Reactions of Zincke's salts with 2,3-dimethylbenzothiazolium iodide

Article abstract of DOI:10.1007/s11172-010-0342-6

Reactions of 1-(2,4-dinitrophenyl)pyridinium chloride and 2-(2,4-dinitrophenyl)isoquinolinium chloride with 2,3-dimethylbenzothiazolium iodide in hot pyridine allows introduction of an aryl residue into the thiazole ring via intermolecular transformation of the pyridine ring of Zincke's salts with participation of the methyl group in position 2 of the benzothiazolium salt.

Full text of DOI:10.1007/s11172-010-0342-6

Russian Chemical Bulletin, International Edition, Vol. 59, No. 10, pp. 1974—1978, October, 2010
1974
Reactions of Zincke´s salts with 2,3ꢀdimethylbenzothiazolium iodide
M. V. Fomina,a N. A. Kurchavov,a L. G. Kuz´mina,b J. A. K. Howard,c and S. P. Gromova
aPhotochemistry Center, Russian Academy of Sciences,
7A ul. Novatorov, 119421 Moscow, Russian Federation.
Fax: +7 (495) 936 1255. Eꢀmail: spgromov@mail.ru
bN. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 954 1279
cDepartment of Chemistry, University of Durham,
South Road, Durham DH1 3LE, United Kingdom
Reactions of 1ꢀ(2,4ꢀdinitrophenyl)pyridinium chloride and 2ꢀ(2,4ꢀdinitrophenyl)isoꢀ
quinolinium chloride with 2,3ꢀdimethylbenzothiazolium iodide in hot pyridine allows introꢀ
duction of an aryl residue into the thiazole ring via intermolecular transformation of the pyriꢀ
dine ring of Zincke´s salts with participation of the methyl group in position 2 of the benzoꢀ
thiazolium salt.
Key words: Zincke´s salts, benzothiazolium salt, ring transformation, 2ꢀphenylbenzothiazole,
2ꢀ(2ꢀnaphthyl)benzothiazole, phenothiazine.
Scheme 1
Ring transformation under the action of nucleophilic
reagents is the very interesting property of quaternary pyꢀ
ridinium salts.1—6 The earliest, best understood transforꢀ
mation of this type was the Zincke—König reaction,2,7 in
which 1ꢀ(2,4ꢀdinitrophenyl)pyridinium decomposes in the
presence of aromatic amines to give glutaconaldehyde diꢀ
anils. However, transformations of Zincke´s salts under
the action of Cꢀnucleophiles that would result in the forꢀ
mation of the benzene ring have not been discovered.2,8
Earlier,9—13 we have found that pyridinium and isoꢀ
quinolinium salts, as well as pyridine and isoquinoline
themselves, react with 4ꢀmethylpyridinium salts in the
presence of methylammonium sulfite to give, as a result of
a new transformation of the pyridine ring, 4ꢀphenylꢀ
pyridine and 4ꢀ(2ꢀnaphthyl)pyridine in up to 57 and 62%
yields, respectively (Scheme 1).
R1, R2 = Me, Et, Pri; R3 = H, Ph,
To reveal the potential scope of this reaction, we studꢀ
ied the possibility of transforming the pyridine ring under
the action of quaternary benzothiazolium salt 1.
chloride (3) would make the pyridine ring more electronꢀ
deficient for its opening to occur under milder conditions.
We found that the pyridine ring undergoes the desired
transformation when heating Zincke´s salts 2 and 3 with
quaternary benzothiazolium salt 1 in pyridine. The target
products 2ꢀphenylbenzothiazole (4) and 2ꢀ(2ꢀnaphthyl)ꢀ
benzothiazole (5) were obtained in 12 and 5% yields, reꢀ
spectively (Scheme 2).
Apparently, the reaction mechanism involves pyridineꢀ
promoted formation of anhydrobase 6 from quaternary
salt 1 followed by a nucleophilic attack of the enamine C
atom on the electronꢀdeficient αꢀposition of the pyridine
However, heating of both 1ꢀmethylpyridinium iodide
and 2ꢀmethylisoquinolinium iodide with benzothiazolium
salt 1 and aqueous methylammonium sulfite gave no
2ꢀarylbenzothiazoles. Opening of the pyridine ring in pyꢀ
ridinium and isoquinolinium salts under the action of
alkylammonium sulfite occurs in strongly basic media at
high temperatures. Apparently, the fiveꢀmembered ring of
benzothiazole is unstable under these conditions, which
results in resinification of the reaction mixture. We asꢀ
sumed that the use of 1ꢀ(2,4ꢀdinitrophenyl)pyridinium
chloride (2) and 2ꢀ(2,4ꢀdinitrophenyl)isoquinolinium
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1924—1927, October, 2010.
1066ꢀ5285/10/5910ꢀ1974 © 2010 Springer Science+Business Media, Inc.

Ring transformation of Zincke´s salts
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
1975
Scheme 2
baseꢀcatalyzed Nꢀdealkylation yields 2ꢀarylbenzothiazoles
4 and 5.
The low yields of compounds 4 and 5 can be attributed
to competitive reactions, e.g., Nꢀdealkylation of the startꢀ
ing salts 1—3 under the action of pyridine. This was
confirmed by the presence of 2ꢀmethylbenzothiazole,
pyridine, and isoquinoline among reaction products,
which are inert to the ring transformation under the
conditions of the reaction studied. Use of other bases
instead of pyridine did not increase the yields of the tarꢀ
get products. Interestingly, the reaction between salts 1
and 3 gives phenothiazine derivative 10 as a byꢀproduct
(Scheme 4).
It is known14,15 that baseꢀcatalyzed opening of the thiꢀ
azolium ring of the quaternary benzothiazolium salt gives
aniline derivative 11. Apparently, phenothiazine 10 is
formed in a reaction of compound 11 with salt 3.
A plausible mechanism involves nucleophilic displaceꢀ
ment of the isoquinoline residue and the formation of
diphenylamine derivative 12 followed by its heterocyclizaꢀ
tion into phenothiazine derivative 10 via intramolecular
nucleophilic ipsoꢀsubstitution (Scheme 5).
ring of salts 2 and 3 (Scheme 3). The resulting adduct 7
undergoes electrocyclic ring opening, probably into interꢀ
mediate 8. Its subsequent cyclization with elimination of
aromatic amine produces quaternary salt 9. In a final step,
Structure 10 was determined by NMR spectroscopy,
mass spectrometry, and elemental analysis. However, acꢀ
cording to Xꢀray diffraction data, a single crystal grown
Scheme 3

1976
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
Fomina et al.
Scheme 4
Scheme 5
Fig. 1. Its crystallographic parameters and the data colꢀ
lection and refinement statistics are given in Table 1.
from a saturated solution in DMSO has the structure of
Sꢀoxide 13 (Scheme 6).
Scheme 6
Table 1. Crystallographic parameters and the data collection and
refinement statistics for structure 13
Parameter
Value
Molecular formula
Molecular mass
Crystal color and shape
Crystal size/mm
Crystal system
Space group
a/Å
b/Å
c/Å
α/deg
C13H10N2O3S
274.29
Yellowish prism
0.28×0.26×0.24
Monoclinic
P21/n
Apparently, phenothiazine 10 is oxidized into sulfoxꢀ
ide 13 during the formation of single crystals. The general
view of structure 13 with atomic numbering is shown in
10.003(5)
11.638(6)
10.003(5)
90
β/deg
93.957(18)
90
1161.7(10)
4
γ/deg
O(2)
C(8)
3
S(1)
V/Å
C(7)
C(2)
C(3)
Z
C(1)
C(9)
N(2)
O(3)
dcalc/mg m–3
μ(MoꢀKα)/mm–1
F(000)
1.568
0.284
568
C(10)
O(1)
C(4)
Scan range θ/deg
Ranges of h, k, l indices
1.75 ≤ θ ≤ 27.00
–8 ≤ h ≤ 12,
–14 ≤ k ≤ 14,
–12 ≤ l ≤ 12
7225
C(12)
N(1)
C(11)
C(6)
C(5)
Number of measured reflections
Number of independent
reflections
Number of parameters refined
GOOF on F2
C(13)
2526
(Rint = 0.1534)
173
Fig. 1. Structure 13 with atomic thermal displacement ellipsoids
(p = 50%). Selected bond lengths: S(1)—O(1), 1.487(4) Å;
S(1)—C(1), 1.768(5) Å; S(1)—C(7), 1.749(5) Å; N(1)—C(6),
1.387(6) Å; N(1)—C(12), 1.402(6) Å; N(1)—C(13), 1.474(6) Å. Seꢀ
lected bond angles: C(1)—S(1)—C(7), 97.0(2)°; O(1)—S(1)—C(1),
107.2(2)°; O(1)—S(1)—C(7), 105.3(2)°; C(6)—N(1)—C(12),
121.2(4)°; C(6)—N(1)—C(13), 119.6(4)°; C(12)—N(1)—C(13),
118.3(4)°.
1.061
R Factors for I > 2σ(I)
R Factors for all reflections
Residual electron
0.0960, 0.2403
0.1394, 0.2721
0.871/–0.790
–3
density (max/min)/e Å

Ring transformation of Zincke´s salts
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
1977
7.42 (m, 1 H, H(5) of benzothiazole); 7.53 (m, 1 H, H(6) of
benzothiazole); 7.57 (m, 2 H, H(6), H(7) of naphthyl); 7.90
(m, 1 H, H(8) of naphthyl); 7.97 (m, 3 H, H(5) of naphthyl,
H(4), H(7) of benzothiazole); 8.14 (d, 1 H, H(4) of naphthyl,
J = 8.6 Hz); 8.23 (dd, 1 H, H(3) of naphthyl, J = 8.6 Hz,
J = 1.8 Hz); 8.59 (s, 1 H, H(1) of naphthyl). MS, m/z (Irel (%)):
261 [M+] (100), 260 (66), 131 (11), 130 (13), 108 (25), 81 (11),
69 (26), 59 (25), 57 (14), 55 (11).
To sum up, we discovered that the pyridine ring in
Zincke´s salts can be transformed into the benzene ring
under the action of Cꢀnucleophiles, which is of theoretical
interest for the chemistry of pyridine.
Experimental
10ꢀMethylꢀ3ꢀnitroꢀ10Hꢀphenothiazine (10), m.p. 155 °C
(from hexane) (cf. Ref. 20: m.p. 144—145 °C). 1H NMR
(DMSOꢀd6), δ: 3.36 (br.s, 3 H, MeN); 6.97—7.04 (m, 3 H,
H(1), H(6), H(8)); 7.14 (d, 1 H, H(9), J = 7.4 Hz); 7.24 (m, 1 H,
H(7)); 7.85 (s, 1 H, H(4)); 8.00 (dd, 1 H, H(2), J = 8.9 Hz,
J = 2.1 Hz). 13C NMR (DMSOꢀd6), δ: 35.76 (s, MeN); 113.95
(C(8)); 115.60 (C(6)); 120.49 (C(4a)); 121.53 (C(4)); 122.52
(C(9a)); 123.97, 124.01 (C(2), C(1)); 126.87 (C(9)); 128.22
(C(7)); 141.72 (C(3)); 143.04 (C(5a)); 150.93 (C(10a)). MS, m/z
(Irel (%)): 258 [M+] (100), 243 (25), 228 (24), 213 (52), 212 (70),
197 (33), 196 (30), 185 (22), 69 (33), 57 (26). Found (%): C, 60.32;
H, 3.51; N, 10.98. C13H10N2O2S. Calculated (%): C, 60.45;
H, 3.90; N, 10.85.
Xꢀray diffraction experiment. Crystals of compound 13 were
obtained by slow evaporation of its solution in DMSO at room
temperature. Reflection intensities from a single crystal were
measured on a Bruker SMARTꢀCCD diffractometer under
cooled (T = 120.0(2) K) nitrogen (MoꢀKα radiation, λ = 0.71073 Å,
graphite monochromator, ω scan mode). The structure was
solved by direct methods and refined in the fullꢀmatrix anisotroꢀ
pic approximation on F2 for nonꢀhydrogen atoms. The hydroꢀ
gen atoms were located geometrically and refined using a riding
model. All calculations were performed with the SHELXTLꢀ
Plus program package.21 Crystallographic parameters and the
data collection and refinement statistics are summarized in
Table 1. Atomic coordinates and other experimental data have
been deposited with the Cambridge Crystallographic Data
Center* (CCDC No. 748 021).
1
H NMR spectra were recorded on a Bruker DRXꢀ500 specꢀ
trometer (500.13 MHz) in CDCl3 and DMSOꢀd6 with residual
signals of the solvent as the internal standards (δ 7.27 and 2.50,
respectively). 13C NMR spectra were recorded on a Bruker
DRXꢀ500 spectrometer (125.76 MHz) in DMSOꢀd6 with its sigꢀ
nal as the internal standard (δ 128.02). Chemical shifts and couꢀ
pling constants were measured to within 0.01 ppm and 0.1 Hz,
respectively. The signals for the protons and carbon atoms were
assigned using homonuclear (1H—1H COSY, NOESY) and hetꢀ
eronuclear techniques (1H—13C COSY, HSQC, HMBC).
Mass spectra were recorded on a Varian MATꢀ311A mass
spectrometer (ionizing energy 70 eV, direct inlet probe).
Elemental analysis was carried out at the Microanalysis Labꢀ
oratory of the A. N. Nesmeyanov Institute of Organoelement
Compounds (Russian Academy of Sciences).
Melting points were determined in capillaries on a MELꢀ
Temp II instrument.
The course of the reactions was monitored by TLC on
DCꢀAlufolien Kieselgel 60 F254 plates (Merck). Column chroꢀ
matography was carried out on Kieselgel 60 (0.063—0.100 mm,
Merck).
2,3ꢀDimethylbenzothiazolium iodide (1), 1ꢀ(2,4ꢀdinitroꢀ
phenyl)pyridinium chloride (2), and 2ꢀ(2,4ꢀdinitrophenyl)ꢀ
isoquinolinium chloride (3) were prepared according to known
procedures.16,17
2ꢀPhenylbenzothiazole (4). A mixture of 1ꢀ(2,4ꢀdinitroꢀ
phenyl)pyridinium chloride (2) (0.282 g, 1 mmol) and 2,3ꢀdiꢀ
methylbenzothiazolium iodide (1) (0.582 g, 2 mmol) was heated
in dry pyridine (5 mL) in a sealed metalꢀjacketed tube on
a Wood´s alloy bath at 180 °C for 40 h. The tube was opened and
the reaction mixture was evaporated to dryness. The residue was
purified by column chromatography on SiO2 with benzene or
pentane—ethyl acetate (20 : 1) as an eluent. The yield of comꢀ
pound 4 was 25 mg (12%), m.p. 113 °C (cf. Ref. 18: m.p.
112—113 °C). 1H NMR (CDCl3), δ: 7.41 (m, 1 H, H(5) of
benzothiazole); 7.51 (m, 4 H, H(2), H(3), H(5), H(6) of pheꢀ
nyl); 7.93 (d, 1 H, H(4) of benzothiazole, J = 8.1 Hz); 8.09—8.12
(m, 3 H, H(6), H(7) of benzothiazole, H(4) of phenyl). MS, m/z
(Irel (%)): 211 [M+] (100), 210 (18), 184 (6), 108 (40), 81 (11),
76 (6), 69 (38), 63 (6), 58 (15), 51 (16).
2ꢀ(2ꢀNaphthyl)benzothiazole (5) and 10ꢀmethylꢀ3ꢀnitroꢀ
10Hꢀphenothiazine (10). A mixture of 2ꢀ(2,4ꢀdinitrophenyl)ꢀ
isoquinolinium chloride (3) (0.332 g, 1 mmol) and 2,3ꢀdimethylꢀ
benzothiazolium iodide (1) (0.582 g, 2 mmol) was heated in dry
pyridine (5 mL) in a sealed metalꢀjacketed tube on a silicone oil
bath at 120 °C for 40 h. The tube was opened, reaction products
were extracted with hot hexane, and the extract was concentratꢀ
ed. The residue was purified by column chromatography on SiO2
with benzene—hexane (1 : 1 and 2 : 1) as an eluent. The yields of
compounds 5 and 10 were 13 mg (5%) and 10 mg (4%), respecꢀ
tively.
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1

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Received October 2, 2009;
in revised form April 30, 2010