Derivatives of α,β-dehydro amino acids: I. Synthesis of 1-aryl-2,4-disubstituted imidazol-5-ones from arylamides of N-benzoyl-α, β-dehydrophenylalanine and trimethylchlorosilane

Article abstract of DOI:10.1007/s11178-005-0072-7

A preparation method was developed for 1-aryl-2,4-disubstituted imidazol-5-ones from N-benzoyl-α,β-dehydrophenylalanine anilides or 2-phenyl-4-benzylidene-5-oxazolone and arylamine in the presence of trimethylchlorosilane. 2004 MAIK "Nauka/Interperiodica"

Full text of DOI:10.1007/s11178-005-0072-7

Russian Journal of Organic Chemistry, Vol. 40, No. 11, 2004, pp. 1644-1646. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 11,
2004, pp. 1692-1694.
Original Russian Text Copyright Ó 2004 by Topuzyan, Oganesyan, Panosyan.
Derivatives of a,b-Dehydro Amino acids: I. Synthesis
of 1-Aryl-2,4-disubstituted Imidazol-5-ones fromArylamides
of N-Benzoyl-a,b-dehydrophenylalanine and
Trimethylchlorosilane
V.O. Topuzyan1,A.A. Oganesyan1,and G.A. Panosyan2
1Institute of Fine Organic Chemistry, National Academy of Sciences of Armenia,
Yerevan, 375014 Armenia
2Center of Molecular Structure Investigation, National Academy of Sciences of Armenia
Received September 10, 2003
Abstract-- A preparation method was developed for 1-aryl-2,4-disubstituted imidazol-5-ones from N-benzoyl-
a,b-dehydrophenylalanine anilides or 2-phenyl-4-benzylidene-5-oxazolone and arylamine in the presence
of trimethylchlorosilane.
Dehydration of amides of N-substituted a,b-dehydro
amino acids can result in 2-imidazolin-5-ones formation
[1], and the trimethylchlorosilane can be used as dehy-
drating agent [2–5].
The reaction of arylamides I–V with Me3SiCl was car-
ried out by heating in DMF. The reaction gave rise to the
corresponding 1-aryl-2-phenyl-4-benzylideneoxazol-5-ones
(VI–X). The effect of temperature and of heating time on
the yield of the target product was studied by an example
of the synthesis of 1-(4-carboxyphenyl)-2-phenyl-4-
benzylideneimidazol-5-one (VII) (see table).As show the
This paper concerns the study of a reaction between
N-substituted a,b-dehydrophenylalanine arylamides (I–
V) and trimethylchlorosilane.
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data in the table the best result at heating on the water
bath (about 90°C) was obtained in 3 h (70%). The yield
of compound VII obtained at boiling the reaction mix-
ture (about 125°C) for 1 h was 84%.
5-ones may be carried out from oxazolone XI and
arylamine in the presence of Me3SiCl (b). Method b
actually afforded the target imidazol-5-ones VI–X but in
relatively low yields (see table).
Boiling of arylamide II in DMF for 1 h without Me3SiCl
did not affect its structure.
Imidazol-5-one (VI) was obtained in a 60% yield at
boiling for 4 h aniline with oxazolone XI in acetic acid in
the presence of sodium acetate [6]. The similar process
in the presence of Me3SiCl afforded compound VI in a
64% yield within 1 h.
It should be mentioned that reaction of oxazolone XI
with arylamines in DMF afforded arylamides I and II.
This result suggests that the synthesis of 2-phenylimidazol-
1070-4280/04/4011-1644Ó2004 MAIK “Nauka/Interperiodica”

DERIVATIVES OF a,b-DEHYDROAMINOACIDS: I.
1645
Scheme.
purity of compounds obtained was checked by TLC on
Silufol UV-254 plates, eluents toluene–hexane, 1:1 (A)
and propanol–water, 7:3 (B); the spots were visualized
by UV irradiation and iodine vapour.
The formation of imidazol-5-one from arylamides of
N-substituted a,b-dehydro amino acids in the presence
of Me3SiCl can be rationalized by the scheme.
The IR spectra of compounds VI–X contain absorp-
–1
N-(N-Benzoyl-a,b-dehydrophenylalanine)-p-ami-
nobenzoic acid (II). To a solution of 1 g (0.004 mol) of
2-phenyl-4-benzylidene-5-oxazolone (XI) in 10 ml of DMF
was added 0.55 g (0.004 mol) of p-aminobenzoic acid,
and the mixture was boiled for 1 h. To the reaction mix-
ture 100 ml of water was added, the separated substance
was filtered off, washed with the hot ethyl acetate
(25 ml), and recrystallized from ethanol. Yield 0.55 g
tion bands at 1700–1710, 1645–1655, and 1615–1630 cm
corresponding to C=O, C=C, and C=N bonds respectively.
In the 1H NMR spectra of compounds VI–X the sin-
glet from the exocyclic CH=C group appeared at 7.20–
7.25 ppm evidencing the Z-configuration of these prod-
ucts. In the UV spectra of compounds VI–X absorption
was observed at 230–240, 290–310, and 377–400 nm.
–1
(35.7%). mp 240–242°C. IR spectrum, n, cm : 1583, 1645,
EXPERIMENTAL
1666, 1705, 3208, 3240. UV spectrum, l, nm (log e): 294
(3.39). 1H NMR spectrum, d, ppm: 7.09 s (1H, C=CH),
7.29 t (1H, C6H5, J 7.2 Hz), 7.36 t (2H, C6H5, J 7.4 Hz),
7.47 t (2H, C6H5, J 7.4 Hz), 7.54 t (1H, 6H5, J 7.0 Hz),
7.64 d (2H, C6H5, J 7.9 Hz), 7.86 and 7.90 m (4H, p-
C6H4, J 8.9 Hz), 8.05 d (2H, C6H5, J 7.8 Hz), 10.01 s
IR spectra were recorded on spectrophotometer
Specord M-40. NMR spectra were registered on
spectrimeter Varian Mercury 300. UV spectra were
measured on spectrophotometer Specord UV-VIS. The
Yields of 1-aryl-2,4-disubstituted imidazol-5-ones VI-X depending on the method and conditions of synthesis
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RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 40 No. 11 2004

TOPUZYAN et al.
1646
(1H, NH), 10.38 s (1H, NH), 12.2 br.s (1H, COOH).
Calculated, %: C 71.52; H 4.69; N 7.25. C23H18N2O4.
Found, %: C 71.20; H 5.00; N 7.09.
8.4 Hz), 7.33–7.50 m (6H), 7.54 d.d (2H, J1 7.1,
J2 1.6 Hz), 8.03 d (2H, J 8.5 Hz), 8.30 d.d (2H, J1 7.7, J2
1.8 Hz), 12.75 br.s (1H, COOH); compound VIII, 1.40 t
(3H, CH3, J 7.1 Hz), 4.36 q (2H, OCH2, J 7.1 Hz), 7.23 s
(1H, CH=C), 7.28 d (2H, J 8.2 Hz), 7.33–7.50 m (6H),
7.54 m (2H), 8.05 d (2H, J 8.5 Hz), 8.30 d.d (2H, J1 7.9,
J2 1.9 Hz); compound IX, 2.43 s (3H, CH3), 7.05 d (2H,
J 8.3 Hz), 7.18 s (1H, CH=C), 7.23 d (2H, J 8.3 Hz),
7.30–7.48 m (6H), 7.56 m (2H), 8.29 d.d (2H, J1 7.9, J2
1.8); compound X, 3.48 s (3H, OCH3), 6.95 d (2H,
J 8.8 Hz), 7.18 s (1H, CH=C), 7.09 d (2H, J 8.8 Hz),
7.31–7.49 m (6H), 7.58 d (DH, J 7.7 Hz), 8.29 d (2H,
J 7.6 Hz).
Likewise were synthesized compounds I, III–V.
1-Aryl-2-phenyl-4-benzylideneimidazol-5-ones
(VI–X). (a) To a solution of 0.026 mol of N-benzoyl-a,b-
dehydrophenylalanine arylamide (I–V) in 10 ml of DMF
was added 1.1 ml of Me3SiCl, and the mixture was heated
as indicated in the table. Then the reaction mixture was
cooled to room temperature, 100 ml of water was added,
and the separated precipitate was filtered off. The re-
crystallization from ethanol furnished 2-phenyl-4-
benzylideneimidazol-5-ones (VI–X).
REFERENCES
(b) To a solution of 0.007 mol of 2-phenyl-4-ben-
zylidene-5-oxazolone (XI) and 0.007 mol of arylamine in
10 ml of DMF was added 1.1 ml of Me3SiCl and the
mixture was heated as indicated in the table. Then the
reaction mixture was cooled to room temperature. The
reaction mixture was worked up as in the procedure (a).
1H NMR spectra (DMSO-d6–CCl4, 1:3), d, ppm: com-
pound VI, 7.21 s (1H, CH=C), 7.29 d.d (2H,
J2 8.0, J2 1.8 Hz), 7.34 t (2H, J 7.9 Hz), 7.38–7.48 m
(7H), 7.55 d (2H, J 8.1 Hz), 8.30 d (2H, J 7.6 Hz);
compound VII, 7.23 s (1H, CH=C), 7.26 d (2H, J
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RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 40 No. 11 2004