Derivatives of α,β-dehydroamino acids: V. Intramolecular cyclization of 2-{2-[(Z)-1-Benzamido-2-phenylvinyl]acetamidomethyl}benzimidazole

Article abstract of DOI:10.1134/S1070428009020109

Reaction of 4-benzylidene-2-phenyl-1,3-oxazol-5(4H)-one with 2-(1H-benzimidazol-2-yl)ethaneamine led to the formation of 2-{2-[(Z)-1- benzamido-2-phenylvinyl]acetamidomethyl}benzimidazole that in a reaction with hexamethyldisilazane in DMF gave 5-benzylid

Full text of DOI:10.1134/S1070428009020109

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 2, pp. 215−217. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.O. Topuzyan, M.M. Kazandzhyan, R.A. Tamazyan, A.G. Aivazyan, 2009, published in Zhurnal Organicheskoi Khimii,
2009, Vol. 45, No. 2, pp. 227−229.
Derivatives of α,β-Dehydroamino Acids: V.
Intramolecular Cyclization of 2-{2-[(Z)-1-Benzamido-
2-phenylvinyl]acetamidomethyl}benzimidazole
V. O. Topuzyan, M. M. Kazandzhyan, R.A. Tamazyan, andA. G.Aivazyan
Mndzhaoyan Institute of Fine Organic Chemistry, Armenian National Academy of Sciences,
Yerevan, 375014 Armenia
e-mail: vtop@web.am
Received February 14, 2008
Abstract—Reaction of 4-benzylidene-2-phenyl-1,3-oxazol-5(4H)-one with 2-(1H-benzimidazol-2-yl)ethaneamine
led to the formation of 2-{2-[(Z)-1-benzamido-2-phenylvinyl]acetamidomethyl}benzimidazole that in a reaction
with hexamethyldisilazane in DMF gave 5-benzylidene-1-(1H-benzimidazol-2-yl)-2-phenyl-3,5-dihydro-4H-imidazol-
4-one. In the presence of K2CO3 in dioxane the reaction with hexamethyldisilazane resulted in the product of
intramolecular addition, N-(4-benzyl-3-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]-benzimidazol-4-yl)benzamide
DOI: 10.1134/S1070428009020109
Derivatives of α,β-dehidroamino acids are widely used
in organic synthesis. As polyfunctional compounds they
are involved into versatile reactions yielding various
heterocyclic systems [1]. α,β-Dehydroamino acids deriv-
atives are employed also in the synthesis of nonprotein
[2, 3] α-amino acids and physiologically active compounds
[4, 5].
(HMDS) suffered dehydration giving the corresponding
5-imidazolones. In order to synthesize 5-benzylidene-1-
(1H-benzimidazol-2-yl)-2-phenyl-3,5-dihydro-4H-imid-
azol-4-one (IV) amide I was treated with HMDS in DMF
at boiling for 2 h. Therewith compound IV was obtained
in 42% yield (Scheme 2).
It is known that with respect to nitrogen heterocycles
the α,β-dehydroamino acids derivatives can serve as
substrates in Michael addition [8–12]. The presence in
the molecule of amide I both of fragments of α,β-dehydro-
amino acid and benzimidazole suggests that under certain
conditions the compound can undergo an intramolecular
cyclization. To investigate this possibility we boiled amide
I in dioxane in the presence of potassium carbonate for
15 h. The reaction progress was monitored by TLC.
After 12 h three spots were found with Rf 0.44, 0.54,
and 0.60. The spot corresponding to the initial amide I
This report deals with the study of the intramolecular
cyclization of 2-{2-[(Z)-1-benzamido-2-phenylvinyl]-
acetamidomethyl}benzimidazole (I) under various condi-
tions.Amide I was obtained from 4-benzylidene-2-phenyl-
1,3-oxazol-5(4H)-one (II) and 2-(1H-benzimidazol-2-
yl)ethaneamine (III) in chloroform at room temperature
(Scheme 1).
We recently demonstrated that primary amides [6]
and hydrazides [7] of N-substituted α,β-dehydroamino
acids in the reaction with 1,1,1,3,3,3- hexamethyldisilazane
Scheme 1.
Ph
O
O O
HN
N
N
Ph
NHCH2
+
O
H2NCH2
N
N
H
N
H
Ph
II
Ph
III
I
215

TOPUZYAN et al.
216
Scheme 2.
O
Ph
O
Ph
Ph
N
K2CO3
(Me3Si)2NH
O
NH
I
N
N
CH2
Dioxane
DMF
N
N
H
NH
Ph
N
IV
V
The structure of compound V was established by XRD
analysis. Its molecules crystallized with solvent molecules
(ethanol) in 1:1 ratio (Fig. 1). The compound is racemic.
In the crystal the D- and L-forms of the molecule of the
studied compound are bound into dimers by double
(Rf 0.54) totally disappeared after 15 h. Then from the
reaction mixture tricyclic benzamide V was isolated in
63% yield and substituted imidazolone IV, in 21% yield
(Scheme 2). Tricycle V is a previously unknown modifica-
tion of imidazo[1,2-a]pyrazine [13, 14].
...
...
hydrogen bonds N8 H33–O33 H11'–N11' [2.815(3)
]
...
...
and N8 H33'–O33' H11–N11 [2.904(3) ] (Fig. 2), and
the dimers are connected into a three-dimensional
...
network by hydrogen bonds N15–H15 O13'’ [2.965(2) ].
EXPERIMENTAL
IR spectra of compounds were recorded on a spec-
1
trophotometer Specord Μ-80. H NMR spectra were
registered on a spectrometer Varian Mercury 300. The
purity of compounds obtained was checked by TLC on
Silufol UV-254 plates, eluent toluene–hexane–ethanol,
1:1.5:1, development under UV radiation and in iodine
vapor.
XRD analysis. XRD study was performed on a trans-
parent colorless crystal of the size 0.4 × 0.35 × 0.3 mm.
The measurement of 9766 independent reflections was
carried out on an automatic diffractometer CAD-4 Enraf
Nonius. Crystals of compound V monoclinic, space group
C2/c, a 30.073(6), b 8.660(2), C 20.854(4) Å, β 124.10(3)
deg. The structure was solved by the direct method using
the program SHELXTL [15]. The hydrogen atoms
coordinate were defined from the difference Fourier
synthesis of the electronic density. Finally all atomic
coordinates including the hydrogen atoms and anisotropic
thermal parameters of the nonhydrogen atoms were
refined together in the full-matrix least-squares method,
the final R-factor equaled 0.051.
Fig. 1. Structure of N-(4-benzyl-3-oxo-1,2,3,4-tetrahydro-
pyrazino[1,2-a]benzimidazol-4-yl)benzamide (V); numera-
tion of atoms adopted in this report. Ellipsoids of thermal
oscillations are shown on the level of 50% probability.
2-{2-[(Z)-1-Benzamido-2-phenylvinyl]acetamido-
methyl}benzimidazole (I). Amixture of 1.0 g (4 mmol)
of 4-benzylidene-2-phenyl-1,3-oxazol-5(4H)-one (II)
[16], 0.88 g(4 mmol) of 2-(1H-benzimidazol-2-yl)-
ethaneamine, and 0.8 g (1.12 ml, 8 mmol) of triethylamine
Fig. 2. Dimer of N-(4-benzyl-3-oxo-1,2,3,4-tetrahydro-
pyrazino[1,2-a]benzimidazol-4-yl)benzamide (V) consisting
of D- and L-forms of the molecule connected with solvent
(ethanol) molecules by double hydrogen bonds
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

DERIVATIVES OF α,β-DEHYDROAMINOACIDS: V.
217
in 25 ml of chloroform was left standing at room
temperature for 24 h. Chloroform was evaporated on
a rotary evaporator, the residue was ground with 30 ml
of 50% ethanol, the formed solid mass was filtered off
and dried in air. Yield 1.57 g (99%), mp 140–142°C (90%
ethanol), Rf 0.54. IR spectrum, ν, cm–1: 3400, 3190, 1675,
Found, %: C 72.45; H 5.30; N 14.43. C24H20N4O2.
Calculated, %: C 72.71; H 5.08; N 14.13.
To the ethanol solution water was added, the separated
precipitate was filtered off. After recrystallization from
50% ethanol we obtained 0.2 g (21%) of compound IV.
1
1650. H NMR spectrum, δ, ppm: 4.64 d (2H, CH2),
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(1H, NH) 10.08 s (1H, NH), 11.40 br.s (1H, NH). Found,
%: C 72.50; H 5.24; N 14.36. C24H20N4O2. Calculated,
%: C 72.71; H 5.08; N 14.13.
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0.5 g (1.26 mmol) of reagent I and 0.61 g (0.79 ml,
3.8 mmol) of HMDS in 5 ml of DMF was boiled for 2 h.
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1
3400, 1710, 1640. H NMR spectrum, δ, ppm: 5.08 s
(2H, CH2), 7.02–7.20 m (3Harom), 7.18 s (1H, CH=C),
7.34–7.42 m (6Harom), 8.04 d (3Harom), 8.26 d (2Harom),
12.24 br.s (1H, NH). Found, %: C 76.52; H 4.51; N 14.93.
C24H18N4O. Calculated, %: C 76.17; H 4.79; N 14.80.
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[1,2-a]benzimidazol-4-yl)benzamide (V).Amixture of
1.0 g(2.52 mmol) of reagent I and 1.74 g (12.6 mmol) of
potassium carbonate in 25 ml of dioxane was boiled for
15 h, cooled, 80 ml of water was added, the solution was
acidified with hydrochloric acid to pH 4, the separated
precipitate was filtered off. Yield 0.63 g (63%), mp 283–
285°C (EtOH), Rf 0.44. IR spectrum, ν, cm–1: 3295, 1690,
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1
1650. H NMR spectrum, δ, ppm: 3.48 d.d (1H, NCH2,
J 17.4, 1.6 Hz), 3.57 d (1H, CH2Ph, J 13.2 Hz), 3.92 d
(1H, CH2Ph, J 13.2 Hz), 4.42 d.d (1H, NCH2, J 17.4,
2.7 Hz), 6.53 m (2Harom), 7.06 m (2Harom), 7.14–7.23 m
(3Harom), 7.40–7.58 m (4Harom), 7.90–8.01 m (3Harom),
8.19 d.d (1H, NHC, J 2.7, 1.6 Hz), 9.73 s (1H, NH).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009