1-R-2-[(1E,3E)-4-Aminobuta-1,3-dien-1-yl]-1H-benzimidazoles. Synthesis and some transformations

Article abstract of DOI:10.1007/s11172-010-0198-9

7-Nitropyridobenzimidazolium salts are cleaved with secondary amines to form 2-[(E,E)-4-aminobuta-1,3-dienyl]-1H-benzimidazoles. The latter react with dimethyl acetylene-dicarboxylate to yield 4a-[(E,Z,E)-6-amino-4,5- dimethoxycarbonylhexa-1,3,5-trien-1-y

Full text of DOI:10.1007/s11172-010-0198-9

Russian Chemical Bulletin, International Edition, Vol. 59, No. 5, pp. 1014—1022, May, 2010
1014
1ꢀRꢀ2ꢀ[(1E,3E)ꢀ4ꢀAminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzimidazoles.
Synthesis and some transformations
A. V. Varlamov,a A. I. Komarova,a A. N. Levov,a E. V. Savitkina,a A. P. Krapivko,a† V. N. Khrustalev,b
E. A. Sorokina,a L. N. Kulikova,a E. V. Nikitina,a V. P. Zaytsev,a and F. I. Zubkova
aPeoples’ Friendship University of Russia,
6 ul. MiklukhoꢀMaklaya, 117198 Moscow, Russian Federation.
Fax: +7 (495) 955 0779. Eꢀmail: fzubkov@sci.pfu.edu.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Eꢀmail: vkh@xray.ineos.ac.ru
7ꢀNitropyridobenzimidazolium salts are cleaved with secondary amines to form 2ꢀ[(E,E)ꢀ
4ꢀaminobutaꢀ1,3ꢀdienyl]ꢀ1Hꢀbenzimidazoles. The latter react with dimethyl acetyleneꢀ
dicarboxylate to yield 4aꢀ[(E,Z,E)ꢀ6ꢀaminoꢀ4,5ꢀdimethoxycarbonylhexaꢀ1,3,5ꢀtrienꢀ1ꢀyl]ꢀ
1,2,3,4ꢀtetra(methoxycarbonyl)ꢀ4a,5ꢀdihydropyrido[1,2ꢀa]benzimidazoles.
Key words: 4ꢀaminobutaꢀ1,3ꢀdiene, cleavage of pyridobenzimidazolium salts, 1Hꢀbenzꢀ
imidazole, pyrido[1,2ꢀa]benzimidazole.
Reactions of 2ꢀaryloxazolo[3,2ꢀa]pyridinium salts
with nucleophilic reagents are studied and described in
the literature in detail.1—3 It was found that these salts
upon the action of secondary amines undergo cleavage of
the pyridine ring to give (1E,3E)ꢀ1ꢀaminoꢀ4ꢀ(oxazolylꢀ
2)butaꢀ1,3ꢀdienes. 1ꢀMethylꢀ2ꢀpꢀnitrophenylimidazoꢀ
[3,2ꢀa]pyridinium perchlorate undergoes analogous transꢀ
formation to 1E,3Eꢀaminobutadienes in the reaction with
piperidine in boiling acetonitrile. Its 5ꢀmethylꢀsubstituted
analog under these conditions undergoes demethylation
to imidazo[3,2ꢀa]pyridine.4 Earlier,5 we have shown that
7ꢀnitropyrido[1,2ꢀa]benzimidazoles with substituted and
unsubstituted pyridine ring upon the action of dimethyl
acetylenedicarboxylate (DMAD) in excess amount
recyclize to 1,2,3,4ꢀtetra(methoxycarbonyl)ꢀ8ꢀnitroꢀ
pyrido[1,2ꢀa]benzimidazoles. There is no literature informꢀ
ation on the reactions of imidazopyridinium salts fused by
the imidazole ring with an electronꢀwithdrawing aromatic
fragment.
In the present work, we have studied reactions of
7ꢀnitropyrido[1,2ꢀa]benzimidazolium 1 and 3ꢀmethylꢀ
diphenylsilylꢀ7ꢀnitropyrido[1,2ꢀa]benzimidazolium salts
2 with secondary amines. Tertiary salts 3—7 were obtained
by the reaction of pyridobenzimidazole 1 (see Ref. 6) with
methyl iodide, benzyl chloride in the presence of KI,
dibromoethane, allyl bromide, and ethyl 4ꢀbromobutyrate
in acetonitrile or DMF, whereas salts 8 and 9, upon the
action of methyl iodide or phenacyl bromide on the silyl
Scheme 1
Comꢀ
pound
R
R´
X
1
2
3
4
5
6
7
8
9
H
—
—
Me
Bn
—
—
I
SiMePh2
H
H
H
H
H
I
CH2CH2Br
Br
Br
Br
I
Allyl
(CH2)3CO2Et
Me
SiMePh2
SiMePh2
CH2COPh
Br
substituted pyridobenzimidazole 2 (see Ref. 7) in boiling
toluene and ethyl acetate (Scheme 1).
The IR spectrum of salt 9 with phenacyl substituent
on the nitrogen atom, in addition to the band for CO at
1696 cm–1, exhibits a broad band for the bound hydroxyl
†
Deceased.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 992—999, May, 2010.
1066ꢀ5285/10/5905ꢀ1014 © 2010 Springer Science+Business Media, Inc.

1ꢀRꢀ2ꢀ[4ꢀAminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzimidazoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1015
Scheme 2
Comꢀ
pound
10
11
12
R´
R″
Comꢀ
pound
15
16
17
R´
R″
Comꢀ
pound
20
21
22
R´
R″
Me
Me
Me
Et
Me
Bn
Allyl
Allyl
Allyl
—(CH2)2NBn(CH2)2—
Allyl
Allyl
CH2CH2Br
CH2CH2Br
(CH2)3CO2Et
—(CH2)2NBn(CH2)2—
Furfuryl
Me
Me
Me —(CH2)2O(CH2)2—
Me
Me
Me
13
14
Furfuryl
—(CH2)5—
18
19
—(CH2)2O(CH2)2—
—(CH2)5—
23
24
—(CH2)2O(CH2)2—
—(CH2)2O(CH2)2—
R´ = Me (25), CH2COPh (26)
at 3430 cm–1, which can indicate the presence of an enol
form . Tertiary
of molecular ions [M]+• of compounds 10—24 consists in
the elimination of dialkylamine radical NR″2. The intenꢀ
sities of ions [M – NR″2]+ are 80—100%. These ions
salts 3—9 are cleaved with secondary amines, viz.,
dimethylꢀ, diethylꢀ, and difurfurylamines, morpholine,
piperidine, and Nꢀbenzylpiperazine, in boiling acetoꢀ
nitrile to the corresponding 1ꢀR´ꢀ2ꢀ[(E,E)ꢀ4ꢀaminobutaꢀ
1,3ꢀdienꢀ1ꢀyl]ꢀ6ꢀnitroꢀ1Hꢀbenzimidazoles 10—26, the
yields of which were 10—75% (Scheme 2).
Cleavage of 3ꢀmethyldiphenylsilylꢀ7ꢀnitropyridoꢀ
[1,2ꢀa]benzimidazolium iodide (8) with dimethylamine
in boiling acetonitrile is accompanied by elimination of
the siliconꢀcontaining substituent and leads to diene 10
(R´ = R″ = Me). The reaction of dimethylamine with
salts 8 and 9 at room temperature allows one to obtain the
target 2´ꢀmethyldiphenylsilylꢀsubstituted butadienes 25
and 26. Compounds 10—26 are red crystals of various
intensities.
further eliminate radicals NO2 and R´• forming fragꢀ
•
ment ions [M – NR″2 – NO2]+ and [M – NR″2 – R´]+.
The latter cation apparently has the structure of 8ꢀnitroꢀ
pyrido[1,2ꢀa]benzimidazole with m/z 213 (Table 1).
The spatial structure of compound 17 was studied by
Xꢀray diffraction (Fig. 1).
The Xꢀray diffraction study confirms unambiguous
E,Eꢀconfiguration of the diene fragment and reveals
virtually planar structure of molecule 17 (except carbon
atoms C(9) and C(10) of the allyl substituent on the nitroꢀ
gen atom N(1)), the deviation of atoms from the meanꢀ
square plane of the molecule, excluding carbon atoms
C(5)
It is interesting that other nucleophiles used in this
work (sodium cyanide, azide, and phenylacetylide) do
not cleave salts 3—9.
O(2)
N(6)
O(1)
C(4)
C(16)
N(14)
N(3)
C(6)
C(7)
C(3A)
C(14)
C(12)
C(2)
The E,Eꢀconfiguration of the diene fragment in comꢀ
pounds 10—24 is inferred from the spinꢀspin coupling conꢀ
stant values JH(1´),H(2´) = 14.3—14.7, JH(2´),H(3´) = 11.3—12.1,
and JH(3´),H(4´) = 12.5—12.8 Hz in their 1H NMR spectra.
These data are in good agreement with those described
for 1ꢀaminoꢀ4ꢀ(oxazolꢀ2ꢀyl)dienes.8,9 The mass spectra
of butadienylamines synthesized exhibit peaks of molecuꢀ
lar ions of low intensities corresponding to their moleꢀ
cular formulas. A principal direction for the fragmentation
C(7A)
C(8)
C(15)
C(13)
N(1)
C(11)
C(9)
C(10)
Fig. 1. Molecular structure of compound 17 in representation of
atoms by 40% probability ellipsoids of anisotropic displacments.

1016
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
Varlamov et al.
Table 1. The yields, physicoꢀchemical and spectral characteristics of 7ꢀnitropyrido[1,2ꢀa]benzimidazolium salts 3—9 and 1ꢀR´ꢀ2ꢀ
[(E,E)ꢀ4ꢀaminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzimidazoles 10—26
Comꢀ Yield
pound (%)
M.p./°С
(AcOEt)
Found
Calculated
Molecular
formula
MS, m/z (Irel (%))
(%)
[M]+ [M – NR″ ]+ [M – NR″ – [M – NR″ –
2
2
2
NO2]+
–NR´2]+
С
Н
N
–
3
66
59
62
83
60
75
75
79
60
57
5
232—234
218—220
224—225
234—236
209—211
233—234
230—231
212—214
173—175
214—216
110—112
202—204
212—214
197—198
129—131
179—181
132—133
107—109
140—142
40.00 2.75
40.58 2.84
50.05 3.10
50.13 3.27
39.10 2.56
38.93 2.76
50.00 3.67
50.32 3.62
49.76 4.37
50.01 4.44
54.20 4.40
54.45 4.02
63.20 4.40
63.16 4.31
61.52 5.63
61.75 5.92
63.52 6.33
63.98 6.71
61.12 5.33
61.13 5.77
64.89 4.35
65.34 4.98
65.12 6.35
65.37 6.45
68.45 6.02
68.47 6.25
68.45 5.63
68.95 5.75
64.35 6.01
64.41 6.08
63.35 5.41
63.52 5.92
67.34 6.21
67.44 6.55
69.24 6.98
69.91 6.34
66.03 5.13
66.97 5.15
11.50 C12H10IN3O2
11.83
9.51 C18H14IN3O2
9.74
10.60 C13H11Br2N3O2
10.48
12.51 C14H12BrN3O2
12.57
10.11 C17H18BrN3O4
10.29
7.55 C25H22IN3O2Si
7.62
7.00 C32H26BrN3O3Si
6.90
20.11 C14H16N4O2
20.58
18.52 C16H20N4O2
18.65
17.52 C16H18N4O3
17.82
13.61 C22H20N4O4
13.85
17.63 C17H20N4O2
17.94
17.12 C23H25N5O2
17.36
15.69 C20H20N4O2
16.08
18.69 C16H18N4O2
18.78
16.09 C18H20N4O3
16.46
16.09 C19H22N4O2
16.56
16.00 C25H27N5O2
16.31
12.50 C24H22N4O4
13.02
15.12 C15H17BrN4O2
15.38
13.12 C17H19BrN4O3
13.76
14.20 C21H26N4O5
13.52
12.02 C27H28N4O2Si
11.96
9.72 C34H32N4O3Si
9.78
—
—
—
—
—
—
—
—
—
—
—
4
—
—
5
—
—
—
6
—
—
—
7
—
—
—
8
—
—
—
9
—
—
—
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
272 (10)
300 (90)
314 (5)
404 (1)
312 (4)
403 (1)
248 (15)
298 (15)
340 (3)
338 (8)
429 (1)
430 (2)
364 (4)*
406 (5)*
414 (30)
468
228 (99)
228 (100)
228 (100)
228 (40)
228 (100)
228 (20)
304 (20)
254 (100)
254 (94)
254 (98)
254 (100)
254 (89)
320 (87)
320 (98)
328 (99)
—
182 (67)
182 (70)
182 (52)
182 (5)
182 (51)
182 (38)
258 (20)
208 (24)
208 (24)
208 (26)
208 (21)
208 (0)
274 (26)
274 (28)
252 (30)
—
213 (25)
213 (2)
213 (15)
213 (48)
—
47
60
75
51
60
65
10
66
213 (3)
213 (5)
213 (15)
213 (8)
213 (7)
213 (2)
213 (22)
213 (9)
213 (89)
213 (73)
—
10 183 (decomp.) 48.95 4.23
49.45 4.69
55
172—173
50.51 4.23
50.25 4.70
60.90 6.23
60.86 6.30
57
151—153
59 140 (decomp.) 69.30 6.00
69.20 6.02
53 152 (decomp.) 71.20 5.69
71.30 5.63
572
—
—
—
* For 79Br.

1ꢀRꢀ2ꢀ[4ꢀAminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzimidazoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1017
Scheme 3
HNO2
Scheme 4
C(9) and C(10), does not exceed 0.06 Å. The planar
structure of the molecule is determined by the elongated
system of conjugate bonds. The Sꢀcisꢀconformation of
the fragment N(3)=C(2)—C(11)=C(12), as well as the
torsional angle N(1)—C(8)—C(9)—C(10) (131.5(2)°)
value are determined by steric effects of substituents. Based
on this, the general structure of compounds 10—26 can
be represented as a planar conjugated system with partial
redistribution of the charge A(δ–)ꢀπꢀD(δ+) (A is an accepꢀ
tor (NO2), D is a donor (NMe2)), which is the one to
determine their bright color.
6ꢀNitrobenzimidazole 12 was reduced to amino deꢀ
rivative 27 with hydrazine in the presence of Raney Ni
(Scheme 3).
Morpholinoꢀsubstituted butadiene 12 upon the action
of nitrous acid is transformed to aldehyde 28 in moderate
yield. The structure of the latter is in good agreement with
the IR and 1H NMR spectroscopic and mass spectroꢀ
metric data. The mass spectrum of compound 28 exhibits
peak of the molecular ion maximum in intensity with
m/z 245 (100%) corresponding to its molecular formula.
The IR spectrum contains a band of stretching vibrations of
the carbonyl group at 1680 cm–1. The signal for the aldeꢀ
hyde proton is found at δ 9.80 in the 1H NMR spectrum.
Benzimidazoles 10—26 contain two nucleophilic cenꢀ
ters for the reactions with activated alkynes: the pyridineꢀ
type nitrogen atom of the imidazole ring and the enamine
fragment. We studied reactions of azadienes 10 and 16
with DMAD in excess amount in dichloromethane. It
turned out that both nucleophilic fragments are involved
into the reaction to form 5ꢀRꢀ1,2,3,4ꢀtetra(methoxyꢀ
carbonyl)ꢀ4aꢀ[(1E,3Z,5E)ꢀ4,5ꢀdi(methoxycarbonyl)ꢀ
6ꢀdimethylaminohexaꢀ1,3,5ꢀtrienꢀ1ꢀyl]ꢀ7ꢀnitroꢀ4a,5ꢀ
dihydropyrido[1,2ꢀa]benzimidazoles 29 and 30 in low
yield (Scheme 4). No other individual products were isoꢀ
lated from the reaction mixture.
i. DMAD, CH2Cl2
R´ = Me (29, 17%), Bn (30, 18%)
General outline of the process is given in Scheme 5
using the transformation of diene 10 to polycycle 29 as an
example. Successive nucleophilic addition of two DMAD
molecules to the pyridine nitrogen atom of the imidazole
ring and then to dimethyl maleate fragment formed leads
to the tetra(methoxycarbonyl)ꢀsubstituted dihydropyridine
ring closure to yield intermediate A.10 The aminodiene
fragment is transformed to the aminotriene one, apparꢀ
ently, through the intermediate step of [2+2] cycloꢀ
addition. Formation of [2+2] cycloaddition products
of alkynes with 1ꢀaminobutaꢀ1,3ꢀdienes is reported in
works.11,12

1018
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
Varlamov et al.
Scheme 5
i. DMAD
The structure of dihydrobenzimidazoles 29 and 30
could not be determined based only on the NMR data.
Their 1H NMR spectra exhibit six signals for the methoxyꢀ
carbonyl groups in the region δ 3.28—4.07, a singlet signal
at δ ~7.49 for the terminal proton of the hexatrienyl fragꢀ
ment, and singlets for the protons of the dimethylamino
group at δ 2.87 or δ 2.86, respectively.
The structure of compound 30 (R´ = Bn) was unamꢀ
biguously determined by Xꢀray diffraction (Fig. 2).
The molecule 30 consists of three substituted fused
rings, viz., benzene, dihydroimidazole, and dihydroꢀ
pyridine, and has an asymmetric carbon atom C(4a). The
presence of bulky substituents on the carbon atom C(4a)
lead to distortion of the planar structure of the nitroꢀ
benzimidazole fragment: the atom C(4a) deviates by
0.27(2) Å from the meanꢀsquare plane drawn through the
rest atoms of this fragment. The dihydropyridine ring
adopts the slightly distorted sofa conformation with deꢀ
viation of the atom C(4a) from the meanꢀsquare plane
drawn through the rest atoms of this fragment by 0.58(2) Å.
O(12)
C(29)
C(28)
C(23)
C(25)
N(23)
O(11)
C(22)
C(21)
N(10)
O(1)
C(11)
C(9A)
C(8)
N(7)
C(18)
C(20)
O(3)
C(10)
C(1)
O(14)
C(26)
O(9)
C(24)
C(19)
O(2)
O(10)
C(9)
C(7)
C(6)
C(12)
C(2)
C(3)
C(27)
C(13)
C(5A)
C(31)
C(13)
O(4)
O(7)
N(5)
C(4A)
C(4)
C(30)
C(14)
C(36)
C(32)
O(5)
C(16)
O(6)
C(15)
C(35)
C(33)
O(8)
C(17)
C(34)
Fig. 2. Molecular structure of compound 30 in representation
of atoms by 40% probability ellipsoids anisotropic displacments
(H atoms are not shown).

1ꢀRꢀ2ꢀ[4ꢀAminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzimidazoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1019
Parameters of unit cells and intensities of 3973 (17) and
7474 (30) reflections were measured on a Siemens P3/PC
automatic fourꢀcircle diffractometer (MoꢀKα irradiation, a
In addition to this, steric effects in the molecule result in
the pyramidal configuration of the nitrogen atom N(5)
(the sum of bond angles at the atom N(5) is 348.2°), the
rest of the nitrogen atoms have planar configuration. Due
to the presence of adjacent methoxycarbonyl groups, the
triene substituent at position 4a is nonplanar with the
trans,gaucheꢀarrangement of the double bonds (the torꢀ
sional angle C(20)—C(21)—C(22)—C(23) is –42.8(8)°),
the C=C bonds have E,Z,Eꢀconfiguration, respectively.
Due to the steric reasons, only one of four methoxyꢀ
carbonyl groups on the carbon atom C(2) is placed in the
plane of the dihydropyridine ring (the torsional angle
C(1)—C(2)—C(12)—O(3) is –0.1(7)°). The rest of the
MeO2C substituents are significantly turned with respect to
this plane (the torsional angles C(2)—C(1)—C(10)—O(1),
C(2)—C(3)—C(14)—O(5) and C(3)—C(4)—C(16)—O(7)
are 109.1(5), –120.3(5) and –129.3(5)°, respectively). The
angle between the planes of nitrobenzimidazole and
phenyl fragments is 74.9(2)°.
In conclusion, we found that 7ꢀnitropyrido[1,2ꢀa]ꢀ
benzimidazolium salts upon the action of secondary
amines undergo cleavage of the pyridine fragment to be
transformed to (E,E)ꢀ4ꢀaminoꢀ1ꢀ(6ꢀnitrobenzimidazolꢀ
2ꢀyl)butaꢀ1,3ꢀdienes. The latter by the reaction with
excess of DMAD are transformed to hexaꢀ1,3,5ꢀtrienylꢀ
substituted pyrido[1,2ꢀa]benzimidazoles through the diꢀ
polar 1,3ꢀ and [2+2] cycloadditions.
graphite monochromator, θ/2θꢀscanning, θ
= 28° (17) and
max
25° (30)). Structures were solved by the direct method and refined
by the leastꢀsquares fullꢀmatrix method in anisotropic approxiꢀ
mation for nonhydrogen atoms. Hydrogen atoms, whose posiꢀ
tions were calculated geometrically, were included into the
refinement in isotropic approximation with the fixed positional
(“riding” model) and thermal parameters. The final divergence
factors R1 = 0.0543 for 2344 independent reflections with
I > 2σ(I) and wR2 = 0.1585 for all the 3724 independent
reflections (17) and R1 = 0.0827 for 3095 independent reflections
with I > 2σ(I) and wR2 = 0.1934 for all the 6980 independent
reflections (30). All the calculations were performed using the
SHELXTL program package.13 Tables of atom coordinates,
bond distances, bond and torsional angles, and parameters of
anisotropic displacements for compounds 17 and 30 were
deposited with the Cambridge Structural Database (CCDC,
12 Union Road, Cambridge CB2 1EZ, UK. Fax: +44 1223 336033;
eꢀmail: deposit@ccdc.cam.ac.uk or www.ccdc.cam.ac.uk).
5ꢀRꢀ7ꢀNitropyrido[2,1ꢀa]benzimidazolium halides (3—9)
(general procedure). Pyridobenzimidazole 1 (1 g, 4.7 mmol) was
refluxed with methyl iodide, benzyl chloride (in the presence of
equimolar amount of anhydrous KI), dibromoethane, allyl
bromide, ethyl 4ꢀbromobutyrate (10—20 mmol) in acetonitrile
(50 mL) or heated in DMF (30 mL) at 100 °C; silylꢀsubstituted
pyridobenzimidazole 2 (1 g, 2.44 mmol) was refluxed with
equimolar amount of methyl iodide or phenacyl bromide in
toluene and ethyl acetate, respectively. The reaction course was
monitored by TLC (~6—7 h is required for the reaction to reach
completion). Then the reaction mixture was cooled, a precipitate
formed was filtered off and recrystallized from ethanol. When
DMF was used as the solvent, water (20 mL) was added to the
reaction mixture, a precipitate was filtered off, dried in air, and
recrystallized from ethyl acetate. Yellow crystals of the following
compounds were obtained: 5ꢀmethylꢀ (3), 5ꢀbenzylꢀ7ꢀnitroꢀ
pyrido[1,2ꢀa]benzimidazolium (4) iodides, 5ꢀbromoethylꢀ (5),
5ꢀallylꢀ (6), and 5ꢀ(3ꢀethoxycarbonylpropyl)ꢀ7ꢀnitropyridoꢀ
[1,2ꢀa]benzimidazolium (7) bromides, 5ꢀmethylꢀ3ꢀmethylꢀ
diphenylsilylꢀ7ꢀnitropyrido[1,2ꢀa]benzimidazolium iodide (8),
3ꢀmethyldiphenylsilylꢀ5ꢀphenacylpyrido[1,2ꢀa]benzimidazolium
bromide (9). The yields, elemental analysis data, and physicoꢀ
chemical constants for quaternary salts 3—9 are given in Table 1.
1ꢀRꢀ2ꢀ[(1E,3E)ꢀ4ꢀAminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzꢀ
imidazoles (10—24) (general procedure). A mixture of salts 3—8
(1.4 mmol) and the corresponding secondary amine (4.2 mmol)
was refluxed in acetonitrile (20 mL) for 0.5—24 h (TLC
monitoring). The mixture was cooled, acetonitrile was evaporated
at reduced pressure. Water (40 mL) was added to the residue and
organic products were extracted with chloroform (3×50 mL).
The extract was dried with magnesium sulfate. Chloroform was
evaporated and the residue was subjected to chromatography
either on SiO2 (eluent: AcOEt—hexane, 1 : 1), or on Al2O3
(eluent: AcOEt—hexane, 1 : 3—1 : 1). Aminodienes 22—24 were
eluted with ethyl acetate. The dienes were recrystallized from
AcOEt—hexane solvent mixture. The following products were
obtained: 2ꢀ[(1E,3E)ꢀ4ꢀN,Nꢀdimethylaminobutaꢀ1,3ꢀdienꢀ
1ꢀyl]ꢀ1ꢀmethylꢀ (10), 2ꢀ[(1E,3E)ꢀ4ꢀN,Nꢀdiethylaminobutaꢀ
1,3ꢀdienꢀ1ꢀyl]ꢀ1ꢀmethylꢀ (11), 1ꢀmethylꢀ2ꢀ[(1E,3E)ꢀ4ꢀmorꢀ
pholinoꢀ (12), 2ꢀ[(1E,3E)ꢀ4ꢀN,Nꢀdifurfurylaminobutaꢀ1,3ꢀdienꢀ
Experimental
Reagents from Acros Organics were used as purchased.
IR spectra of compounds 9 and 28 were recorded on a Infralum
1
FTꢀ801 Fourierꢀspectrometer in KBr pellets. H NMR spectra
(δ, J/Hz) were recorded on a Bruker WHꢀ400 spectrometer
(400.13 MHz for 1H and 100.6 MHz for 13C) in CDCl3 at 27 °C.
Residual signals of the solvent were used as a reference: δ 7.26
(in the1H NMR spectra) and δ 77.4 (in the 13C NMR spectra).
Mass spectra (EI, 70 eV) were recorded on a HР MS 5988 mass
spectrometer or Finnigan MATꢀ95ꢀXL GLCꢀMS spectrometer
with direct injection of the sample in the source of ions. Silufol
UVꢀ254 plates were used for thinꢀlayer chromatography (visualiꢀ
zation with iodine vapors), neutral activated Al2O3 (Brockmann II)
or Merck silica gel (230Ѕ400 mesh) were used for column
chromatography.
Melting points, yields, parameters of mass spectra, and
elemental analysis data for all the compounds synthesized are
given in Table 1.
Xꢀray diffraction study. Compound 17. Dark red crystals
(C16H18N4O2, M = 298.34), triclinic, space group P–1, at
T = 293 K a = 8.4565(17) Å, b = 9.3177(19) Å, c = 11.531(2) Å,
3
α = 68.83(3)°, β = 85.42(3)°, γ = 65.58(3)°, V = 769.0(3) Å ,
Z = 2, dcalc = 1.289 g cm–3, F(000) = 316, μ = 0.088 mm–1
.
Compound 30. Orange crystals (C38H38N4O14, M = 774.72),
triclinic, space group P1–; at T = 293 K a = 8.9655(18) Å,
b = 13.950(3) Å, c = 16.451(3) Å, α = 83.41(3)°, β = 79.87(3)°,
3
γ = 84.06(3)°, V = 2004.7(7) Å , Z = 2, dcalc = 1.283 g cm–3
,
F(000) = 812, μ = 0.099 mm–1
.

1020
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
Varlamov et al.
1
Table 2. H NMR spectra (CDCl3, 400 MHz) of 1ꢀR´ꢀ2ꢀ[(E,E)ꢀ4ꢀaminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzimidazoles 10—27
Comꢀ
pound
δ (J/Hz)
Н(4)
(d)
Н(5) Н(7)
(m)
NR´
Н(1´)
(d)
Н(2´)
(dd)
Н(3´)
(dd)
Н(4´)
(d)
NR″
2
10
11
12
13
14
15
16
17
7.54
(J = 9.2)
8.00—8.19 3.71 (s, 2 Ме)
8.08—8.13 3.72 (s, 2 Ме)
8.12—8.16 3.75 (s, 2 Ме)
8.10—8.15 3.73 (s, 2 Ме)
8.10—8.15 3.73 (s, 2 Ме)
8.10—8.16 3.73 (s, 2 Ме)
5.98
7.71
5.27
6.71
2.90 (s, Me)
(J = 14.3) (J = 14.3,
J = 11.6)
(J = 12.5, (J = 12.5)
J = 11.6)
7.53
(J = 9.5)
5.95
7.71
5.33
6.72
1.18 (t, J = 7.2);
(J = 14.4) (J = 14.4,
J = 11.4)
(J = 12.6, (J = 12.6) 3.21 (q, J = 7.2)
J = 11.4)
7.56
(J = 8.5)
5.98
7.72
5.47
6.60
3.18 (СН2О);
(J = 14.3) (J = 14.3,
J = 11.5)
(J = 12.5, (J = 12.5) 3.65 (СН2N)
J = 11.5)
7.58
(J = 8.5)
5.97
7.71
5.47
6.65
4.35 (s, NCH2); 6.22 (d,
(J = 14.4) (J = 14.4,
J = 11.6)
(J = 12.6, (J = 12.6) J = 2.7); 6.38 (dd, J = 2.7,
J = 11.6)
J = 1.7); 7.35 (d, J = 1.7)
1.63 (s, 6 Н);
7.56
(J = 9.5)
5.96
7.74
5.42
6.68
(J = 14.4) (J = 14.4,
J = 11.6)
(J = 12.8, (J = 12.8) 3.19 (m, 4 Н)
J = 11.6)
7.56
(J = 9.4)
6.01
7.69
5.40
6.62
3.54 (s, CH2Ph); 3.22,
(J = 14.2) (J = 14.2,
J = 11.6)
(J = 12.8, (J = 12.8) 2.49 (both t, J = 4.7);
J = 11.6)
7.28—7.32 (m, Ph)
2.89 (s, Me)
7.59
(J = 8.9)
8.09—8.15 4.72 (br.s, CH2Ph);
7.10—7.30 (m, Ph)
5.97
7.76
5.23
6.72
(J = 14.3) (J = 14.3,
J = 11.3)
(J = 12.5, (J = 12.5)
J = 11.3)
7.57
8.09—8.20 4.74 (m, CH2);
5.93
7.74
5.25
6.71
2.90 (s, Me)
(J = 8.5)
5.03 (m, CH2=СН); (J = 14.3) (J = 14.3,
(J = 12.5, (J = 12.5)
J = 11.3)
5.93 (m, CH2=СН);
5.94 (m, CH2=СН)
J = 11.3)
18
19
20
21
7.58
(J = 8.8)
8.10—8.15 4.72 (m, CH2);
5.98
7.89
5.42
6.59
3.18 (t, (СН2)2О,
4.99 (d, CH2=СН,
J = 17.1); 5.24 (d,
CH2=СН, J = 10.3);
5.94 (m, CH2=СН)
(J = 14.6) (J = 14.6,
J = 11.2)
(J = 12.9, (J = 12.9) J = 4.9); 3.65
J = 11.2)
(t, (СН2)2N, J = 4.9)
7.55
(J = 8.8)
8.00—8.10 4.75 (m, CH2);
5.85
7.65
5.25
6.58
1.60 (br.s, 6 Н);
4.99 (d, CH2=СН,
J = 17.0); 5.20 (d,
CH2=СН, J = 10.5);
(J = 14.6) (J = 14.6,
J = 11.3)
(J = 12.5, (J = 12.5) 3.19 (br.s, 4 Н,
J = 11.3)
NCH2)
5.90 (m, CH2=СН)
7.55
(J = 8.4)
8.03—8.10 4.70 (m, CH2); 4.97
5.85
7.63
5.30
6.56
3.51 (s, CH2Ph);
(d, CH2=СН, J = 16.3); (J = 14.6) (J = 14.6,
5.22 (d, CH2=СН,
J = 10.4);
(J = 12.6, (J = 12.6) 3.15, 2.42 (both m,
J = 11.6)
J = 11.6)
NCH2);
7.26 (m, Ph)
5.86 (m, CH2=СН)
7.58
(J = 8.5)
8.10—8.15 4.72 (m, CH2);
5.05 (d, CH2=СН,
6.01
7.76
5.57
6.82
4.32 (s, NCH2);
(J = 14.4) (J = 14.4,
J = 11.7)
(J = 12.9, (J = 12.9) 6.21 (d, J = 2.7);
J = 11.7)
J = 17.1); 5.25 (d,
CH2=СН, J = 10.5);
5.93 (m, CH2=СН)
6.38 (dd, J = 2.7,
J = 1.7); 7.38
(d, J = 1.7)
22
23
24
7.57
(J = 8.9)
8.15—8.20 3.71 (m, 2 Н, CH2N);
6.01
7.71
5.27
6.73
2.90 (s, Me)
4.32 (m, 2 Н, CH2Br) (J = 14.3) (J = 14.3,
J = 11.6)
8.13—8.15 3.75 (m, 2 Н, CH2N)
4.52 (m, 2 Н, CH2Br) (J = 14.3) (J = 14.3,
J = 11.6)
8.12—8.14 1.16—1.28 (m, 2 Н);
1.34 (t, Ме);
(J = 12.1, (J = 12.1)
J = 11.6)
7.56
(J = 8.5)
5.91
7.71
5.25
6.71
3.20 (СН2О)
(J = 12.5, (J = 12.5) 3.63 (СН2N)
J = 11.6)
7.57
(J = 8.8)
6.07
7.71
5.44
6.59
3.18 (СН2О)
(J = 14.3) (J = 14.3,
J = 11.6)
(J = 12.1, (J = 12.1) 3.72 (СН2N)
J = 11.6)
4.12—4.36 (m, 6 Н)
(to be continued)

1ꢀRꢀ2ꢀ[4ꢀAminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1Hꢀbenzimidazoles
Table 2. (continued)
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1021
Comꢀ
pound
δ (J/Hz)
Н(4)
(d)
Н(5) Н(7)
(m)
NR´
Н(1´)
(d)
Н(2´)
(dd)
Н(3´)
(dd)
Н(4´)
(d)
NR″
2
25
26
27
7.66
(J = 9.5)
8.11—8.12 3.45 (s, Ме)
6.68
7.46
0.88
5.76
(c)
2.77 (s, Me)
2.77 (s, Me)
(J = 13.7)(d, J = 13.7) (s, SiMe);
7.30—7.62
(m, Ph)
7.72
(J = 8.9)
7.99—8.14 5.20 (s, CH2CO)
7.10—7.84 (m, Ph)
6.65
7.42
0.81
5.76
(c)
(J = 13.7)(d, J = 13.7) (s, SiMe);
7.10—7.84
(m, Ph)
7.41
7.42—7.50 3.60 (s, Ме)
6.10
6.60
5.41
6.43
3.18 (m, (СН2)2О);
(J = 8.1)
(J = 13.5) (J = 13.5,
J = 11.6)
(J = 12.0, (J = 12.0) 3.72 (m, (СН2)2N)
J = 11.6)
1ꢀyl]ꢀ1ꢀmethylꢀ (13), 1ꢀmethylꢀ2ꢀ[(1E,3E)ꢀ4ꢀpiperidinoꢀ (14),
2ꢀ[(1E,3E)ꢀ4ꢀNꢀbenzylpiperazinobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1ꢀmethylꢀ
6ꢀnitroꢀ1Hꢀbenzimidazoles (15); 1ꢀbenzylꢀ2ꢀ[(1E,3E)ꢀ4ꢀ(N,Nꢀ
dimethylamino)butaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ6ꢀnitroꢀ1Hꢀbenzimidazole
(16); 1ꢀallylꢀ2ꢀ[(1E,3E)ꢀ4ꢀN,Nꢀdimethylaminoꢀ (17), 1ꢀallylꢀ
2ꢀ[(1E,3E)ꢀ4ꢀmorpholinoꢀ (18), 1ꢀallylꢀ2ꢀ[(1E,3E)ꢀ4ꢀpipeꢀ
ridinoꢀ (19), 1ꢀallylꢀ2ꢀ[(1E,3E)ꢀ4ꢀNꢀbenzylpiperazinoꢀ (20),
1ꢀallylꢀ2ꢀ[(1E,3E)ꢀ4ꢀN,Nꢀdifurfurylaminobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ
6ꢀnitroꢀ1Hꢀbenzimidazoles (21); 1ꢀbromoethylꢀ2ꢀ[(1E,3E)ꢀ
4ꢀN,Nꢀdimethylaminoꢀ (22), 1ꢀbromoethylꢀ2ꢀ[(1E,3E)ꢀ
4ꢀmorpholinoꢀ1ꢀbromoethylꢀ2ꢀ[(1E,3E)ꢀ4ꢀbutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ
6ꢀnitroꢀ1Hꢀbenzimidazoles (23); 1ꢀ(3ꢀethoxycarbonylpropylꢀ1)ꢀ
2ꢀ[(1E,3E)ꢀ4ꢀmorpholinobutaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ6ꢀnitroꢀ1Hꢀbenzꢀ
imidazole (24). The yields, elemental analysis results, and
physicoꢀchemical characteristics of aminodienes 10—24 are
(3E)ꢀ4ꢀ(1ꢀMethylꢀ6ꢀnitroꢀ1Hꢀbenzimidazolꢀ2ꢀyl)butꢀ3ꢀenal
(28). Sodium nitrite (0.25 g, 3.62 mmol) was added in five
portions over 1.5 h to a stirred solution of diene 12 (0.5 g,
1.59 mmol) in ~15% aq. hydrochloric acid (6 mL) at 20 °C.
After the addition was over, the mixture was stirred at room
temperature for another 1 h. Then the reaction mixture was
poured into water (10 mL) and neutralized with aq. ammonia
to pH ~7. A precipitate formed was filtered off and recrystallized
from AcOEt to obtain aldehyde 28 (0.15 g, 35%), pale yellow
crystals with m.p. 214—216 °C. IR, ν/cm–1: 1680 (C=O).
Found (%): C, 58.65; H, 4.10; N, 17.03. C12H11N3O3. Calculꢀ
ated (%): C, 58.77; H, 4.52; N, 17.13. 1H NMR (CDCl3), δ:
3.73 (s, 3 H, NMe); 3.95 (m, 2 H, CH2CHO); 6.71 (d, 1 H,
H(4), J = 14.5 Hz); 7.10 (m, 1 H, H(3)); 7.60 (d, 1 H, H(4´),
J = 8.7 Hz); 8.10—8.15 (m, 2 H, H(5´), H(7´)); 9.80 (s, 1 H,
CHO). MS, m/z: 245 [M]+.
1
given in Table 1, the H NMR spectral data, in Table 2.
2ꢀ[(1E,3E)ꢀ4ꢀ(N,NꢀDimethylamino)ꢀ2ꢀmethyldiphenylsilylꢀ
butaꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ1ꢀmethylꢀ6ꢀnitroꢀ1Hꢀbenzimidazole (25) and
2ꢀ[(1E,3E)ꢀ4ꢀ(N,Nꢀdimethylamino)ꢀ2ꢀmethyldiphenylsilylbutaꢀ
1,3ꢀdienꢀ1ꢀyl]ꢀ6ꢀnitroꢀ1ꢀphenacylꢀ1Hꢀbenzimidazole (26).
A 30% aq. dimethylamine (0.5 mL) was added to a solution of
salts 8 or 9 (0.36 mmol) in acetonitrile (10 mL) at 20 °C. After
1 h, a precipitate was filtered off, washed with water, dried in
air, and recrystallized from AcOEt—hexane solvent mixture
to obtain silylꢀsubstituted azadienes 25 and 26. The yields,
elemental analysis results, and physicoꢀchemical characteristics
of organosilicon derivatives 25 and 26 are given in Table 1,
1H NMR spectral data, in Table 2.
4aꢀ[(1E,3Z,5E)ꢀ4,5ꢀDi(methoxycarbonyl)ꢀ6ꢀdimethylaminoꢀ
hexaꢀ1,3,5ꢀtrienꢀ1ꢀyl]ꢀ1,2,3,4ꢀtetra(methoxycarbonyl)ꢀ
5ꢀmethylꢀ7ꢀnitroꢀ4a,5ꢀdihydropyrido[1,2ꢀa]benzimidazole (29).
A mixture of 1,3ꢀdiene (10) (0.6 g, 2.2 mmol) and DMAD (3 g,
21.1 mmol) was refluxed in dichloromethane (20 mL) for 3 h
(TLC monitoring). After evaporation of the solvent, the residue
was subjected to chromatography on a column with SiO2 (eluent:
AcOEt—hexane, 1 : 1) to obtain compound 29 (0.25 g). Recrysꢀ
tallization from ethyl acetate gave brown crystals, the yield was
17%, m.p. 116—118 °C. Found (%): C, 55.38; H, 4.67; N, 8.00.
C32H34N4O14. Calculated (%): C, 55.01; H, 4.91; N, 8.02.
1H NMR (CDCl3), δ: 2.86 (s, 6 H, NMe2); 3.06 (s, 3 H,
N(5)Me); 3.62, 3.72, 3.79, 3.80, 3.83, 4.04 (all s, 3 H each,
OMe); 5.65 (d, 1 H, H(1´), J = 15.2 Hz); 6.14 (d, 1 H, H(3´),
J = 11.2 Hz); 6.63 (d, 1 H, H(9), J = 8.8 Hz); 7.26 (dd, 1 H,
H(2´), J = 11.2 Hz, J = 15.2 Hz); 7.36 (d, 1 H, H(6),
J = 2.0 Hz); 7.49 (s, 1 H, H(6´)); 7.68 (dd, 1 H, H(8), J = 8.8 Hz,
J = 2.0 Hz). 13C NMR (CDCl3), δ: 33.5, 43.2 (2 C), 51.0, 51.8,
52.2, 52.5, 52.6, 53.6, 86.8, 96.3, 103.2, 108.2, 108.9, 116.4,
118.0, 127.0, 130.9, 131.9, 132.5, 134.8, 135.4, 137.0, 143.0,
145.0, 151.0, 162.6, 163.0, 163.4, 166.0, 167.7, 169.0. MS, m/z:
698 [M]+.
6ꢀAminoꢀ1ꢀmethylꢀ2ꢀ[(1E,3E)ꢀ4ꢀmorpholinoꢀ1,3ꢀdienꢀ1ꢀyl]ꢀ
1Hꢀbenzimidazole (27). Raney nickel (50 mg) was added in
portions over 15 min to a stirred solution of diene 12 (0.5 g,
1.8 mmol) and hydrazine hydrate (2 mL) in ethanol (10 mL).
Then the reaction mixture was heated for 3 h at ~30 °C (TLC
monitoring). The catalyst was filtered off. The alcohol was
evaporated in vacuo, water (10 mL) was added to the residue,
followed by extraction with chloroform (3×20 mL). The extract
was dried with MgSO4. After evaporation of chloroform, the
residue was recrystallized from AcOEt to obtain diene 27
(90 mg, 20%), red crystals, m.p. 184—186 °C (with decomp.).
Found (%): C, 67.50; H, 6.84; N, 19.91. C16H20N4O. Calculꢀ
5ꢀBenzylꢀ4aꢀ[(1E,3Z,5E)ꢀ4,5ꢀdi(methoxycarbonyl)ꢀ
6ꢀdimethylaminohexaꢀ1,3,5ꢀtrienꢀ1ꢀyl]ꢀ1,2,3,4ꢀtetra(methoxyꢀ
carbonyl)ꢀ7ꢀnitroꢀ4a,5ꢀdihydropyrido[1,2ꢀa]benzimidazole (30).
Compound 30 (60 mg) was obtained similarly to the synthesis
1
ated (%): C, 67.58; H, 7.09; N, 19.70. H NMR data are given
in Table 2. MS, m/z: 284 [M]+.

1022
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
Varlamov et al.
of polycycle 29 from butadiene 16 (0.15 g, 0.43 mmol) and
DMAD (0.61 g, 4.3 mmol), the yield was 18%, orange crystals,
m.p. 181—183 °C (from AcOEt). Found (%): C, 58.75; H, 4.62;
N, 7.13. C38H38N4O14. Calculated (%): C, 58.91; H, 4.94;
N, 7.23. 1H NMR (CDCl3), δ: 2.87 (s, 6 H, NMe2); 3.28, 3.64,
3.74, 3.77, 3.82, 4.07 (all s, 3 H each, OMe); 4.29 (d, 1 H,
NCH2A, J = 16.8 Hz); 5.08 (d, 1 H, NCH2B, J = 16.8 Hz); 5.74
(d, 1 H, H(1´), J = 15.3 Hz); 6.17 (d, 1 H, H(3´), J = 11.3 Hz);
6.68 (d, 1 H, H(9), J = 8.9 Hz); 7.01 (d, 1 H, H(6), J = 2.1 Hz);
7.11—7.40 (m, 6 H, H(2´), Ar); 7.49 (s, 1 H, H(6´)); 7.69 (dd,
1 H, H(8), J = 8.9 Hz, J = 2.1 Hz). MS, m/z: 774 [M]+.
5. A. V. Varlamov, E. A. Savitkina, A. I. Chernyshev, A. P.
Krapivko, Khim. Geterotsikl. Soedin., 1997, 1137 [Chem.
Heterocycl. Compd. (Engl. Transl.), 1997, 33, 994].
6. K. Osterheld, B. Prajsnar, H. J. Hanser, Chem. Ztg., 1979,
103, 190.
7. A. P. Krapivko, E. A. Savitkina, Kuanu A. Antares, A. A.
Astakhov, A. V. Varlamov, Khim. Geterotsikl. Soedin., 1996,
338 [Chem. Heterocycl. Compd. (Engl. Transl.), 1996, 32, 290].
8. D. A. Maiboroda, E. V. Babaev, L. V. Goncharenko, Khim.
Pharm. Zh., 1998, 32 (6), 24 [Pharm. Chem. J. (Engl. Transl.),
1998, 32, 310].
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Eur. J. Org. Chem., 1998, 193.
10. R. M. Acheson, M. W. Foxton, P. J. Abbot, K. R. Mills,
J. Chem. Soc. (C), 1967, 882.
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Received May 15, 2009;
in revised form January 12, 2010