Theoretical and experimental study on cyclic 6-methyl-2,3,4- tris(hydroxymethyl)pyridin-5-ol acetonides

Article abstract of DOI:10.1134/S1070428010040202

Methods for the preparation of three cyclic 2,3,4-tris(hydroxymethyl)-6- methylpyridin-5-ol acetonides have been developed by variation of the reaction conditions. The six-membered acetonide turned out to be thermodynamically more stable than the seven-me

Full text of DOI:10.1134/S1070428010040202

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 561–567. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © N.V. Shtyrlin, O.A. Lodochnikova, M.V. Pugachev, T.I. Madzhidov, L.P. Sysoeva, I.A. Litvinov, E.N. Klimovitskii, Yu.G. Shtyrlin,
2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 4, pp. 569–575.
Theoretical and Experimental Study on Cyclic 6-Methyl-
2,3,4-tris(hydroxymethyl)pyridin-5-ol Acetonides
N. V. Shtyrlina, O. A. Lodochnikovab, M. V. Pugacheva, T. I. Madzhidova, L. P. Sysoevaa,
I. A. Litvinovb, E. N. Klimovitskiia, and Yu. G. Shtyrlina
a Butlerov Chemical Institute, Kazan State University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia
e-mail: Yurii.Shtyrlin@ksu.ru
b Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
Received June 5, 2009
Abstract—Methods for the preparation of three cyclic 2,3,4-tris(hydroxymethyl)-6-methylpyridin-5-ol
acetonides have been developed by variation of the reaction conditions. The six-membered acetonide turned out
to be thermodynamically more stable than the seven-membered acetonide and bis-acetonide. The experimental
data were consistent with the results of quantum-chemical calculations. The structure of the isolated com-
pounds was proved by X-ray analysis.
DOI: 10.1134/S1070428010040202
Protection of glycols via transformations into cyclic
acetonides is used more frequently than other protec-
tive groups [1–3] due to facile introduction of aceto-
nide protection, stability of acetonides in neutral and
alkaline media, and their lability under relatively mild
conditions of acid hydrolysis. The formation, stability,
and conformational specificity of cyclic acetals derived
from pyridoxine attract both practical and considerable
theoretical interest [4]. Pyridoxine can be converted
into two cyclic six- and seven-membered acetonides,
depending on the concentration of acid catalyst [5, 6].
At low concentration of hydrogen chloride or p-tolu-
enesulfonic acid, kinetically controlled product is
obtained, whereas at higher concentration of the acid
catalyst the product is thermodynamically more stable
six-membered acetonide.
We previously developed a new and convenient
procedure for the synthesis of 2,3,4-tris(hydroxy-
methyl)-6-methylpyridin-5-ol (I) [7]. Unlike pyridox-
ine, compound I could give rise to four cyclic aceto-
nides: three monoacetonides II–IV and tricyclic bis-
acetonide V. We calculated the energies of formation
Scheme 1.
Me
Me
O
OH
O
Me2CO–HCl (6%)
HO
Me
HO
Me
O
O
Me
Me
HO
OH
N
N
HO
Me
OH
OH
II
IV
Me
N
Me
Me
O
O
I
Me
Me2CO–HCl (25%)
Me2CO–HCl (14%)
O
O
O
O
Me
Me
OH
OH
Me
N
Me
N
III
V
561

SHTYRLIN et al.
562
Table 1. Calculated energies of formation ΔGf° (kcal/mol) of
cyclic acetals II–V
The experimental data in combination with quan-
tum-chemical calculations showed that six-membered
acetal III is thermodynamically controlled product and
that the formation of other cyclic acetals is unfavorable
from the viewpoint of energy; on the other hand, it was
possible to isolate acetonides II and V due to poor
solubility of their pyridinium salts in acetone (so that
they were removed from the reaction sphere).
Gaussian 98
Comp. Priroda
no.
PBE/3z
HF/6-31G(d,p) B3LYP/6-31G(d,p)
V
6.26
1.28
3.84
0.39
6.48
1.21
IV
II
4.16
1.97
4.62
To obtain crystals suitable for X-ray analysis, cyclic
acetonides of compound I were isolated as the corre-
sponding p-toluenesulfonates according to the proce-
dure described in [6]. By reaction of acetone with com-
pound I in the presence of an equimolar amount of
p-toluenesulfonic acid we obtained p-toluenesulfonate
VI of seven-membered acetal II. Using of 3 equiv of
p-toluenesulfonic acid we selectively synthesized bis-
acetal V p-toluenesulfonate VII, while larger amount
of the catalyst ensured formation of six-membered
acetal III p-toluenesulfonate.
III
–0.64–
–2.55–
–0.21–
of acetonides II–V. According to the results of ab
initio quantum-chemical calculations, in all cases the
twist conformation of seven-membered ring turned out
to be more energetically favorable, whereas the six-
membered ring is most likely to adopt distorted boat
conformation. These findings are consistent with the
results of our previous studies on conformations of
pyridoxine acetals [4]. In keeping with the calculated
energies of formation ΔG°f in the gas phase at 298 K
(Table 1), the formation of six-membered acetal III is
preferred, while the formation of the other acetals is
considerably less probable.
According to the X-ray diffraction data, the pyri-
dine ring in molecule III in crystal (Fig. 1) is planar,
while the six-membered acetal ring adopts a distorted
boat conformation. Both free hydroxy groups appear
at the same side of the aromatic fragment. Crystal
packing of compound III is determined mainly by
formation of classical intermolecular hydrogen bonds
(Fig. 2). The nitrogen atom acts as proton acceptor, the
hydroxy group on C2 is a proton donor, and the hy-
droxy group on C3 is simultaneously donor and accep-
tor of proton. As a result of such interactions, each
molecule is linked to four neighboring molecules.
Compound I was subjected to acetalization with
acetone according to standard procedure [4]. At high
concentration of acid catalyst (HCl, >25%), pyridini-
um salt of six-membered acetal III was formed (the
product is soluble in acetone). At lower HCl concen-
tration, we obtained insoluble pyridinium salts of
acetal II and bisacetal V (Scheme 1). Acetonides III
and V can also be synthesized using compound II as
substrate. Thus variation of the reaction conditions
makes it possible to isolate three different cyclic
acetonides, which opens wide prospects in selective
functionalization of compound I. However, we failed
to find experimental conditions ensuring formation of
seven-membered acetonide IV.
The seven-membered heteroring in molecule VII
has twist conformation, and the six-membered ring has
a boat conformation. The hydrogen atom on the proto-
nated N1 nitrogen atom is involved in H-bond with the
oxygen atom in the p-toluenesulfonate ion (Fig. 3).
Compound VI crystallized in two polymorphous
forms: triclinic (VIa) and monoclinic (VIb). The cati-
onic fragments in these forms differed by conforma-
tion of the hydroxymethyl substituent: molecule VIa
is characterized by twisted conformation along the
C2–C13 bond [the torsion angle C3C2C13O13 is 54.2(2)°]
(Fig. 4), while the corresponding fragment in mono-
clinic modification VIb occurs in eclipsed conforma-
tion [the torsion angle N1C2C13O13 is –9.8(2)°] (Fig. 5).
Also, the conformations of the hydroxy group on C10
in VIa and VIb are different (the torsion angle
C11C10O10H10 is 12 and 4.63°, respectively). The above
conformational differences originate primarily from
C14
C11
C10
O8
N1
C9
C4
C7
O12
C12
C2
C3
C15
O13
O6
C5
C13
Fig. 1. Structure of the molecule of 5,6-bis(hydroxymethyl)-
2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine (III) accord-
ing to the X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

THEORETICAL AND EXPERIMENTAL STUDY ON CYCLIC 6-METHYL-...
563
O3b
C15
O6
C5
O2b
O8
C11
C7
C9
C3
C10
C2
N1
C12
O12
C4
C13
C14
O1b
N1
O13
C16
C2
C7
C6
C17
O13c
O10
C3
O13
N1d
C4
O15
C14
C9
C19
C5
O8
C11
C12
C18
C20
Fig. 3. Structure of 3,3,5,9,9-pentamethyl-7,11-dihydro-1H-
[1,3]dioxepino[5,6-b][1,3]dioxino[5,4-d]pyridinium p-tolu-
enesulfonate (VII) according to the X-ray diffraction data.
Hydrogen bond is shown with dotted line.
Fig. 2. A fragment of crystal packing of compound III. Hy-
drogen bonds are shown with dashed lines.
O3
O3
C21
S1
S1
O1
C20
O2
C21
C19
C16
C20
C16
C18
O2
C22
C17
C17
C18
O1
C19
O13
C22
C14
C14
C4
O7
C13
N1
O7
C13
C3
C2
O13
C6
C15
O5
C8
C4
C3
C2
C6
N1
C10
C9
C9
O10
C8
C11
O10
O5
C12
C10
C11
C15
C12
Fig. 4. Structure of 9-hydroxy-6-hydroxymethyl-3,3,8-tri-
methyl-1,5-dihydro[1,3]dioxepino[5,6-c]pyridinium p-tolu-
enesulfonate (VIa, triclinic) according to the X-ray diffrac-
tion data.
Fig. 5. Structure of 9-hydroxy-6-hydroxymethyl-3,3,8-tri-
methyl-1,5-dihydro[1,3]dioxepino[5,6-c]pyridinium p-tolu-
enesulfonate (VIb, monoclinic) according to the X-ray dif-
fraction data.
differences in the hydrogen bond systems (Figs. 6, 7).
The cationic fragments in crystals of VIa give rise
to infinite chains as a result of O10–H10···O13 hydrogen
bonding. p-Toluenesulfonate ion is linked by hydrogen
bonds O2 ···H1–N1 and O1 ···H13–O13 to two cationic
fragments, so that the chains are combined into layers.
The cationic fragments in the crystalline structure
of VIb are linked in pairs through hydrogen bond
N1–H1 ···O13, and p-toluenesulfonate ions connect
paired cationic fragments through O2 ···H13–C13 and
O3 ···H10–O10 interactions to form zigzag layers. In
both structures, stacks with alternation of cationic and
anionic fragments with almost parallel orientation of
the aromatic rings may be distinguished; however,
fairly long interplanar distances (>3.6 Å) indicate the
absence of π–π interactions in crystal.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

SHTYRLIN et al.
Series II analyzer. The progress of reactions and the
564
purity of products were monitored by TLC on Silufol
UV-254 plates using ethanol–chloroform (4:1) as
eluent. Preparative chromatography was performed on
KSKG silica gel (Ekofarm, grain size 0.10–0.16 mm).
The mass spectrum of compound V (electron im-
pact, 70 eV) was obtained on a Trace MS Finnigan
MAT instrument; ion source temperature 200°C; batch
inlet temperature programming from 35 to 150°C at
a rate of 35 deg/min. The data were processed using
Xcalibur program.
O10
O1
O13
N1
O2
The calculations were performed at the BT cluster,
Supercomputer Collective Use Center, Kazan Research
Center, Russian Academy of Sciences [bt.knc.ru;
8 two-processor nuclei (AMD Opteron 2.0 GHz), 1 GB
RAM per nucleus, 2*Gigabit Ethernet commutation]
using Priroda 2.02 [9] and Gaussian 98 software pack-
ages [10]. Priroda software involved PBE functional
[11] with augmented triple zeta basis set, while
Gaussian 98 utilized Hartree–Fock procedure with
B3LYP functional [12] and 6-31G(d,p) basis set. The
calculations were performed with full geometry opti-
mization, and minima on the potential energy surface
were localized by calculating the second derivative
matrix in which all elements for the structures listed in
Table 1 were positive.
Fig. 6. A fragment of crystal packing of compound VIa
(triclinic). Hydrogen bonds are shown with dashed lines.
X-Ray analysis. Single crystals of compounds VII,
VIa, and VIb were obtained by crystallization from
methanol, and single crystals of III, by crystallization
from chloroform. X-Ray diffraction data were acquired
on a Bruker Smart Apex II diffractometer [λ(MoKα) =
0.71073 Å, 293 K]. The principal crystallographic and
structure refinement parameters for compounds III,
VIa, VIb, and VII are given in Tables 2, 3. Absorption
by crystals was taken into account semiempirically
using SADABS program. The structures were solved
by the direct method. The positions and thermal
parameters of non-hydrogen atoms were refined first in
isotropic and then in anisotropic approximation by
full-matrix least-squares procedure. Hydrogen atoms
not involved in hydrogen bonding were placed into
positions calculated on the basis of geometry con-
siderations and were refined using riding model. The
hydroxy hydrogen atoms were visualized by difference
Fourier series, and their positions were refined in iso-
tropic aproximation. All calculations were performed
using SHELXL-97 software package [8]. The com-
plete sets of crystallographic parameters for com-
pounds III, VIII, VIa, and Vb, were deposited to the
Cambridge Crystallographic Data Centre (entry
nos. CCDC 721614, 721615, 721616, 721617).
N1
O13
O2
O3
O10
Fig. 7. A fragment of crystal packing of compound VIb
(monoclinic). Hydrogen bonds are shown with dashed lines.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Varian
Unity-300 spectrometer at 300 MHz using hexameth-
yldisiloxane as internal reference. The elemental com-
positions were determined on a Perkin–Elmer 2400
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

THEORETICAL AND EXPERIMENTAL STUDY ON CYCLIC 6-METHYL-...
565
Table 2. Parameters of hydrogen bonds in the crystalline structures of compounds III, VIa, VIb, and VII according to
the X-ray diffraction data
Comp.
no.
Hydrogen
bond
Symmetry
Distance
D–H, Å
Distance
H···A, Å
Distance
D···A, Å
∠DHA, deg
transformationa
III
O12–H1···O13
O13–H2···N1
N1–H1···O2
O10–H10···O13
O13–H13···O1
N1–H1···O13
N1–H1···O13
O10–H10···O3
O13–H13···O2
N1–H1···O1
[3/2 – x, –1/2 + y, z]
[1/2 + x, 3/2 – y, –z]
–
0.99(6)
1.05(6)
0.89(2)
0.80(2)
0.78(3)
0.85(2)
0.85(2)
0.75(2)
0.85(2)
1.00(4)
1.76(6)
1.76(6)
1.83(2)
1.87(2)
1.90(3)
2.24(2)
2.17(2)
1.89(2)
1.80(2)
1.75(4)
2.745(5)
2.794(5)
2.729(2)
2.635(2)
2.680(2)
2.683(1)
2.893(2)
2.632(2)
2.653(2)
2.723(5)
172(6)
171(6)
177(2)
163(3)
174(2)
113(2)
144(2)
167(2)
178(3)
165(4)
VIa
[ x, 1 + y, z]
[1 – x, 1 – y, 1 – z]
–
VIb
[1 – x, 2 – y, 1 – z]
–
[1 – x, 1/2 + y, 1/2 – z]
[–1 + x, y, 1 + z]
VII
a
Symmetry transformation for intermolecular hydrogen bonds.
Table 3. Principal crystallographic parameters and parameters of X-ray diffraction experiments for compounds III, VIa,
VIb, and VII
Parameter
Compound III
Compound VII
Compound VI
Formula
C12 H17NO4
239.27
Rhombic
Pbcn
C22H29NO7S
451.52
C19H25NO7S
411.46
Molecular weight
Crystal system
Space group
a, Å
Monoclinic
P21/n
Triclinic (VIa)
Monoclinic (VIb)
P21/c
P-1
8.2111(6)
8.3101(6)
16.6225(12)
091.3290(10)0
099.3900(10)0
112.7550(10)0
1027.29(13)
2
10.534(5)
10.731(6)
020.978(11)
90
09.151(3)
18.819(6)
13.201(4)
90.000(0)
90.379(4)
90.000(0)
2273.3(12)
4
11.3827(8)
12.1300(9)
014.8605(11)
90.000(00)
105.1320(10)
90.000(00)
1980.7(2)
4
b, Å
c, Å
α, deg
β, deg
90
γ, deg
V, Å3
90
2371(2)
8
Z
d
calc, g cm–3
1.340
1.319
1.330
1.380
μ, cm–1
0.101
0.185
0.197
0.205
Total number of reflections (Rint)
Number of reflections with I > 2σ(I)
Number of refined parameters
R1 [reflections with I > 2σ(I)]
wR2 (all reflections)
32347 (0.1155)
1429
16237 (0.0711)
2829
14366 (0.0147)
3971
16380 (0.0169)
3880
0166
0290
0269
0269
0.0778
0.1959
0.0852
0.0408
0.0396
0.2400
0.1215
0.1216
6-Hydroxymethyl-3,3,8-trimethyl-1,5-dihydro-
[1,3]dioxepino[5,6-c]pyridin-9-ol (II). Gaseous hy-
drogen chloride, 0.81 g (22.2 mmol), was passed under
stirring through a suspension of 0.5 g (2.53 mmol) of
2,3,4-tris(hydroxymethyl)-6-methylpyridin-5-ol (I) in
12 ml (163 mmol) of acetone and 4 ml (28.9 mmol) of
2,2-dimethoxypropane. The mixture was stirred for
20 h at room temperature, the precipitate was filtered
off and neutralized with an aqueous solution of potas-
sium carbonate, the solvent was distilled off under
reduced pressure, the solid residue was washed with
boiling acetone, and the filtrate was evaporated under
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

SHTYRLIN et al.
566
reduced pressure. Yield 0.76 g (88%), light yellow
crystals, mp 161°C [4].
(2H, CH2), 4.91 s (2H, CH2). Found: Hact 7.82.
m/z 279.10 [M]+ . Calculated: Hact 7.82. M 279.33.
b. Gaseous hydrogen chloride, 2.08 g (57.1 mmol),
was passed under stirring through a suspension of 0.6 g
(2.53 mmol) of compound II in 12 ml (163 mmol) of
acetone and 4 ml (28.9 mmol) of 2,2-dimethoxy-
propane. The mixture was stirred for 20 h at room
temperature and treated as described above in a. Yield
0.49 g (70%), colorless oily substance.
5,6-Bis(hydroxymethyl)-2,2,8-trimethyl-4H-
[1,3]dioxino[4,5-c]pyridine (III). a. Gaseous hydro-
gen chloride, 8 g (219 mmol), was passed under
stirring through a suspension of 1 g (5.05 mmol) of
compound I in 22 ml (300 mmol) of acetone and 8 ml
(57.8 mmol) of 2,2-dimethoxypropane. The mixture
was stirred for 30 h at room temperature and neutral-
ized with aqueous potassium carbonate, the solvent
was distilled off under reduced pressure, the oily
residue was washed with chloroform, the filtrate was
evaporated under reduced pressure, and the oily mate-
rial was washed with diethyl ether. Yield 0.57 g (57%),
9-Hydroxy-6-hydroxymethyl-3,3,8-trimethyl-1,5-
dihydro[1,3]dioxepino[5,6-c]pyridinium p-toluene-
sulfonate (VI). p-Toluenesulfonic acid monohydrate,
0.48 g (2.53 mmol), was added under stirring to a sus-
pension of 0.5 g (2.53 mmol) of compound I in 10 ml
(136 mmol) of acetone and 5 ml (36.1 mmol) of
2,2-dimethoxypropane. The mixture was stirred for
20 h at room temperature, and the precipitate was
filtered off and washed with acetone. Yield 0.76 g
(88%), colorless crystals, mp 145°C (VIa, triclinic);
1
colorless crystals, mp 144–145°C. H NMR spectrum
(CDCl3), δ, ppm: 1.55 s (6H, CH3), 2.39 s (3H, CH3),
4.54 s (2H, CH2), 4.73 s (2H, CH2), 4.98 s (2H, CH2).
Found, %: C 59.77; H 7.13; N 5.72. C12H17NO4. Cal-
culated, %: C 60.24; H 7.16; N 5.85.
1
mp 151°C (VIb, monoclinic). H NMR spectrum
b. p-Toluenesulfonic acid monohydrate, 3.35 g
(17.6 mmol), was added under stirring to a suspension
of 0.5 g (2.53 mmol) of compound I in 14 ml
(191 mmol) of acetone and 6 ml (43.4 mmol) of
2,2-dimethoxypropane. The mixture was stirred for
30 h at room temperature and was treated as described
above in a. Yield 0.17 g (34%), colorless crystals,
mp 144–145°C.
(DMSO-d6), δ, ppm: 1.44 s (6H, CH3), 2.29 s (3H,
CH3), 2.53 s (3H, CH3), 4.63 s (2H, CH2), 4.89 s (2H,
CH2), 4.94 s (2H, CH2), 7.09 and 7.12 (1H each, C6H4,
3
AB system, J = 8.1 Hz), 7.46 and 7.48 (1H each,
3
C6H4, AB system, J = 8.1 Hz). Found, %: C 53.70;
H 5.87; N 3.16. C22H29NO7S. Calculated, %: C 55.46;
H 6.12; N 3.40.
3,3,5,9,9-Pentamethyl-7,11-dihydro-1H-[1,3]di-
oxepino[5,6-b][1,3]dioxino[5,4-d]pyridinium p-tolu-
enesulfonate (VII). p-Toluenesulfonic acid mono-
hydrate, 1.44 g (7.58 mmol), was added under stirring
to a suspension of 0.5 g (2.53 mmol) of compound I in
10 ml (136 mmol) of acetone and 5 ml (36.1 mmol) of
2,2-dimethoxypropane. The mixture was stirred for
20 h at room temperature, and the precipitate was
filtered off and washed with acetone. Yield 0.54 g
c. Gaseous hydrogen chloride, 8 g (219 mmol), was
passed under stirring through a suspension of 1.21 g
(5.05 mmol) of compound II in 22 ml (300 mmol) of
acetone and 8 ml (57.8 mmol) of 2,2-dimethoxy-
propane. The mixture was stirred for 30 h at room
temperature and was treated as described above in a.
Yield 0.64 g (64%), colorless crystals, mp 144–145°C.
3,3,5,9,9-Pentamethyl-7,11-dihydro-1H-[1,3]di-
oxepino[5,6-b][1,3]dioxino[5,4-d]pyridine (V).
a. Gaseous hydrogen chloride, 2.08 g (57.1 mmol),
was passed under stirring through a suspension of 0.5 g
(2.53 mmol) of compound I in 12 ml (163 mmol) of
acetone and 4 ml (28.9 mmol) of 2,2-dimethoxy-
propane. The mixture was stirred for 20 h at room
temperature, the precipitate was filtered off and neu-
tralized with an aqueous solution of potassium carbon-
ate, the solvent was distilled off under reduced pres-
sure, the solid residue was washed with chloroform,
and the filtrate was evaporated under reduced pressure.
1
(63%), colorless crystals, mp 189–189.5°C. H NMR
spectrum (CDCl3), δ, ppm: 1.45 s (6H, CH3), 1.53 s
(6H, CH3), 2.29 s (3H, CH3), 2.43 s (3H, CH3), 4.80 s
(2H, CH2), 4.90 s (2H, CH2), 5.01 s (2H, CH2), 7.10
3
and 7.13 (1H each, C6H4, AB system, J = 8.1 Hz),
7.47 and 7.49 (1H each, C6H4, AB system, 3J = 8.1 Hz).
Found, %: C 58.27; H 6.47; N 3.04. C22H29NO7S. Cal-
culated, %: C 58.62; H 6.47; N 3.10.
REFERENCES
1. Greene, T.W. and Wuts, P.G.M., Protective Groups in
Organic Synthesis, New York: Wiley, 1999, 3rd ed.
1
Yield 0.57 g (81%), colorless oily substance. H NMR
spectrum (CDCl3), δ, ppm: 1.49 s (6H, CH3), 1.52 s
2. De Belder, A.N., Adv. Carbohydr. Chem., 1965, vol. 20,
(6H, CH3), 2.39 s (3H, CH3), 4.60 s (2H, CH2), 4.71 s
p. 219.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

THEORETICAL AND EXPERIMENTAL STUDY ON CYCLIC 6-METHYL-...
567
3. Showler, A.J. and Darley, P.A., Chem. Rev., 1967,
Burant, J.C., Dapprich, S., Millam, J.M., Daniels, A.D.,
Kudin, K.N., Strain, M.C., Farkas, O., Tomasi, J.,
Barone, V., Cossi, M., Cammi, R., Mennucci, B.,
Pomelli, C., Adamo, C., Clifford, S., Ochterski, J.,
Petersson, G.A., Ayala, P.Y., Cui, Q., Morokuma, K.,
Malick, D.K., Rabuck, A.D., Raghavachari, K., Fores-
man, J.B., Cioslowski, J., Ortiz, J.V., Stefanov, B.B.,
Liu, G., Liashenko, A., Piskorz, P., Komaromi, I.,
Gomperts, R., Martin, R.L., Fox, D.J., Keith, T., Al-
Laham, M.A., Peng, C.Y., Nanayakkara, A., Gonza-
lez, C., Challacombe, M., Gill, P.M.W., Johnson, B.,
Chen, W., Wong, M.W., Andres, J.L., Gonzalez, C.,
Head-Gordon, M., Replogle, E.S., and Pople, J.A.,
Gaussian 98, Revision A.3; Pittsburgh PA: Gaussian,
1998.
vol. 67, p. 427.
4. Petukhov, A.S., Strel’nik, A.D., Fedorenko, V.Yu., Litvi-
nov, I.A., Lodochnikova, O.A., Shtyrlin, Yu.G., and
Klimovitskii, E.N., Russ. J. Gen. Chem., 2007, vol. 77,
p. 1416.
5. Korytnyk, W., J. Org. Chem., 1962, vol. 27, p. 3724.
6. Korytnyk, W., J. Med. Chem., 1973, vol. 16, p. 1096.
7. Shtyrlin, N.V., Strel’nik, A.D., Sysoeva, L.P., Lodoch-
nikova, O.A., Klimovitskii, E.N., and Shtyrlin, Yu.G.,
Russ. J. Org. Chem., 2009, vol. 45, p. 1266.
8. Sheldrick, G.M., SHELXL-97, Göttingen: Univ. of
Göttingen, 1997.
9. Laikov, D.N., Chem. Phys. Lett., 1997, vol. 281, p. 151.
11. Perdew, J.P., Burke, K., and Ernzerhof, M., Phys. Rev.
Lett., 1996, vol. 77, p. 3865.
12. Becke, A.D., J. Chem. Phys., 1993, vol. 98, p. 1372.
10. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuse-
ria, G.E., Robb, M.A., Cheeseman, J.R., Zakrzew-
ski, V.G., Montgomery, J.A., Stratmann, R.E., Jr.,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010