Environmentally friendly one-pot synthesis of substituted thiazoles and thiazolylpyrazoles

Full text of DOI:10.1134/S1070363212080257

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 8, pp. 1464–1467. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © S. Penta, R. Rao Vedula, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 8, pp. 1403–1406.
LETTERS
TO THE EDITOR
Environmentally Friendly One-Pot Synthesis
of Substituted Thiazoles and Thiazolylpyrazoles
S. Penta and R. Rao Vedula
National Institute of Technology, Warangal-506 004, A.P. India
e-mail: vrajesw@yahoo.com
Received August 25, 2011
DOI: 10.1134/S1070363212080257
Over the past several years chemists have been
trying to develop new synthetic routes to widely used
organic compounds from readily available starting
materials, reagents, and reaction conditions that reduce
risks to the humans and environment. Heterocycles are
widely used in the development of modern pharma-
ceuticals, therefore this is one of the reasons why
continuous efforts are directed towards the design of
amenable synthetic approaches for the synthesis of
new heterocyclic systems. 3-Acetyl-4-hydroxy-6-
methyl-2H-pyran-2-one (dehydroacetic acid) is a
convenient starting material, and its derivatives find
wide application in the synthesis of heterocyclic
compounds [1–4]. Some 4-hydroxy-2-pyrans have also
been tested as anticoagulant agents [5]. The nitrogen
and sulfur heterocyclic systems are very interesting
because of their physicochemical properties with
relevance to the design of new drugs. The compounds
containing a thiazole ring play a prominent role in
nature as they are found in numerous biologically
active compounds. Thiazole ring systems are known to
possess various pharmacological properties such as
anti-tubercular [6], antifungal [7], analgesic [8], and
anticancer activity [9]. Pyrazoles have emerged as a
group of compounds possessing a broad spectrum of
useful medicinal properties such as herbicides,
fungicides, and analgesics activities [10–11]. The
Schiff bases form a significant class of compounds in
medicinal and pharmaceutical chemistry with several
biological applications that include antibacterial,
antifungal, and antitumor activity [12–18].
incorporating pyran moiety. So we have developed a
practical, solvent-free, one-pot method for the
synthesis of the title compounds.
The multicomponent reactions are one-pot
processes, in which more than two reagents directly
get converted into their products. The multicomponent
reactions play an important role in modern organic
chemistry, because they generally exhibit higher
selectivity as well as produce fewer by-products com-
pared to the classic multistep synthesis. Furthermore,
in many cases the multicomponent reactions are easy
to perform, inexpensive, quick, consume less energy,
and involve simple experimental procedures.
As a part of our continuing work on the synthesis of
new heterocyclic systems [19–24], a facile and
convenient approach was developed for the synthesis
of various 4-hydroxy-3-[2-(N′-substituted hydrazino)
thiazol-4-yl]-6-methylpyran-2-one and 4-hydroxy-6-
methyl-3-[2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazol-4-
yl]-2H-pyran-2-one derivatives. The reaction of an
equimolar mixture of 3-(2-bromoacetyl)-4-hydroxy-6-
methyl-2H-pyran-2-one I, thiosemicarbazide II,
carbonyl compound III, or acetyl acetone V while
stirring at room temperature for 10 min results in the
title compounds IV or VI.
A plausible mechanism of this reaction can be
described as follows. The bromine atom of 3-(2-
bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one is
replaced by the sulfur atom of thiosemicarbazide to
yield an open-chain α-thioketone followed by trans-
protonating into 4-hydroxythiazoline derivative. It
subsequently undergoes the dehydration to give in situ
2-hydrazinothiazole derivative followed by con-
densation with various carbonyl compounds to give the
In view of various biological activities of thiazoles,
Schiff bases, and pyrazoles our current studies are
focused on the development of new routes to the
synthesis of thiazoles and thiazolylpyrazoles
1464

ENVIRONMENTALLY FRIENDLY ONE-POT SYNTHESIS
1465
R2
R1
N
HN
S
N
O
O
OH
OH
H
Br
O
N
NH2
+
+
H2N
R1
R2
S
H3C
H3C
O
O
O
IIIа−IIIj
IVа−IVj
II
I
III, IV, R1 = R2 = Me (а); R1 = Me, R2 = Ph (b); R1 = Me, R2 = p-tolyl (c); R1 = Me, R2 = p-anisyl (d); R1 = Me, R2 = Et (e);
R1 = R2 = cyclohexylidene (f); R1 = H, R2 = Ph (g); R1 = H, R2 = о-hydroxyphenyl (h); R1 = H, R2 = p-tolyl (i); R1 = H, R2 =
p-anisyl (j).
CH3
H3C
N
N
N
OH
O
O
O
S
+
I
II +
H3C
CH3
H3C
O
V
VI
All the reagents and solvents were pure, purchased
from commercial sources, and were used without
further purification unless otherwise stated. 3-(2-
Bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one was
prepared by the literature procedure [25].
final product IV. This is in accordance with the
modified Hantzsch thiazole synthesis. Probably in the
synthesis of thiazole first the thiosemicarbazide II
undergoes condensation with 3-(2-bromoacetyl)-4-hyd-
roxy-6-methyl-2Н-pyran-2-one I with a loss of water
and HBr molecules to give the corresponding cyclic
product. Further, the latter undergoes condensation
with acetyl acetone to give the target product.
The IR spectra were recorded on a Thermo Nicolet
1
Nexus 670 instrument from KBr pellets. The H NMR
spectra were registered on a Bruker WM-400 spec-
trometer using TMS as an internal reference. The mass
spectra (ESI-MS) were taken on a Perkin Elmer
SCIEX API- 2000 instrument at 12.5 eV. The melting
points were determined in open capillaries with a
Cintex melting point apparatus (Mumbai, India) and
were uncorrected. The CHNS-analysis was done on a
Carlo Erba EA 1108 automatic elemental analyzer.
The purity of the compounds obtained was monitored
by TLC.
The structure of the compounds obtained was
proved by the IR and NMR spectroscopy. Thus, the IR
spectrum of compound IVb contains the absorption
bands at 1731 and 3367 cm–1 originating from the
lactone and hydroxy group of pyran ring, respectively.
1
In the H NMR spectrum of IVb there are charac-
teristic singlets of the CH3-moiety of the pyran ring at
δ 2.24 ppm, of the C5H proton of the pyran ring at δ
6.23 ppm and of the thiazole proton at δ 7.81 ppm. The
1H NMR spectrum of VI contains the corresponding
singlet signals at δ 2.22 (CH3, pyran), 2.27 and 2.62
(CH3, pyrazole), 6.30 (pyran and pyrazole rings), 7.89
ppm (thiazole). The remaining protons were observed
in the expected regions.
General procedure for the synthesis of 4-hyd-
roxy-3-[2-(N′-substituted-hydrazino)thiazol-4-yl]-6-
methylpyran-2-one (IVa–IVj). A mixture of 1 mmol
of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-
2-one I, 1 mmol of thiosemicarbazide II, and 1 mmol
of the corresponding carbonyl compound III was
stirred at room temperature for about 10 min. The
solids obtained were filtered off, washed with water,
and recrystallized from ethanol.
In conclusion, we developed a simple, rapid,
efficient, and green method of the synthesis of a
variety of thiazoles and thiazolylpyrazole derivatives
via the three-component reaction in the one-pot
procedure. This method does not involve the use of the
volatile organic solvents and thus is an environ-
mentally friendly process.
4-Hydroxy-3-[2-(N′-isopropylidenehydrazino)-
thiazol-4-yl]-6-methylpyran-2-one (IVa). Yield
0.25 g (92%), mp 182–184°C, pale yellow crystals. IR
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 8 2012

1466
PENTA, RAO VEDULA
spectrum, ν, cm–1: 1717 (C=O, lactone), 3251 (NH),
3370 (OH). H NMR spectrum, δ, ppm: 1.96 s (6H,
3-[2-(N′-sec-Butylidenehydrazino]thiazol-4-yl]-
4-hydroxy-6-methylpyran-2-one(IVe). Yield 0.23 g
(80%), mp 216–218°C, pale yellow crystals. IR
spectrum, ν, cm–1: 1721 (C=O, lactone), 3261 (NH),
1
CH3), 2.23 s (3H, CH3), 6.20 s (1H, CН5, pyran), 7.31
s (1H, thiazole), 11.11 s (1H, NH), 14.57 s (1H, OH).
13С NMR spectrum, δC, ppm: 17.9, 19.3, 24.7, 93.8,
101.1, 103.3, 140.8, 152.9, 161.7, 162.0, 168.0, 168.6.
Mass spectrum, m/z: 278 [M + H]+. Found, %: C 51.5;
H 4.63; N 15.12. C12H13N3O3S. Calculated, %: C
51.60; H 4.69; N 15.04.
1
3392 (OH). H NMR spectrum, δ, ppm: 1.06 t (3H,
CH3, J 7.6 Hz), 1.94 s (3H, CH3), 2.23 s (3H, CH3),
2.29 q (2H, CH2, J 7.6 Hz), 6.20 s (1H, C5Н, pyran),
7.33 s (1H, thiazole), 11.22 s (1H, NH), 14.82 s (1H,
OH). 13С NMR spectrum, δC, ppm: 10.3, 16.7, 19.3,
31.0, 93.5, 101.0, 103.5, 139.7, 156.9, 161.8, 162.1,
168.0, 168.6. Mass spectrum, m/z: 293 [M + H]+.
Found, %: C 53.18; H 5.10; N 14.27. C13H15N3O3S.
Calculated, %: C 53.23; H 5.15; N 14.32.
4-Hydroxy-6-methyl-3-{2-[N′-(1-phenylethylidene)-
hydrazino]thiazol-4-yl}pyran-2-one (IVb). Yield
0.27 g (80%), mp 197–199°C, pale yellow crystals. IR
spectrum, ν, cm–1: 1731 (C=O, lactone), 3247 (NH),
1
3367 (OH). H NMR spectrum, δ, ppm: 2.24 s (3H,
3-[2-(N′-Cyclohexylidenehydrazino]thiazol-4-yl]-
4-hydroxy-6-methylpyran-2-one (IVf). Yield 0.25 g
(81%), mp 256–258°C, pale yellow crystals. IR
spectrum, ν, cm–1: 1737 (C=O, lactone), 3252 (NH)
and 3420 (OH). 1H NMR spectrum, δ, ppm: 1.60–1.63
m (6H, 3CH2, cyclohexyl), 2.23 s (3H, CH3), 2.27–
2.29 m (2H, CH2), 2.43–2.46 m (2H, CH2, cyclohexyl),
6.21 s (1H, C5Н, pyran), 7.33 s (1H, thiazole), 11.50 s
(1H, NH), 14.77 s (1H, OH). 13С NMR spectrum, δC,
ppm: 19.4, 24.8, 25.5, 26.7, 27.7, 34.6, 93.0, 100.9,
104.0, 137.9, 160.1, 162.0, 162.4, 167.7, 168.6. Mass
spectrum, m/z: 320 [M + H]+. Found, %: C 56.37; H
5.32; N 13.12. C15H17N3O3S. Calculated, %: C 56.41;
H 5.37; N 13.16.
CH3), 2.35 s (3H, CH3), 6.23 s (1H, C5Н, pyran), 7.39–
7.46 m (5H, Ph), 7.81 s (1H, thiazole), 11.57 s (1H,
NH), 14.50 s (1H, OH). 13С NMR spectrum, δC, ppm:
14.2, 19.3, 94.1, 101.1, 104.0, 125.8, 128.4, 129.1,
137.3, 142.2, 148.5, 161.5, 161.9, 168.2, 168.5. Mass
spectrum, m/z: 340 [M + H]+. Found, %: C 59.85; H
4.40; N 13.26. C17H15N3O3S. Calculated, %: C 59.81;
H 4.43; N 12.31.
4-Hydroxy-6-methyl-3-{2-[N′-(1-p-tolylethylidene)-
hydrazino]thiazol-4-yl}pyran-2-one(IVc). Yield 0.28
g (80%), mp 237–239°C, pale yellow crystals. IR
spectrum, ν, cm–1:1727 (C=O, lactone), 3248 (NH),
1
3377 (OH). H NMR spectrum, δ, ppm: 2.24 s (3H,
CH3), 2.32 s (3H, CH3), 2.33 s (3H, CH3), 6.22 s (1H,
C5Н, pyran), 7.25 d (2H, Ph, J8.0 Hz), 7.41 s (1H,
thiazole), 7.70 d (2H, Ph, J 8.0 Hz), 11.50 s (1H, NH),
14.90 s (1H, OH). 13С NMR spectrum, δC, ppm: 14.2,
19.3, 20.8, 93.9, 101.1, 104.0, 125.8, 129.0, 134.5,
138.8, 141.5, 148.9, 161.6, 161.9, 168.0, 168.5. Mass
spectrum, m/z: 356 [M + H]+. Found, %: C 60.78; H
4.78; N 11.76. C18H17N3O3S. Calculated, %: C 60.83;
H 4.82; N 11.82.
3-[2-(N′-Benzylidenehydrazino]thiazol-4-yl]-4-
hydroxy-6-methylpyran-2-one (IVg). Yield 0.25 g
(77%), mp 227–229°C, pale yellow crystals. IR
spectrum, ν, cm–1: 1728 (C=O, lactone), 3217 (NH),
1
3431 (OH). H NMR spectrum, δ, ppm: 2.24 s (3H,
CH3), 6.22 s (1H, C5Н, pyran), 7.41–7.47 m (5H, Ph;
1Н, thiazole), 8.08 s (1H, CH=N), 12.47 s (1H, NH),
14.88 s (1H, OH). 13С NMR spectrum, δC, ppm: 16.3,
99.9, 128.4, 128.5, 129.0, 129.1, 152.3, 156.5, 161.1,
162.1, 162.8, 163.9, 166.7, 193.2. Mass spectrum, m/z:
328 [M + H]+. Found, %: C 58.65; H 3.96; N 12.80.
C16H13N3O3S. Calculated, %: C 58.70; H 4.00; N 12.84.
4-Hydroxy-3-(2-{N′-[1-4-methoxyphenyl)ethyl-
idene]hydrazino}thiazol-4-yl)-6-methyl-pyran-2-one
(IVd). Yield 0.30 g (82%), mp 232–234°C, pale
yellow crystals. IR spectrum, ν, cm–1: 1728 (C=O,
lactone), 3263 (NH), 3370 (OH). 1H NMR spectrum, δ,
ppm: 2.24 s (3H, CH3), 2.31 s (3H, CH3), 3.80 s (3H,
OCH3), 6.22 s (1H, C5Н, pyran), 6.99 d (2H, Ph, J
8.8 Hz), 7.40 s (1H, thiazole), 7.75 d (2H, Ph, J 8.8
Hz), 11.47 s (1H, NH), 14.87 s (1H, OH). 13С NMR
spectrum, δC, ppm: 14.1, 19.3, 55.2, 94.2, 101.1, 103.6,
113.8, 127.3, 129.8, 142.5, 148.3, 160.1, 161.5, 161.8,
168.3, 168.5. Mass spectrum, m/z: 372 [M + H]+.
Found, %: C 58.26; H 4.56; N 11.34. C18H17N3O4S.
Calculated, %: C 58.21; H 4.61; N 11.31.
4-Hydroxy-3-{2-[N′-(2-hydroxybenzylidene)hyd-
razino]thiazol-4-yl}-6-methylpyran-2-one (IVh).
Yield 0.29 g (87%), mp 243–245°C, pale yellow
crystals. IR spectrum, ν, cm–1: 1707 (C=O, lactone),
1
3207 (NH), 3370 (OH). H NMR spectrum, δ, ppm:
2.24 s (3H, CH3), 6.23 s (1H, C5Н, pyran), 6.85–6.92
m (4H, Ph), 7.33 s (1H, thiazole), 8.06 s (1H, CH=N),
11.32 s (1H, NH), 14.82 s (1H, OH). 13С NMR spec-
trum, δC, ppm: 19.8, 94.9, 101.4, 104.0, 116.5, 116.6,
119.7, 120.2, 126.7, 131.5, 143.4, 156.6, 161.8, 162.4,
167.3, 168.8. Mass spectrum, m/z: 342 [M + H]+.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 8 2012

ENVIRONMENTALLY FRIENDLY ONE-POT SYNTHESIS
REFERENCES
1467
Found, %: C 55.93; H 3.78; N 12.20. C16H13N3O4S.
Calculated, %: C 55.97; H 3.82; N 12.24.
1. Prakash, O.M., Kumar, A., Sadana, A., and Singh, S.P.,
Synth. Commun., 2002, vol. 32, p. 2663.
4-Hydroxy-6-methyl-3-{2-[N′-(4-methylbenzyl-
idene)-hydrazino]thiazol-4-yl}pyran-2-one (IVi).
Yield 0.27 g (80%), mp 237–239°C, pale yellow
crystals. IR spectrum, ν, cm–1: 1717 (C=O, lactone),
2. Singh, S.P., Grover, M., Tarar, L.S., Elguero, J., and
Martinez, A.,J. Heterocycl.Chem., 1990, vol. 27, p. 865.
3. Singh, S.P., Kumar, D., Batra, H., Naithani, R., Rozas, J.,
and Elguero, J., Can. J. Chem., 2000, vol. 78, p. 1109.
4. Rehse, K., Schinkel, W., and Siemann, U., Arch.
Pharm., 1980, vol. 313, p. 344; Rehse, K. and Schinkel, W.,
Arch. Pharm., 1983, vol. 316, p. 845; Rehse, K. and
Schinkel, W., Arch. Pharm., 1983, vol. 316, p. 988;
Rehse, K. and Brandt, F., Arch. Pharm., 1983, vol. 316,
p. 1030; Rehse, K. and Ruther, D., Arch. Pharm., 1984,
vol. 317, p. 262.
1
3242 (NH), 3366 (OH). H NMR spectrum, δ, ppm:
2.24 s (3H, CH3), 2.34 s (3H, CH3), 6.22 s (1H, C5Н,
pyran), 7.26 d (2H, Ph, J 8.0 Hz), 7.41 s (1H, thiazole),
7.59 d (2H, Ph, J 8.0 Hz), 8.05 s (1H, CH=N), 12.42 s
(1H, NH), 14.82 s (1H, OH). 13С NMR spectrum, δC,
ppm: 19.4, 21.0, 94.0, 100.9, 104.0, 126.6, 129.4,
129.6, 131.1, 134.0, 139.7, 144.2, 161.5, 162.1, 167.0,
168.4, 192.6. Mass spectrum, m/z: 342 [M + H]+.
Found, %: C 59.77; H 4.40; N 12.28. C17H15N3O3S.
Calculated, %: C 59.81; H 4.43; N 12.31.
5. Mehra, S.C., Zaman, S., and Khan, A.A., J. Indian
Chem. Soc., 1980, vol. 47, p. 829.
6. Pattan, R.S., Reddy, V.V.K., and Bhat, A.R., Indian. J.
Chem. B, 2006, vol. 45, p. 1778.
7. Ali, M.S., Pattan, J.S, Purohit, S.S, Reddy, V.V.K., and
Pattan, R.S., Indian J. Chem. B, 2006, vol. 45, p. 1929.
8. Narayan, B. et al., Indian J. Chem. B, 2006, vol. 45,
p. 1704.
9. Altintes, H., Otuk, G., Ates, O., and Birteksoz, S.,
Indian J. Chem. B, 2005, vol. 44, p. 585.
4-Hydroxy-3-{2-[N′-(4-methoxybenzylidene)hyd-
razino]thiazol-4-yl}-6-methylpyran-2-one (IVj).
Yield 0.27 g (78%), mp 273–275°C, pale yellow
crystals. IR spectrum, ν, cm–1: 1712 (C=O, lactone),
1
3234 (NH), 3438 (OH). H NMR spectrum, δ, ppm:
10. Ren, X., Li, H., Wu, C., and Yang, H., Arkivok, 2005,
vol. 15, p. 59.
11. Chai, B., Qian, X., Cao, S., Liu, H., and Song, G.,
Arkivoc, 2003, vol. 2, p. 141.
2.24 s (3H, CH3), 2.31 s (3H, CH3), 3.80 s (3H,
OCH3), 6.21 s (1H, C5Н, pyran), 7.13 d (2H, Ph, J
8.4 Hz), 7.39 s (1H, thiazole), 7.64 d (2H, Ph, J
8.0 Hz), 8.03 s (1H, CH=N), 11.22 s (1H, NH), 14.82 s
(1H, OH). 13С NMR spectrum, δC, ppm: 19.5, 55.3,
99.5, 113.7, 114.4, 129.1, 130.4, 131.3, 160.7, 161.7,
162.2, 163.8, 163.9, 164.2, 191.2. Mass spectrum, m/z:
358 [M + H]+. Found, %: C 57.10; H 4.20; N 11.71.
C17H15N3O4S. Calculated, %: C 57.13; H 4.23; N 11.76.
12. Abu-Hussen, A. and Azza, A., J. Coord. Chem., 2006,
vol. 59, p. 157.
13. Sithambaram, K.M., Jagadesh, P.D., Poojary, B.,
Subramanyahat, K., and SuchethaKumara, N., Bioorg.
Med. Chem., 2006, vol. 14, p. 7482.
14. Panneerselvam, P., Nair, R.R., Vijayalakshmi, G.,
Subramanian, E.H., and Sridhar, S.K., Eur. J. Med.
Chem., 2005, vol. 40, p. 225.
15. Sridhar, S.K., Saravan, M., and Ramesh, A., Eur. J.
Med. Chem., 2001, vol. 36, p. 615.
16. Pandeya, S.N., Sriram, D., Nath, G., and Declercq, E.,
Eur. J. Pharm. Sci., 1999, vol. 9, p. 25.
17. Mladenova, R., Ignatova, M., Manolova, N., Petrova, T.,
and Rashkov, I., Eur. Polym. J., 2002, vol. 38, p. 989.
18. Walsh, O.M., Meegan, M.J., Prendergast, R.M., and
Nakib, T.A., Eur. J. Med. Chem., 1996, vol. 31, p. 989.
19. RajeswarRao, V. and Vijaya Kumar, P., Synth.
Commun., 2006, vol. 36, p. 2157.
4-Hydroxy-6-methyl-3-[2-(3,5-dimethyl-1H-pyra-
zol-1-yl)thiazol-4-yl]-2H-pyran-2-one(VI). A mix-
ture of 1 mmol of 3-(2-bromoacetyl)-4-hydroxy-6-
methyl-2H-pyran-2-one I, 1 mmol of thiosemicar-
bazide II, and 1 mmol of acetyl acetone V was stirred
at room temperature for about 10 min. The solid
obtained was filtered off, washed with water, and
recrystallized from ethanol. Yield 0.26 g (88%), mp
217–219°C, pale yellow crystals. IR spectrum, ν, cm–1:
1
1727 (C=O, lactone), 3437 (OH). H NMR spectrum,
δ, ppm: 2.22 s (3H, CH3), 2.27 s (3H, CH3), 2.62 s
(3H, CH3), 6.20 s (1H, C5Н, pyran; 1Н, pyrazole), 7.95
s (1H, thiazole), 13.27 s (1H, OH). Mass spectrum,
m/z: 303 [M + H]+. Found, %: C 55.40; H 4.28; N
13.81. C14H13N3O3S. Calculated, %: C 55.43; H 4.32;
N 13.85.
20. Chunduru, V.S.R. and RajeswarRao, V., J. Chem. Res.,
2010, p. 50.
21. Venkata, S.R., Chunduru, and RajeswarRao, V., J. Sulfur
Chem., 2010, vol. 31, p. 545.
22. Vijaya Kumar, P. et al., Indian J. Chem. B, 2010,
vol. 49, p. 836.
23. Srimanth, K. and RajeswarRao, V., J. Chem. Res.,
2002, vol. 9, p. 420.
24. Madan Mohan, P. and RajeswarRao, V., Indian J. Het.
Chem., 2003, vol. 13, p.69.
25. Harris, T.M., Harris, C.M., and Brush, C.K., J. Org.
Chem., 1970, vol. 5, p. 1329.
ACKNOWLEDGMENTS
The authors are thankful to the Director of National
Institute of Technology, Warangal, A.P., India, for
providing financial support and facilities.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 8 2012