Dearylation with aromatization on cyclocondensation of 4-(dimethyl-amino) benzaldehyde, 2-phenacylaza-heterocycles, and 1,3-[N,C]dinucleophiles

Article abstract of DOI:10.1007/s10593-009-0230-x

Three-component cyclocondensation involving p-(dimethylamino)benzaldehyde, 2-phenacylazahetero-cycle, and a 1,3-[N,C]-nucleophile (3,5-dimethoxyaniline, 6-amino-1,3-dimethylpyrimidine-2,4-dione, 1-amino-3-methyl-5-phenylpyrazole) in boiling acetic acid is

Full text of DOI:10.1007/s10593-009-0230-x

Chemistry of Heterocyclic Compounds, Vol. 45, No. 1, 2009
DEARYLATION WITH AROMATIZATION
ON CYCLOCONDENSATION OF 4-(DIMETHYL-
AMINO)BENZALDEHYDE, 2-PHENACYLAZA-
HETEROCYCLES, AND 1,3-[N,C]DINUCLEOPHILES
I. B. Dzvinchuk1*
Three-component cyclocondensation involving p-(dimethylamino)benzaldehyde, 2-phenacylazahetero-
cycle, and a 1,3-[N,C]-nucleophile (3,5-dimethoxyaniline, 6-amino-1,3-dimethylpyrimidine-2,4-dione,
1-amino-3-methyl-5-phenylpyrazole) in boiling acetic acid is accompanied by aromatization of the
initially formed annelated 4-(p-dimethylaminophenyl)-3-hetaryl-2-phenyl-1,4-dihydropyridines, the
direction of which, with splitting off the dimethylaminophenyl substituent or its retention, is determined
by the basicity of the hetaryl residue and the structure of the second ring, constructed on the
binucleophile. A possible reaction mechanism is discussed.
Keywords: aldehydes, anilines, benzimidazoles, benzothiazoles, imidazoles, pyrazoles, pyrazolo-
[3,4-b]pyridines, pyrido[2,3-d]pyrimidines, pyrimidines, quinolines, aromatization, dearylation,
Hantzsch reaction, selectivity.
The method of obtaining pyridines according to Hantzsch, based on the cyclocondensation of aldehydes,
acetoacetic ester, and ammonia with subsequent oxidation of the resulting 1,4-dihydropyridine, has been
developed by modifying the synthesis conditions and the nature of the initial reactants [1, 2]. The three-
component interaction of aldehydes with various carbonylmethylene-reactive compounds and 1,3-[N,C]-
dinucleophiles is used in the synthesis of 1,4-dihydropyridines [2], pyrazolo[3,4-b]quinolines [3], and
pyrido[2,3-d]pyrimidines [4].
The indicated reaction does not proceed selectively when using formaldehyde, which hinders the
synthesis of compounds unsubstituted at position 4 of the pyridine ring [5-7]. It is known that formaldehyde may
be replaced by other aldehydes, since on heating the reaction mixture in acetic acid the resulting products with
an alkyl(aryl)-substituted dihydropyridine ring are inclined to undergo aromatization as a result of dealkylation
(or dearylation) [4, 8]. The merit of such a method of synthesis is the combination into one process of the
preparation of the dihydropyridine compound and its subsequent aromatization without the use of an oxidizing
agent. However reaction with each of the studied aldehydes, with the exception of 4-(dimethyl-
amino)benzaldehyde (1) is distinguished by a long duration (48 h) and low selectivity (10-55% yields) [4].
_______
* To whom correspondence should be addressed, e-mail: rostov@ioch.kiev.ua.
1Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev 02094.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 101-109, January, 2009. Original
article submitted June 20, 2007; revision submitted November 19, 2007.
0009-3122/09/4501-0085©2009 Springer Science+Business Media, Inc.
85

In the case of aldehyde 1 the formation of the corresponding compound containing a 1,4-dihydropyridine ring
was smooth and accompanied selectively by aromatization as a result splitting off N,N-dimethylaniline [8]. On
the basis of this a new approach was developed to the synthesis of compounds with no substituent in position 4
of the pyridine ring, used for obtaining derivatives of acridine [8], pyrazolo[3,4-b]pyridine [9], and pyrido-
[2,3-d]pyrimidine [10].
The three-component interaction of aldehyde 1, 2-phenacylazaheterocycles 2a-d, and certain 1,3-[N,C]-
dinucleophiles has been studied in the present work with the aim of extending the scope of the indicated method
and of clarifying the mechanism of aromatization (see Scheme 1).
Scheme 1
OMe
O
Me
N
NMe2
H2N
OMe
H2N
N
O
Het
Ph
3
Me
6
+
AcOH, 120°C, 2 h
AcOH, 120°C, 2 h
O
OHC
2a–d
1
NMe2
NMe2
O
Me
N
AcOH,
120°C,
2 h
OMe
H
H
N
Het
Het
Ph
Me
O
H2N
N
Ph
9
Ph
N
H
N
N
H
OMe
Me
4a–d
7a–d
NMe2
– PhNMe2
O
– PhNMe2
OMe
H
Me
N
Het
Ph
Me
Het
Het
Ph
N
N
N
O
N
Ph
N
H
N
OMe
Me
Ph
5a–d
8a–d
10a–d
NMe2
Me
Het
(10 a,b)
(10c)
Me
N
N
11c
+
Het
– PhNMe2
–PhNMe2,
–H2
N
Ph
N
Ph
N
Ph
N
11a,b
– H2 (10d)
Ph
12a
12b
2,4,5,7,8,10,11 а Het = 2-quinolyl, b Het = 2-benzothiazolyl;
2,4,5,7,8,10 с Het = 2-(1-methyl)benzimidazolyl, d Het = 2-imidazolyl;
12 а Het = 2-(1-methyl)benzimidazolyl, b Het = 2-imidazolyl
86

TABLE 1. Characteristics of the Synthesized Compounds
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °С
Yield, %*
С
Н
N
5a
C26H20N2O2
C24H18N2O2S
C25H21N3O2
C20H17N3O2
C24H18N4O2
C22H16N4O2S
C23H19N5O2
C18H15N5O2
C28H20N4
79.41
79.57
72.19
72.34
75.79
75.93
72.33
72.49
72.94
73.08
65.83
65.99
69.37
69.51
64.68
64.86
5.03
5.14
4.38
4.55
5.18
5.35
5.23
5.17
4.68
4.60
4.22
4.03
4.68
4.82
4.36
4.54
7.22
7.14
6.89
7.03
10.47
10.63
12.47
12.68
14.12
14.20
13.77
13.99
17.47
17.62
20.89
21.01
145.0-146.5
183.5-185.0
198.5-200.0
269.5-271.0
233.0-234.5
286.5-288.0
227.0-228.5
277.0-278.5
153.0-154.5
191.5-193.0
335.0-337.0
75
81
73
62
80
84
77
81
75
90
19
5b
5c
5d
8a
8b
8c
8d
11a
11b
12d
81.38
81.53
74.48
74.62
76.38
76.57
4.78
4.89
4.18
4.34
5.66
5.57
13.37
13.58
13.22
13.39
17.73
17.86
C26H18N4S
C30H26N6
_______
*Yields indicated are before purification by recrystallization.
We found that, as in the examples studied previously, the condensation of reactants 1, 2a-d, and 3,5-di-
methoxyaniline (3), as the 1,3-dinucleophile, did not stop at the formation of compounds with a 1,4-dihydro-
pyridine ring of type 4, but was accompanied readily and selectively by the splitting off of N,N-dimethylaniline
with the formation of the previously unknown quinoline derivatives 5a-d.
The reaction proceeds analogously in the case of 6-amino-1,3-dimethylpyrimidine-2,4-dione (6) through
intermediates of type 7 and the subsequent formation of new pyrido[2,3-d]pyrimidine derivatives 8a-d.
In the case of 5-amino-3-methyl-1-phenylpyrazole (9) the direction of aromatization of the
cyclocondensation products depends on the nature of the initial 2-phenacylazaheterocycle 2. With the
derivatives of quinoline and benzothiazole 2a,b, as in the examples given above, pyrazolo[3,4-b]pyridines 11a,b
are formed from products 10a,b. On the other hand, when using derivatives of 1-methylbenzimidazole and
imidazole 2c,d aromatization of products 10c,d takes place with retention of the (dimethylamino)phenyl
substituent. In the case of reactant 2c a mixture is formed of product 11c, unsubstituted at position 4, and its
1
4-(p-dimethylaminophenyl) derivative 12a in a molar ratio of 3:1 (according to data of H NMR), which we
were unable to separate. On using reactant 2d only the (dimethylamino)phenyl-substituted product 12b was
successfully isolated from the reaction mixture in 19% yield.
The obtained results indicate that the the direction of aromatization of the intermediates 4, 7, and 10 is
determined by the structure of the ring condensed with the dihydropyridine ring, and the basicity of the Het
substituent. Reaction with retention of the C6H4NMe2 group occurs only in the case of compounds 10c,d, having
a substituted pyrazole ring and the most basic Het substituents, 2-(1-methyl)benzimidazolyl and 2-imidazolyl
respectively.
Analysis of the data given above permits expression of a possible mechanism for aromatization. The
bonding of the nitrogen atom of the 2-azahetaryl fragment of compounds 4, 7, and 10 with acetic acid via a
hydrogen bond leads to an adduct represented in Scheme 2 by the generalized formula A. In the case of X = CMe a
proton of the acetic acid of this adduct may at enhanced temperatures protonate the electron-rich C-1"
87

88

atom of the dimethylaminophenyl substituent located nearby with transfer of a positive charge to the
dimethylamino group and the formation of salt B. Subsequently, as a result of fission of proton from the
+
nitrogen atom of the dihydropyridine ring and synchronous transfer of the negative charge from it to the NMe2
group, it readily undergoes aromatization with simultaneous splitting off dimethylaniline and formation of the
final product 11. However if the Het substituent in adduct A possesses enhanced basicity then the ability to
transfer proton from the nitrogen atom to an oxygen atom is reduced. In such a case aromatization is also
possible due to air-oxidation or disproportionation, which leads to the formation of a product of type 12.
TABLE 2. Data of 1H NMR Spectra of the Synthesized Compounds
Com-
pound
Chemical shifts, δ, ppm, SSCC (J, Hz)
5a
3.95 (3Н, s, 5-ОCH3); 4.00 (3Н, s, 7-ОCH3); 6.74 (1H, d, J = 1.8, H-6);
7.07-7.10 (2H, m, H-8,3'*); 7.17-7.33 (3H, m, 3H-m, -p Ph);
7.38 (2H, d, J = 7.5, 2H-o Ph); 7.60 (1H, m, H-6'); 7.78 (1H, m, H-7');
7.91 (1H, d, J = 8.1, H-5'); 8.06 (1H, d, J = 8.1, H-4'); 8.10 (1H, d, J = 8.4, H-8');
8.71 (1H,s, H-4)
5b
5c
5d
8a
3.95 (3Н, s, 5-OCH3); 4.03 (3Н, s, 7-OCH3); 6.76 (1H, d, J = 1.8, H-6);
7.08 (1H, d, J = 1.8, H-8); 7.37-7.51 (7H, m, C6H5, H-5',6'); 7.96 (1H, d, J = 7.8, H-7');
8.02 (1H, d, J = 7.8, H-4'); 8.98 (1H, s, H-4)
3.10 (3H, s, NCH3); 3.98 (3Н, s, 5-OCH3); 4.00 (3Н, s, 7-OCH3); 6.78 (1H, d, J = 1.8, H-6);
7.15 (1H, d, J = 1.8, H-8); 7.23-7.36 (5H, m, H-5',6', 3H-m, -p Ph);
7.42 (3H, m, 2H-o Ph, H-7'); 7.68-7.72 (1H, m, H-4'); 8.62 (1H, s, H-4)
3.94 (3Н, s, 5-OCH3); 4.00 (3Н, s, 7-OCH3); 6.71 (1H, d, J = 1.8, H-6); 6.97 (1H, s, H-5');
7.06 (1H, d, J = 1.8, H-8); 7.11 (1H, s, H-4'); 7.32-7.35 (3H, m, 3H-m, -p Ph);
7.38 (2H, d, J = 8.1, 2H-o Ph); 8.49 (1H, s, H-4); 11.91 (1H, s, NH)
3.36 (3H, s, 1-CH3); 3.66 (3H, s, 3-CH3); 7.05 (1H, d, J = 8.1, H-3');
7.32 (2H, t, J = 6.9, 2H-m Ph); 7.38-7.42 (3H, m, 3H-o, -p Ph); 7.62 (1H, m, H-6');
7.79 (1H, m, H-7'); 7.93 (1H, d, J = 8.1, H-5'); 8.05 (1H, d, J = 8.1, H-4');
8.14 (1H, d, J = 8.7, H-8'); 8.62 (1H, s, H-5)
8b
8c
3.37 (3H, s, 1-CH3); 3.64 (3H, s, 3-CH3); 7.39-7.57 (7H, m, C6H5, H-5',6');
7.97 (1H, d, J = 7.8, H-7'); 8.03 (1H, d, J = 8.1, H-4'); 8.86 (1H, s, H-5)
3.12 (3H, s, 1'-CH3); 3.35 (3H, s, 1-CH3); 3.70 (3H, s, 3-CH3); 7.24-7.27 (2H, m, H-5',6');
7.31 (2H, t, J = 6.9, 2H-m Ph); 7.35-7.45 (4H, m, 3H-o, -p Ph, H-7');
7.68-7.72 (1H, m, H-4'); 8.53 (1H, s, H-5)
8d
3.33 (3H, s, 1-CH3); 3.62 (3H, s, 3-CH3); 6.98 (1H, s, H-5'); 7.15 (1H, s, H-4');
7.33-7.42 (5H, m, C6H5); 8.41 (1H, s, H-5); 12.08 (1H, s, NH)
11a
2.70 (3H, s, 3-CH3); 7.15 (1H, d, J = 8.1, H-3');
7.31-7.35 (4H, m, 3H-m, -p CPh, H-p NPh); 7.42-7.44 (2H, m, 2H-o CPh);
7.55-7.60 (2H, m, 2H-m NPh); 7.63 (1H, m, H-6'); 7.80 (1H, m, H-7');
7.95 (1H, d, J = 7.8, H-5'); 8.07 (1H, d, J = 8.1, H-4'); 8.15 (1H, d, J = 8.7, H-8');
8.38 (2H, d, J = 7.5, 2H-o NPh); 8.68 (1H, s, H-4)
11b
11c
2.71 (3H, s, 3-CH3); 7.41-7.59 (9H, m, 4-C6H5, 3H-m, -p NPh, H-5',6');
7.98-8.05 (2H, m, H-4',7'); 8.30 (2H, d, J = 8.2, 2H-o NPh); 8.89 (1H, s, H-4)
2.68 (3H, s, 3-CH3); 3.14 (3H, s, 1'-CH3);
7.25-7.37 (6H, m, H-5',6', H-p NPh, 3H-m, -p CPh); 7.43 (3H, m, 2H-o CPh, H-7');
7.58 (2H, t, J = 7.8, 2H-m NPh); 7.68-7.70 (1H, m, H-4'); 8.37 (2H, d, J = 7.5, 2H-o NPh);
8.70 (1H, s, H-4)
12a
12b
2.13 (3H, s, 3-CH3); 2.84 (6H, s, N(CH3)2); 3.23 (3H, s, 1'-CH3);
6.59 (2H, d, J = 7.8, 2H-m Ar*2); 7.13-7.22 (7H, m, H-5',6', 2H-o Ar*2, 3H-m, -p CPh);
7.32-7.39 (4H, m, 2H-o CPh, H-p NPh, H-7'); 7.53-7.58 (3Н, m, 2H-m NPh, H-4');
8.34 (2Н, d, J = 7.5, 2H-o NPh)
2.09 (3H, s, 3-CH3); 2.91 (6H, s, N(CH3)2); 6.63 and 7.08 (2Н and 2H, two d, J = 7.8, Ar*2);
6.77 and 6.88 (1Н and 1H, two s, H-4' and H-5');
7.27-7.33 (4H, m, 3H-m, -p CPh, H-p NPh);
7.38-7.40 (2H, m, 2H-o CPh); 7.56 (2H, t, J = 7.8, 2H-m NPh);
8.33 (2H, d, J = 7.8, 2H-o NPh); 11.72 (1H, s, NH)
_______
* Here and subsequently the position of the proton in the Het substituent
is marked with a prime.
*2 Ar = C6H4N(CH3)2-p.
89

If X = COMe or C=O then binding of the oxygen atom of these fragments with acetic acid by an
intermolecular hydrogen bond and the formation of adduct C is fully possible. In the latter the process of proton
transfer to atom C-1" may occur analogously to that considered above or through the formation of the solvated
salt D. Subsequent aromatization with splitting off dimethylaniline and decomposition of the acetic acid adduct
(on diluting the reaction mixture with water) leads to a product of type 11. In this case the enhanced basicity of
the Het substituent is not a hindrance to the splitting off dimethylaniline, but its reduced basicity and the
presence of the oxygen-containing fragment X are correspondingly especially favorable.
The phenomenon of accelerating reactions under the influence of neighboring groups is known under
the name synarthetic (or anchimeric) acceleration [11]. In the actual case it is evident that C-protonation at
position 1" of the 4-(dimethylamino)phenyl substituent without the participation of neighboring functional
groups must experience significant difficulty, since the direct approach of proton to the reaction center is
blocked by significant steric hindrance.
The specific behavior of aldehyde 1 in the Hantzsch reaction is, very probably, not peculiar to it alone.
Similar behavior may be expected for aldehydes in which the formyl group is under a powerful electron-
donating influence. The latter takes place, for example, in 4-(dialkylamino)benzaldehydes,
pyrrolecarbaldehydes, 3-indolecarbaldehydes, etc. The clear advantage of compound 1 over others is its
availability.
The composition and structure of the obtained compounds are in accordance with the data of elemental
analysis (Table 1) and 1H NMR spectra (Table 2).
Three-component condensation involving dimethylaminobenzaldehyde has been studied on new
examples in the present work. The results obtained show the possibility of two routes for aromatization of the
initially formed products with a p-dimethylaminophenyl-substituted dihydropyridine ring (with and without
splitting off dimethylaniline) and enable factors affecting the direction of this process to be clarified.
EXPERIMENTAL
A check on the progress of reactions and the purity of the compounds synthesized was carried out by
TLC on Silufol UV-254 plates in the solvent system benzene–ethanol, 9:1, with visualization in UV light. The
1H NMR spectra of compounds were recorded on a Varian VXR-300 (300 MHz) in DMSO-d6, standard was
TMS. All the compounds synthesized were dried for 5 h at 125oC before carrying out elemental analysis and
spectral investigations.
Cyclocondensation of 4-(Dimethylamino)benzaldehyde (1), 2-(Phenacylazaheterocycles 2a-d and
3,5-Dimethoxyaniline (3) or Heterocyclic Amines 6, 9 (General Method). A mixture of aldehyde 1
(10 mmol), compound 2 (10 mmol), amine 3 (1.5 mmol), or amine 6, 9 (1.0 mmol), and glacial acetic acid
(2 ml) (in the case of compound 2d 1 ml acid was used) was maintained at 120°C for 2 h. The methods of
processing the cooled reaction mixture, isolating, and purifying the products are given below.
5,7-Dimethoxy-2-phenyl-2',3-biquinoline (5a) was obtained from compounds 1, 2a, and 3. Water (8
ml) was added to the reaction mass and the mixture heated to boiling with stirring. After cooling, the solidified
oil was triturated to a powder, which was filtered off, washed with water, dried, and dissolved in the minimum
quantity of benzene. The solution obtained was applied to a column of aluminum oxide (neutral) and eluted with
benzene, collecting the light-yellow fraction, which was then evaporated to dryness. The residue was dissolved
with heating in cyclohexane (10 ml), hexane (5 ml) was added to the solution, and the mixture maintained at
20°C for 4 h, and at 0oC for 1h. The separated solid product 5a was filtered off, and washed with hexane.
3-(1,3-Benzothiazol-2-yl)-5,7-dimethoxy-2-phenylquinoline (5b) was obtained from compounds 1,
2b, and 3. Water (2 ml) was added to the reaction mass, which was boiled with stirring until the start of
90

crystallization. After cooling, the solid product 5b was filtered off, washed with a mixture of 2-propanol–water,
1:1, dried, and recrystallized from a mixture of pyridine–water, 1:1.
5,7-Dimethoxy-3-(1-methyl-1H-benzimidazol-2-yl)-2-phenylquinoline (5c) was obtained from
compounds 1, 2c, and 3. Water (8 ml) was added to the reaction mass and the mixture heated to boiling with
stirring. After cooling, the solid product 5c was triturated, filtered off, washed with a mixture of 2-propanol–water,
1:1, dried, and recrystallized from a mixture of pyridine–water, 3:2.
3-(1H-Imidazol-2-yl)-5,7-dimethoxy-2-phenylquinoline (5d) was obtained from compounds 1, 2d,
and 3 in glacial acetic acid (1 ml). As in the procedure given above for compound 5c the reaction mass was treated
with water (4 ml), and product 5d isolated, and purified, then recrystallized from a mixture of pyridine–water, 1:1.
1,3-Dimethyl-7-phenyl-6-quinol-2-ylpyrido[2,3-d]pyrimidine-2,4-(1H,3H)-dione (8a) was obtained from
compounds 1, 2a, and 6. As in the procedure given for compound 5b the reaction mass was treated with water (2 ml).
Product 8a was isolated, washed, and dried, then recrystallized from a mixture of pyridine–water, 2:1.
6-(1,3-Benzothiazol-2-yl)-1,3-dimethyl-7-phenylpyrido[2,3-d]pyrimidine-2,4-(1H,3H)-dione
was obtained from compounds 1, 2b, and 6 as for 8a.
(8b)
1,3-Dimethyl-6-(1-methyl-1H-benzimidazol-2-yl)-7-phenylpyrido[2,3-d]pyrimidine-2,4-(1H,3H)-
dione (8c) and 6-(1H-Imidazol-2-yl)-1,3-dimethyl-7-phenylpyrido[2,3-d]pyrimidine-2,4-(1H,3H)-dione
(8d) were obtained from compounds 1, 2c, and 6 in acetic acid (2 ml) and from compounds 1, 2d, and 6 in acetic
acid (1 ml) respectively. In the first case the reaction mass was treated with water (8 ml) and in the second with
water (4 ml). In the rest of the treatment the isolation and purification of products 8c,d were analogous to that
indicated for compound 8a.
2-(3-Methyl-1,6-diphenyl-1H-pyrazolo[3.4-b]pyrid-5-yl)quinoline (11a) was obtained from
compounds 1, 2a, and 9. Water (8 ml) was added to the reaction mass and the mixture heated to boiling with
stirring. The cooled mass was filtered, the solid washed with water, dried, and dissolved in the minimum amount
of methylene chloride. The solution was applied to a column of aluminum oxide (neutral), eluted with diethyl
ether, collecting the first colorless fraction, which was evaporated to dryness. The residue, product 11a, was
triturated to a powder, and recrystallized from a mixture of 2-propanol–water, 5:1.
5-(1,3-Benzothiazol-2-yl)-3-methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine (11b) was obtained
from compounds 1, 2b, and 9. The reaction mass was treated by the procedure given for compound 5b. The
isolated solid product 11b was recrystallized from toluene.
3-Methyl-5-(1-methyl-1H-benzimidazol-2-yl)-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine (11c) and
3-Methyl-4-[4-(dimethylamino)phenyl]-5-(1-methyl-1H-benzimidazol-2-yl)-1,6-diphenyl-1H-pyrazolo-
[3,4-b]pyridine (12a) were obtained from compounds 1, 2c, and 9. Water (8 ml) was added to the reaction mass
and the mixture was heated to boiling with stirring. After cooling solid-1 was filtered off, washed with water,
dried, and boiled with stirring in acetonitrile (2 ml) for 2-3 min. Solid-2, isolated after cooling, was filtered off, and
washed with acetonitrile. Solid-2 was a mixture of products 11c and 12a in a molar ratio of 3 : 1 (according to data
of 1H NMR), its mp 196-198oC was unchanged after crystallization from a mixture of pyridine–water, 2:1.
4-[4-(Dimethylamino)phenyl]-5-(1H-imidazol-2-yl-3-methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyri-
dine (12b) was obtained from compounds 1, 2d, and 9. As in the procedure given for compound 5b the reaction
mass was treated with water (2 ml), the solid filtered off, washed, and dried, to give the solid product 12b, which
was recrystallized from a mixture of pyridine–water, 2:1.
REFERENCES
1.
2.
C. Simon, T. Constantieux, and J. Rodriguez, Eur. J. Org. Chem., 4957 (2004).
F. E. Sausinsh and G. Ya. Duburs, Khim. Geterotsikl. Soedin., 435 (1992). [Chem. Heterocycl. Comp.,
28, 363 (1992)].
91

3.
4.
5.
6.
7.
8.
J. Quiroga, B. Insuastu, A. Hormaza, C. Saitz, and C. Julian, J. Heterocycl. Chem., 35, 575 (1998).
A. Agarwal and P. M. S. Chauhan, Synth. Commun., 34, 4447 (2004).
B. Loev and K. M. Snader, J. Org. Chem., 30, 1914 (1965).
A. Singer and S. M. McElvain, Org. Synth. Coll., 2, 214 (1943).
G. Ya. Vanag and E. I. Stankevich, Zh. Obshch. Khim., 3287 (1960).
I. B. Dzvinchuk and N. A. Tolmacheva, Khim. Geterotsikl. Soedin., 554 (2001). [Chem. Heterocycl.
Comp., 37, 506 (2001)].
9.
10.
I. B. Dzvinchuk, Khim. Geterotsikl. Soedin., 578 (2007). [Chem. Heterocycl. Comp., 43, 474 (2007)].
I. B. Dzvinchuk and M. O. Lozinskii, Khim. Geterotsikl. Soedin., 585 (2007). [Chem. Heterocycl.
Comp., 43, 480 (2007)].
11.
V. M. Potapov, Stereochemistry [in Russian], Khimiya, Moscow (1988), p. 246.
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