Investigations in the field of benzoxa- zines. 15. Tandem heterocyclizations with the participion of 2-formylbenzoic acid. the synthesis of isoindolo[1,2-b][1, 3]- and -[2,1-a][1, 3]benzoxazinones

Article abstract of DOI:10.1007/s10593-010-0476-3

Single stage reactions of 2-formylbenzoic acids with substituted 2-(1-aminoalkyl)phenols and 2-amino-phenylcarbinols give a novel series of isomeric isoindolobenzoxazinones. X-ray analysis was used to study the molecular structure of 9-bromo-5,5-diphenyl-5H-isoindolo[2,1-a][1, 3]benzoxazin-11(6aH)- one and 2-bromo-8,10-dimethyl-10H-isoindolo[1,2-b][1, 3]-benzoxazin-12(4bH)-one.

Full text of DOI:10.1007/s10593-010-0476-3

Chemistry of Heterocyclic Compounds, Vol. 46, No. 1, 2010
INVESTIGATIONS IN THE FIELD OF BENZOXA-
ZINES. 15*. TANDEM HETEROCYCLIZATIONS
WITH THE PARTICIPION OF 2-FORMYLBENZOIC
ACID. THE SYNTHESIS OF ISOINDOLO[1,2-b][1,3]-
AND -[2,1-a][3,1]BENZOXAZINONES
E. V. Gromachevskaya1**, A. S. Pilipenko1, A. V. Butin1,
V. E. Zavodnik1, and G. D. Krapivin1
Single stage reactions of 2-formylbenzoic acids with substituted 2-(1-aminoalkyl)phenols and 2-amino-
phenylcarbinols give a novel series of isomeric isoindolobenzoxazinones. X-ray analysis was used to
study the molecular structure of 9-bromo-5,5-diphenyl-5H-isoindolo[2,1-a][3,1]benzoxazin-11(6aH)-
one and 2-bromo-8,10-dimethyl-10H-isoindolo[1,2-b][1,3]-benzoxazin-12(4bH)-one.
Keywords: 2-(1-aminoalkyl)phenols, 2-aminophenylcarbinols, 10H-isoindolo[1,2-b][1,3]benzoxazin-
12(4bH)-ones, 5H-isoindolo[2,1-a][3,1]benzoxazin-11(6aH)-ones, 2-formylbenzoic acids.
Tetracyclic condensed structures containing an annelated isoindole fragment are widely distributed in
nature and have a broad spectrum of biological activity that is well reflected in recent reviews [2, 3]. Hence
there is much interest in developing new routes for their synthesis. The isoindolo[2,1-a][3,1]benzoxazine system
has been described in the literature, however, most data concerns isoindolo[2,1-a][3,1]benzoxazine-5,11-diones
[4-7], while the synthesis of derivatives of 5,6a-dihydroisoindolo[2,1-a][3,1]benzoxazin-11-ones has been
reported in only one publication [8] to our knowledge. The authors of this article used the 2-amino ketone
phthalimides A as starting compounds, and these were converted to the respective structures B through a simple
sequence of reactions.
Despite the simplicity of the scheme, this method still has an important drawback, since the use of
asymmetrically substituted phthalic anhydrides in the synthesis of the phthalimides A should lead to a mixture
of isomeric alcohols C. To avoid this difficulty, derivatives of 2-formylbenzoic acid can be used. It is well
known that 2-formylbenzoic acids can react with binucleophiles containing at least one primary amino group to
give annelated isoindolinones [9-12].
_______
* For Communication 14 see [1].
** To whom correspondence should be addressed, e-mail: organics@kubstu.ru.
1 Research Institute of Heterocyclic Compounds Chemistry, Kuban State Technological University, Krasnodar
350072, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 125-136, January, 2010. Original
article submitted March 4, 2009.
106
0009-3122/10/4601-0106©2010 Springer Science+Business Media, Inc.

O
O
O
p-TsOH
NaBH4
N
N
N
H
O
O
OH
O
R
R
HO
R
A
B
C
R = Me, Ph
The aim of our work was to develop a versatile, preparative method leading not only to isoindolo-
[2,1-a][3,1]benzoxazines (for which only two of the compounds of type B given above have been reported [8])
but also to related isoindolo[1,2-b][1,3]benzoxazines [12].
We have used the 2-(aminoalkyl)phenols 2 (obtained by a standard method [14]) as binucleophiles in
reaction with the 2-formylbenzoic acids 1 [13]. Reaction of equimolar amounts of reagents 1 and 2 in refluxing
toluene with a catalytic amount of p-toluenesulfonic acid and azeotropic distillation of water gave the tetracyclic
10H-isoindolo[1,2-b][1,3]benzoxazin-12H(4bH)-ones 3.
R3
4
O
6
6
R2
R3
R2
OH
4b
O
5
7
+
1
NH2
10
R1
HO
N
12
R1
– 2H2O
3
9
O
R
R
O
1
2a–b, d–e
3a–k
a R = R3 = H, R1 = R3 = Cl; b−k R = Me, b−f R3 = H, b R1 = Me, R2 = Br; c R1 = Me, R2 = Cl;
d R1 = Cl, R2 = Br; e R1 = OMe, R2 = Cl; f R1 = R2 = Cl; g R1 = OMe, R2 = NO2, R3 = Cl;
h R1 = Me, R2 = NO2, R3 = Cl; i R1 = R3 = Cl, R2 = NO2; j R1 = Cl, R2 = R3 = OMe;
k R1 = R2 = R3 = OMe
The synthesis reaction time is virtually independent of the nature of the substituent in the 2-(1-amino-
alkyl)phenol molecules 2 but it does depend markedly on the type of substituent in the formylbenzoic acid.
Acceptor substituents (NO2 or two halogen) shorten the reaction time to 40-60 min while electron donors
(methoxy groups) increase the time for reaction completion to 10-12 h. Evidently this is connected with the
change in electrophilicity of the formyl carbon atom and, possibly, the carbon atom of the azomethine group of
the Schiff base formed in the first stage of the reaction. The fact that a Schiff base is actually an intermediate in
the complex sequence of reactions is indirectly indicated by a change in the color of the reaction mixture during
the synthesis. Initially colorless it takes on a strong yellow color and this disappears when the reaction is
complete. TLC also indicates the appearance and disappearance of a strongly colored reaction intermediate. An
azomethine is the only intermediate product of those possible.
The isoindolobenzoxazinones 3a-k are colorless, crystalline substances readily soluble in most organic
solvents (Table 1). The IR spectra of compounds 3 show characteristic stretching absorptions for a lactam
carbonyl group at 1645-1700 cm-1. The compound 3a molecule has one chiral center at atom 4b and this is
clearly revealed in the 1H NMR spectrum. The diastereotopic protons of the 10-CH2 function absorb as a pair of
doublets with a geminal spin-spin coupling of J = 17.1 Hz (Table 2). Compounds 3b-k have two chiral centers at
1
atoms 4b and 10 and can, in principle, exist as two pairs of enantiomers. The H NMR spectra of these
substances show only one set of signals, typical of which are a three-proton doublet at high field and a one-
proton quartet at medium field for the A3X system formed by the H-10 and CH3 group protons and also a sharp
107

TABLE 1. Physicochemical Characteristics for the Isoindolobenzoxazi-
nones 3a-k and 5a-k
Found, %
Calculated, %
Rf
——————
Com-
pound*
Empirical
formula
Yield,
%
(Silufol
UV-254)
mp,. °С
С
Н
N
3а
3b
3c
3d
3e
3f
С15H9Cl2NO2
C17H14BrNO2
C17H14ClNO2
C16H11BrClNO2
C17H14ClNO3
C16H11Cl2NO2
C17H13ClN2O5
C17H13ClN2O4
C16H10Cl2N2O4
C18H16ClNO4
C19H19NO5
59.11
58.82
59.66
59.30
68.62
68.11
52.50
52.67
64.42
64.66
60.35
60.00
56.71
56.59
59.41
59.22
52.91
52.60
62.32
62.52
67.03
66.86
63.62
63.83
66.48
66.30
56.72
56.96
77.60
77.81
83.41
83.29
2.51
2.94
4.35
4.07
4.32
4.67
3.15
3.02
4.58
4.44
3.27
3.44
3.53
3.61
3.92
3.77
2.61
2.74
4.61
4.63
5.85
5.57
3.80
3.55
3.51
3.68
3.30
3.16
6.33
6.48
4.56
4.88
4.35
4.58
4.25
4.07
4.35
4.67
3.96
3.84
4.32
4.44
4.52
4.38
7.90
7.77
8.01
8.13
7.42
7.67
4.30
4.05
4.29
4.31
9.71
9.93
5.32
5.16
4.71
4.43
4.92
4.78
3.85
3.60
208-210
149-150
132-133
151-152
147-148
180-181
179-180
183-185
199-200
181-182
151-152
112-113
115-116
141-142
100-122
210-211
160-161
>250
0.58
0.52
0.60
0.62
0.37
0.65
0.50
0.60
0.55
0.25
0.20
0.67
0.78
0.86
0.38
0.59
0.46
0.65
0.31
0.46
0.78
0.85
60
65
68
65
58
70
65
65
67
62
65
75
72
70
75
77
80
75
75
65
70
75
3g
3h
3i
3j
3k
5a
5b
5c
5d
5e
5f
C15H10N2O4
C15H10ClNO2
C15H10BrNO2
C19H19NO2
C27H19NO2
C19H18N2O4
C27H18N2O4
C21H23NO4
67.65
67.46
74.41
74.65
71.58
71.39
77.38
77.51
61.51
61.29
69.45
69.23
5.21
5.33
4.02
4.15
6.41
6.52
5.21
5.12
4.70
4.84
4.02
3.85
8.42
8.28
6.63
6.45
4.08
3.97
3.35
3.12
3.88
3.76
3.15
2.99
5g
5h
5i
171-172
>230
C29H23NO4
5j
C19H18BrNO2
C27H18BrNO2
147-149
236-238
5k
_______
35
79
* Mass spectra, m/z of isotopes Cl; Br; 5b = 271 [M]+; 5c = 315 [M]+;
5h = 353 [M]+; 5j = 371 [M]+; 5k = 467 [M]+
one-proton singlet for the H-4b proton at 5.85-6.30 ppm. The absence of a long range stereospecific constant for
the H-4b and H-10 protons supports a structure with a transoid orientation of these hydrogen atoms relative to
the oxazine ring (an R,S-S,R enantiomeric pair), i.e. a stereochemical control of the sequence of cyclization
reactions.
X-ray analytical data for compound 3b is fully in agreement with this proposal. The crystal actually
contains one pair of enantiomers while in the unit cell each enantiomer is present as two conformational isomers
(see Fig. 1 for the two independent molecules E and F with the same 4bR,10S-configuration). The
108

molecules E and F differ only in the conformation of the oxazine ring. In both cases it has the form of a half
chair with a plane based on the five atoms N(1)–C(16)–C(15)–C(10)–O(1) (plane 1, mean deviation of the
atoms from the plane for molecule E being 0.0123 Å and for F 0.0208 Å). The angle between plane 1 and the
N(1)–C(9)–O(1) plane (plane 2) is 132.4º in E and 136.8º in F.
Fig. 1. Projection of the steric model for the conformational isomers of (4bR, 10S)-2-bromo-
8,10-dimethyl-10H-isoindolo[1,2-b][1,3]benzoxazin-12(4bH)-one (3b) in the crystal.
Otherwise independent molecules are virtually identical. The plane of the benzene ring C(10)···C(15)
deviates from plane 1 by 2.9 and 3.1º and the isoindole fragment plane is twisted relative to plane 2 by 60.4 and
60.5º for the molecules E and F respectively. As regards the planar-trigonal geometry of the N(1) atom: the
sums of the valence angles at this nitrogen atom are 359.9 and 359.7º for molecules E and F respectively.
The reaction of equimolar amounts of the formylbenzoic acids 1 and 2-aminophenylcarbinols 4a-c in
acetic acid [15, 16] give the isoindolobenzoxazinones 5 in a single stage without separation of intermediate
products. The reaction also occurs readily in toluene in the presence of a catalytic amount of p-toluenesulfonic
acid but, in this case, an additional operations is needed for neutralization of the catalyst and removal of solvent.
In the previous case the separation of the product just needs dilution of the reaction mixture with water.
109

110

111

In the two successive heterocyclization reactions the first is closure of the oxazine ring and this is
confirmed by the structure of the intermediate compound 6 obtained as 4,5-dimethoxy-2-(4,4-diphenyl-1,4-di-
hydro-2H-3,1-benzoxazin-2-yl)benzoic acid. It can be converted to the corresponding isoindolobenzoxazinone
5i in almost quantitative yield by short heating in acetic acid (see Experimental).
R
R
R
R
4
3
2
OH
NH2
O
1
+
6a
10
– 2H2O
7
N
1
R2
11
4a–c
O
R1
Ph
Ph
3
– H2O
5
8
5a–k
6
7
O
3'
2
1
OMe
OMe
N
2'
5i
– H2O
HO2C
1'
6'
6
4а R = H, b R = Et, c R = Ph; 5a−g R2 = H, a R = H, R1 = NO2; b R = H, R1 = Cl;
c R = H, R1 = Br; d R = Et, R1 = H; e R = Ph, R1 = H; f R = Et, R1 = NO2;
g R = Ph, R1 = NO2; h R = Et, R1 = R2 = OМе; i R = Ph, R1 = R2 = OМе;
j R = Et, R1 = Br, R2 = H; k R = Ph, R1 = Br, R2 = H
On a qualitative level the results of the experimental studies showed that acceptor substituents in the
formylbenzoic acids 1 (NO2, Cl, Br) and donor substituents in the aminophenylcarbinol 4b shortened the
reaction time for the synthesis of compounds 5. Thus the syntheses of isoindolobenzoxazinones 5a-d,f,j were
complete and in quite high yields after 30-45 min while in the preparation of compounds 5e,g-i,k it was
expedient to carry out the reaction at 45-50ºC for 1-1.5 h.
The isoindolobenzoxazinones of formula 5 are colorless crystals, the physicochemical parameters of
which are reported in Table 1. The IR spectra of benzoxazinones 5, as in the case of the spectra of compounds 3,
show an absorption stretching band for the lactam carbonyl at 1645-1700 cm-1 (Table 2). The molecules of
compound 5 have one chiral center at the 6a atom and this results in the prochiral 5-CH2 methylene hydrogen
1
atoms in molecules 5a-c becoming diastereotopic and resonating in the H NMR spectra as a pair of doublets
with a geminal constant of J = 14.8 to 15.2 Hz (Table 2). A similar situation occurs in molecules 5d,f,h,j which
have two prochiral methylene units in the ethyl substituents at the C(5) atom. The protons of these methylene
units absorb as two doublets of quartets but with different geminal constants of about 6-8 and 16-18 Hz
(Table 2).
An unambiguous confirmation of the structure of the isoindolobenzoxazines 5 was carried out by the
X-ray analysis of a single crystal of compound 5k. The projection of the steric model for this molecule is given
in Fig. 2. The interatomic distances and valence angles are close to standard values.
The determination of the conformation of the oxazine ring was performed from the experimental values
of six dihedral angles using the RICONF software package [17]. The folding parameters found were: S = 0.866,
θ = 30.66º, and ψ (2) = 7.78º and according to data in [18] this would indicate a slightly distorted
chair conformation. Its base at atoms C(1), N(1), C(9), C(14), and C(15) forms plane 1 (mean deviation of the
atoms from the mean-square plane 1 is 0.0355 Å). The O(1) oxygen atom deviates from this plane by 0.6336 Å
and, with atoms C(10) and C(15) forms the chair back which deviates from plane 1 by 127º. In its turn, the chair
base plane deviates from the plane of benzene ring A by 3.7º.
112

Fig. 2. Projection of the steric model for the molecule of 9-bromo-5,5-diphenyl-5H-isoindolo-
[2,1-a][3,1]benzoxazin-11(6aH)-one (5k) from X-ray structural data and the atomic numbering
(the number of the hydrogen atoms corresponds to the numbering of the carbon atoms).
In general, the isoindolone fragment in the molecule is not totally planar. The angle between the planes of
the benzene ring D and the mean square plane of the lactam ring (average deviation of planar atoms 0.0193 Å) is
176.2º. None the less, if the isoindolone fragment is considered as a plane (plane 2, mean deviation of the atoms
0.0355 Å) the angle between planes 1 and 2 is 155.8º. Evidently such a powerful twist in the molecule along the
C(1)–N(1) bond is due to the sp3-hybridization of the C(1) atom.
O1
Ph
Ph
ϕ
X
X = A, B or C
Fig. 3. Twist of the phenyl substituent relative to the plane of the three atoms – oxazine oxygen,
methine carbon, and the carbon atom of the phenyl substituent bonded to the methine carbon.
The mutual arrangement of the phenyl substituents A, B, and C at atom C(15) can be considered as a
nonsymmetrical propeller in which each of the rings is turned to the same side relatively to the corresponding
plane of three atoms O(1), C(15), and the aromatic ring added to the latter by the corresponding angles (Fig. 3):
ϕA = 29.5, ϕB = 54.6, and ϕC = 35.4º.
113

As is evident, the aromatic ring A bound to atom C(15) (with a further three atom link) has the smallest
rotation angle ϕ. Practically, the same nonsymmetrical propeller conformation occurs in triphenylmethane
crystals [19] but, of course, with other phenyl substituent rotation angles.
In conclusion it should be noted that 2-formylbenzoic acids can be used as specific structural units for
the construction of an isoindolone fragment in tandem heterocyclization reactions and in reactions with other
N,O- N,N- and N,S-binucleophiles for synthesizing aza- and thiaaza heterocyclic systems and this will be
revealed in subsequent publications.
EXPERIMENTAL
IR spectra were recorded in vaseline oil on a Specord IR-71 instrument. 1H NMR spectra were taken on
Bruker AC-200 (200 MHz), WM-250 (250 MHz), AM-300 (300 MHz), and DR-500 (500 MHz) instruments
with TMS as internal standard. Mass spectra were recorded on a Varian CH-6 instrument using a direct
introduction method of the sample into the ion source at a temperature of 50-180ºC and an electron ionization
energy of 70 eV. TLC was carried out for compounds 5a-k and 3a-k on Silufol UV-254 plates in the systems
benzene–acetone (4:1 and 2:1 respectively) and revealed using iodine vapor.
X-ray Study of Compounds 3b and 5k. Colorless monoclinic crystals of 2-bromo-8,10-dimethyl-10H-
isoindolo[1,2-b][1,3]benzoxazin-12(4bH)-one (3b) were grown by crystallization from ethanol: a = 12.949(3),
b = 8.438(2), c = 27.120(3) Å, α = γ = 90, β = 91.29(1)º, V = 2962(1) Å3, d = 1.543 g/cm3. Space group P2(1)/c,
Z = 8. X-ray analysis was carried out on a CAD 4 circle automatic diffractometer (graphite monochromator,
MoKα radiation, θ/2θ scanning 1.5 to θmax = 22.98º). Crystal size 0.40×0.32×0.25 mm.
4112 Reflections with I > 3σ(I) were obtained. The structure was solved by a direct method using the
SHELXTL program package [20] and refined in the anisotropic approximation (isotropic for hydrogen atoms) to
divergence factors of R = 0.0389 and wR = 0.0925. The atomic coordinates have been placed in the Cambridge
Structural Database (reference CCDC 720446).
Colorless monoclinic crystals of 9-bromo-5,5-diphenyl-5H-isonidolo[2,1-a][3,1]benzoxazin-11(6aH)-
one (5k) were grown by crystallization from ethanol: a = 11.805(2), b = 12.717(3), c = 14.603(3) Å, α = γ = 90,
β = 107.61(3)º, V = 2089.5(7) Å3, d = 1.489 g/cm3. Space group P2(1)/n, Z = 4. X-ray analysis was carried out
on the CAD 4 circle automatic diffractometer (graphite monochromator, MoKα radiation, θ/2θ scanning 1.95 to
θmax = 24.98º). Crystal size 0.24×0.16×0.15 mm. 3667 Reflections were obtained with I > 3σ(I). The structure
was solved by a direct method using the SHELXTL program package [20] and refined in the anisotropic
approximation (isotropic for hydrogen atoms) to divergence factors of R = 0.0370 and wR = 0.0781. The atomic
coordinates have been placed in the Cambridge structural database (reference CCDC 710445).
4,5-Dimethoxy-2-(4,4-diphenyl-1,4-dihydro-2H-3,1-benzoxazin-2-yl)benzoic Acid (6). 2-Formyl-4,5-di-
methoxybenzoic acid (1.05 g, 5 mmol) was added to a solution of 2-aminophenyldiphenylcarbinol (4c) (1.38 g,
5 mmol) in glacial acetic acid (5 ml) cooled to 0ºC. The mixture was stirred with cooling (ice bath) for 30 min.
The precipitate formed was filtered off and recrystallized from benzene to give compound 6 (1.63 g, 70%) with
mp > 250ºC and Rf 0.20 (benzene–acetone, 4:1). IR spectrum, ν, cm-1: 3560-3500 (COOH), 3370 (NH).
1H NMR spectrum (DMSO-d6), δ, ppm: 3.81 (3H, s, OCH3); 3.85 (1H, s, H-2); 3.90 (3H, s, OCH3); 6.23 (1H, s,
H-3'); 7.00 (15H, m, 14 H arom + NH); 7.60 (1H, s, H-6'); 12.60 (1H, br. s, COOH). Found, %: C 74.68; H 5.27;
N 2.91. C29H25NO5. Calculated, %: C 74.52; H 5.35; N 3.00.
8,9-Dimethoxy-5,5-diphenyl-5H-isoindolo[2,1-a][3,1]benzoxazin-11(6aH)-one (5i). A. A mixture of
carbinol 4c (1.38 g, 5 mmol) and 2-formyl-4,5-dimethoxybenzoic acid (1.05 g, 5 mmol) in glacial acetic acid
(10 ml) was stirred at room temperature for 5-10 min, heated to 45-50ºC, and stirred for a further 1 h. At the end
of the reaction (TLC monitoring) the precipitate formed was filtered and a further portion of precipitate was
separated from the filtrate using an aqueous alcohol mixture (7:3). The precipitates were combined and
recrystallized from an alcohol–benzene mixture (4:1). Yield 1.46 g (65%).
114

B. A solution of the amino acid 6 (2.34 g, 5 mmol) and glacial acetic acid (10 ml) was stirred for 30 min
at a temperature not exceeding 50ºC. Separation was carried out as in procedure A. Yield 2.02 g (90%).
Benzoxazines 5e,g,h,k were prepared similarly (method A).
5,5-Diethyl-9-nitro-5H-isoindolo[2,1-a][3,1]benzoxazin-11(6aH)-one (5f). A mixture of the 2-amino-
phenyldiethylcarbinol 4b (0.89 g, 5 mmol) and 2-formyl-5-nitrobenzoic acid (0.97 g, 5 mmol) in glacial acetic
acid (10 ml) was stirred for 45 min at room temperature. At the end of the reaction (TLC monitoring) compound
5f was precipitated from the reaction mixture by addition of an aqueous alcohol mixture (7:3). The precipitate
was filtered off and recrystallized from an alcohol–benzene mixture (4:1). Yield 1.35 g (80%).
Benzoxazines 5a-d,j were prepared similarly.
2-chloro-8,10-dimethyl-10H-isoindolo[1,2-b][1,3]benzoxazin-12(4bH)-one (3c). A mixture of 2-(1-
aminoethyl)-4-methylphenol 2b (0.75 g, 5 mmol) and 5-chloro-2-formylbenzoic acid (0.76 g, 5 mmol) in
absolute toluene (50 ml) and a catalytic amount of p-toluenesulfonic acid was refluxed for 1-3 h with azeotropic
distillation of alcohol until the calculated amount had separated. Solvent was evaporated and the residue was
purified by column chromatography on KSK silica gel (5-40 µm fraction) using benzene-petroleum ether (1: 4)
as eluent. Yield 0.92 g (60%).
Compounds 3a-b,d-k were prepared similarly. The synthesis of the isoindolobenzoxazinones 3j-k was
carried out for 10-12 h.
2-Aminophenylcarbinols 4b,c were prepared by treating methyl anthranilate with the corresponding
alkylmagnesium halides [1, 15].
2-(Aminoalkyl)phenols 2a-b,d-e (Table 3) were prepared using method [14].
The synthesis of the formylbenzoic acids 1 has been reported in [13].
REFERENCES
1.
2.
3.
E. V. Gromachevskaya, T. P. Kosulina, and A. A. Borodavko, Khim. Geterotsikl. Soedin., 1230 (2006).
[Chem. Heterocycl. Comp., 42, 1068 (2006)].
E. V. Boltukhina, F. I. Zubkov, and A. V. Varlamov, Khim. Geterotsikl. Soedin., 963 (2006). [Chem.
Heterocycl. Comp., 42, 831 (2006)].
E. V. Boltukhina, F. I. Zubkov, and A. V. Varlamov, Khim. Geterotsikl. Soedin., 1123 (2006). [Chem.
Heterocycl. Comp., 42, 971 (2006)].
4.
5.
M. Lanchem, J. Chem. Soc. C, 573 (1966).
P. Aeberli and W. J. Houlihan, J. Org. Chem., 33, 2402 (1968).
6.
7.
V. Balasubramaniyan and N. P. Argade, Tetrahedron, 45, 835 (1989).
E. Desarbre and J. Y. Merour, Heterocycles, 41, 1987 (1995).
8.
9.
10.
11.
P. Pigeon, J. Sikoraiova, S. Marchalin, and B. Decroix, Heterocycles, 56, 129 (2002).
P. Sohar, G. Stajer, A. E. Szabo, J. Szuyog, and G. Bernath, Heterocycles, 48, 175 (1998).
А. R. Katritzky, Y.-J. Xu, H.-Y. He, and P. J. Steel, J. Chem. Soc., Perkin Trans. 1, 1767 (2001).
T. M. V. D. Pinho e Melo, C. I. A. Santos, A. M. d'A. Rocha Gonzales, J. A. Paixao, and A. M. Beja,
Tetrahedron, 60, 3949 (2004).
12.
13.
I. Szatmari, A. Hetenyi, L. Lazar, and F. Fulor, J. Heterocyclic Chem., 41, 367 (2004).
V. T. Abaev, A. S. Dmitriev, A. V. Gutnov, S. A. Podelyakin, and A. V. Butin, J. Heterocyclic Chem.,
43, 1195 (2006).
14.
15.
Weygand-Hilgetag, Experimental Methods in Organic Chemistry [Russian translation], Khimiya (1968),
p. 944.
E. V. Gromachevskaya, V. G. Kul'nevich, T. P. Kosulina, and V. S. Pustovarov, Khim. Geterotsikl.
Soedin., 842 (1988). [Chem. Heterocycl. Comp., 24, 692 (1988)].
115

16.
E. V. Gromachevskaya, I. S. Arustamova, A. G. Sakhabutdinov, and V. G. Kul'nevich, Khim.
Geterotsikl. Soedin., 1670 (1988). [Chem. Heterocycl. Comp., 24, 1381 (1988)].
A. Yu. Zotov, V. A. Palyulin, and N. S. Zefirov, J. Chem. Inf. Sci., 37, 766 (1997).
N. S. Zefirov and V. A. Palyulin, Dokl. Akad. Nauk, 252, 111 (1980).
P. C. Riche and B. C. Pascard, J. Am. Chem. Soc., 96, 1874 (1974).
G. M. Sheldrick, Computational Crystallography, Oxford University Press, New York, Oxford (1982),
506 pp.
17.
18.
19.
20.
116