Synthesis of azepino[1,2-a]benzimidazoles and imidazo[1,2-a]azepines

Article abstract of DOI:10.1007/s10593-011-0829-6

Fusion of 4-bromo-1,3-diphenyl-2-buten-1-ones (γ-bromodypnones) with 1,2-dimethyl-1H-benzimidazole and further treatment of the reaction product with a base (morpholine) gives 7,9-diaryl-5-methyl5,10-dihydroazepino[1,2-a] benzimidazol-11-ium bromides. The

Full text of DOI:10.1007/s10593-011-0829-6

Chemistry of Heterocyclic Compounds, Vol. 47, No. 6, September 2011 (Russian original Vol. 47, No. 6, June, 2011)
SYNTHESIS OF AZEPINO[1,2-a]BENZIMIDAZOLES
AND IMIDAZO[1,2-a]AZEPINES
L. M. Potikha1*, A. R. Turelyk1, and V. A. Kovtunenko1
Fusion of 4-bromo-1,3-diphenyl-2-buten-1-ones (ꢀ-bromodypnones) with 1,2-dimethyl-1H-benzimidazo-
le and further treatment of the reaction product with a base (morpholine) gives 7,9-diaryl-5-methyl-
5,10-dihydroazepino[1,2-a]benzimidazol-11-ium bromides. The reaction of ꢀ-bromodypnone with 1-al-
kyl-2-methyl-1H-imidazoles in benzene at 25ºC gives quaternary azolium salts. Upon heating their solu-
tions in alcohol in the presence of K2CO3 the latter cyclize to 1-R-6,8-diaryl-1,5-dihydroimidazo[1,2-a]-
azepin-4-ium bromides or 1-R-6,8-diaryl-1H-imidazo[1,2-a]azepines depending on the nature of the
substituent in the benzene rings and the substituent at the N(1) atom of the imidazole.
Keywords: azepino[1,2-a]benzimidazole, ꢀ-bromodypnone, imidazo[1,2-a]azepine, cyclization.
Amongst azepino[1,2-a]benzimidazole and imidazo[1,2-a]azepine condensed systems there are found
highly active compounds which are proposed as antagonists of choline, histamine, and dopamine receptors
[1–4], for the regulation of sodium or potassium ion transport through a cell membrane [3, 5], and as antitumor
agents [2]. However, the studied compounds structure in this series vary mainly in the azole part of the bicycle
but the azepine part unsaturation degree and the effect of substituents in azepine ring on the compound
properties has been little studied.
Continuing our investigation of the heterocyclization of 4-bromo-1,3-diphenyl-2-buten-1-one (ꢀ-bromo-
dypnone, 1a, Scheme 1) [6, 7] we propose a method for the synthesis of 7,9-diarylazepino[1,2-a]benzimidazoles
(2) and 6,8-diarylimidazo[1,2-a]azepines 3 and 4. Aiming the biological potential evaluation of compounds in
this series we have calculated the spectrum of their biological activity using the PASS program (Prediction of
Activity Spectra for Substances) [8–10]. Amongst a broad spectrum of predicted features the most widespread
are their potential as ligands (substrates) of enzyme CYP2D16 (polypeptide 16, gene family 2, subfamily D of
cytochrome P450) and as antagonists of the subtype A receptor of ꢀ-aminobutyric acid (GABA).
Higher activity (Pa > 80%) is predicted for compounds with a hydrogenated azepine fragment. For
these, a high likelihood of the appearance of dopamine receptor agonist and antidepressant properties should be
noted.
_______________
*To whom correspondence should be addressed, e-mail: potikha_l@mail.ru.
1Taras Shevcheko National University, 64 Volodymyrska St., Kiev 01033, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 901–912, June 2011. Original
article submitted March 18, 2010.
0009-3122/11/4706-0745©2011 Springer Science+Business Media, Inc.
745
ꢀ

Scheme 1
Ar
Ar
+
N
K2CO3
_
+
Ar
Br
+
N
_
Ar
Ar
N
Br
Ar
N
R
O
Me
Br
N
_
N
Me
Me
3a–h
6
K2CO3
N
2a–d
NaOH
(3a,e)
Me
(1c)
N
N
N
(5a–e,h,i)
Me
Me
Morpholine
Me
Ar
Ar
O
Ar
Ar
O
N
N
K2CO3
Me
N
R
+
N
R
Br
N
Ar
Me
Ar
(5f,g)
1a–d
4a–d
N
R
_
(1a,b,d)
Br
5a–i
1,2 a Ar = Ph, b Ar = 4-ClC6H4, c Ar = 4-BrC6H4, d Ar = 4-MeOC6H4; 3 a–d Ar = Ph, a R = Me, b R = Et2N(CH2)2, c R = Bn,
d R = 4-BrC6H4CH2; e–g R = Me, e Ar = 4-ClC6H4, f Ar = 4-BrC6H4, g Ar = 4-MeOC6H4; h Ar = 4-MeOC6H4, R = Bn;
4 a–ꢀ Ar = 4-ClC6H4, a R = Bn, b R = 4-BrC6H4CH2, c R = Me; d Ar = Ph, R = Bn; 5 a–d Ar = Ph, a R = Me, b R = Et2N(CH2)2,
c R = Bn, d R = 4-BrC6H4CH2; e–g Ar = 4-ClC6H4, e R = Me, f R = Bn, g R = 4-BrC6H4CH2, h, i Ar = 4-MeOC6H4,
h R = Me, i R = Bn; 6 Ar = 4-Brꢀ6ꢁ4
The basis for the proposed method of synthesis of aryl derivatives of the diazolo[1,2-a]azepines lies in ad-
ding of the azepine ring to an azole one. Although this has been extensively developed in recent years [11–15], the
route to building these systems via a [4+3] type cyclization has only been employed in few cases [15–17]. We have
previously found that melting the ꢀ-bromodypnone 1a with 1,2-dimethyl-1H-benzimidazole at 110ºC and further
work up of the reaction product with base (morpholine) gives the 5-methyl-7,9-diphenyl-5,10-dihydroazepino-
[1,2-a]benzimidazol-11-ium bromide (2a) [6]. Under the same conditions the ꢀ-bromodypnone derivatives 1b–d
also form the azepino[1,2-a]benzimidazolium bromides 2b–d (Table 1). A difference in behavior is only noted for
the 4-methoxy-substituted ꢀ-bromodypnone 1d which is converted to a 1:1 mixture of salt 2d and
2,4-bis(4-methoxyphenyl)furan as the product of an intramolecular cyclization. The increasing tendency towards
formation of the latter in the presence of base is a characteristic feature of the ꢀ-bromodypnone 1d [18]. The
mixture obtained could be separated by column chromatography.
Attempts to separate the quaternary benzimidazolium salt intermediate product of this reaction proved to
be unsuccessful. Holding a mixture of the starting reagents at room temperature or heating in benzene or
acetonitrile principally gives the 1,2-dimethyl-1H-benzimidazole hydrobromide. However, in the case of the
reaction of the ꢀ-bromodypnones 1a–d with 1-alkyl-2-methyl-1H-imidazoles in benzene at 25ºC the corres-
ponding quaternary salts were obtained and, in several cases, could be separated in a pure state. Hence the reac-
tion of compound 1a with 1,2-dimethyl- or 1-arylmethyl-2-methyl-1H-imidazoles gave the 1-R-3-[(Z)-2,4-di-
1
aryl-4-oxo-2-butenyl]-2-methyl-1H-imidazol-3-ium bromides 5a,c,d. Their structures were established from H
NMR and IR spectroscopic data which were in agreement with previously obtained results for 1-alkyl-3-[(Z)-
2,4-diaryl-4-oxo-2-butenyl]-1H-imidazol-3-ium bromides [7] (Tables 2 and 3). In the remaining cases, the reac-
tion of the ꢀ-bromodypnones 1a,b,d with 2-methylimidazole derivatives gave mixtures with salts 5b,e–i content
not less than 70% (from 1H NMR spectroscopic data). The reaction of ꢀ-bromodypnone 1c with
1,2-dimethyl-1H-imidazole also gives a quaternary imidazolium salt but its structure proved different and
corresponded to the 3-[2,4-bis(4-bromophenyl)-4-oxo-1-butenyl]-1,2-dimethyl-1H-imidazol-3-ium bromide (6).
746
ꢀ

1
The differences in the dypnone structural residue in the alkylation product 6 were indicated by the H NMR
spectroscopic data. Hence the signal for the methylene group protons is seen at 4.42 at higher field than the same
for type 5 salts which have the methylene group protons signal at 5.85–5.87 ppm. The doublet for the ortho
protons of the benzene ring at the carbonyl group was also shifted to high field to 7.87 ppm while, in all of the
other imidazolium [7] and 2-methylimidazolium salts 5a–i it is found at 8.10–8.13 ppm. In addition, the infrared
stretching band for the carbonyl group in compound 6 is shifted by an average of 25 cm–1 to higher frequency
when compared to the type 5 salts. The complex of these factors can be rationalized by the existence of a tauto-
meric form in which the methylene is found at the ꢁ-position to the carbonyl group. The reason for its formation
is an increase in the mobility of the protons at the C(1') atom in structure type 5 which is due to the increase in
the electron-acceptor properties of the para substituent in the benzene rings. These structural conclusions for the
salt 6 were confirmed by the results of 1H NMR NOE experiments (Figure 1a) which also permit the assignment
of its configuration as the (E)-isomer.
7.62
H
H
7.87
H
H
4.42
a
N
O
H
H3C
+
7.47
7.35
Cl
H
N
7.84
H
H3C
H
5.18
H
H
8.04
H
6.30
H
H
+
7.63
H
N
7.90
H
H
H
6.99
b
c
N
5.95
H
7.61
H
N
N
7.27
H3C
H 7.57
3.98
6.62
H
H
Br
5.41 H
7.41
H
7.20
H
7.56
H
Cl
Fig. 1. Structurally significant NOE correlations for compound 6 in DMSO-d6 (a), 3e in
DMSO-d6 (b), and 4b in CD3CO2D (c).
Heating salts 5a–i and 6 in ethanol or methanol in the presence of potassium carbonate caused an in-
tramolecular condensation at the 2-methyl group and the formation of imidazo[1,2-a]azepine system derivatives.
Hence it was found that the structure of the cyclization product is determined by the nature of the substituent in
the benzene rings and at the N(1) atom. The majority of the 1-alkylimidazolium salts 5a–e,h,i and 6 are conver-
ted to the 6,8-diarylimidazo[1,2-a]azepin-4-ium bromides 3a–h but for Ar = 4-ClC6H5 and R = ArCH2 (salts
5f,g) the reaction leads to the formation of the 1-R-6,8-bis(4-chlorophenyl)-1H-imidazo[1,2-a]azepines 4a,b.
The structure of the reaction products 3 and 4 was confirmed by their elemental analysis data and from
1
spectroscopic examination. The H NMR spectra of salts 3a–h (Table 2) show a two-proton singlet for the
methylene group and two aromatic singlets assigned to the azepine ring as is seen in the spectra of the benz-
imidazo derivatives 2a–d. In order to determine the precise signal assignments and to determine the position of
the methylene group, we have carried out NOE experiments for compound 3e (Figure 1b). The similarity of the
salts 2a–d and 3a–h structures was confirmed from their IR and UV spectra which show a series of analogies.
Hence the UV spectra of salts of type 2 and 3 are characterized by the presence of two absorption maxima in the
747
ꢀ

ranges 260–274 and 325–332 nm with intensities log ꢂ 4.00–4.88. Compounds 4a,b differ from the salts of type
2 and 3 in chemical and spectroscopic properties. They are less soluble in polar solvents (DMSO, DMF) and
more deeply colored. The UV spectra of compounds 4a,b show a bathochromic shift and hypochromic effect for
the long-wavelength maximum (ꢃ 385 and 389 nm respectively). The high frequency shift in the C=C IR
stretching vibrations at 1662 and 1671 cm–1 should be noted and are characteristic of nonaromatic multiple
1
bonds. The most marked differences in the spectroscopic behavior are seen when comparing the H NMR
spectra (in DMSO-d6) of salts 2, 3 and compounds 4a,b. Most notable are the absence of a methylene group
signal in the azepine fragment in the spectra of compounds 4a,b and, at higher field, the presence of one-proton
methine singlets at 6.4 and 5.7 ppm.
The NOESY spectroscopic data for compound 4b permits exact assignment of the signals (Figure 1c)
1
and confirms the conclusions regarding the structure of the cyclization products. The H NMR spectra of
compounds 4a,b, recorded in CF3CO2D (4a) or CD3CO2D (4b) differ from the spectra in DMSO-d6 and this is
due to a solvent effect. Hence all of the protons signals are shifted to lower field with the exception of one. The
H-5 singlet is seen at 6.30 ppm for 4a in CF3CO2D and 4b in CD3CO2D while in DMSO-d6 it is observed at 7.33
ppm. It seems likely that this is the result of localization of the trifluoroacetate and acetate anions in the
complexes 4aꢂCF3CO2D and 4bꢂCD3CO2D, close to atom C(5).
The observed results of the cyclization can be explained in the following way. With an increase in the
acceptor properties of the substituent in the benzene rings of the ꢀ-bromodypnone and the substituent at the N(1)
atom of the diazole, the likelihood for formation of a quaternary salt of type 6 is increased (Scheme 2), which
can be obtained even in the presence of the starting diazole as a weak base. It is logical to assume that they cyc-
lize to derivatives of type 7 or 8. Evidently compounds with this positioning of multiple bonds in the azepine
fragment are thermodynamically unstable and are readily converted to derivatives of type 2 and 3 as indicated
by the result of converting salt 6 to the imidazo[1,2-a]azepine 3f. If the acceptor properties of the R substituent
in structure 7 or 8 are stronger (e.g. benzyl when compared to a methyl group) then in the presence of potassium
carbonate as a base there occurs the loss of HBr molecule to form imidazo[1,2-a]azepine derivatives of type 4,
which on the other hand can be formed by an alternative route from the salts of the structure 2, 3. However,
prolonged heating (3–6 h) of compounds 2a, 3c,e in ethanol or methanol in the presence of potassium carbonate
did not give a marked change in their structure. It appears that such a reaction occurs under more severe
1
conditions in the presence of KOH (according to the H NMR spectra of the mixture obtained) but this is
accompanied by the formation of a large amount of side products.
Scheme 2
Ar
O
_
Ar
Ar
Ar
Ar
Br
_
+
+
Br
B:
B:
N
N
N
Ar
Me
N
R
N
R
H+
N
R
4
2, 3
5
B:
Ar
O
B: – HBr
_
_
_
+
Ar
Ar
Ar
Ar
Br
N
Br
N
+
N
+
N
Br
B:
N
Ar
Me
or
N
R
R
R
6
7
8
748
ꢀ

TABLE 1. Physicochemical Properties of Synthesized Compounds
Found, %
Com-
pound
Empirical
formula
Yield,
%
Calculateded, %
mp, °C*
C
H
Br
N
2b*2
C25H19BrCl2N2
C25H19Br3N2
C27H25BrN2O2
C21H19BrN2
60.08
60.27
51.10
51.14
66.24
66.26
66.45
66.50
67.20
67.24
71.27
71.21
60.65
60.70
56.32
56.28
47.00
46.96
62.78
62.88
67.54
67.58
73.18
73.14
62.12
62.09
63.41
63.48
68.53
68.50
58.67
58.72
3.78
3.84
3.30
3.26
5.20
5.15
5.07
5.05
6.55
6.51
5.12
5.09
4.18
4.15
3.80
3.82
3.22
3.19
5.25
5.28
5.29
5.28
4.50
4.55
3.70
3.67
5.39
5.33
5.30
5.32
4.40
4.38
16.07
16.04
40.86
40.83
16.30
16.33
21.10
21.07
17.18
17.20
17.58
17.55
29.87
29.91
17.80
17.83
44.61
44.63
18.21
18.19
15.45
15.50
15.95
15.99
15.28
15.30
20.08
20.11
16.90
16.88
28.95
28.94
5.65
5.62
4.79
4.77
5.75
5.72
7.41
7.39
9.06
9.05
6.19
6.15
5.26
5.24
6.26
6.25
5.24
5.22
6.40
6.38
5.44
5.43
6.30
6.32
5.39
5.36
7.07
7.05
5.96
5.92
5.10
5.07
203–205
202–203
206–208
40
42
25
90
76
83
75
78
72
86
81
89
78
84
78
80
76
2c
2d
3a
291–292
(decomp.)
3b
C26H30BrN3
224–225
(decomp.)
3c
C27H23BrN2
194–195
3d
C27H22Br2N2
C21H17BrCl2N2
C21H17Br3N2
C23H23BrN2O2
C29H27BrN2O2
C27H20Cl2N2
C27H19BrCl2N2
C21H21BrN2O
C27H25BrN2O
C27H24Br2N2O
C21H19Br3N2O
294–295
(decomp.)
3e**
259–260
(decomp.)
3f
214–215
3g
284–285
(decomp.)
3h
280–281
(decomp.)
4a
> 300
(decomp.)
4b**
> 300
(decomp.)
5a
204–205
214–215
196–197
212–214
5c
5d
6
45.48
45.44
3.41
3.45
43.22
43.18
5.09
5.05
_______
* Solvents: MeCN (compounds 2b,c), 2-PrOH (compounds 2d, 3a–h,
5a,c,d, 6), AcOH (compounds 4a,b).
*2 Analytical data for Cl (Found/Calculated, %) for compounds:
2b = 14.22/14.23, 3e = 15.84/15.82, 4b = 13.54/13.58.
Hence the degree of conversion of compounds 3c,e to 4c,d by heating for 3 h amounts to about 50% but
further heating leads to the decomposition of the reaction products (as reported [19] previously for condensed
azepine derivatives). Hence, in our opinion, a more likely route for conversion of compounds 5f,g to 4a,b
includes the stage of formation of structural type 6 and 7 or 8.
It should be noted that, in the study [19] concerned with the properties of 10H-pyrido[1,2-a]azepinium
salts (structurally similar to the imidazo[1,2-a]azepinium salts 2 and 5) there was also observed the formation of
deprotonated forms at the azepine fragment of type 4 under the action of base. It was also noted that this reaction
is readily reversible in the presence of acid.
The susceptibility of the azepino[2,1-b]benzimidazole system to protonation at position 6 in the struc-
1
tural type 4 was observed by H NMR in CF3CO2D for trimethyl 5-methyl-6-phenylazepino[2,1-b]benzimid-
azole-8,9,10-tricarboxylate [20]. In our case, the protonated forms of compounds 4a,b proved to be unstable and
were not detected by 1H NMR taken in CF3CO2D or CD3CO2D.
749
ꢀ

750
ꢀ

751
ꢀ

TABLE 3. IR Spectra of Synthesized Compounds
Compound
ꢄ, cm–1
2b
2c
2d
3a
3b
3c
3d
3025, 1622 (C=N), 1575, 1480, 1407, 1091, 1010, 839, 820, 766
3020, 1622 (C=N), 1575, 1480, 1404, 1071, 1004, 836, 817, 766
3003, 2930, 2835, 1600, 1572, 1513, 1259 (ꢀꢅꢃ), 1180, 1024, 828, 750
3059, 1625 (ꢀ=N), 1583, 1443, 1245, 1225, 792, 775, 758, 699
3031, 2969, 2790, 1627 (C=N), 1586, 1443, 1261, 1211, 764, 747, 694
3092, 2964, 2835, 1602 (C=N), 1569, 1513, 1290, 1250, 1183, 1035, 825, 738, 710
3059, 3031, 2964, 1661, 1634, 1592, 1578, 1491, 1443, 1413, 1256, 1074, 1015, 792,
766, 697
3e
3f
3059, 1631 (C=N), 1586, 1491, 1094, 1007, 839, 825, 786, 512
3036, 2964, 2723, 2627, 1662, 1631, 1583, 1410, 1373, 1007, 831, 820, 705
3047, 3020, 1603 (C=N), 1580, 1513, 1290, 1245 (CꢅO), 1183 (C-O), 1021, 839, 811
3064, 3031, 1631 (C=N), 1586, 1497, 1443, 1256 (CꢅO), 764, 755, 719, 697
3180, 1661, 1446, 1424, 1360, 1315, 845, 669
3g
3h
4a
4b
5a
5c
5d
6
3185, 1671, 1477, 1454, 1378, 885, 847, 708, 665
3053, 1659 (ꢀ=ꢃ), 1620, 1220, 1161, 775, 702, 657
3031, 2975, 1653 (ꢀ=ꢃ), 1614, 1449, 1220, 1172, 755, 719, 697, 666
3126, 2980, 1656 (ꢀ=ꢃ), 1611, 1449, 1220, 1172, 1015, 752, 702, 691
3048, 1681 (ꢀ=ꢃ), 1583, 1485, 1396, 1214, 1071, 1010, 990, 822, 775
EXPERIMENTAL
IR spectra were recorded on a Perkin-Elmer Spectrum BX instrument for KBr tablets. UV spectra were
1
taken on a UV-vis Lambda 20 Spectrometer using methanol as solvent. H NMR spectra were recorded on a
1
Bruker AVANCE DRX 500 instrument (500 MHz). Experiments on 2D correlation H and 13C NMR spectra
were performed on a Varian Mercury 400 instrument (400 and 100 MHz respectively) using TMS as internal
standard. Monitoring of the purity of the compounds obtained was carried out by HPLC mass spectrometry on
an Agilent 1100 Series instrument with an Agilent LC/MSD SL detector (sample introduction in a CF3CO2H
matrix, EI ionization).
( Z)-4-Bromo-1,3-diphenyl-2-buten-1-one (1a) was prepared by method [21] and the (Z)-1,3-diaryl-
4-bromo-2-buten-1-ones 1b–d by method [18].
7,9-Diaryl-5-methyl-5,10-dihydroazepino[1,2-a]benzimidazol-11-ium Bromides 2a–c were obtained
by the method reported in [16].
Compound 2a. UV spectrum, ꢃmax, nm (log ꢂ): 244 (4.23), 270 (4.29), 326 (4.20), 332 (4.18).
Compound 2b. UV spectrum, ꢃmax, nm (log ꢂ): 242 (4.22), 274 (4.34), 326 (4.21), 332 (4.20).
7,9-bis(4-Methoxyphenyl)-5-methyl-5,10-dihydroazepino[1,2-a]benzimidazol-11-ium Bromide (2d).
A mixture of the ꢀ-bromodypnone (1.2 g, 3.32 mmol) and 1,2-dimethyl-1H-benzimidazole (0.49 g, 3.32 mmol)
was melted on an oil bath at 110ºC for 20 min. The melt was dissolved in morpholine (2.5 ml) and water (50 ml)
was added. The precipitate formed was filtered off, dried thoroughly, and methyl tert-butyl ether (10 ml) was
added. The precipitate was filtered off to give a 1:1 mixture of the product 2d and 2,4-bis(4-methoxy-
phenyl)furan which was separated by column chromatography on 40/60 silica gel using chloroform and ethyl
acetate as eluent (70:30).
1-R-3-[(Z)-2,4-Diaryl-4-oxo-2-butenyl]-2-methyl-1H-imidazol-3-ium Bromides 5a,c,d (General
Method). The 1-alkyl-2-methyl-1H-imidazole (3.32 mmol) was added to a solution of the ꢀ-bromodypnone (1 g,
752
ꢀ

3.32 mmol) in benzene (30 ml). The mixture was held for 1–2 days at room temperature. The precipitate formed
was filtered off, washed with acetone, and recrystallized from nitromethane.
3-[(1E)-2,4-Bis(4-bromophenyl)-4-oxo-1-butenyl]-1,2-dimethyl-1H-imidazol-3-ium Bromide (6)
was prepared by the method applied for the synthesis of 5a,c,d but using compound 1c as starting material.
1-R-6,8-Diaryl-1H,5H-imidazo[1,2-a]azepin-4-ium Bromides 3a,c,d,f. A mixture of salts 5a,c,d or 6
(1.15 mmol) and K2CO3 (0.32 g, 2.3 mmol) in ethanol (15 ml) was heated for 1 h. After cooling, the precipitate
was filtered off. The solvent was evaporated from the filtrate and the residue was treated with 2-propanol
(30 ml). The precipitate formed was filtered off and washed with a small amount of 2-propanol.
Compound 3a. UV spectrum, ꢃmax, nm (log ꢂ): 208 (4.28), 242 (4.09), 260 (4.24), 326 (4.03). 13C NMR
spectrum, (DMSO-d6), ꢆ, ppm: 149.3 (C-8); 142.3 (C-9a); 140.5 (C-6); 139.2 (C-1''); 138.1 (C-1'); 130.3 (C-4'');
129.7 (C-4'); 129.4 (C-3',5',3'',5''); 128.1 (C-2'',6''); 127.8 (C-7); 127.5 (C-2',6'); 126.1 (C-2); 121.4 (C-3); 110.1
(C-9); 48.1 (C-5); 36.0 (CH3).
Compound 3c. UV spectrum, ꢃmax, nm (log ꢂ): 208 (4.36), 242 (4.02), 270 (4.00), 342 (4.06).
1-R-6,8-Diaryl-1,5-dihydroimidazo[1,2-a]azepin-4-ium Bromides 3b,e,g,h. 1-Alkyl-2-methyl-1H-
imidazole (3.55 mmol) was added to a solution of the ꢀ-bromodypnone 1a,b,d (3.55 mmol) in benzene (30 ml).
The mixture was held for 1–2 days at room temperature. The solvent was evaporated, the residue dissolved in
ethanol (20 ml), and K2CO3 (0.7 g, 5.0 mmol) was added. The mixture was refluxed for 1 h, cooled, and the
precipitate was filtered off. The filtrate was evaporated, the residue was treated with 2-propanol or hexane
(50 ml), and the precipitate formed was filtered off and washed with a small amount of 2-propanol.
Compound 3e. UV spectrum, ꢃmax, nm (log ꢂ): 208 (4.27), 232 (4.10), 267 (4.28), 325 (4.10).
1-R-6,8-Bis(4-chlorophenyl)-1H-imidazo[1,2-a]azepines 4a,b were prepared from ꢀ-bromodypnone
1b and 1-benzyl- or 1-(4-bromophenyl)methyl-2-methyl-1H-imidazole using the method applied for the synthe-
sis of compounds 3b,e,g,h with methanol as solvent and the mixture was refluxed for 30–40 min. The inorganic
residue was filtered off from the hot solution. The filtrate was evaporated, the residue was treated with 2-propa-
nol (50 ml), and the precipitate was filtered off and washed with a small amount of 2-propanol.
Compound 4a. UV spectrum, ꢃmax, nm (log ꢂ): 205 (3.82), 238 (3.56), 262 (3.56), 289 (3.48), 385
(3.33). 1H NMR spectrum (CF3CO2D), ꢆ, ppm (J, Hz): 7.44 (3ꢁ, m, ꢁ-3'''–ꢁ-5'''); 7.36 (3ꢁ, m, ꢁ-3,3'',5''); 7.32
(1ꢁ, s, ꢁ-2); 7.28 (2ꢁ, d, 3J = 7.5, ꢁ-3',5'); 7.18 (2ꢁ, d, 3J = 8.0, ꢁ-2'',6''); 7.03 (2ꢁ, d, 3J = 7.5, ꢁ-2''',6'''); 6.94
(2ꢁ, m, ꢁ-2',6'); 6.40 (1ꢁ, s, ꢁ-9); 6.30 (1ꢁ, s, ꢁ-5); 5.98 (1ꢁ, s, ꢁ-7); 5.31 (2ꢁ, s, CH2).
Compound 4b. UV spectrum, ꢃmax, nm (log ꢂ): 202 (3.81), 221 (3.68), 266 (3.41), 307 (3.29), 389
1
(3.43). H NMR spectrum (CD3CO2D), ꢆ, ppm (J, Hz): 7.63 (1ꢁ, s, ꢁ-3), 7.61 (1ꢁ, s, ꢁ-2); 7.56 (2ꢁ, d,
3J = 8.0, ꢁ-3''',5'''); 7.41 (2ꢁ, d, 3J = 8.0, ꢁ-3'',5''); 7.35 (2ꢁ, d, 3J = 8.0, ꢁ-3',5'); 7.27 (2ꢁ, d, 3J = 8.0, ꢁ-2'',6'');
7.20 (2ꢁ, d, 3J = 8.0, ꢁ-2''',6'''); 6.98 (2ꢁ, d, 3J = 8.0, ꢁ-2',6'); 6.62 (1ꢁ, s, ꢁ-9); 6.30 (1ꢁ, s, ꢁ-5); 5.95 (1ꢁ, s,
ꢁ-7); 5.41 (2ꢁ, s, CH2).
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