Synthesis of 2,4-diphenyl-1H-pyrrol-1-amine derivatives

Article abstract of DOI:10.1007/s10593-009-0269-8

The direction of the reaction of 4-bromo-1,3-diphenyl-2-buten-1-one (γ-bromodypnone) with hydrazines depends on the nature of the substituent they contain. Reaction with 1-methylhydrazinium hydrosulfate gives 1-methyl-3,5-diphenylpyridazin-1-ium bromide b

Full text of DOI:10.1007/s10593-009-0269-8

Chemistry of Heterocyclic Compounds, Vol. 45, No. 3, 2009
SYNTHESIS OF 2,4-DIPHENYL-
1H-PYRROL-1-AMINE DERIVATIVES
L. M. Potikha1*, V. A. Kovtunenko1, A. V. Turov1,
G. V. Palamarchuk2, R. I. Zubatyuk2, and O. V. Shishkin2
The direction of the reaction of 4-bromo-1,3-diphenyl-2-buten-1-one (γ-bromodypnone) with hydrazines
depends on the nature of the substituent they contain. Reaction with 1-methylhydrazinium hydrosulfate
gives 1-methyl-3,5-diphenylpyridazin-1-ium bromide but carboxylic acid hydrazides give N-(2,4-diphenyl-
1H-pyrrol-1-yl)carboxylic acid amides. γ-Bromodypnone and phenylhydrazine give both 1,3,5-triphenyl-
1,4-dihydropyridazine and N,2,4-triphenyl-1H-pyrrol-1-amine (15%). 1-(2,4-Dinitrophenyl)hydrazine
gives the 2,4-dinitrophenylhydrazone of (Z)-4-bromo-1,3-diphenyl-2-buten-1-one. Condensation of
2,4-diphenyl-1H-pyrrol-1-amine with aromatic aldehydes readily leads to N-(arylmethylidene)-
2,4-diphenyl-1H-pyrrol-1-amines and alkylation with methyl iodide gives N,N-dimethyl-2,4-diphenyl-
1H-pyrrol-1-amine.
Keywords: 1-aminopyrrole, γ-bromodypnone, 2,4-diphenyl-1H-pyrrol-1-amine, 3,5-diphenylpyri-
dazine.
Interest in arylpyrroles has steadily increased over the last 30 years. Among them are substances with a
high level of biological activity which are used for treatment of cardiovascular, immunological, and CNS
diseases [1, 2]. A number of arylpyrroles are used in agriculture, in the food industry, and in preparation of
novel polymeric materials [2]. In this respect it is undoubtedly important to develop novel routes for the
synthesis of 1-aminopyrroles as promising compounds for studying both their biological activity [3, 4] and their
synthetic potential [5, 6].
Rather little attention has been paid to methods for obtaining 1-aminopyrroles via reaction of
γ-halocarbonyl compounds with hydrazines [7]. It is known that these reactions can lead to pyridazine [8] or
1-aminopyrrole [7] derivatives depending on the structure of the reagents. Hence treatment of 4-bromo-
1,3-diphenyl-2-buten-1-one (γ-bromodypnone) (1) with hydrazine hydrate gives 2,4-diphenyl-1H-pyrrol-
1-amine (2) [9] and arylhydrazines give 1,3,5-triphenylpyridazines [9]. Our work relates to a wider investigation
of the synthetic process for N-substituted 2,4-diphenyl-1H-pyrrol-1-amine derivatives 2.
_______
* To whom correspondence should be addressed, e-mail: potikha_l@mail.ru.
1Taras Shevchenko National University, Kiev 01033, Ukraine.
2Institute for Single Crystals, Ukraine National Academy of Sciences, Kharkiv 61001; e-mail:
roman@xray.isc.kharkov.com.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 404-414, March, 2009. Original
article submitted December 6, 2007.
0009-3122/09/4503-0327©2009 Springer Science+Business Media, Inc.
327

We have studied the reaction of γ-bromodypnone 1 with 1-methylhydrazinium hydrosulfate under
varying conditions: melting, heating the starting materials with and without the presence of base, and heating in
acetic acid. Investigations have shown that, when the reaction is carried out in the absence of base and
independently of the conditions, it gives 2,4-diphenylfuran which is readily formed via intramolecular
condensation of compound 1 induced by weak nucleophiles or in an acidic medium [10, 11]. In fact, in the
presence of base (AcONa in the case of melting or NaHCO3 when refluxing in alcohol) the 1H NMR data shows
a mixture of 2,4-diphenylfuran and the product of intermolecular condensation of γ-bromodypnone 1 and
methylhydrazine is formed. The highest yield of the condensation product (53%) is achieved when the reaction
is carried out in alcohol. According to elemental and mass-spectrometric analysis the reaction product is a
bromide salt but attempts to liberate the free base from the salt using triethylamine led to its degradation.
Ph
Br
COPh
N2H4
MeNHNH2 . H2SO4
.
1
Ph
Ph
Ph
–
RCONHNH2
ArCHO
+
Ph
N
N
N
Ph
Ph
NH2
Br
Me
2
3
MeI
Ph
N
Ph
N
N
Ph
HN
O
6a–f
R
5a,b
Ar
Ph
N
NMe2
4
6 a R = Ph, b R = 2-ClC6H4, c R = 4-ClC6H4, d R = 4-O2NC6H4, e R = CH2Ph,
f R = CH2CN; 5 a Ar = Ph, b Ar = 4-MeOC6H4
1
In order to reveal the structure of the synthesized compound we have measured its H and 13C NMR
spectra and also carried out 2D homonuclear (COSY, NOESY) and heteronuclear 13C/1H (HMQC, HMBC)
1
correlation experiments. As in that of the starting compound 1 [12] the H NMR spectrum of the condensation
product shows the presence of aromatic protons signals as a narrow multiplet at 7.69 ppm (6H) and at lower
field (around 8.30 ppm) two signals for the o-protons of the phenyl substituents. The spectrum also shows a
methyl group singlet at 4.71 ppm and two one-proton singlets at lower field (10.49 and 9.31 ppm) which do not
exchange with D2O. According to the NOESY spectrum data the singlet at 10.49 ppm has a correlation with the
methyl group proton signal and with the multiplet for the ortho protons of one of the benzene rings (8.28 ppm).
This points to their steric proximity. On the basis of this analytical and spectroscopic data we have proposed that
the condensation product of the γ-bromodypnone 1 with methylhydrazine hydrosulfate is the 1-methyl-
3,5-diphenylpyridazin-1-ium bromide (3).
Further support for this conclusion was found by us in the heteronuclear correlation spectra (Fig. 1).
Table 1 shows the position of the cross peaks found in the 2D HMQC, HMBC, and NOESY spectra for each of
the 1H NMR signals.
The presence of a correlation between the proton singlet at 10.49 ppm for H-6 and the methyl group
carbon atom at 52.98 ppm (the protons of which also correlate with the tertiary C-6 atom at 147.5 ppm)
328

confirms the structure as the 1-methyl-3,5-diphenyl-substituted pyridazine. In an alternative variant as 1-methyl-
4,6-diphenylpyridazin-1-ium bromide the lowest field singlet (H-3) is separated by more than 3 chemical bonds
and cannot give a correlation in the HMBC spectrum.
7.77
8.28
6.80
137.5
(1' ' ')
9.31
129.1
135.5 (1' ')
7.90
122.3
131.6 (1' ')
132.9 (1')
8.34
151.9
146.0
30.0
146.9
161.3
N
CH2
4.31
N
147.5
11.43
10.49
HN
Br
N
+
144.3
(1')
52.98
CH3
4.71
O2N
130.5
A
B
Fig. 1 Signal assignments. The arrows indicate HMBC structural correlations for compounds 3 (A) and 10 (B).
Since efforts to prepare an N-methyl-substituted 2,4-diphenyl-1H-pyrrol-1-amine in the absence of base
in the reaction mixture gave only 2,4-diphenylfuran, we have attempted to carry out the synthesis via alkylation
of the 2,4-diphenyl-1H-pyrrol-1-amine (2). However, heating a solution of compound 2 in acetonitrile with
methyl iodide (independently of the ratio of reagents) did not stop at the monoalkylation stage but gave the
N,N-dimethyl-2,4-diphenyl-1H-pyrrol-1-amine (4). This was supported by the absence of NH group signals in
the IR or 1H NMR spectra and the presence of methyl group signals at 2.19 and 1.87 ppm of overall intensity 6H
in the proton spectrum (Tables 2, 3). The N-methyl groups in structure 4 are nonequivalent and this can point to
hindered rotation of the dimethylamino groups relative to the pyrrole ring and to coplanarity. The reaction of
compound 2 under the same conditions with other alkylating reagents (benzyl halides, γ-bromo-dypnone) gave a
complex mixture of reaction products which we could not separate.
TABLE 1. Proton-Carbon and Proton-Proton Correlations for the 1-Methyl-
pyridazinium Salt 3 and Hydrazone 10
Com-
pound
δ, ppm
1Н NMR
НМQС
НМВС
NOESY
10.49
3
4.71
7.69
52.98
147.5
133.05, 130.31,
130.13
128.8, 129.01, 130.1, 130.3,
131.6, 132.9, 133.0
8.28, 8.34
8.28
129.01
128.8, 133.0, 146.9
7.69, 9.31,
10.49
8.34
9.31
10.49
11.43
8.93
8.42
8.21
7.90
7.77
7.50
128.80
129.1
129.0, 133.0, 161.3
7.69, 9.31
8.28, 8.34
4.71, 8.28
—
131.6, 132.9, 147.5, 161.3
52.98, 128.8, 131.6, 146.9
151.95, 144.3, 130.53, 117.33
144.3, 138.4, 130.94, 130.53
144.3
147.5
10
—
123.4
—
130.94
117.33
127.68
127.5
8.21
138.4, 130.94, 130.53
151.95, 131.3
8.42
7.50
146.0, 129.95, 127.5
137.5, 135.5, 129.6, 129.4,
127.68, 127.5
4.31, 6.80, 7.50
7.90, 7.77
131.3, 129.95,
129.6, 129.4
122.3
6.80
4.31
146.0, 137.5, 135.5, 30.03
146.0, 137.5, 123.3
7.77
7.77
30.03
329

TABLE 2. IR Spectra of the 1-Aminopyrroles 4-6, 8
Com-
pound
ν, cm–1
4
3050, 1600, 1570, 745, 723, 680
5a
5b
6a
6b
6c
6d
6e
6f
8
3010, 1610 (C=N), 1495, 1475, 1460, 1405, 1333, 1232, 1195, 755, 695
3000, 2940, 1602 (C=N), 1510, 1460, 1405, 1330, 1302, 1250 (C–O), 1163, 1035, 752
3210 (NH), 1660 (C=O), 1605, 1480, 1280, 750, 685
3220 (NH), 3020, 1660 (C=O), 1295, 910, 750, 690
3200 (NH), 3020, 1660 (C=O), 1590, 1295, 910, 750, 690
3230 (NH), 1650 (C=O), 1590, 1470, 1315 (NO2), 1260, 750, 685
3220 (NH), 3030, 1660 (C=O), 1610, 1335, 1035, 730
3220 (NH), 3050, 2260 (CN), 1660 (C=O), 1205, 740, 680
3310 (NH), 3040, 1590, 1480, 745, 685
TABLE 3. 1H NMR Spectra of Compounds 4-6 and 8
Chemical shifts, δ, ppm (J, Hz)
Com-
pound
NH,
1H, s
Other
signals
ArH *
4
—
7.55 (2Н, d, J = 8.0, H-2',6'); 7.49 (2Н, d, J = 8.0, H-2'',6'');
7.36-7.30 (4Н, m, H-3',5',3'',5''); 7.22 (1Н, t, J = 8.0, H-4');
7.13 (1H, t, J = 8.0, H-4''); 7.11 (1H, d, J = 1.6, H-5);
6.68 (1H, d, J = 1.6, H-3)
2.19
(3Н, s, СН3);
1.87
(3Н, s, СН3)
5a
5b
6a
—
—
8.18 (1H, d, J = 1.2, H-5); 7.80 (2Н, m, H-2''',6''');
7.70 (2Н, d, J = 8.0, H-2',6'); 7.65 (2Н, d, J = 8.0, H-2'',6'');
7.45 (3H, m, Н-3'''-Н-5'''); 7.42 (2Н, t, J = 8.0, H-3',5');
7.36 (2Н, t, J = 8.0, H-3'',5''); 7.29 (1Н, t, J = 8.0, H-4');
7.18 (1H, t, J = 8.0, H-4''); 6.75 (1H, d, J = 1.2, H-3)
8.90
(1H, s,
–N=CH–)
8.09 (1H, d, J = 1.2, H-5); 7.74 (2Н, d, J = 8.5, H-2''',6''');
7.70 (2Н, d, J = 8.0, H-2',6'); 7.63 (2Н, d, J = 7.5, H-2'',6'');
7.40 (2Н, t, J = 8.0, H-3',5'); 7.35 (2Н, t, J = 7.5, H-3'',5'');
7.28 (1Н, t, J = 8.0, H-4'); 7.17 (1H, t, J = 7.5, H-4'');
6.99 (2Н, d, J = 8.5, H-3''',5'''); 6.71 (1H, d, J = 1.2, H-3)
8.82
(1H, s,
–N=CH–);
3.85
(3Н, s, СН3)
11.74
7.89 (2Н, d, J = 8.0, H-2''',6'''); 7.59-7.47 (7Н, m, ArH);
7.36-7.30 (5H, m, H-3',5',3'',5'', H-5); 7.23 (1H, t, J = 7.5, H-4');
7.15 (1H, t, J = 8.0, H-4''); 6.70 (1H, d, J = 1.2, H-3)
—
6b
6c
11.67
11.81
7.57 (4H, m, ArH); 7.49-7.27 (10H, m, ArH, H-5);
7.15 (1H, t, J = 8.0, H-4''); 6.67 (1H, d, J = 2.0, H-3)
—
—
7.90 (2Н, d, J = 8.0, H-2''',6'''); 7.58 (2Н, d, J = 8.0, H-2',6');
7.52 (4H, m, H-3''',5''', H-2'',6'');
7.32 (5H, m, H-3',5', H-3'',5'', H-5); 7.22 (1H, t, J = 7.5, H-4');
7.14 (1H, t, J = 7.5, H-4''); 6.69 (1H, s, H-3)
6d
12.09
8.33 (2Н, d, J = 8.2, H-3''',5'''); 8.12 (2Н, d, J = 8.2, H-2''', H-6''');
7.57 (2Н, d, J = 8.0, H-2',6'); 7.52 (2Н, d, J = 8.0, H-2'',6'');
7.37-7.31 (5H, m, H-3',5', H-3'',5'', H-5);
—
7.24 (1H, t, J = 8.0, H-4'); 7.15 (1H, t, J = 7.5, H-4'');
6.71 (1H, d, J = 2.0, H-3)
6e
6f
8
11.36
11.58
9.20
7.53 (2Н, d, J = 8.0, H-2',6'); 7.37 (2Н, d, J = 8.0, H-2'',6'');
7.32-7.21 (10H, m, ArH); 7.17 (1H, d, J = 2.0, H-5);
7.12 (1H, t, J = 7.5, H-4''); 6.61 (1H, d, J = 2.0, H-3)
3.52
(2H, s, CH2)
7.54 (2Н, d, J = 8.0, H-2',6'); 7.46 (2Н, d, J = 8.0, H-2'',6'');
7.40 (2Н, t, J = 8.0, H-3',5'); 7.33 (3Н, m, H-3'',5'',4');
7.24 (1H, s, H-5); 7.15 (1H, t, J = 7.5, H-4''); 6.65 (1H, s, H-3)
7.60 (2Н, d, 3J = 8.0, H-2',6'); 7.55 (2Н, d, 3J = 8.0, H-2'',6'');
7.29 (4Н, m, H-3',5',3'',5''); 7.22 (1Н, d, 4J = 1.6, Н-5);
7.18 (1Н, t, 3J = 7.5, H-4'); 7.11 (3Н, m, H-3''',5''',4'');
6.72 (2Н, m, H-3, H-4'''); 6.46 (2Н, d, 3J = 8.0, H-2''',6''')
3.75
(2H, s, CH2)
—
_______
* Numbering of the benzene ring aromatic protons: 2-Ph – 2' to 6', 4-Ph –
2'' to 6'', 1-N-Ar – 2''' to 6'''
330

The 2,4-diphenyl-1H-pyrrol-1-amines 2 and 4 do not form stable protonated salts. It should be noted that
such salts have only been described for the more basic trialkyl-substituted 1H-pyrrol-1-amines [13]. Attempts to
prepare a quaternary methylammonium salt of compound 4 were also unsuccessful. Prolonged heating of the
N,N-dimethyl derivative 4 with methyl tosylate or dimethyl sulfate led only to its partial degradation.
Condensation of the pyrrol-1-amine 2 with aromatic aldehydes occurred comparatively readily in alcohol.
In this way the 2,4-diphenyl-N-(arylmethylidene)-1H-pyrrol-1-amines 5a,b were prepared in 75-76% yield.
Prolonged heating (10 h) of compound 2 in acetic anhydride in the presence of sodium acetate did not give
the N-(2,4-diphenyl-1H-pyrrol-1-yl)acetamide acylation product. However, the corresponding N-(2,4-diphenyl-
1H-pyrrol-1-yl)carboxylic acid amides 6a-f were readily prepared by refluxing the γ-bromodypnone 1 with
carboxylic acid hydrazides in alcohol. Fusing the components in the presence of sodium acetate gave the same
result but in lower yield. In the case of the arylcarboxylic acid hydrazides having electron acceptor substituents in
the benzene ring fusing in the presence of sodium acetate also gave a significant amount (~ 50% according to
1H NMR spectroscopic data) of 2,4-diphenylfuran and the yield of the target reaction products was less than 20%.
The structure of compounds 6 was determined on basis of its spectroscopic data (Tables 2 and 3). Hence
1
there are signals for the NH group in the IR spectra at 3200-3250 cm-1 and in the H NMR spectra at
12.09-11.36 ppm. Characteristic signals for the pyrrole ring [11] protons in the 2,4-diphenylpyrroles are seen as
singlets or doublets with J3,5 = 1.2-2.0 Hz at 7.30-7.17 (H-5) and 6.71-6.61 ppm (H-3).
NO2
NHNH2
Ph
Ph
Ph
O2N
PhNHNH2
1
+
N
Ph
N
N
Ph
Ph
HN
8
7
Ph
Ph
Ph
Br
Ph
N
N
NH
.
HBr
N
2,4-(O2N)2C6H3
2,4-(O2N)2C6H3
10
9
The results of the experiments with acid hydrazides show that the direction of the reaction of the
γ-bromodypnone 1 with hydrazines is determined by the nature of the substituent in the latter. The presence of
donor substituents (alkyl) leads to pyridazine derivatives whereas acceptor substituents (acyl) principally give
1-aminopyrroles. Such a dependence is also seen in the reaction of γ-bromodypnone 1 with arylhydrazines.
Hence treatment of γ-bromodypnone 1 with phenylhydrazine gave 1,3,5-triphenyl-1,4-dihydropyridazine (7) [9].
However, according to TLC data, compound 7 is not the sole reaction product. We were able to separate a low
yield (15%) of N,2,4-tri-phenyl-1H-pyrrol-1-amine (8) from the reaction mixture. This structure for 8 is
1
supported by the IR and H NMR data, primarily the presence of signals for the NH group and pyrrole ring
protons (doublet with 4J = 1.6 at 7.22 (H-3) and signal at 6.72 ppm (H-5)). Treatment of the γ-bromodypnone 1
with alkylphenyl-hydrazines [9] led exclusively to a pyridazine derivatives.
It would be logical to expect that the use of arylhydrazines with acceptor substituents in the ring in the
reaction would lead to an increased content of the N-arylpyrrole in the reaction mixture. With this aim we have
used 1-(2,4-dinitrophenyl)hydrazine. Heating a mixture of the reagents in alcohol gave a single product
1
according to TLC data and this was separated in high yield (84%). The H NMR spectrum of the product
obtained showed methylene group protons signals (s, 2H at 4.31 ppm), a methine proton (s, 1H at 6.80 ppm) and
a proton which exchanged with D2O (s, 1H at 11.43 ppm). According to elemental analytical data the molecule
of this compound contains a bromine atom. This suggests that the reaction product is not a pyrrole
331

derivative (the probability of forming an unstable 5H-form is very low) but it might be the pyridazine
hydrobromide 9 or have the noncyclic hydrazone 10 structure. To clarify the structure of the reaction product the
2D (HMQC, HMBC, NOESY) spectra were studied. Analysis of the heteronuclear correlations in the HMBC
spectrum (Table 1 and Fig. 1) showed unambiguously the presence of the dypnone structural fragment in the
molecule and excludes the possibility of a 1,4-dihydropyridazine type structure 7. This is supported by the
correlation between the singlet at 6.80 ppm (1H) and both of the quaternary carbon atoms of the benzene rings
C-1'' (135.3) and C-1''' (137.5 ppm). A correlation for the methylene group protons (4.31 ppm) is also observed
but only with carbon atom (C-1''').
The final conclusion for the structure of the reaction product as the N-(2,4-dinitrophenyl)hydrazone of
(Z)-4-bromo-1,3-diphenyl-2-buten-1-one (10) was confirmed by X-ray structural analysis (Fig. 2 and Tables 4
and 5).
The hydrazone fragment lies virtually in the plane of the dinitrophenyl ring (torsional angles C(2)–C(1)–
N(3)–N(4) 0.3(5)º and C(1)–N(3)–C(4)–C(7) -174.3(3)º) leading to the formation of an intramolecular hydrogen
bond N(3)–H···O(4) (H···O 2.00 Å, N–H···O 127º). The phenyl substituent C(8)···C(13) is somewhat
C(11)
C(10)
C(12)
C(9)
C(13)
C(8)
C(7)
N(4)
C(14)
C(18)
C(2)
C(1)
N(3)
C(16)
C(15)
C(17)
C(3)
C(19)
C(20)
O(2)
C(6)
Br(1)
C(4)
C(5)
N(1)
O(1)
C(21)
C(22)
N(2)
O(3)
O(4)
Fig. 2. Structure of the compound 10 molecule.
TABLE 4. Some Valence (ω) and Torsional (ϕ) Angles for Compound 10
Molecule
Angle
ω, deg
Angle
ϕ, deg
С(1)–N(3)–N(4)
С(7)–N(4)–N(3)
118.6(3)
118.1(3)
116.5(3)
126.5(3)
117.0(3)
122.1(4)
120.1(3)
129.0(3)
120.5(3)
121.4(3)
118.1(3)
113.0(3)
120.7(4)
120.5(4)
C(1)–N(3)–N(4)–С(7)
N(4)–N(3)–C(1)–С(2)
N(3)–N(4)–C(7)–С(8)
N(3)–N(4)–C(7)–С(14)
C(14)–C(7)–C(8)–С(13)
N(4)–C(7)–C(8)–С(9)
-174.3(3)
0.3(5)
N(4)–C(7)–C(8)
177.4(3)
-0.3(5)
N(4)–C(7)–C(14)
С(8)–C(7)–C(14)
С(13)–C(8)–C(7)
С(9)–C(8)–C(7)
С(15)–C(14)–C(7)
С(14)–C(15)–C(17)
С(14)–C(15)–C(16)
С(17)–C(15)–C(16)
С(15)–C(16)–Br(1)
С(18)–C(17)–C(15)
С(22)–C(17)–C(15)
-15.4(5)
-14.5(5)
-60.0(6)
122.3(4)
2.7(6)
N(4)–C(7)–C(14)–С(15)
C(8)–C(7)–C(14)–С(15)
C(7)–C(14)–C(15)–С(16)
C(17)–C(15)–C(16)–Br(1)
C(14)–C(15)–C(17)–С(18)
C(16)–C(15)–C(17)–С(22)
54.5(4)
38.6(5)
40.2(5)
332

TABLE 5. Some Bond Lengths (l) in the Compound 10 Molecule
Bond
Br(1)–С(16)
N(3)–С(1)
N(3)–N(4)
N(4)–С(7)
C(7)–С(8)
l, nm
Bond
C(7)–С(14)
C(14)–С(15)
C(15)–С(17)
C(15)–С(16)
l, nm
1.930(4)
1.354(5)
1.368(4)
1.285(5)
1.482(5)
1.494(5)
1.320(5)
1.487(5)
1.502(5)
twisted relative to this fragment (torsional angle N(4)–C(7)–C(8)–C(9) -14.5(5)º) as a result of repulsion
between the C(14) and H(13A) atoms (distance 2.59 Å, sum of van der Waal radii [14] 2.87 Å). The steric
effects (shortening of the intramolecular contacts C(16)···N(5) 3.059 (sum of van der Waal radii 3.21),
N(3)···H(16B) 2.55 (2.66), C(16)···H(3A) 2.56, C(16)···H(22A) 2.77 Å, and C(14)···H(18A) 2.73 Å) are also
specified by rotation of the plane of the double bond C(14)–C(15) both relative to the phenyl substituent
C(17)···C(22) and to the plane of the hydrazone fragment (torsional angles C(14)–C(15)–C(17)–C(18) 38.6(5)º
and C(15)–C(14)–C(7)–N(4) -60.0(6)º). This accompanies a disturbance of the conjugation between the
π-systems of the double bond and the fragments mentioned above as indicated by lengthening of the C(14)–C(7)
and C(15)–C(17) bonds to 1.494(5) and 1.487(5) Å respectively (mean value for a conjugated C(sp2)–C(sp2)
bonds = 1.43 Å [15]).
It was interesting to note the formation in the crystal of a shortened Br(1)···C(19)' intramolecular contact
(x, y, 1+z) of 3.51 Å (sum of van der Waal radii 3.68 Å [15]) inferring the presence of an attractive Br···π
interaction (C–Br···C angle 164.1º) which can be considered as a halogen bond [16].
TABLE 6. Physicochemical Characteristics of the Compounds Synthesized
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °C*
Yield, %*2
C
H
Hal
N
3
C17H15BrN2
C18H18N2
62.21
62.40
82.56
82.41
85.73
85.68
81.83
81.79
81.50
81.63
73.91
74.09
73.99
74.09
72.25
72.05
81.86
81.79
75.85
75.73
85.20
85.13
55.00
54.90
4.32
4.62
7.03
6.92
5.71
5.63
5.79
5.72
5.16
5.36
4.52
4.60
4.64
4.60
4.53
4.47
5.79
5.72
5.19
5.02
5.89
5.85
3.61
3.56
24.48
24.42
8.60
8.56
10.54
10.68
8.53
8.69
7.92
7.95
8.30
8.28
7.55
7.51
7.48
7.51
10.86
10.96
8.00
7.95
19.88
19.94
9.01
9.03
11.62
11.64
227-230 (dec.)
88-91
53
41
75
76
55
50
51
52
68
62
15
84
4
—
—
—
—
5a
5b
6a
6b
6c
6d
6e
6f
8
C23H18N2
131-133
182-183
208-209
210-212
224-226
253-255
228-229
235-237 (dec.)
162-165
182-185
C24H20N2O
C23H18N2O
C23H17ClN2O
C23H17ClN2O
C23H17N3O3
C24H20N2O
C19H15N3O
C22H18N2
9.56
9.51
9.49
9.51
—
—
—
—
10
C22H17BrN4O4
16.63
16.60
_______
* Solvent for recrystallization: AcOH (compounds 3, 10), 2-PrOH
(compounds 4, 8), EtOH (compounds 5a,b, 6e), MeCN (compounds 6a-d,f).
*2 Yields of compounds 6a-f obtained using method B.
333

An attempt to carry out cyclization of hydrazone 10 by heating a suspension in ethanol in the presence
of base (Et3N, morpholine) gave a complex mixture of products which could not be separated.
EXPERIMENTAL
IR spectra (KBr tablets) were recorded on a Pye Unicam SP3-300 instrument. 1H and 13C NMR spectra
were taken on a Varian Mercury 400 instrument (400 and 100 MHz respectively) using DMSO-d6 solvent and
with TMS as internal standard. UV spectra for compound 10 were obtained on a Lambda 20 UV-vis
spectrometer using methanol. Mass spectra were taken for compounds 3, 8 using HPLC with an AGILENT/100
apparatus (CI, acetonitrile, 0.05% formic acid). Monitoring of the course of the reaction and the purity of the
product obtained was carried out using TLC on Silufol UV-254 plates. The physicochemical characteristics of
the compounds synthesized are given in Table 6.
2,4-Diphenyl-1H-pyrrol-1-amine (2) was prepared by the method reported in [9]. IR spectrum, δ, cm-1:
3370 (NH), 3350 (NH), 3045, 1595, 1470, 880, 745, 690.
1-Methyl-3,5-diphenylpyridazin-1-ium Bromide (3). A mixture of 1-methylhydrazinium hydrosulfate
(0.48 g, 3.32 mmol) and NaHCO3 (0.28 g, 3.32 mmol) in ethanol (50 ml) was heated for 10 min and the solid
residue was filtered off. γ-Bromodypnone 1 (1 g, 3.32 mmol) was added and the mixture was refluxed for 30
min. The solvent was evaporated and the residue was recrystallized from AcOH. IR spectrum, δ, cm-1: 3020,
1
1600 (C=N), 1385, 1250, 755, 667. H NMR spectrum, δ, ppm (J, Hz): 10.49 (1H, s, H-6); 9.31 (1H, s, H-4);
8.34 (2H, dd, 3J = 8.0, 4J = 4.0, H-2',6'); 8.28 (2H, m, H-2'',6''); 7.69 (6H, m, H-3'–H-5', H3''–H-5''); 4.71 (3H, s,
CH3). 13C NMR spectrum, δ, ppm: 161.29 (C-3); 147.48 (C-6); 146.86 (C-5); 133.09 (C-4'); 133.01 (C-4'');
132.88 (C-1'); 131.57 (C-1''); 130.31 (C-3',5'); 130.13 (C-3'',5''); 129.03 (C-4); 129.01 (C-2',6'); 128.80 (C-2'',
6''); 52.98 (CH3). Mass spectrum, m/z (Irel, %): 249 (70), 247 [M-Br]+ (100).
N,N-Dimethyl-2,4-diphenyl-1H-pyrrol-1-amine (4). Methyl iodide (0.13 ml, 2.13 mmol) was added to
a solution of 1-aminopyrrole 2 (0.5 g, 2.13 mmol) in acetonitrile (45 ml) and refluxed for 1 h. A further 0.13 ml
of methyl iodide was added and refluxing continued for 2 h. The solvent was evaporated. 2-Propanol was added
to the oily residue and heated to full solution. The precipitate formed on cooling was filtered off and washed
with 2-propanol.
N-(Arylmethylidene)-2,4-diphenyl-1H-pyrrol-1-amines 5a,b. Benzaldehyde (0.22 ml, 2.13 mmol) or
anisaldehyde was added to a solution of 1-aminopyrrole 2 (0.5 g, 2.13 mmol) in ethanol (60 ml) and refluxed for
30 min. The precipitate formed on cooling was filtered off and washed with alcohol.
N-(2,4-diphenyl-1H-pyrrol-1-yl)carboxylic acid amides 6a-f. A. A mixture of γ-bromodypnone 1
(1 g, 3.32 mmol), sodium acetate (0.27 g), and benzoic acid hydrazide (0.45 g, 3.32 mmol) was fused on an oil
bath at 120-130ºC for 15 min. After cooling, water (10 ml) was added to the melt and triturated thoroughly. The
filtered solid residue was thoroughly washed with water and 2-propanol and recrystallized. Yield 0.4 g (36%).
B. A mixture of the γ-bromodypnone 1 (1 g, 3.32 mmol) and the carboxylic acid hydrazide (3.32 mmol)
in ethanol (50 ml) was heated to full solution of the γ-bromodypnone and refluxed for a further 3 h. The
precipitate formed on cooling was filtered off and washed with alcohol.
N,2,4-Triphenyl-1H-pyrrol-1-amine (8). The method used was as reported in [9]. A mixture of the
γ-bromodypnone 1 (1 g, 3.32 mmol) and phenylhydrazine (0.33 ml, 3.32 mmol) in alcohol (50 ml) was refluxed
for 15 min. Solvent was evaporated and the residue was dissolved with heating in alcohol. The solution was
cooled for 1 h to form a precipitate of the 1,3,5-triphenyl-1,4-dihydropyridazine 7. After 3 days a precipitate of
compound 8 was formed in the filtrate and this was filtered off and washed with a small amount of 2-propanol.
Mass spectrum, m/z (Irel, %): 311 [M+1]+ (100), 309 [M-1]+ (20).
2,4-Dinitrophenylhydrazone of (Z)-4-bromo-1,3-diphenyl-2-buten-1-one (10). A mixture of the
γ-bromodypnone 1 (1 g, 3.32 mmol) and 2,4-dinitrophenylhydrazine (0.66 g, 3.32 mmol) in alcohol (50 ml) was
334

refluxed for 3 h. The solution was cooled and the precipitate formed was filtered off, washed with alcohol and
recrystallized from acetic acid. IR Spectrum, δ, cm-1: 3300 (NH), 1610 (C=N), 1569 (asNO2), 1500, 1420, 1335
(sNO2), 1313, 1112, 760. UV spectrum, λmax, nm (ε x 10-3): 202 (45.13), 247 (23.34, sh), 382 (26.12). 1H NMR
spectrum, δ, ppm (J, Hz): 11.43 (1H, s, NH); 8.93 (1H, d, 4J = 1.2, H-3'); 8.42 (1H, dd, 3J = 8.0, 4J = 1.2, H-5');
8.21 (1H, d, 3J = 8.0, H-6'); 7.90 (2H, m, H-2'',6''); 7.77 (2H, d, 3J = 7.5, H-2''',6'''); 7.57-7.42 (6H, m, H-3''-H-5'',
H-3'''–H-5'''); 6.80 (1H, s, H-2); 4.31 (2H, s, 4-CH2). 13C NMR spectrum, δ, ppm: 151.95 (C-1); 146.0 (C-3);
144.3 (C-1'); 138.4 (C-4'); 137.5 (C-1'''); 135.5 (C-1''); 131.3 (C-4''); 130.94 (C-5'); 130.53 (C-2'); 129.95
(C-4'''); 129.6 (C-3'',5''); 129.4 (C-3''',5'''); 127.68 (C-2'',6''); 127.5 (C-2''',6'''); 123.6 (C-3'); 122.3 (C-2); 117.33
(C-6'); 30.03 (C-4).
Crystallographic data. Crystals of 10 are monoclinic and grown from acetic acid, C22H17BrN4O4, at
293ºK: a = 11.5767(5) Å, b = 25.5245(9) Å, c = 7.3670(3) Å, β = 106.589(4)º, V = 2086.3(1) Å3, Mr = 481.31,
Z = 4, space group P21/c, dcalc = 1.532 g/cm3, µ(MoKα) = 2.008 mm-1, F(000) = 976. The unit cell parameters
and intensities of 16,116 reflections (4719 independent, Rint = 0.037) were measured on an Xcalibur
diffractometer (MoKα radiation, CCD detector, graphite monochromator, ω-scanning to 2θmax = 55º). The
structure was solved by a direct method using the SHELXTL program package [17]. The positions of the
hydrogen atoms were revealed using electron density difference synthesis and refined with the "riding" model
with Uiso = 1.2 Ueq for the non-hydrogen atom bound to the given hydrogen. The structure was refined using F2
full matrix least squares analysis in the anisotropic approximation for non-hydrogen atoms to wR2 = 0.149 for
4705 reflections (R1 = 0.059 for 2803 reflections with F >4σ(F), S = 1.00). The full X-ray structural analytical
data can be obtained from the Cambridge Crystallographic Data Centre (CCDC 670372).
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