Synthesis and tautomerization study of pseudonitrosites to 1,2-nitroximes

Article abstract of DOI:10.1139/V08-011

4-R-Substituted 2-nitro-1-nitrosoethylbenzenes (R = H, CH₃, OCH₃, Cl, F) have been synthesized under solvent-free conditions and the mechanism of their tautomerization to 2-isonitroso-1-nitro-2-phenylethanes have been investigated by ¹H NMR spectroscopy.

Full text of DOI:10.1139/V08-011

248
Synthesis and tautomerization study of
pseudonitrosites to 1,2-nitroximes
Ahmad Shaabani, Hamid Reza Bijanzadeh, Ali Reza Karimi,
Mohammad Bagher Teimouri, and Kamal Soleimani
Abstract: 4-R-Substituted 2-nitro-1-nitrosoethylbenzenes (R = H, CH3, OCH3, Cl, F) have been synthesized under sol-
vent-free conditions and the mechanism of their tautomerization to 2-isonitroso-1-nitro-2-phenylethanes have been in-
1
vestigated by H NMR spectroscopy.
1
Key words: tautomerization, pseudonitrosite, mechanism, 2-nitro-1-nitrosoethylbenzene, H NMR spectroscopy.
Résumé : Opérant dans des conditions n’impliquant aucun solvant, on a réalisé la synthèse de 2-nitro-1-
nitrosoéthylbenzènes substitués en position 4 par des groupes R = H, CH3, OCH3, Cl et F et, faisant appel à la spec-
1
troscopie RMN du H, on a étudié leur tautomérisation en 2-isonitroso-1-nitro-2-phényléthanes.
1
Mots-clés : tautomérisation, pseudonitrosite, mécanisme, 2-nitro-1-nitrosoéthylbenzène, spectroscopie RMN du H.
[Traduit par la Rédaction] Shaabani et al. 252
Introduction
because they may result in less environmental impact during
industrial applications (12, 13). Since tautomerization of C-
nitroso compounds to the more stable oximes occurs readily
in solutions, we have attempted to find solvent-free reactions
that result in selective transformation of the styrene and
para-substituted styrenes (1) to 2-nitro-1-nitrosoethyl-
benzenes (2) without further tautomerization to 2-isonitroso-
1-nitro-2-phenylethanes (3). (Scheme 1)
C-Nitroso compounds are characterized as white solid
dimers that result from a N-N connection to give diazene di-
oxides (14). Since 2-nitro-1-nitrosoethylbenzene derivatives
are a monomer and has an asymmetric center, the dimer ex-
ists in two diastereomeric isomers namely meso (R,S) and
racemate (R,R and S,S) (15). When the dimers are dissolved
and (or) heated in an inert low polarity solvent, such as
CH2Cl2 or ether, dissociation into blue (aliphatic) or green
(aromatic) monomers usually occurs (1, 16–18).
The discovery of important roles of C-nitroso compounds
in various biological metabolic processes has generated a
renewed interest in the general chemical properties of
nitrosoarenes (1). For example, identification of the
nitrosbenzene adduct of hemoglobin as a product of
nitrobenzene poisoning (2, 3) and the realization that some
amine containing drugs may metabolize to nitroso deriva-
tives (4–7) led to an increased desire to study the biochemi-
cal properties of C-nitroso compounds. To this end, many
studies have been reported on the fundamental chemistry of
C-nitroso compounds under conditions that either stabilize
the C-nitroso functionality or enhance their reactivity toward
isomerization or reactivity with substrate.
There is a considerable variety of synthetic routes avail-
able for the preparation of C-nitroso compounds (1, 8–11).
However, a major difficulty in C-nitroso chemistry is that
the necessary high reactivity of these compounds imposes
constraints upon the methods employed for their preparation,
particularly with regard to the yield of the desired product.
For example, the ease of oxidation of the desired nitroso
product to its nitro derivative or its isomerization to corre-
sponding oximes can restrict the choice of solvent for the
preparation of these compounds.
Experimental
Melting points were measured on an Electrothermal 9100
apparatus and are uncorrected. Elemental analyses were
performed using a Heraeus CHN-O-Rapid analyzer. NMR
spectra were recorded on BRUKER DRX-500 AVANCE
spectrometer. Temperatures ranged from 298 to 313 K.
Infrared spectra were taken on a Shimadzu IR-470 spectro-
photometer. Mass spectra were recorded on a FINNIGAN-
MAT 8430 mass spectrometer operating at an ionization
potential of 70 eV.
Solvent-free reactions are of increasing importance be-
cause of their potential use in combinatorial chemistry and
Received 13 August 2007. Accepted 4 December 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 14 February 2008.
General procedure
A. Shaabani,1 A.R. Karimi, M.B. Teimouri, and
K. Soleimani. Department of Chemistry, Shahid Beheshti
University, P.O. Box 19839-4716, Tehran, Iran.
H.R. Bijanzadeh. Department of Chemistry, Tarbiat
Modarres University, P.O. Box 14155-4838, Tehran, Iran.
Cation exchange resine (Rexyn 101 H obtained from
Fisher Scientific, 0.350 g) and sodium nitrite (0.345 g,
5 mmol) were ground separately in a mortar and added to
styrene or substituted styrene (2 mmol) in a round-bottomed
flask. The reaction mixture was stirred magnetically at room
temperature until TLC analysis indicated that all of the sty-
1Corresponding author (e-mail: a-shaabani@cc.sbu.ac.ir).
Can. J. Chem. 86: 248–252 (2008)
doi:10.1139/V08-011
© 2008 NRC Canada

Shaabani et al.
249
Scheme 1.
1
Table 1. Physical and spectral data (IR, H, and 13C NMR, MS) of compounds 2b–2e and 3b–3e.
Compound
Selected data
White powder. Mp 119–121 °C. IR (KBr) (υmax, cm–1): 1376 and 1559. H NMR (Aceton-d6) δH: 2.33 (3H, s, CH3),
1
2b
2
3
2
3
4.98 (1H, dd, JHH = 16.0 Hz, JHH = 3.0 Hz, CHH), 5.39 (1H, dd, JHH = 16.0 Hz, JHH = 11.1 Hz, CHH), 6.90
3
3
3
(1H, dd, JHH = 11.1 Hz, JHH = 3.0 Hz, CH), 7.24 and 7.38 (4H, 2d, JHH = 7.9 Hz, arom.). 13C NMR (Aceton-
d6) δC: 20.29 (CH3), 67.50 and 73.37 (C-N=O and C-NO2), 127.69, 129.37, 129.57 and 139.57 (arom.). MS m/z
(%): 194 (M+, 5), 148 (4), 117 (100), 91 (38), 30 (72). Anal. calcd. for C9H10N2O3 (194.21) (%): C 55.66, H
5.19, N 14.42; found: C 55.51, H 5.28, N 14.50.
1
2c
2d
2e
White powder. Mp 124–126 °C. IR (KBr) (υmax, cm–1): 1387, 1560. H NMR (Aceton-d6) δH: 3.82 (3H, s, OCH3),
2
3
2
3
4.97 (1H, dd, JHH = 15.9 Hz, JHH = 3.0 Hz, CHH), 5.42 (1H, dd, JHH = 15.9 Hz, JHH = 11.1 Hz, CHH), 6.88
3
3
3
(1H, dd, JHH = 11.0 Hz, JHH = 3.0 Hz, CH), 6.96 and 7.45 (4H, 2d, JHH = 9.3 Hz, arom.). 13C NMR (Aceton-
d6) δC: 55.36 (OCH3), 67.69 and 73.27 (C-N=O and C-NO2), 114.52, 120.61, 129.01 and 160.73 (arom.). MS m/z
(%): 210 (M+, 8),179 (2), 121 (75), 91(45), 30 (100). Anal. calcd. for C9H10N2O4 (210.21) (%): C 51.42, H 4.79,
N 13.33; found: C 51.52, H 4.90, N 13.30.
White powder. Mp 128–129 °C. IR (KBr) (υmax, cm–1): 1375, 1484 and 1558. H NMR (Aceton-d6) δH: 5.08 (1H,
dd, JHH = 15.8 Hz, JHH = 2.5 Hz, CHH), 5.58 (1H, dd, JHH = 15.8 Hz, JHH = 11.0 Hz, CHH), 6.88 (1H, dd,
1
2
3
2
3
3JHH = 11.0 Hz, JHH = 2.5 Hz, CH), 7.23 and 7.34 (4H, 2d, JHH = 8.1 Hz, arom.). 13C NMR (Aceton-d6) δC:
67.55 and 72.63 (C-N=O and C-NO2), 128.42, 128.97, 129.68 and 135.16 (arom.). MS m/z (%): 214 (M+, 2), 168
(4), 138 (100), 103 (91), 30 (90). Anal. calcd. for C8H7N2O3Cl (214.63) (%): C 44.77, H 3.29, N 13.05; found: C
44.82, H 3.34, N 13.14.
3
3
White powder. Mp 129–131 °C. IR (KBr) (υmax, cm–1): 1390, 1562. H NMR (Aceton-d6) δH: 5.03 (1H, dd, JHH
=
1
2
3
2
3
3
16.0 Hz, JHH = 3.0 Hz, CHH), 5.45 (1H, dd, JHH = 16.0 Hz, JHH = 11.1 Hz, CHH), 6.96 (1H, dd, JHH = 11.1
Hz, JHH = 3.0 Hz, CH), 7.20 and 7.61 (4H, 2m, arom.). 13C NMR (Aceton-d6) δC: 66.91 and 73.06 (C-N=O and
3
2
4
3
1
C-NO2), 115.84 (d, JFC = 22.0 Hz), 126.29 (d, JFC = 3.5 Hz), 130.38 (d, JFC = 8.8 Hz), and 163.31 (d, JFC
=
247.3 Hz). MS m/z (%): 198 (M+, 5), 168 (7), 122 (98), 109 (60), 75 (45), 30 (100). Anal. calcd. for C8H7N2O3F
(198.17) (%): C 48.49, H 3.56, N 14.13; found: C 48.53, H 3.60, N 14.24.
1
3b
3c
3d
3e
Yellow oil. IR (KBr) (υmax, cm–1): 3100–3500 (O-H), 1669, 1597, and 1551. H NMR (Aceton-d6) δH: 2.34 (3H, s,
3
CH3), 5.84 (2H, s, CH2), 7.24 and 7.65 (4H, 2d, JHH = 8.7 Hz, arom.), 11.40 (1H, s, OH). 13C NMR (Aceton-
d6) δC: 20.32 (CH3), 68.16 (C-NO2), 125.94, 129.68, 130.35 and 139.38 (arom.), 146.11 (C=N). MS m/z (%): 194
(M+, 2), 176 (7), 136 (98), 119 (100), 91 (75), 65 (27).
1
Yellow oil. IR (KBr) (υmax, cm–1): 3100–3500 (O-H), 1549, and 1500. H NMR (Aceton-d6) δH: 3.83 (3H, s,
3
OCH3), 5.84 (2H, s, CH2), 6.97 and 7.70 (4H, 2d, JHH = 9.0 Hz, arom.). 11.24 (1H, s, OH). 13C NMR (Aceton-
d6) δC: 67.02 (OCH3), 73.40 (C-NO2), 114.81, 121.08, 129.06 and 160.89 (arom.), 139.46 (C=N). MS m/z (%):
210 (M+, 3), 179 (15), 134 (100), 110(10), 76 (23).
1
Yellow oil. IR (KBr) (υmax, cm–1): 3100–3500 (O-H), 1652, 1582 and 1548. H NMR (Aceton-d6) δH: 5.86 (2H, s,
3
CH2), 7.46 and 7.78 (4H, 2d, JHH = 8.6 Hz, arom.), 11.59 (1H, s, OH). 13C NMR (Aceton-d6) δC: 68.00 (C-
NO2), 127.66, 128.75, 133.19 and 134.99 (arom.), 146.90 (C=N). MS m/z (%): 214 (M+, 5), 181 (23), 139 (100),
111(75), 75 (61).
1
Yellow oil. IR (KBr) (υmax, cm–1): 3100–3500 (O-H), 1560 and 1508. H NMR (Aceton-d6) δH: 5.89 (2H, s, CH2),
7.21 and 7.82 (4H, 2m, arom.), 11.35 (1H, s, OH). 13C NMR (Aceton-d6) δC: 67.38 (C-NO2), 115.72 (d, JFC
=
2
4
3
1
23.5 Hz), 125.75 (d, JFC = 3.5 Hz), 130.26 (d, JFC = 8.9 Hz), 147.07 (C=N), 163.20 (d, JFC = 247.3 Hz). MS
m/z (%): 198 (M+, 5), 180 (5), 121 (100), 109(90), 100 (75), 94 (60).
© 2008 NRC Canada

250
Can. J. Chem. Vol. 86, 2008
1
Fig. 1. H NMR spectra of the appearance and disappearance of methylene signals of compound 3c and 2c at 298 K.
rene or substituted styrene had reacted. The product was
separated by washing with acetone (3 × 10 mL) and the fil-
trate was evaporated to give the product. Compound 2 was
obtained as a white solid, which without further purification
was used for studying tautomerization.
group, which upon addition of one drop of D2O to the solu-
1
tion disappeared. The H decoupled 13C NMR spectrum of
3b showed the distinct resonances in agreement with the
proposed structure. Partial assignment of these resonances is
given in the experimental section.
1
13
The H and C NMR spectra of 2a, 2c–2e and 3a, 3c–3e
are similar to those of 2b and 3b, except for the phenyl
groups, which exhibit characteristic signals with appropriate
chemical shifts, respectively. The results are summarized in
the experimental section.
Results and discussion
Products from the reaction of styrene and para-
substituted styrenes
All of the products (except 2a and 3a (19)) are new com-
1
pounds, which were identified from their IR, H, and 13C
Kinetics of the reaction of tautomerization
The discovery of new prototropic tautomerization and the
study of its mechanism is one of the most important subjects
in physical organic chemistry, and investigations on tauto-
meric processes were surveyed by several reviews (20–28).
Tautomerization of 2-nitro-1-nitrosoethylbenzenes to the
more stable oximes occurs readily in solution. Oximes are,
of course, important synthons in many organic reactions of
which Beckman rearrangement is illustrated (29, 30).
For the tautomerization study, a fresh sample of 4-X-
substituted of 2-nitro-1-nitrosoethylbenzene (2) was dis-
solved in (CD3)2CO (0.01 g in 0.4 mL (CD3)2CO in 5 mm
NMR tube) and equilibrated at the required temperature. The
progress of the tautomerization was monitored by recording
the appearance and disappearance of the methylene signal of
3 and 2, respectively, (Fig. 1). Integration of the area under
the methylene signal of 3 with respect to that of the methy-
lene signals of 2 gave the relative concentrations of the spe-
cies present, [C]. The rate of the reaction is given by rate =
+k[C]x, where x is the reaction order. The integrated rate
equation for a first order reaction is ln[C]t = kt + ln[C]0. A
NMR spectra. The mass spectra of these compounds dis-
played molecular ion peaks at appropriate m/z values (Ta-
ble 1).
1
The H NMR spectrum of 2b exhibited a single sharp line
arising from methyl protons (δ 2.33) along with a three-spin
AMX system for methylene and methine protons. This leads
to a doublet of doublets for each of the protons of HA, HM,
2
3
and HX at 4.98 (1H, dd, JHH = 16.0 Hz, JHH = 3.0 Hz,
2
3
CHAH), 5.39 (1H, dd, JHH = 16.0 Hz, JHH = 11.1 Hz,
CHHM), and 6.90 ppm (1H, dd, JHH = 11.1 Hz, JHH
3
3
=
3.0 Hz, CHX), respectively. The aromatic protons appear at
3
1
7.24 and 7.38 ppm (4H, 2d, JHH = 7.9 Hz). The H decoup-
led 13C NMR spectrum of 2b showed the distinct resonances
in agreement with the proposed structure.
1
The H NMR spectrum of 3b exhibited two single sharp
lines readily recognized as arising from methyl (2.34 ppm)
and methylene (5.84 ppm) protons. The 4-substituted phenyl
moiety gave rise to characteristic signals in the aromatic re-
3
gion of the spectrum (7.24 and 7.65 ppm, JHH = 8.7 Hz). A
fairly broad singlet (11.40 ppm) is observed for the OH
© 2008 NRC Canada

Shaabani et al.
251
Scheme 2.
Table 2. Kinetic parameters for the tautomerization of com-
pounds 2 to 3.
Fig. 2. Plot of log(kx/k0) vs. σp constant for para-subsituted sty-
rene.
Eact
(kJ·mol–1)
∆S #
∆H #
Entry
X
(J·mol–1 K–1)
(kJ·mol–1)
2a
2b
H
CH3
26.8
28.4
–191.8
–183.4
24.2
25.9
2c
OCH3
34.7
–161.4
32.2
2d
2e
Cl
F
35.9
25.9
–166.1
–193.6
32.6
23.4
Table 3. Rates of tautomerization of 2 to 3 at 298 K in acetone.
k (min–1) × 10–2
σp
a
Entry
X
0.00
–0.14
–0.28
2a
2b
H
CH3
4.5 0.4
4.9 0.4
2c
OCH3
5.7 0.3
2d
2e
aRef. 31.
Cl
F
3.4 0.4
4.1 0.3
0.25
0.15
line or reaction constant, ρ. A Hammett plot of these data vs.
σp (Fig. 2) gives a good straight line through the points for
the para-H, CH3, OCH3, Cl, and F compounds and a value
for ρ = –0.38 0.02 (R2 = 0.96) at 298 K. The very small
magnitude of ρ indicates relative insensitivity of the reaction
to electronic effects.
plot of ln[C]t vs. time should yield a straight line if the reac-
tion is first order. The slope of this line is equal to k. The
rate constants were obtained at several temperatures: 298,
303, 308, and 313 K.
By taking the natural logarithm of the Arrhenius equation,
the activating energy, Eact, was obtained from a plot of lnk
vs. 1/T. Enthalpies of activation, ∆H#, were also obtained
from a plot of ln(k/T) vs. 1/T. Furthermore, the intercept in
such a correlation gives enthropies of activation, ∆S#. These
data (Eact, ∆H# and ∆S#) are given in Table 2.
According to the Hammett equation of log(kx/k0) = ρσp,
where kx is the rate constant of the tautomerization being
studied with a substituted X present and k0 is the corre-
sponding rate constant of the unsubstituted compound (X =
H) (Table 3), a plot of log(kx/k0) vs. σp gives the slope of the
The magnitude of the activation parameters, ∆H# and ∆S#,
reflects the transition state structure. It can be seen from Ta-
ble 2 that the relatively low entropy of activation for this
tautomerization suggests a mechanism that is compatible
with a cyclic activated complex, in which bond-making ac-
companies bond-breaking. In addition, the fact that the
entropies of activation are negative and their magnitudes are
relatively large refers to the loss of rotational, translational,
and vibrational degrees of freedom associated with highly
ordered transition states supporting this complex formation.
In summary, all of the preceding data are fully consistent
with and indicative of an intramolecular concerted 1,3-
© 2008 NRC Canada

252
Can. J. Chem. Vol. 86, 2008
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(pathway A) or an intermolecular dimeric mechanism (path-
way B) where O–H bond formation cannot significantly pre-
cede C–H bond-breaking to be consistent with observed ∆H#
and ρ (Scheme 2).
The results of modern studies have shown that the mecha-
nism of proton transfer through an intramolecular mecha-
nism are sometimes both energetically and geometrically
unfavorable (20). From this viewpoint and the negative large
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Acknowledgement
We gratefully acknowledge the financial support from the
Research Council of Shahid Beheshti University.
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