of positively charged electrophiles. Whereas the neutral tetrazolopyridines remained
unreactive twowards dienes, alkylated ones were shown to be able to react with cyclopentadiene
and in some cases with isoprene and 2,3-dimethylbutadiène, which indicates an increase in the
electrophilicity after N-alkylation [38].
In order to extend this activating methodology to other electrophilic compounds, we describe in
this paper the N-alkylation of a series of benzochalcogenadiazoles bearing an NO2 group. The
regioselectivity of obtained salts was determined by NMR spectroscopy and supported by
theoretical calculations at the DFT level.
2. Results and discussion
2.1. Synthesis of N-alkylated benzochalcogenadiazoles
One of the most important factors governing the reactivity of substances is their degree of electric
charge. In this paper we describe the synthesis of a new series of positively charged electrophiles
from neutral benzochalcogenadiazoles. We first proceeded to the nitration of the aromatic ring of
1a-c by a mixture of nitric and sulfuric acids to obtain the new starting reacts 2a-c. The nitration of
benzofurazan, benzothiadiazol, and benzoselenadiazol occurred regioselectively at C4 position of
the aromatic ring (Scheme 1) [39].
NO2
3
N
4
7
3
4
9
9
8
H2SO4/HNO3
0 °C
N
5
6
5
6
X
2
X
2
N
N
8
1
7
1
1a-c
2a-c
(a: X = O, b: X = S, c: X = Se)
Scheme 1. Nitration of benzochalcogenadiazoles 1a–c.
The use of strong alkylating agents seems to be necessary to N- alkylate polynitrogen
heteraromatic compounds. Alkyl halides R-X (R= Me, Et, n-Pr, n-Bu, and X= halide), mesylates R-
OMs and tosylates R-Ots have not always been effective [40]. For example, Ralph and Nunn

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showed that, even with the use of a polar solvent like nitrobenzene, no quaternary salt could be
isolated from 2,1,3-benzothiadiazole or from 2,1,3-nitrobenzothiadiazole when they were boiled
under reflux with methyl or ethyl iodide for a period of 9 hours [40a]. Dimethyl sulfate Me2SO4 and
its derivatives R2SO4 are more reactive than alkylating agents previously cited, but their use is
limited due to their toxicity [41].
The choice of strong alkylating agents like trialkyloxoniums R3O+X- is more appropriate than the
previously cited ones; these are commercial products that are able to alkylate many heteroaromatics
in mild conditions [42,43]. Known as Meerwein salt [44], trimethyloxonium tetrafluoroborate
seems to be well adapted to the alkylation of our polynitrogen heteroaromatics [45].
The alkylated products were obtained by the addition of 4 equivalents of trimethyloxonium
tetrafluoroborate in toluene as a mixture of two N1/N3 isomers (Scheme 2). Unfortunately, the
separation of the two regioisomers 3a-c and 3’a-c was not possible due to their instability in the
majority of solvents. Brown solids were obtained and the NMR studies showed that 3a-c is the
major regioisomere. Nevertheless different regioisomers ratios have been obtained when varying X
(Table 1).
Table 1. N-alkylation of 2a–c by the trimethyloxonium salt.
Ratio N1/N3
Mp
(°C)
130
147
171
Entry
Yield (%)
(%)
76/24
95/5
-
29%
52%
57%
X = O
X = S
X = Se
X = Se; N3 isomer was formed only in trace quantities.
In an attempt to improve yields and optimize operating conditions of the process, the reaction has
been further investigated under microwave irradiation instead of conventional heating. The best
results were obtained with 4 equiv. of trimethyloxonium at 115 °C. As described in Table 2, we
failed to increase yields but reaction time was reduced from 48 hours to 30 minutes whilst a slight
decrease in yields and a change in regioisomeres ratios were recorded.
Table 2. N-alkylation of 2a–c by the trimethyloxonium salt under microwave irradiation.
Ratio N1/N3
Entry
Yield [%]
(%)
80/20
90/10
-
16%
45%
35%
X = O
X = S
X = Se
X = Se; N3 isomer was formed only in trace quantities.

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It is to note that alkylated 4-nitrobenzoselenadiazoles have been described by Bella’s group as
intermediates, but they have never been isolated or chareacterized [46]. In the present work, most of
1
the synthesized salts were characterized through H NMR, 13C NMR, 19F NMR and mass
spectrometry (see Exp. Section). The spectroscopic data were fully consistent with the proposed
structures.
NO2
NO2
NO2
-
3
3
3
4
4
4
BF4
-
9
9
9
N
N
Me3O+, BF4
N
5
6
5
6
5
6
+
X
2
+
X
2
X
2
+
N
1
-
N
N
1
8
toluene, 80 °C, 48h
8
8
BF4
7
7
7
1
1a-c
2a-c
2'a-
(a: X = O, b: X = S, c: X = Se)
Scheme 2. -Methylation of 4-nitrobenzochalcogenadiazoles 2a–c.
N
A major diagnostic feature for salts 3a-c and 3’a-c is the signal towards δ = -152 ppm, which is
–
typical of the fluorine atoms of a BF4 moiety and the singlet appearing between δ = 4.67 ppm and δ
= 5.15 which is characteristic of the methyl group deshielded by the positively charged nitrogen
atom. It is also important to note that most of the resonances in 3a-c and 3’a-c are manifestly
shifted to the low fields, compared with those in the starting materials 2a-c. In the case of 3b for
example, ꢀδ ≈ 0.59 ppm for H6 and ꢀδ ≈ 8.36 ppm for C6 (Table 3). These shifts reflect the strong
electron-withdrawing effect exerted by the alkylated five-membered ring.
Table 3. Diagnostic 1H, and 13C NMR chemical shift variations upon
N-alkylation of 2b by trimethyloxonium Salts.
1H
13C
2b
3b
-
2b
3b
-
8.55
7.82
8.39
-
δC-4
δC-5
δC-6
δC-7
δC-8
δC-9
δMe
141.29
128.81
129.48
129.80
157.63
147.82
-
141.39
131.49
137.84
122.54
148.92
145.85
40.02
δH-4
δH-5
δH-6
δH-7
δH-8
δH-9
δMe
8.85
8.41
8.41
-
-
-
-
4.69
For the rest of the discussion, we will consider the case of the methylated 4-nitrobenzothiadiazole
1
taken as an example (Table 3). H NMR spectra recorded for 3b in CD3CN reveals two signals
corresponding to the three protons H5, H6 and H7. The doublet at 8.85 ppm is relative to H5 and
the multiplet appearing at 8.41 ppm is attributed to the overlapping resonance signals of H6 and H7.
The HMQC spectra recorded for the same product allows an easy assignment of C5, C6 and C7
whereas attribution of signals to quaternary carbons of the molecule requires HMBC spectra: C8 (δ

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= 148.92) is clearly discriminated from the CNO2/C9 atoms due to the absence of any correlation
with H5, however a correlation spot of C8 with H6 or H7 can be observed. When examining the
3
2
molecular structure of 3b, only J coupling with H6 and J coupling with H7 are possible for C8.
This observation allows us to say that H7 is more deshielded than H6. The signal at δ = 145.85 is
attributed to C9 (correlation with H7) and the signal at δ = 141.39 is attributed to CNO2. The same
HMBC spectra showed a nice correlation between C8 and hydrogen atoms of the methyl group
(CH3-N), from this observation it is determined that the major regioisomer is alkylated at N1.
Similar studies performed with 3a, 3c and 3’a also revealed that the major isomer always has the
methyl group at the N1 position of the 4-nitrobenzochalcogenadiazolium salts.
The main results presented in the experimental part are: i) The methylation reaction is carried out
on one of the two nitrogen atoms N1 and N3, ii) The addition is always majorly on N1, iii) The
alkylation reaction yield increases from X = O (29%) to X = Se (57%).
2.2. Theoretical approach
In order to theoretically rationalize the observed experimental results, consistent theoretical
calculations realized by means of the density functional theory (DFT), will then be introduced. In
fact, a number of global and local reactivity descriptors were computed to confront the observed
experimental
reactivity
of
4-nitrobenzochalcogenadiazoles
versus
trimethyloxonium
tetrafluoroborate and to define the reactive sites on these molecules. The electrostatic potential
(MEP) and theoretical NMR data along with the electronic properties such as frontier molecular
orbital (HOMO and LUMO), Fukui functions (ƒ- and ƒ+) and atomic charges (Q+ and Q-) were
investigated here to get a better insight of the molecular properties of 2a-c.
2.2.1. Molecular electrostatic potential (MEP) and global chemical reactivity descriptors of
benzochalcogenadiazoles 2a-c
All calculations were performed with the Gaussian 09 program [47] and the GaussView (5.0.8)
molecular visualization program package [48] by using personal computer. The geometries of 4-
nitrobenzochalcogenadiazoles 2a-c were first optimized, by using the density functional theory with
the hybrid functional method B3LYP and 6-311g (d,p) as basis set [49,50]. All of the geometries
were performed in toluene as a solvent media by the polarizable continuum model (PCM)
(Figure.1). For distances and angles values, see the supporting information.

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2b
2c
2a
Fig. 1. Optimized molecular structures for 4-nitrobenzochalcogenadiazoles 2a-c
In order to find the reactive sites of each compound, the molecular electrostatic potential (MEP)
analysis of each benzozochalcogenadiazole has been then studied. The obtained results are
illustrated in Figure 2 where the electrostatic potential contour map with the negative regions
(assigned to red) are related to electrophilic attaks and the positive regions (assigned to blue) are
related to nucleophilic reactivity.
The observation of Molecular electrostatic potential surface of 4-nitrobenzochalcogenadiazoles
2a-c shows that the red color surface surrounded by the nitro group and the nitrogen atom N3
represents the region of maximum electronegativity, and this cannot account for a favorable
-
electrostatic interaction with the ion pair (Me)3O+, BF4 . Besides, the blue color surface
accumulated on carbocycles shows their electrophilicity which is in perfect agreement with what is
known in literature concerning the electrophilic character of the carbocyclic ring of 4-
nitrobenzochalcogenadiazols.
The HOMO and LUMO energetic level diagrams of 2a-c and trimethyloxonium ion are then
calculated. From Figure 3, we can compare the differences ELUMO-EHOMO. As attempted, the weak
difference is between the ELUMO (Me3O+) and EHOMO (2-ac) in accordance with the electrophilic role
of the former and the nucleophilic one of the latter.
The chemical reactivity descriptors such as total energy (E), chemical hardness (η), electronic
chemical potential (ꢁ) and electrophilicity (ω) were also calculated for the model structures of
chalcogenadiazoles 2a-c. We gathered in Table 4 the main global descriptors of the reacts 2a-c.
Only EHOMO shows a regular increase from X = O to X = Se. For this reason we calculated the two
local reactivity descriptors: the fukui indices (Table 5) and the atomic charges (Table 6).

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2a
2b
2c
Fig. 2. Molecular electrostatic potential (MEP) plots of 4-nitrobenzochalcogenadiazoles 2a-c optimized molecular
structures.
Fig. 3. HOMO and LUMO energetic level diagrams of 2a-c and trimethyloxonium ion.
Table 4. Principal electronic descriptors of the starting materials 2a-c.
2a
2b
2c
Me3O+
-14.87
-4.98
9.88
EHOMO (eV)
ELUMO (eV)
-7.76
-3.65
4.11
-2.08
0.24
3.95
-7.52
-3.40
4.12
-2.09
0.24
3.16
-7.36
-3.45
3.91
-1.97
0.25
3.73
η
ꢀ
(eV)
(eV)
-4.94
0.10
S (eV)
(eV)
ω
1.23

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2.2.2. Local reactivity descriptors of benzochalcogenadiazols
Theoretically, the binding of nucleophiles 2a-c with the Me3O+ cations can take place via N1 or
N3 atoms. The electrophilic and nucleophilic characters of these two centers are studied using fukui
functions (ƒ) and individual atomic charges (Q). The two parameters were evaluated by Mulliken
+
-
population analysis (MPA). Table 5 collects the calculated values of ƒ
and ƒ functions of
N
N
nitrogens N1 and N3 in 2a-c molecules using Mulliken population analysis at B3LYP/6-311g(d,p)
level.
Table 5. Fukui functions
ƒ
of nitrogen centers of the nucleophiles 2a-c calculated using DFT.
N1
N3
ƒ-
ƒ+
ƒ-
ƒ+
2a
2b
2c
0.10533
0.07706
0.07635
0.08240
0.06814
0.07119
0.09587
0.04361
0.03700
0.05350
0.03858
0.04309
The higher is the nucleophilic activation (ƒ-) value, the greater is the nucleophilicity of nitrogen
atoms. Regarding molecules 2a-c, there are two nucleophilic nitrogen sites (N1, N3) available for
coupling with Me3O+ cations. The calculated ƒ- for 2b indicates that the N1site is more nucleophilic
(ƒ- = 0.077) than the N3 one (ƒ- = 0.0436), (Table 5). A similar nucleophilic trend is observed in
benzochalcogenadiazoles 2a and 2c. These calculated values support our experimental results where
the methyl group is attached at the N1 (major) and N3 (minor) positions of the
benzochalcogenadiazoles 2a-c.
Besides, ranging from 2a to 2c, the difference between Fukui functions values calculated for N1
and N2 is varying from 0.009, 0.033 to 0.032 electron. This result is in perfect agreement with
regioisomers ratios deducted from NMR spectra of alkylated benzochalcogenadiazols 3a-c and 3’a-
c (Table 1).
The values of Q- were also calculated and the obtained results are reported in Table 6. As can be
seen, the individual atomic charges revealed that nitrogen N1 is more nuclephilic than nitrogen N3.
This result is consistent with the preceding conclusion that the reaction between the 4-
nitrobenzochalcogenadiazoles 2a-c and the meerwein salt occurs preferentially at the N1 position.
Table 6. Atomic charges (Q- and Q+) for the nucleophiles 2a-c calculated using DFT.
N1
N3
Q-
Q+
Q-
Q+
2a
2b
-0.20505
-0.52477
-0.12265
-0.37956
-0.17718
-0.47561
-0.02780
-0.39342

-0A.44C18C5EPTE-0.D361M75ANUSCRIPT
2c
-0.49374
-0.34619
The above mentioned differences on atomic charge and Fukui indices explain the qualitative
behavior of the observed reactions but they are not enough to interpret the great differences of
yields. We can correlate those differences to the chalcogene atomic charge which varies from -
-
0.114 on oxygen to 0.945 on sulfur and 0.965 on selenium. If it is, so the intervention of the BF4
ion is important in the observed reactivity. Only a deeper study of kinetic and solvent effects is able
to offer an explanation. It is in progress in our laboratory.
2.2.3. NMR spectral analysis
The theoretical calculations of NMR parameters were also performed in order to confront the
experimental attributions. Besides, the combination of multinuclear magnetic resonance
spectroscopy with gauge including atomic orbital (GIAO) DFT calculations is a powerful tool in the
structural elucidation for alkylated heterocycles and in the determination of the orientation of the N-
alkylation of these compounds [51].
The chemical shifts of the hydrogen and carbon atoms were calculated with the GIAO model
using B3LYP functional with 6-311g (d,p) basis set in the acetonitrile solvent using the polarizable
continuum model (PCM). The obtained values are regrouped in Tables 7 and 8.
All the obtained values fit well with the experimental ones and confirm all the attributions except
the value obtained for H7 in 2a. At this stage, we have no explanation for this inconsistent value.
When plotting the calculated isotropic chemicals shielding for the 1H nucleus (σ 1H), and for the
1
13C nucleus (σ 13C) versus the H and 13C experimental chemical shifts, respectively, two linear
correlations were obtained (Figures 4 and 5).
According to Figure 4, the calculated regression equation between experimental chemical shift
values and the calculated shieldings for the 1H nucleus is given by:
δ (1H) = 33.85 − 1.06 σ (1H)
(R2 = 0.9982)
(1)
For the 13C, the relationship between the DFT-calculated values of the isotropic
shieldings and the observed chemical shifts is expressed by the following equation:
δ (13C) = 179.17 − 0.99 σ (13C)
(R2 = 0.9975)
(2)
The squared correlation coefficients are at least 0.9975. This implies that the calculated values
1
13
are in good agreement with the experimental chemical shifts. The slope values for H and C are
1.06 and 0.99, respectively. Ideally, this value should be 1.00 but all the points are located on,
or very close to, the straight line, pointing out the systematic nature of this slight deviation
between the experimental and the theoretical values. Interestingly, it has been shown that, in the

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case of a slope equal to 1.0 [51,52], the value derived from the intercept of the straight lines
and the ordinate axis could be used to find the chemical shift of the reference. As the
slopes of our straight lines are very close to unity (Figures 4 and 5 ), it seems reasonable to use
the data derived from the correlations to estimate the absolute chemical shifts of TMS. From
1
the Correlation plot for the H chemical shifts, a value of 31.93 ppm was obtained for TMS by
dividing 33.85 by 1.06. This value is close to the experimental data reported in the literature (32.77
ppm) [53]. The chemical shift of the 13C reference may also be determined using the data
derived from the plot of Figure 5. By dividing 179.17 by 0.99, a value of 180.98 ppm was obtained
for TMS, which is, also, not very far from the experimental value reported in the literature
(186.40 ppm) [54].
Table 7. 1H experimental chemical shift of the hydrogen atoms and 1H theoretical absolute shielding
σ (ppm) in CD3CN
of alkylated compounds
1H theoretical absolute shielding
σ
1H experimental chemical shift
δ
X
O
CH3
H5
H6
H7
CH3
H5
H6
H7
NO2
26.58
22.96
23.62
21.85
23.70
23.85
23.25
23.24
23.56
4.98
8.83
8.37
8.37
8.41
8.19
8.68
-
4
5 H
5
N3
9
X 2
26.98
27.04
26.78
27.09
27.20
23.07
23.32
22.87
23.11
23.70
23.57
23.67
23.86
23.86
23.90
4.69
4.67
5.15
4.63
-
8.85
8.59
9.11
-
8.41
8.19
8.11
-
S
Se
O
S
6
1
8
6 H
N
7
CH3
7H
NO2
CH3
N 3
4
5H
6H
5
9
8
X2
6
N 1
7
-
-
-
Se
7 H
Table 8. 13C experimental chemical shift (ppm) of the carbon atoms and 13C theoretical absolute shielding
δ σ (ppm) in
CD3CN of alkylated compounds.
X
CH3
C4
138.36
40.67
141.39
35.99
142.95
35.52
135.70
39.98
-
C5
135.76
43
C6
142.81
38.50
137.84
41.56
137.23
41.89
135.88
44.25
-
C7
119.55
50.87
122.54
59.65
122.97
60.22
127.59
48.89
-
C8
142.16
38.16
148.92
32.98
153.27
31.49
155.74
22.98
-
C9
43.36
148.16
31.57
145.85
35.66
149.72
32.84
134.36
43.85
-
δ
O
NO2
137.58
40.02
139.97
41.57
139.09
47.95
134.55
42.86
137.61
-
σ
δ
σ
δ
σ
δ
σ
δ
σ
δ
4
5 H
5
N3
9
131.49
48.65
129.91
50.68
143.55
36.80
-
X 2
S
Se
O
6
1
8
6 H
N
7
CH3
7H
NO2
CH3
N 3
4
5H
6H
5
9
8
X2
6
N 1
S
7
38.26
-
41.64
-
49.13
-
46.14
-
25.61
-
41.64
-
7 H
Se

ACCEPTED MANUSC5R0I.2P7T
141.08
38.84
45.88
49.47
22.29
41.43
σ
180
160
140
120
100
80
10
9
8
7
6
60
5
40
4
20
21
22
23
24
25
26
27
28
0
20
40
60
80
100
120
140
160
σ (1H) chemical shieldings, ppm
σ (13C) chemical shieldings, ppm
Fig. 5. Experimental 13C NMR chemical shifts (δ 13C)
versus theoretical chemical shieldings (σ 13C) in ppm.
Fig. 4. Experimental 1H NMR chemical shifts (δ 1H) versus
theoretical chemical shieldings (σ 1H) in ppm.
A major message that emerges from this study is the consistency observed for all
the spectroscopic data. As can be seen, the experimental results are well reproduced by the
calculated ones. Theoretical calculations and experimental NMR spectroscopy lead to the same
structure for each alkylated benzochalcogenadiazole.
3. Conclusion
The alkylation of the 4-nitrobenzochalcogenadiazoles to give the expected
benzochalcogenadiazolium salts as a mixture of two N1/N3 isomers in good yields in toluene has
been investigated. A complete structural study of N-alkylated salts is reported here for the first time.
This study confirms the obtention of the expected structures and showed that alkylation occurs
majorly at the N1 position. In a subsequent theoretical study, we tried to find an explanation for the
observed regioselectivity. The obtained results for atomic charges and Fukui indices explain the
qualitative behavior of the observed reactions but they are not enough to interpret the great
-
differences of yields. However, a deep study of the intervention of the BF4 ion, kinetic and solvent
effects is able to offer an explanation. It is in progress in our laboratory.
4. Experimental section
All Solvents and Chemical Reagents were purchased from commercial suppliers and used
without further purifications. 1H, 13C and 19F NMR spectra were recorded on a Brucker 300 and 200
1
MHz spectrometer. NMR data was acquired in CD3CN (acetonitrile, H: δ = 1.95 ppm; CD3CN,
13C: δ = 117.1 ppm). Coupling constants J are listed in Hz and Chemical shifts are reported in parts
per million (ppm). Multiplicities are reported as singlet (s), doublet (d), triplet (t), doublet of

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doublets (dd), and multiplet (m). The assignment of carbons and protons for all compounds is based
on the 1D and 2D NMR spectroscopic experiments. Melting points were recorded on a Büchi
1
Melting Point B-540 apparatus and are uncorrected.NMR spectroscopic data of 2a–c, including H
and 13C NMR chemical shifts regarding those compounds, have been previously published and our
spectroscopic data are in full agreement with those described in literature [55-57]. Recently, we
have briefly described the N-alkylation’s Synthetic procedure of benzochalcogenadiazoles by the
1
13
trimethyloxonium salt, the H and C NMR data of 4-nitrobenzothiaiazol have also been reported
[58]. In the present work a complete spectroscopic study of all salts is reported and all the
spectroscopic data is provided. Remaining the minor species, characterization of products 3’a-c was
only possible when X= O.
N1-methyl-4-nitrobenzofurazanium tetrafluoroborate:
1H NMR (300.13 MHz, CD3CN-d3) δH 8.83 (1H, dd, J1 = 6, J2 = 2.1), 8.37 (2H, m), 4.98 (3H, s);
19
13C NMR (75.47 MHz, CD3CN-d3) δC 148.16, 142.81, 142.16, 138.36, 135.76, 119.55, 43.36; F
-
NMR(188.31 MHz,CD3CN-d3) δF -152.77 (BF4 ) ; HRMS: m/z calcd. For [MH]+ 180.0409; found
180.0406.
N3-methyl-4-nitro-2,1,3-benzofurazanium tetrafluoroborate:
1H NMR (300.13 MHz, CD3CN-d3) δH 9.11 (1H, d, J = 7.5), 8.68 (1H,d, J = 9), 8.11 (1H, dd, J1 =
9, J2 = 7.5) ), 5.15 (3H, s);13C NMR (75.47 MHz, CD3CN-d3) δC 155.74, 143.55, 135.88, 135.70,
-
134.36, 127.59,47.95; 19F NMR(188.31 MHz,CD3CN-d3) δF -152.77 (BF4 ) ; HRMS: m/z calcd.
For [MH]+ 180.0409; found 180.0406.
N1-methyl-4-nitro-2,1,3-benzothiadiazolium tetrafluoroborate:
1H NMR (300.13 MHz, CD3CN-d3) δ 8.85 (d, 1 H, J = 7.2), 8.41 (2 H, m), 4.69 (s, 3H); 13C NMR
19
(75.47 MHz, CD3CN-d3) δ 148.92, 145.85, 141.39, 137.84, 131.49, 122.54, 40.02; F NMR (188
-
.31 MHz, CD3CN-d3) δF -151.84 (BF4 ); HRMS: m/z calcd. For [MH]+ 196.0181; found 196.0181.
N1-methyl-4-nitro-2,1,3-benzotselenadiazolium tetrafluoroborate:
1H NMR (300.13 MHz, CD3CN-d3) δH 8.59 (1H, m), 8.19 (2 H, m), 4.66 (3H, s); 13C NMR (75.47
MHz, CD3CN-d3) δC 153.27, 149.72, 142.95, 137.23, 129.91, 122.97, 41.57; 19F NMR (188.31
MHz, CD3CN-d3) δF -151.54 (BF4-) ; HRMS: m/z calcd. For [MH]+ 237.9685; found 237.9685.
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Highlights
The N-methylation of a series of 4-nitrobenzochalcogenadiazoles was described. A complete
structural study of the synthesized products was provided. In addition, the experimental
results were supported with a theoretical study.