Alkylation of 1,2,3-benzotriazole with iodomethyl ketones

Article abstract of DOI:10.1134/S1070428012120111

Solvent-free reactions of 1,2,3-benzotriazole with 1-iodopropan-2-one and 1,3-diiodopropan-2-one in the absence of a catalyst involved alkylation of the heteroring at the N¹ atom and subsequent quaternization at the N ³ atom with formation of 1,3-bis(2-oxopropyl)-1H-1,2,3- benzotriazolium triiodide which is a new conducting ionic liquid. The reaction of 1,2,3-benzotriazole with 1,3-diiodopropan-2-one was accompanied by reductive deiodination of the iodomethyl groups in the initial ketone with hydrogen iodide liberated by N¹-alkylation. Triiodide ion readily exchanges for nitrate ion by the action of AgNO₃ to produce 1,3-bis(2-oxopropyl)- 1H-1,2,3-benzotriazolium nitrate. The reaction of 1,2,3-benzotriazole with 2-iodo-1-phenylethan-1-one in melt resulted in the formation of 1,3-bis(2-oxo-2-phenylethyl)-1H-1,2,3-benzotriazolium triiodide.

Full text of DOI:10.1134/S1070428012120111

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 12, pp. 1561–1563. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © L.G. Shagun, I.A. Dorofeev, I.A. Tokareva, L.I. Larina, M.G. Voronkov, 2012, published in Zhurnal Organicheskoi Khimii, 2012,
Vol. 48, No. 12, pp. 1590–1592.
Alkylation of 1,2,3-Benzotriazole with Iodomethyl Ketones
L. G. Shagun, I. A. Dorofeev, I. A. Tokareva, L. I. Larina, and M. G. Voronkov
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: shag@irioch.irk.ru
Received May 15, 2012
Abstract—Solvent-free reactions of 1,2,3-benzotriazole with 1-iodopropan-2-one and 1,3-diiodopropan-2-one
in the absence of a catalyst involved alkylation of the heteroring at the N1 atom and subsequent quaternization
at the N3 atom with formation of 1,3-bis(2-oxopropyl)-1H-1,2,3-benzotriazolium triiodide which is a new
conducting ionic liquid. The reaction of 1,2,3-benzotriazole with 1,3-diiodopropan-2-one was accompanied by
reductive deiodination of the iodomethyl groups in the initial ketone with hydrogen iodide liberated by
N1-alkylation. Triiodide ion readily exchanges for nitrate ion by the action of AgNO3 to produce 1,3-bis(2-
oxopropyl)-1H-1,2,3-benzotriazolium nitrate. The reaction of 1,2,3-benzotriazole with 2-iodo-1-phenylethan-
1-one in melt resulted in the formation of 1,3-bis(2-oxo-2-phenylethyl)-1H-1,2,3-benzotriazolium triiodide.
DOI: 10.1134/S1070428012120111
N-Alkyl-1,2,3-benzotriazoles and their derivatives
exhibit analgesic, anti-inflammatory, diuretic, antiviral,
antihypertensive, and antitumor activity [1, 2] and are
used as herbicides [3], insecticides [4], and acaricides
[5]. The main procedures for the synthesis of N-akyl-
benzotriazoles are based on alkylation of benzotriazole
with various halogen derivatives in the presence of
bases, crown ethers, or phase-transfer catalysts [1, 6].
The reaction in the absence of a catalyst is successful
when the alkylating agent molecule contains a group
that weakens the C–Hlg bond. A regioselective route to
N1-substituted benzotriazoles comprises alkylation of
benzotriazole with α-chloro(bromo) ketones in the ab-
sence of a base on heating in benzene or toluene; as
a result, α-(1,2,3-benzotriazol-1-yl) carbonyl com-
pounds are formed as a single isomer in quantitative
yield [7]. Alkylation of benzotriazole with α-iodo
ketones was not studied.
We examined alkylation of 1,2,3-benzotriazole (I)
with 1-iodopropan-2-one (IIa) under solvent-free con-
ditions in the absence of a catalyst. The reaction was
carried out on heating to 90°C, and it afforded 67% of
1,3-bis(2-oxopropyl)-1H-1,2,3-benzotriazolium tri-
iodide (IIIa) (Scheme 1). NMR monitoring of the
reaction progress showed that the primary intermediate
is N1-substituted benzotriazole A. Hydrogen iodide
Scheme 1.
O
N
N
R
O
N
N
N
N
IIa, IIb, I2
+
I
I3
N
N
R
–HI
R
N
R
H
O
O
I
IIa, IIb
A
IIIa, IIIb
O
IIa, IIb
+
HI
+
I2
I2
+
I–
I3
Me
R
R = Me (a), Ph (b).
1561

SHAGUN et al.
1562
Scheme 2.
N
N
O
N
N
IIa
N
+
I
I
IIIa
–HI
–I2
I
N
H
O
I
IV
B
IV
+
HI
IIa
+
I2
I2
+
I–
I3
liberated in the first alkylation step partly reduces the
initial iodomethyl ketone to molecular iodine, and the
latter not only initiates generation of carbocation from
ketone IIa but also favors formation of triiodide ion.
and 191.73 ppm (IIIb). Compounds IIIa and IIIb
displayed in the two-dimensional 15N HMBC spectra
1H–15N cross peaks between protons in the methylene
groups and N1/N3 (δN –154. 8 ppm) and N2
(δN –23.9 ppm). In the UV spectra of quaternary salts
IIIa and IIIb absorption bands typical of triiodide ion
were observed at λ 293 and 358 nm [8].
The physicochemical parameters of triiodide IIIa
(a dark red thick oily substance), specifically the elec-
tric conductivity of its 0.1 N solution in THF equal to
1.5 ×10–3 Ω–1 cm–1, give grounds to recognize it as
a new conducting ionic liquid.
Using compound IIIa as an example, we demon-
strated the possibility for exchange of triiodide ion for
nitrate by the action AgNO3 (Scheme 3). As a result,
we synthesized for the first time 1,3-bis(2-oxopropyl)-
1H-1,2,3-benzotriazolium nitrate (V) as a colorless
powder (mp 159–160°C) with a conductivity of 4.7×
10–12 Ω–1 cm–1. Compound V showed in the IR spec-
trum a strong absorption band at 1384 cm–1 and a weak
band at 825 cm–1 due to inorganic nitrate ion [9].
Likewise, the reaction of benzotriazole I with
2-iodo-1-phenylethan-1-one (Ib) in melt (reaction time
3 h) led to the formation of 1,3-bis(2-oxo-2-phenyl-
ethyl)-1H-1,2,3-benzotriazolium triiodide (IIIb) in
71% yield.
According to [7], N1-alkylation of benzotriazole
with 1,3-dichloropropan-2-one requires two equiv-
alents of a base and yields bis(benzotriazol-1-yl)-
acetone. However, in the reaction of 1,3-diiodopropan-
2-one (IV) with compound I we unexpectedly isolated
1,3-bis(2-oxopropyl)-3H-1,2,3-benzotriazolium tri-
iodide (IIIa) (Scheme 2).
Scheme 3.
O
Me
N
IIIa
+
AgNO3
NO3
N
1
The IR, UV, and H, 13C, and 15N NMR spectra of
–AgI
N
Me
compound IIIa suggest that hydrogen iodide liberated
in the first alkylation step reduces the iodomethyl
group in adduct B thus preventing formation of
1,3-bis(benzotriazol-1-yl)acetone. It is also possible
that HI reduces one iodomethyl group in initial diiodo
ketone IV to monoiodo derivative IIa with liberation
of molecular iodine which catalyzes quaternization of
adduct B at the N3 atom.
O
V
We can conclude that, unlike α-chloro(bromo)
ketones studied previously [6, 7], high lability of the
iodine atom in iodomethyl ketones not only promotes
N1-alkylation and N3-quaternization of 1,2,3-benzotri-
azole but also gives rise to I3– ion.
The structure of triiodides IIIa and IIIb was con-
firmed by their elemental composition and IR, UV, and
1H, 13C, and 15N NMR spectra. The IR spectra of IIIa
and IIIb contained absorption bands at 1739 and
1685 cm–1 typical of carbonyl stretching vibrations.
Methylene groups on the nitrogen atoms in IIIa and
IIIb gave signals at δ 6.41 and 6.63 ppm in the
1H NMR spectra and at δC 61.35 and 54.99 ppm in the
13C NMR spectra, respectively. Carbonyl carbon atoms
resonated in the 13C NMR spectra at δC 197.39 (IIIa)
EXPERIMENTAL
The IR spectra were recorded on a Bruker Vertex
70 spectrometer from samples prepared as KBr pellets
1
or films. The H, 13C, and 15N NMR spectra were
measured on a Bruker DPX-400 instrument at 400.13,
100.61, and 40.56 MHz, respectively, using acetone-d6
1
as solvent and reference (for H and 13C). The UV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

ALKYLATION OF 1,2,3-BENZOTRIAZOLE WITH IODOMETHYL KETONES
1563
spectra were recorded on a Perkin Elmer Lambda 35
UV-Vis spectrophotometer. The electric conductivities
were measured using a Radelkis OK-102/1 conduc-
tivity meter. The progress of reactions and the purity of
products were monitored by TLC on Silufol UV-254
plates using chloroform–acetone (10:1) as eluent.
spectrum, δC, ppm: 54.99 (CH2), 111.41–145.02
(Carom), 191.73 (C=O). 15N NMR spectrum, δN, ppm:
–154.8 (N1, N3), –23.9 (N2). Found, %: C 35.44;
H 2.70; I 50.63; N 6.10. C22H18I3N3O2. Calculated, %:
C 35.82; H 2.44; I 51.69; N 5.69.
1,3-Bis(2-oxopropyl)-1H-1,2,3-benzotriazolium
nitrate (V). A solution of 0.24 g (9 mmol) of AgNO3
in a mixture of alcohol with acetone was slowly added
to a solution of 0.6 g (6 mmol) of triiodide IIIa in 5 ml
of acetone until the originally dark red solution turned
blue–violet. The mixture was heated for 1 h under
reflux and was then kept for 1 h at room temperature
until it turned light blue. The precipitate of AgI was
filtered off, the filtrate was evaporated under reduced
pressure, and the residue was dissolved in acetonitrile
(5 ml) and precipitated with hexane (10 ml). The prod-
uct was dried under reduced pressure. Yield 0.13 g
(45%), light brown powder, mp 159–160°C. IR spec-
trum, ν, cm–1: 1736 (C=O); 1384, 825 (NO3). 1H NMR
spectrum, δ, ppm: 5.81 s (4H, CH2), 7.36–8.26 m (4H,
1,3-Bis(2-oxopropyl)-1H-1,2,3-benzotriazolium
triiodide (IIIa). a. A mixture of 2 g (1 mmol) of
ketone IIa and 0.5 g (0.5 mmol) of 1,2,3-benzotriazole
(I) was heated under stirring at 80°C in an argon
atmosphere until the initial ketone disappeared (9 h).
The resulting thick material was dissolved in 10 ml of
acetone and precipitated with 30 ml of hexane. This
procedure was repeated in triplicate. The oily material
was repeatedly washed with diethyl ether and dried
under reduced pressure. Yield 1.72 g (67% on the
reacted 1,2,3-benzotriazole), red thick oily substance.
1H NMR spectrum, δ, ppm: 2.54 s (6H, CH3), 6.41 s
(4H, CH2), 8.04–8.30 m (4H, Harom). 13C NMR spec-
trum, δC, ppm: 27.47 (CH3), 61.35 (CH2), 110.94–
15
135.87 (Carom), 197.39 (C=O). N NMR spectrum, δN,
H
arom). 13C NMR spectrum, δC, ppm: 56.65 (CH2),
110.61–145.91 (Carom), 200.32 (C=O). Found, %:
C 48.44; H 4.63; N 18.89. C12H14N4O5. Calculated, %:
C 48.97; H 4.76; N 19.04.
ppm: –154.8 (N1, N3), –23.9 (N2). Found, %: C 23.72;
H 2.31; I 58.75; N 7.76. C12H14I3N3O2. Calculated, %:
C 23.49; H 2.28; I 62.15; N 6.85.
b. A mixture of 2 g (0.6 mmol) of diiodo ketone IV
and 0.36 g (0.3 mmol) of 1,2,3-benzotriazole (I) in
5 ml of anhydrous acetone was heated under reflux in
an argon atmosphere until the initial ketone disap-
peared (7 h). After cooling, 10 ml of hexane was
added, and the product was isolated as described above
in a. Yield 0.8 g (43% on the reacted I), red thick oily
substance. Its properties were identical to those of
a sample prepared as described in a.
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1
red thick oily substance. H NMR spectrum, δ, ppm:
6.63 s (4H, CH2), 7.45–8.54 m (14H, Harom). 13C NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012