Alkylation of 3-Nitro-1,2,4-triazole with allyl bromide and cyclohexa-1,3-diene in acid medium

Full text of DOI:10.1134/S1070428012040288

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 610–612. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © Yu.V. Grigoriev, S.V. Voitekhovich, O.A. Ivashkevich, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 4,
pp. 611–613.
SHORT
COMMUNICATIONS
Alkylation of 3-Nitro-1,2,4-triazole with Allyl Bromide
and Cyclohexa-1,3-diene in Acid Medium
Yu. V. Grigoriev, S. V. Voitekhovich, and O. A. Ivashkevich
Research Institute for Physical Chemical Problems, Belarusian State University,
ul. Leningradskaya 14, Minsk, 220030 Belarus
e-mail: azole@bsu.by
Received November 17, 2011
DOI: 10.1134/S1070428012040288
Nitro derivatives of 1,2,4-triazoles possess a com-
bination of unique properties, such as high energy
capacity but considerable heat resistance, biological
activity, and complexing ability. Therefore, these com-
pounds are promising from the viewpoint of their ap-
plication in various fields of human activity, specialty
devices, industry, agriculture (as fungicides and herbi-
cides), biochemistry, and pharmacology [1]. Elabora-
tion of methods for the synthesis of nitro-substituted
1,2,4-triazoles seems to be important for the develop-
ment of the reactivity theory of heterocycles and
procedures for regioselective functionalization of am-
bident compounds.
of alkylating agent is also an important factor respon-
sible for the reaction selectivity. Taking the above
stated into account, it seemed reasonable to examine
the behavior of nitro-substituted 1,2,4-triazoles in
reactions with other alkylating agents, specifically with
allyl bromide and cyclohexa-1,3-diene which were
successfully used by us previously for N-functional-
ization of tetrazole ring [13, 14].
We found that the alkylation of 3-nitro-1H-1,2,4-tri-
azole (I) with allyl bromide under conditions analo-
gous to the alkylation of 5-R-tetrazoles (concentrated
sulfuric acid, 7 days) [13] gave 65% of a mixture of
isomeric N-alkyl derivatives with appreciable preva-
lence of 1-(1-bromopropan-2-yl)-5-nitro-1H-1,2,4-tri-
azole (IIa). The ratio of regioisomers IIa, IIb, and IIc
was estimated at 1:0.3:0.2 by the intensities of NMR
signals from the CH proton in the triazole ring.
Predominant formation of isomer IIa is likely to be
determined by protonation of initial triazole I in sul-
furic acid with formation of 3-nitro-1H-1,2,4-triazol-4-
ium cation where only the N2 atom is accessible to
attack by the cation generated from allyl bromide. This
mechanism was recently proposed to rationalize selec-
tive alkylation of triazole (I) with tert-butyl alcohol
[12] and was based on the data for selective acid-
catalyzed N2-alkylation of tetrazoles as structural
analogs of I [15]. Isomeric products IIb and IIc may
be formed as a result of electrophilic attack on unpro-
tonated 3-nitro-1,2,4-triazole species present in the
reaction mixture at a small concentration.
Up to now, alkylation of relatively accessible 5-sub-
stituted 3-nitro-1,2,4-triazoles has been studied in suf-
ficient detail. The presence in their molecules of three
potential reactions centers for attack by electrophilic
reagents, one pyrrole- and two pyridine-type nitrogen
atoms, implies that the alkylation may involve either of
them. In fact, treatment of these compounds with alkyl
halides, dialkyl sulfates [2–7], halocarboxylic acid
esters [8, 9], chloroethanol, and oxirane [10] in basic
or neutral medium often leads to formation of three
isomeric N-substituted 3-nitro-1,2,4-triazoles.
Some advances were achieved in the alkylation of
5-R-3-nitro-1,2,4-triazoles with alcohols in acid
medium. In particular, Saraev et al. [11] reported on
their selective alkylation at N1 with adamantan-1-ol
and tert-butyl alcohol in sulfuric acid, whereas the
alkylation with isopropyl alcohol afforded exclusively
the corresponding N2-derivative [12]. The observed
regioselectivity may be interpreted in terms of weakly
basic properties of triazoles which undergo protonation
at the most basic nitrogen atom. Obviously, the nature
Concentrated phosphoric acid turned out to be the
most efficient medium for the alkylation of triazole I
with cyclohexa-1,3-diene. Such acids as sulfuric and
perchloric could not be used because of oligo- and
610

ALKYLATION OF 3-NITRO-1,2,4-TRIAZOLE WITH ALLYL BROMIDE
611
NO2
NO2
CH2=CHCH2Br
H2SO4
NO2
Br
Br
Br
N
N
N
N
+
+
N
N
N
N
NO2
N
N
Me
Me
Me
N
IIa
IIb
IIc
N
, H3PO4
NO2
H
N
I
N
N
III
polymerization of the alkylating agent. The alkylation
of I with cyclohexa-1,3-diene in phosphoric acid
occurred at a fairly high rate (50–60 min) at room tem-
perature, and 1-(cyclohex-2-en-1-yl)-3-nitro-1H-1,2,4-
triazole was selectively formed in a good yield (60%).
The product was assigned the structure of 1-substituted
(1H, HC=N). 13C NMR spectrum, δC, ppm: 19.1
(CH3), 35.6 (CH2), 56.3 (CH), 149.4 (C5), 152.3 (C3).
1-(1-Bromopropan-2-yl)-3-nitro-1H-1,2,4-tri-
1
azole (IIc). H NMR spectrum, δ, ppm: 1.73 d (3H,
CH3), 3.76 m (2H, CH2), 4.67 sext (1H, CH), 8.87 s
(1H, HC=N). 13C NMR spectrum, δC, ppm: 146.1 (C5),
162.9 (C3); the other signals were not assigned unam-
biguously.
1
triazole on the basis of its H and 13C NMR spectra
which were consistent with published data for analo-
gous 1-substituted 3-nitro-1,2,4-triazoles [4–6].
1-(Cyclohex-2-en-1-yl)-3-nitro-1H-1,2,4-triazole
(III). Cyclohexa-1,3-diene, 0.44 g (0.0055 mol), was
added dropwise over a period of 10 min under stirring
at room temperature to a solution of 0.57 g (0.005 mol)
of 3-nitro-1H-1,2,4-triazole in 10 ml of 87% phos-
phoric acid. The mixture was stirred for 50–60 min at
room temperature, poured into water (50 ml), and ex-
tracted with methylene chloride (2×25 ml). The com-
bined extracts were dried over anhydrous magnesium
sulfate and filtered, and the solvent was distilled off
under reduced pressure. Yield 0.57 g (60%), viscous
The selective formation of compound III was sur-
prising. It may be rationalized assuming isomerization
of the initially formed N2-derivative into the N1-isomer
in a way similar to the isomerization of 2-cyclo-
hexenyltetrazole under analogous conditions [14]. The
driving force of such isomerization is higher thermo-
dynamic stability of 1-alkyl-3-nitro-1,2,4-triazoles
compared to 2- and 4-alkyl derivatives [16].
Alkylation of 3-nitro-1H-1,2,4-triazole with allyl
bromide. Allyl bromide, 1.3 g (0.011 mol), was added
under stirring to a solution of 1.0 g (0.0088 mol) of
3-nitro-1H-1,2,4-triazole in 7 ml of 96% sulfuric acid.
The mixture was stirred for 7 days at room tempera-
ture, poured onto ice, and extracted with methylene
chloride (4 × 25 ml), the combined extracts were
washed with 10 ml of water, 10 ml of 5% aqueous
sodium carbonate, and 10 ml of water again, and dried
over anhydrous magnesium sulfate, and the solvent
was distilled off under reduced pressure. The residue,
1.3 g (65%), was a viscous oily material containing
isomeric N-(1-bromopropan-2-yl)-3-nitro-1,2,4-tri-
azoles IIa–IIc.
1
oily substance. H NMR spectrum, δ, ppm: 1.04–
2.18 m (6H, CH2), 5.14–5.23 m (1H, CH), 5.76–5.82 m
(1H, CH=), 6.08–6.15 m (1H, =CH), 8.86 s (1H, 5-H).
13C NMR spectrum, δC, ppm: 18.5 (CH2), 23.9 (CH2),
28.8 (CH2), 56.4 (CH), 123.4 and 133.5 (CH=CH),
145.7 (C5), 161.9 (C3). Found, %: C 49.12; H 5.31;
N 28.49. C8H10N4O2. Calculated, %: C 49.48; H 5.19;
N 28.85.
1
The H and 13C NMR spectra were recorded on
a Bruker Avance-500 spectrometer at 500 and
100 MHz, respectively, using DMSO-d6 as solvent.
This study was performed under financial support
by the Belarusian Republican Foundation for Basic
Research (project no. Kh10SO-016).
1-(1-Bromopropan-2-yl)-5-nitro-1H-1,2,4-tri-
1
azole (IIa). H NMR spectrum, δ, ppm: 1.62 d (3H,
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