Synthesis of the functionally 4-substituted 1-methyl-3-thioxo-2,3,5,6,7,8- hexahydroisoquinolines by SNVin reaction of 2-acetyl-1-(N- morpholinyl)cyclohexene with malonothio(dithio)amides

Article abstract of DOI:10.1134/S1070363212020156

4-Carbamoyl(thiocarbamoyl)-3-thioxo-2,3,5,6,7,8-hexahydroisoquinolines were synthesized by the SNVin reaction of 2-acetyl-1-(N-morpholinyl) acetylcyclohexene with malonothio(dithio)amides. The cyclo-condensation direction was confirmed with the X-ray diff

Full text of DOI:10.1134/S1070363212020156

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 2, pp. 251–255. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © I.V. Dyachenko, M.V. Vovk, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 2, pp. 256–250.
Synthesis of the Functionally 4-Substituted
1-Methyl-3-thioxo-2,3,5,6,7,8-hexahydroisoquinolines
by SNVin Reaction of 2-Acetyl-1-(N-morpholinyl)cyclohexene
with Malonothio(dithio)amides
I. V. Dyachenkoa and M. V. Vovkb
a Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91011 Ukraine
е-mail: ivladya87@e-mail.ua
b Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received December 20, 2010
Abstract—4-Carbamoyl(thiocarbamoyl)-3-thioxo-2,3,5,6,7,8-hexahydroisoquinolines were synthesized by the
SNVin reaction of 2-acetyl-1-(N-morpholinyl)acetylcyclohexene with malonothio(dithio)amides. The cyclo-
condensation direction was confirmed with the X-ray diffraction analysis of 1-methyl-3-methylthio-5,6,7,8-
tetrahydroisoquinoline-4-carboxamide.
DOI: 10.1134/S1070363212020156
The nucleophilic vinyl substitution (SNVin) of
amino enones is widely used in the synthesis of
biologically active nitrogen heterocycles [1–3]. Pre-
viously it has been used in the synthesis of 4-cyano-
substituted 1-alkyl(phenyl)-3-oxo(thioxo, selenoxo)-
5,6,7,8-tetrahydroisoquinolines [4, 5], which are
promising intermediates in the search for substances
with cardiac [6–9], antitumor [10] and inhibiting the
HIV-1 reverse transcriptase [11] actions.
latter by the X-ray diffraction method (see the figure
and the table) allowed an unequivocal establishment of
the heterocyclization course of intermediate A to salt
III and to exclude a possible cyclization of inter-
mediate B into isoquinolin-3-one VI, an isomer of
compound IV. A clear choice in favor of isomer IV or
VI on the basis of IR and NMR spectra was not
possible.
The cyclohexene ring is in a semichair con-
formation with a planar С6–С3–С4–С9 fragment
[torsion angle 179.17(11)°]. The atoms C7 and C8 are
disordered over two positions, A and B, with the
relative occupancy of 0.671(7):0.329(7), which cor-
responds to two mirror symmetrical semichair con-
formations of the ring. The atoms C7 and C8 deviate
from the mean plane of the remaining ring atoms by
0.465(6) and –0.315(5) Å (conformation A), –0.440(11)
and 0.367(11) Å (conformation B), respectively. The
amide moiety is strongly turned relative to the pyridine
ring plane [the C3C2C11O1 torsion angle is –71.99(16)°],
which leads to the strong disturbance of the
conjugation between the π-systems of the substituent
and the pyridine ring. This causes the elongation of
С2–С11 bond to 1.5097(15) Å as compared with an
average value of 1.50 Å [15]. The C10-methyl group
lies in the ring plane and is oriented towards the N1
atom [torsion angle C10S1C1N1 4.77(11)°].
The subject of this study is the reaction of pre-
paratively available [12] 2-acetyl-1-(N-morpholinyl)
acetylcyclohexene I with malonic thio(dithio)amides
in order to obtain new polyfunctional hexahydroiso-
quinolines. The condensation of cyclic enaminone I
with malonothioamide II was found to proceed in
anhydrous ethanol at 20°C in the presence of sodium
ethoxide to give sodium 4-carbamoyl-1-methyl-5,6,7,8-
tetrahydroisoquinoline-3-thiolate III. We think that the
scheme of the process most likely includes the stage of
nucleophilic vinyl substitution at the C1 atom of alkene
to form intermediate A, which undergoes a chemo-
selective cyclization into thiolate III. Treating of the
latter with hydrochloric acid solution yields compound
IV, which like 2-thioxo-5,6,7,8-tetrahydroquinoline
[5, 13] exists mainly in the thion form.
The alkylation of salt III with methyl iodide in
DMF solution results in compound V. The study of the
251

252
DYACHENKO, VOVK
NH2
NH2
O
S
S
S
O
II
N
NH2
NH2
EtONa
O
Me
O
Me
O
H2N
Me
O
H2N
O
I
A
B
O
O
O
S
HCl
MeI
NH2
NH2
NH2
SMe
NH2
+
− Na
S
Me
N
Me
N
S
Me
N
Me
N
O
H
H
IV
V
III
VI
In the crystal the molecules form the centro-
symmetric dimers through the hydrogen bonding
between the amide groups N2–H2b···O1i (1 – x, 1 – y, –z)
[H···O 2.021(16) Å, N–H···O 175.5(16)°]. In the
crystal is formed also a relatively weak hydrogen bond
involving the pyridine nitrogen atom N(2)–H2a···N1ii
(–x, 1 – y, 1 – z) [H···N 2.335(15) Å, N–H···N
167.7(16)°].
Malonic acid dithioamide (VII) is found to be
equally effective in the SNVin reaction with morpho-
linocyclohexene I. The use of the conditions similar to
those for the CH-acid II allows us obtaining 1-methyl-
3-thioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbo-
thioamide VIII in 69% yield omitting the intermediate
thiolate isolation. Heating of compound VII in glacial
acetic acid is accompanied with the hydrogen sulfide
NH2
NH2
S
S
S
S
CN
S
Cl
CN
VII
ΑcΟΗ
−Η2S
NH2
I
EtONa
Me
N
H
Me
N
H
Me
N
S
O
IX
VIII
XII
Cl
EtONa
O
Br
XI
Br
NH2
O
XIII
CN
CN
S−
+
Na
S
Me
N
Me
N
Me
N
S
O
O
X
XV
XIV
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012

SYNTHESIS OF THE FUNCTIONALLY 4-SUBSTITUTED
elimination and transformation into the previously
253
described 1-methyl-3-thioxo-2,3,5,6,7,8-hexahydro-
isoquinoline-4-carbonitrile IX [4]. The treatment of the
latter with an alcoholic solution of sodium ethoxide
leads to 1-methyl-4-cyano-5,6,7,8-tetrahydroiso-
quinoline-3-sodium thiolate X stable in the solid state.
The latter is a convenient reagent for the subsequent
modification that is illustrated by the example of its
alkylation with α-bromoacetophenone XI to form
thioester XIІ. In the case of α-bromomethylcyclo-
propylketone XIІІ corresponding thioether XIV cannot
be isolated due to its fast intramolecular cyclization by
Thorpe reaction into thieno[2,3-c]isoquinoline deri-
vative XV.
The structure of the synthesized compounds was
confirmed by the spectroscopic data. The IR spectra of
key compounds III–V contain the absorption band at
1680–1702 cm–1 belonging to C=O group of carba-
General view of molecule VI.
moyl moiety. The IR spectra of compounds X and XII
include a weak band of the C≡N group at 2214 and
2222 cm–1, respectively.
Bond lengths (d) and angles (ω) in the structure of VI
Bond
S1–C1
d, Å
Angle
C1S1C10
C5N1C1
N1C1C2
N1C1S1
ω, deg
1.7636(12)
1.7752(15)
1.2242(15)
1.3410(14)
1.3431(13)
1.3166(16)
0.807(15)
0.878(16)
1.3897(16)
1.3913(16)
1.5097(15)
1.4022(16)
1.5083(17)
1.3897(17)
1.5129(16)
1.5099(16)
1.510(3)
103.37(6)
118.31(10)
122.60(10)
119.27(9)
118.12(8)
118.89(10)
121.42(10)
119.68(10)
118.88(11)
119.81(10)
121.31(11)
118.06(10)
120.37(10)
121.54(11)
123.24(10)
115.70(11)
121.05(11)
112.79(14)
111.0(2)
1
S1–C10
O1–C11
N1–C5
N1–C1
N2–C11
N2–H2A
N2–H2B
C1–C2
C2–C3
C2–C11
C3–C4
C3–C6
C4–C5
C4–C9
C5–C12
C6–C7A
C6–C7B
A characteristic feature of the H NMR spectra of
isoquinolines III–V, VIII, and X is the presence of
singlet signals of methyl groups at 2.12–2.52 ppm, as
well as the typical multiplet signals of the tetra-
methylene protons at 1.55–2.78 ppm and low-field
signals of the protons of chalcogen-containing amide
group. In addition, in the spectra of isoquinoline-3-
thione IV and VIII derivatives there are the signals of
NH-protons of the the endocyclic thioamide fragment
at 11.87 and 13.79 ppm, respectively. Comparing the
13C NMR spectra of related compounds IV and VIII a
significant effect of 4-(thio)carbamoyl substituent on
the chemical shifts of the thiopyridone carbon atoms
was revealed. Compound IV was characterized by the
signals at 114.22 (C6), 127.63 (C4), 146.05 (C1),
161.45 (C3), 163.71 (C5) ppm, and the compound VIII,
by the signals at 121.19 (C6), 151.70 (C4), 155.77 (C1),
167.30 (C5), 173.95 (C3) ppm.
C2C1S1
C1C2C3
C1C2C11
C3C2C11
C2C3C4
C2C3C6
C4C3C6
C5C4C3
C5C4C9
C3C4C9
N1C5C4
N1C5C12
C4C5C12
C3C6C7A
C3C6C7B
C8AC7AC6
C8BC7BC6
C7AC8AC9
C7BC8BC9
C8BC9C4
C4C9C8A
O1C11N2
O1C11C2
N2C11C2
1.555(6)
C
7A–C8A
1.510(6)
C7B–C8B
C8A–C9
C8B–C9
1.505(13)
1.530(4)
108.9(3)
EXPERIMENTAL
110.1(7)
1.509(8)
111.0(3)
The crystals of compound IV are triclinic,
C12H16N2OS, at 298 K а 7.9528(13), b 8.9781(14), c
9.1514(17) Å, α 79.179(14)°, β 68.028(16)°, γ
84.970(13)°, V 595.07(17) Å3, Mr 236.33, Z 2; space
group Р1¯, dcalc 1.319 g cm–1, μ(MoKα) 0.253 mm–1,
F(000) 252. The unit cell parameters and intensities of
6315 reflections (3878 independent, Rint 0.014) were
108.3(6)
113.8(3)
112.52(17)
123.39(11)
120.59(11)
115.99(11)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012

254
DYACHENKO, VOVK
measured on a Xcalibur 3 automatic four-circle diff-
ractometer (MoKα, graphite monochromator, CCD
detector, ω-scanning, 2θmax 64.8°).
kept for 48 h. The formed precipitate was filtered off,
washed with water, ethanol, and hexane. Yield 1.71 g
(77%), yellow powder, mp 245–248ºС (АсOH). IR
spectrum, ν, cm–1: 3300, 3176, 1702, 1649, 1287 (NH,
The structure was solved by the direct method
using SHELX-97 program package [15]. The positions
of hydrogen atoms were geometrically calculated and
refined by a rider model with Uiso = nUeq for the
carrier atom (n = 1.5 for CH3-groups and n = 1.2 for
methylene groups). The structure was refined with
respect to F2 using full-matrix anisotropic approxi-
mation for non-hydrogen atoms to wR2 0.099 for 3878
reflections (R1 0.039 for 2474 reflections with F > 4σ(F),
S 1.00). The bond lengths and angles are given in the
table.
1
CONH2), 1230 (C=S). Н NMR spectrum, δ, ppm:
11.87 br.s (1Н, NH), 7.27 br.s (2Н, NH2), 2.59 t (2Н,
СН2, J 5.13 Hz), 2.45 t (2Н, СН2, J 5.22 Hz), 2.28 s
(3Н, Ме), 1.55–1.69 m (4Н, 2 СН2). 13С NMR
spectrum, δС, ppm: 20.76 (CH3), 21.81 (CH2), 22.75
(CH2), 25.13 (CH2), 25.31 (CH2), 114.22 (C6), 127.63
(C4), 146.05 (C1), 161.45 (C3), 163.71 (C5), 164.81 [C
(О)NH2]. Mass spectrum, m/z (Irel, %): 221 [M – 1]+
(100). Found, %: С 59.35; Н 6.28; N 12.51.
C11H14N2ОS. Calculated, %: С 59.43; Н 6.35; N 12.60.
1-Methyl-3-methylthio-5,6,7,8-tetrahydroisoquino-
line-4-carboxamide (V). A mixture of 2.44 g (10 mmol)
of thiolate III and 0.62 ml (10 mmol) of methyl iodide
in 15 ml of DMF was stirred for 3 h, then kept for 1
day and diluted with the equal volume of water under
stirring. The formed precipitate was filtered off,
washed with water, ethanol, and hexane. Yield 1.82 g
(77%), colorless crystals, mp 235–238ºС (АсOH). IR
spectrum, ν, cm–1: 3336, 3125, 1680, 1247 (CONH).
1Н NMR spectrum, δ, ppm: 7.66 br. S (1Н, NH2), 7.49
br.s (1Н, NH2), 2.78 t (2Н, СН2, J 5.11 Hz), 2.67 t
(2Н, СН2, J 5.19 Hz), 2.52 s (3Н, SМе), 2.40 s (3Н,
Ме), 1.82 m (2Н, СН2), 1.64 m (2Н, СН2). 13С NMR
spectrum, δС, ppm: 12.58 (SCH3), 21.32 (CH3), 21.84
(CH2), 22.00 (CH2), 25.01 (CH2), 25.94 (CH2), 125.97
(C4), 130.20 (C6), 141.79 (C5), 148.83 (C3), 155.41
(C1), 168.08 [C(O)NH2]. Mass spectrum, m/z (Irel, %):
237 [M + 1]+ (100). Found, %: С 60.83; Н 6.74; N
11.78. C12H16N2ОS. Calculated, %: С 60.99; Н 6.82; N
11.85.
The melting points were determined on a Koeffler
block. The IR spectra were recorded on a Spectrum
One (Perkin Elmer) FIR-spectrometer from KBr
1
pellets. The H and 13С NMR spectra were registered
on a Bruker DR×500 spectrometer (500.068 and
125.7578 MHz, respectively) in DMSO-d6 relative to
internal reference TMS. The mass spectra were taken
on a Crommas GC/MS-Hewlett-Packard 5890/5972
spectrometer, column HP-S MS (70 eV) in CH2Cl2
solution. The reaction progress and purity of the
compounds were monitored by TLC on Silufol UV
254 plates eluting with an acetone–hexane mixture
(3:5) and detecting with iodine vapor and ultraviolet
irradiation.
Sodium 4-carbamoyl-1-methyl-5,6,7,8-tetrahyd-
roisoquinoline-3-thiolate (III). To a stirred mixture of
2.1 g (10 mmol) of enamino ketone I and 1.2 g
(10 mmol) of thioamide II in 15 ml of anhydrous
ethanol at 20°С was added sodium ethylate solution
prepared from 0.23 g (10 mmol) of sodium and 5 ml of
anhydrous ethanol. The mixture was stirred for 30 min
and kept for 1 day. The formed precipitate was filtered
off, washed with anhydrous ethanol and hexane. Yield
1.67 g (74%), yellow powder, mp 230ºС (decomp.). IR
spectrum, ν, cm–1: 3315, 3195, 1688, 1230 (CONH2).
1Н NMR spectrum, δ, ppm: 7.34 br.s (1Н, NH2), 7.21
br.s (1Н, NH2), 2.59 m (2Н, СН2), 2.48 m (2Н, СН2),
2.26 s (3Н, Ме), 1.68 m (4Н, 2СН2). Mass spectrum,
m/z (Irel, %): 221 [M – Nа]+ (100). Found, %: С 53.95;
Н 5.28; N 11.33. NаC11H13N2ОS. Calculated, %: С
54.08; Н 5.36; N 11.47.
1-Methyl-3-thioxo-2,3,5,6,7,8-hexahydroisoquino-
line-4-carbothioamide (VІІІ) was prepared similarly
from 1.34 g (10 mmol) of malonic acid dithioamide.
The formed precipitate was washed with water and
dried. Yield 1.64 g (69%), brown powder, mp 250–
253ºС. IR spectrum, ν, cm–1: 3314, 3182, 1695 (NH,
1
NH2С=S), 1210 (C=S). Н NMR spectrum, δ, ppm:
13.79 br.s (1Н, NH), 9.63 br.s (1Н, NH2), 9.33 br.s
(1Н, NH2), 2.73 m (2Н, СН2), 2.42 m (2Н, СН2), 2.34
s (3Н, Ме), 1.56–1.64 m (4Н, 2 СН2). 13С NMR
spectrum, δС, ppm: 16.61 (CH3), 20.65 (CH2), 21.06
(CH2), 23.55 (CH2), 28.70 (CH2), 121.19 (C6), 151.70
(C4), 155.77 (C1), 167.30 (C5), 173.95 (C3), 176.16
[C(S)NH2]. Mass spectrum, m/z (Irel, %): 205 [M – H2S +
1]+ (100). Found, %: С 55.39; Н 5.88; N 11.66.
C11H14N2S2. Calculated, %: С 55.43; Н 5.92; N 11.75.
1-Methyl-3-thioxo-2,3,5,6,7,8-hexahydroisoquino-
line-4-carboxamide (ІV). A stirred suspension of
2.44 g (10 mmol) of thiolate III in 20 ml of ethanol
was diluted with 10% hydrochloric acid till pH 5 and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012

SYNTHESIS OF THE FUNCTIONALLY 4-SUBSTITUTED
255
1-Methyl-3-thioxo-2,3,5,6,7,8-hexahydroisoquino-
line-4-carbonitrile (ІX). A suspension of 2.38 g
(10 mmol) of compound VІІІ in 20 ml of glacial acetic
acid was heated to the boiling. After 1 day, the
precipitate was filtered off, washed with glacial acetic
acid and diethyl ether. Yield 1.71 g (84%), yellow
powder, mp 290–292ºС (292–294°С [4]). 13С NMR
spectrum, δС, ppm: 16.64, 20.62, 21.03, 23.55, 28.70,
112.69, 115.98, 121.25, 151.73, 155.76, 173.89. Mass
spectrum, m/z (Irel, %): 205 [M + 1]+ (100).
irradiation. IR spectrum, ν, cm–1: 3392, 3318, 3295
(NH2), 1648 [δ(NH2)], 1712 (C=О). Н NMR spec-
1
trum, δ, ppm: 7.65 br.s (2Н, NH2), 3.20 m (2Н, СН2),
2.62 m (2Н, СН2) 2.45 s (3Н, Ме), 2.11 m (1Н,
СНС=О), 0.96–1.11 m (4Н, 2СН2). Mass spectrum,
m/z (Irel, %): 287 [M + 1]+ (100). Found, %: С 67.01; Н
6.25; N 9.66. C16H18N2OS. Calculated, %: С 67.10; Н
6.33; N 9.78.
REFERENCES
Sodium 1-methyl-4-cyano-5,6,7,8-tetrahydroiso-
quinoline-3-thiolate (X). To a stirred suspension of
2.04 g (10 mmol) of compound IX in 25 ml of
anhydrous ethanol was added sodium ethylate,
prepared from 0.23 g (10 mmol) of sodium and 5 ml of
anhydrous ethanol. The reaction mixture was stirred
for 10 min, the precipitate was filtered off and washed
with anhydrous diethyl ether. Yield 2.06 g (94%),
yellow powder, mp 215ºС (decomp.). IR spectrum, ν,
cm–1: 2214 (C≡N). 1Н NMR spectrum, δ, ppm: 2.71 m
(2Н, СН2), 2.42 m (2Н, СН2), 2.32 s (3Н, Ме), 1.61–
1.73 m (4Н, 2 СН2). Mass spectrum, m/z (Irel, %): 203
[M – Na – 1]+ (100). Found, %: С 58.25; Н 4.88; N
12.23. NaC11H11N2S. Calculated, %: С 58.39; Н 4.90;
N 12.38.
1. Dyachenko, V.D. and Tkachev, R.P., Zh. Org. Khim.,
2003, vol. 39, no. 6, p. 807.
2. Dyachenko, V.D. and Tkachev, R.P., Zh. Org. Khim.,
2006, vol. 42, no. 2, p. 167.
3. Dyachenko, V.D. and Tkachev, R.P., Selected Methods
for Synthesis and Modification of Heterocycles, IBS
PRESS, 2002, vol. 2, p. 33.
4. Sharanin, Yu.A., Shestopalov, A.M., Promonenkov, V.K.,
and Rodinovskaya, L.A., Zh. Org. Khim., 1984, vol. 20,
no. 11, p. 2432.
5. Shestopalov, A.M., Rodinovskaya, L.A., Sharanin, Yu.A.,
and Litvinov, V.P., Zh. Obshch. Khim., 1988, vol. 58,
no. 4, p. 840.
6. Kaiho, T., Sannohe, R., Kajiya, S., Suzuki, T., Otsuka, K.,
Jfo, T., Kamiya, J., and Maruyama, M., J. Med. Chem.,
1989, vol. 32, no. 2, p. 351.
1-Methyl-3-[2-(4-chlorophenyl)-2-oxoethylthio]-
5,6,7,8-tetrahydroisoquinoline-4-carbonitrile (XII)
was prepared similarly to compound V from 2.5 g
(10 mmol) of thiolate X and 2.33 g (10 mmol) of α-
bromoacetophenone XІ. Yield 2.78 g (78%), colorless
crystals, mp 130–132ºС (АсОН). IR spectrum, ν, cm–1:
1704 (С=О), 2222 (C≡N). 1Н NMR spectrum, δ, ppm:
8.08 d (2Н, НAr, J 8.56 Hz), 7.61 d (2Н, НAr, J 8.56 Hz),
4.78 s (2Н, SCH2), 2.78 m (2Н, СН2), 2.49 m (2Н,
СН2), 2.12 s (3Н, Ме), 1.59–1.73 m (4Н, 2 СН2). Mass
spectrum, m/z (Irel, %): 357 [M + 1]+ (100). Found, %:
С 63.88; Н 4.71; N 7.82. C19H17ClN2ОS. Calculated,
%: С 63.95; Н 4.80; N 7.85.
7. Japan Patent no. 0604270, 1987; С. А., 1987, vol. 106,
no. 19, 156296u.
8. Japan Patent Appl. 62-4270, 1987; Ref. Zh. Khim.,
1988, 8 О 98 P.
9. Japan Patent no. 61229865, 1985; С. А., 1987, vol. 106,
no. 19, 156291p.
10. WO Patent Appl. 1623987, 2006; Ref. Zh. Khim., 2007,
07.10–19 О 115 P.
11. Elgemeie, G.E.H., Affia, A.M.T., and Fathy, N.M.,
Nucleosides and Nucleotides, 1997, vol. 16, no. 4,
p. 485.
12. Zhang, P. and Li, L., Synt. Commun., 1986, vol. 16, no. 8,
p. 957.
13. Dyachenko, V.D. and Dyachenko, A.D., Zh. Org.
Khim., 2008, vol. 44, no. 3, p. 415.
(1-Amino-5-methyl-6,7,8,9-tetrahydrothieno[2,3-
c]isoquinolin-2-yl)(cyclopropyl)methanone (XV) was
prepared similarly to compound V from 2.5 g (10 mmol)
of thiolate X and 1.63 g (10 mmol) of α-bromoketone
XІІІ. Yield 2.14 g (75%), yellow powder, mp 195–
197ºС (АсOH). There is fluorescence under UV
14. Burgi, H.-B. and Dunitz, J.D., Structure Correlation,
1994, Weinheim: VCH, vol. 2, p. 741.
15. Sheldrick, G., Acta Cryst. (A), 2008, vol. 64, no. 1,
p. 112.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012