Derivatives of α,β-dehydro amino acids: III. Reaction of 4-arylmethylidene-4,5-dihydro-1,3-oxazol-5-ones with hexamethyldisilazane

Article abstract of DOI:10.1134/S1070428007060127

4-Arylmethylidene-4,5-dihydro-1,3-oxazol-5-ones reacted with hexamethyldisilazane in ethyl acetate, acetonitrile, or DMF at room temperature to give mainly 2-acylamino-3-arylmethylideneprop-2-enamides, whereas in boiling DMF the corresponding 4-arylmethyl

Full text of DOI:10.1134/S1070428007060127

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 6, pp. 868–871. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © V.O. Topuzyan, L.G. Arutyunyan, A.A. Oganesyan, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 6,
pp. 870–873.
Derivatives of α,β-Dehydro Amino Acids:
III. Reaction of 4-Arylmethylidene-4,5-dihydro-1,3-oxazol-5-ones
with Hexamethyldisilazane
V. O. Topuzyan, L. G. Arutyunyan, and A. A. Oganesyan
Institute of Fine Organic Chemistry, National Academy of Sciences of Armenia,
pr. Azatutyana 26, Erevan, 375014 Armenia
e-mail: vtop@web.am
Received May 4, 2006
Abstract—4-Arylmethylidene-4,5-dihydro-1,3-oxazol-5-ones reacted with hexamethyldisilazane in ethyl
acetate, acetonitrile, or DMF at room temperature to give mainly 2-acylamino-3-arylmethylideneprop-2-
enamides, whereas in boiling DMF the corresponding 4-arylmethylidene-4,5-dihydro-1H-imidazol-5-ones were
formed. The reaction of 2-benzoylamino-3-phenylprop-2-enamide with hexamethyldisilazane also led to the
formation of 4-benzylidene-2-phenyl-4,5-dihydro-1H-imidazol-5-one, while its reaction with chlorotrimethyl-
silane afforded either a 1:1 mixture of 4-benzylidene-2-phenyl-4,5-dihydro-1,3-oxazol-5-one and 4-benzyli-
dene-2-phenyl-4,5-dihydro-1H-imidazol-5-one or only the latter, depending on the solvent.
DOI: 10.1134/S1070428007060127
Hexamethyldisilazane (HMDS) in reactions with
carboxylic acid derivatives (such as anhydrides and
acid chlorides) can act as a source of ammonia to give
primary amides [1, 2]. In the present work we ex-
amined reactions of 4-arylmethylidene-4,5-dihydro-
1,3-oxazol-5-ones I–XIII with HMDS. Oxazolone II
reacted with HMDS at a ratio of 1:3 in ethyl acetate,
acetonitrile, or DMF at room temperature to form
2-benzoylamino-3-phenylprop-2-enamide (XV)
(Scheme 1). The best yield of XV (85%, reaction time
24 h) was obtained when the reaction was carried out
in ethyl acetate. Therefore, the other primary amides
(compounds XIV and XVI–XXIV) were synthesized
from the corresponding oxazolones and HMDS in
ethyl acetate at room temperature. In the reaction of II
with HMDS in DMF or acetonitrile (24 h), the yield of
Scheme 1.
O
O
Ar
Ar
Ar
(Me3Si)2NH, 25°C
AcOEt or DMF
(Me3Si)2NH or Me3SiCl
DMF, 140°C
O
NH2
N
O
N
NH
R
N
H
O
R
R
I–XIII
XIV–XXIV
(Me3Si)2NH, DMF, 140°C
Me3SiCl, DMF, Δ
Me3SiCl, MeCN, Δ
XXV–XXXIII
XV
II
+
XXV
XV
II
I, XIV, Ar = Ph, R = Me; II, XV, XXV, Ar = R = Ph; III, XVI, XXVI, R = Ph, Ar = 4-MeOC6H4; IV, XVII, XXVII, R = Ph, Ar =
4-i-PrOC6H4; V, XVIII, XXVIII, R = Ph, Ar = 4-ClC6H4; VI, XIX, XXIX, R = 2-MeC6H4, Ar = 4-ClC6H4; VII, XXX, R =
2-MeC6H4, Ar = 3,4-CH2O2C6H4; VIII, XX, XXXI, R = 4-MeC6H4, Ar = 2-furyl; IX, XXXII, R = 4-t-BuC6H4, Ar = Ph; X, XXI,
XXXIII, R = 2-MeOC6H4, Ar = 4-BrC6H4; XI, XXII, R= 4-MeOC6H4, Ar = Ph; XII, XXIII, R = 2-furyl, Ar = 3-O2NC6H4; XIII,
XXIV, R = 2-furyl, Ar = 4-(4-MeC6H4SO2)C6H4.
868

DERIVATIVES OF α,β-DEHYDRO AMINO ACIDS: III.
869
Scheme 2.
SiMe3
Cl–
O
Cl–
H2N
OH
H2N
N
Ph
O
N
NH2
Ph
Me3Si
Ph
H
O
O
OH
O
Me3SiCl
NH2
Ph
N
H
Ph
N
Ph
O
Ph
Ph
–Me3SiOH
–HCl
–Me3SiNH2
–HCl
a
b
O
O
Ph
Ph
N
NH
Ph
N
O
Ph
XXV
II
XV was relatively poor (57 and 20%, respectively).
Moreover, the reaction in DMF was accompanied by
formation of 7% of imidazolone XXV. The yield of the
latter increased to 84% when the reaction mixture was
heated for 1 h under reflux. By heating oxazolones I–
XIII with 3 equiv of HMDS in boiling DMF we syn-
thesized the corresponding 2-substituted 4-arylmethyli-
dene-4,5-dihydro-1H-imidazol-5-ones XXV–XXXIII
(Scheme 1).
disilazane provides a convenient method of synthesis
of both 2-acylamino-3-arylprop-2-enamides and 2-sub-
stituted 4-arylmethylidene-4,5-dihydro-1H-imidazol-5-
ones.
The IR spectra of amides XIV–XXIV contained
characteristic absorption bands in the regions 1620–
1645 (C=C), 1670–1690 (C=O), and 3120–3150,
3320–3350, and 3450–3490 cm–1 (N–H). Imidazol-5-
ones XXV–XXXIII displayed absorption bands at
1640–1650 (C=C), 1700–1710 (C=O), and 3330–
Presumably, imidazol-5-ones XXV–XXXIII are
formed from oxazol-5-ones I–XIII through the corre-
sponding primary amides. This follows from the fact
that heating of amide XV with HMDS in boiling DMF
for 1 h gave imidazolone XXV in 73% yield. The reac-
tion of HMDS with amide XV is likely to involve
silylation of the latter. To verify this assumption we
examined the reaction of amide XV with Me3SiCl.
Chlorotrimethylsilane is known to act as condensing
agent in the synthesis of carboxylic acid esters [3],
acetals [4], dioxolanes, oxazolidinones [5], and 2,4-di-
substituted 1-arylimidazol-5-ones [6]. By reaction of
XV with Me3SiCl at a ratio of 1:3 in boiling DMF we
obtained a mixture of products; according to the IR
and 1H NMR data, this mixture consisted of 4-benzyli-
dene-2-phenyl-4,5-dihydro-1H-imidazol-5-one (XXV)
and 4-benzylidene-2-phenyl-4,5-dihydro-1,3-oxazol-5-
one (II) at a ratio of 4.7:5.3. When the reaction was
performed in acetonitrile, oxazolone II was obtained as
the only product (yield 16%). The formation of com-
pounds XXV and II in the reaction of amide XV with
Me3SiCl may be rationalized as shown in Scheme 2.
The reaction in DMF is likely to follow both pathways
a and b, while in MeCN, only pathway b.
1
3360 cm–1 (N–H). In the H NMR spectra of amide
XV and imidazol-5-one XXV, the exocyclic vinyl
proton (CH=C) resonated at δ 6.96 ppm, indicating Z
configuration of these compounds. Initial oxazolone II
is also Z isomer.
EXPERIMENTAL
The IR spectra were recorded on a Specord M-80
1
spectrometer. The H NMR spectra were measured on
a Varian Mercury 300 instrument. The purity of the
products was checked by TLC on Silufol UV-254
plates using toluene–hexane–ethanol (1:1:1) as eluent;
spots were visualized under UV light or by treatment
with iodine vapor. Initial oxazolones I–XIII were syn-
thesized according to the procedure reported in [7].
2-Benzoylamino-3-phenylprop-2-enamide (XV).
Hexamethyldisilazane, 2.53 ml (1.93 g, 12 mmol), was
added to a solution of 1.0 g (4 mmol) of 4-benzyli-
dene-2-phenyl-4,5-dihydro-1,3-oxazol-5-one in 15 ml
of ethyl acetate, and the mixture was stirred for 24 h at
room temperature. The precipitate was filtered off,
washed with diethyl ether, dried in air, and recrystal-
lized from ethanol. Yield 0.9 g (85%), mp 170–172°C;
published data [8]: mp 168–169°C; Rf 0.58. IR spec-
We can conclude that the reaction of 4-arylmethyli-
dene-4,5-dihydro-1,3-oxazol-5-ones with hexamethyl-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

TOPUZYAN et al.
870
trum, ν, cm–1: 1700, 1630, 3175, 3265, 3390. 1H NMR
spectrum (DMSO), δ, ppm: 6.96 s (1H, CH=C), 7.22–
8.06 m (10H, Harom, and 2H, NH2), 9.64 s (1H, NH).
Found, %: C 72.33; H 5.02; N 10.24. C16H14N2O2. Cal-
culated, %: C 72.16; H 5.30; N 10.52.
Rf 0.63. Found, %: C 64.41; H 6.03; N 13.39.
C11H12N2O2. Calculated, %: C 64.69; H 5.92; N 13.72.
2-(4-Methoxybenzoylamino)-3-phenylprop-2-en-
amide (XXII). Yield 59%, mp 227–229°C, Rf 0.69.
IR spectrum, ν, cm–1: 1690, 1635, 3155, 3255, 3390.
Found, %: C 68.10; H 5.69; N 9.87. C17H16N2O3. Cal-
culated, %: C 68.89; H 5.44; N 9.45.
Amides XIV and XVI–XXIV were synthesized in
a similar way.
When the reaction was carried out in DMF, the
mixture was diluted with water, and the precipitate was
filtered off, dried, and ground with diethyl ether. The
undissolved material (compound XV) was filtered off
and recrystallized from ethanol. Yield 0.6 g (57%).
Evaporation of the filtrate gave compound XXV. Yield
0.07 g (7%), yellow crystalline substance, mp 272–
275°C (from ethanol). IR spectrum, ν, cm–1: 1640,
1690, 3380.
2-(2-Furoylamino)-3-(3-nitrophenyl)prop-2-en-
amide (XXIII). Yield 80%, mp 202–205°C, Rf 0.42.
IR spectrum, ν, cm–1: 1695, 1635, 3165, 3270, 3450.
Found, %: C 56.15; H 4.00; N 14.19. C14H11N3O5. Cal-
culated, %: C 55.80; H 3.68; N 13.95.
2-(2-Furoylamino)-3-(4-tosyloxyphenyl)prop-2-
enamide (XXIV). Yield 88%, mp 292–295°C, Rf 0.40.
Found, %: C 59.31; H 4.56; N 6.91. C21H18N2O6S. Cal-
culated, %: C 59.14; H 4.25; N 6.57.
2-Acetylamino-3-phenylprop-2-enamide (XIV).
Yield 61%, mp 209–211°C, Rf 0.46. IR spectrum, ν,
cm–1: 1690, 1625, 3135, 3305. Found, %: C 64.41;
H 6.03; N 13.39. C11H12N2O2. Calculated, %: C 64.69;
H 5.92; N 13.72.
4-[(Z)-Benzylidene]-2-phenyl-4,5-dihydro-1H-
imidazol-5-one (XXV). A mixture of 1.0 g (4 mmol)
of oxazolone II and 2.53 ml (1.94 g, 12 mmol) of
HMDS in 10 ml of DMF was heated for 1 h under
reflux. The mixture was cooled, diluted with 50 ml of
water, acidified with hydrochloric acid to pH 6, and
left to stand for 2 h at 0°C. The precipitate was filtered
off and recrystallized from ethanol. Yield 0.8 g (80%),
mp 273–275°C, Rf 0.71. IR spectrum, ν, cm–1: 1640,
2-Benzoylamino-3-(4-methoxyphenyl)prop-2-en-
amide (XVI). Yield 76%, mp 189–191°C; published
data [8]: mp 190–192°C; Rf 0.44. IR spectrum, ν, cm-1:
1690, 1630, 3215, 3450. Found, %: C 69.09; H 5.62;
N 9.67. C17H16N2O3. Calculated, %: C 68.89; H 5.44;
N 9.45.
1
1690, 3380. H NMR spectrum (DMSO), δ, ppm:
6.96 s (1H, CH=), 7.22–8.06 m (10H, Harom), 11.90 s
(1H, NH). Found, %: C 77.03; H 5.10; N 11.59.
C16H12N2O. Calculated, %: C 77.40; H 4.87; N 11.28.
2-Benzoylamino-3-(4-isopropoxyphenyl)prop-2-
enamide (XVII). Yield 81%, mp 197–199°C, Rf 0.53.
IR spectrum, ν, cm–1: 1900, 1635, 3115, 3280, 3490.
Found, %: C 70.00; H 6.54; N 8.29. C19H20N2O3. Cal-
culated, %: C 70.34; H 6.20; N 8.63.
4-[(Z)-4-Methoxybenzylidene]-2-phenyl-4,5-dihy-
dro-1H-imidazol-5-one (XXVI). Yield 80%, mp 280–
281°C, Rf 0.61. IR spectrum, ν, cm–1: 1700, 1630, 3110.
Found, %: C 73.51; H 5.29; N 10.52. C17H14N2O2. Cal-
culated, %: C 73.36; H 5.07; N 10.06.
2-Benzoylamino-3-(4-chlorophenyl)prop-2-en-
amide (XVIII). Yield 78%, mp 172–174°C, Rf 0.57.
IR spectrum, ν, cm–1: 1690, 1635, 3155, 3225, 3450.
Found, %: C 64.03; H 4.10; N 9.53. C16H13ClN2O2.
Calculated, %: C 63.89; H 4.35; N 9.31.
4-[(Z)-4-Isopropoxybenzylidene]-2-phenyl-4,5-
dihydro-1H-imidazol-5-one (XXVII). Yield 64%,
mp 255–258°C, Rf 0.77. IR spectrum, ν, cm–1: 1700,
1625, 3120. Found, %: C 74.02; H 5.78; N 9.60.
C19H18N2O2. Calculated, %: C 74.49; H 5.52; N 9.14.
3-(4-Chlorophenyl)-2-(2-methylbenzoylamino)-
prop-2-enamide (XIX). Yield 65%, mp 205–208°C,
Rf 0.65. IR spectrum, ν, cm–1: 1695, 1630, 3155, 3225,
3480. Found, %: C 63.77; H 4.51; N 9.07.
C17H15ClN2O2. Calculated, %: C 63.85; H 4.76; N 8.76.
4-[(Z)-4-Chlorobenzylidene]-2-phenyl-4,5-di-
hydro-1H-imidazol-5-one (XXVIII). Yield 54%,
mp 224–227°C, Rf 0.78. IR spectrum, ν, cm–1: 1700,
1625, 3120. Found, %: C 68.11; H 4.07; N 10.14.
C16H11ClN2O. Calculated, %: C 67.97; H 3.92; N 9.91.
3-(2-Furyl)-2-(4-methylbenzoylamino)prop-2-
enamide (XX). Yield 80%, mp 170–172°C, Rf 0.50. IR
spectrum, ν, cm–1: 1680, 1630, 3190, 3390, 3440.
Found, %: C 67.01; H 5.43; N 10.60. C15H14N2O3. Cal-
culated, %: C 66.60; H 5.20; N 10.36.
4-[(Z)-4-Chlorobenzylidene]-2-(2-methylphenyl)-
4,5-dihydro-1H-imidazol-5-one (XXIX). Yield 55%,
mp 294–297°C, Rf 0.65. IR spectrum, ν, cm–1: 1700,
1625, 3150. Found, %: C 68.45; H 4.05; N 9.91.
C17H13ClN2O. Calculated, %: C 68.81; H 4.41; N 9.44.
3-(4-Bromophenyl)-2-(2-methoxybenzoylamino)-
prop-2-enamide (XXI). Yield 76%, mp 174–176°C,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

DERIVATIVES OF α,β-DEHYDRO AMINO ACIDS: III.
871
which was identified as oxazolone II. Yield 0.15 g
(16%), mp 165–166°C [7], Rf 0.88. IR spectrum, ν,
4-[(Z)-1,3-Benzodioxol-5-ylmethylidene]-2-
(2-methoxyphenyl)-4,5-dihydro-1H-imidazol-5-one
(XXX). Yield 56%, mp 341–343°C, Rf 0.72. IR spec-
trum, ν cm–1: 1700, 1630, 3150. Found, %: C 70.29;
H 4.18; N 9.50. C18H14N2O3. Calculated, %: C 70.58;
H 4.61; N 9.34.
1
cm–1: 1650 (C=C), 1770 (C=O). H NMR spectrum
(DMSO-d6), δ, ppm: 7.20 s (1H, CH=C), 7.40–8.32 m
(Harom). The filtrate was evaporated to obtain a white
amorphous substance (0.8 g) whose physical constants
coincided with those of initial amide XV, mp 172–
175°C, Rf 0.51.
4-[(Z)-Furfurylidene]-2-(4-methylphenyl)-4,5-di-
hydro-1H-imidazol-5-one (XXXI). Yield 17%,
mp 296–299°C, Rf 0.62. IR spectrum, ν, cm–1: 1705,
1630, 3140. Found, %: C 71.64; H 5.00; N 11.56.
C15H12N2O2. Calculated, %: C 71.42; H 4.79; N 11.12.
b. A mixture of 1.0 g (3.7 mmol) of amide XV and
1.2 g (1.4 ml, 11 mmol) of chlorotrimethylsilane in
10 ml of DMF was heated for 1 h under reflux. The
mixture was then diluted with 100 ml of water and
acidified with hydrochloric acid to pH 2. The light
yellow precipitate was filtered off and treated with
10 ml of diethyl ether, and the solution was separated
from the undissolved material, 0.2 g (22%), mp 273–
276°C, Rf 0.71. IR spectrum, ν, cm–1: 1645 (C=C),
4-[(Z)-Benzylidene]-2-(4-tert-butylphenyl)-4,5-di-
hydro-1H-imidazol-5-one (XXXII). Yield 59%,
mp 254–256°C, Rf 0.66. IR spectrum, ν, cm–1: 1710,
1635, 3160. Found, %: C 81.13; H 6.51; N 9.62.
C20H20N2O. Calculated, %: C 81.54; H 6.62; N 9.20.
1
4-[(Z)-4-Bromobenzylidene]-2-(4-methoxyphen-
yl)-4,5-dihydro-1H-imidazol-5-one (XXXIII). Yield
66%, mp 270–272°C, Rf 0.74. IR spectrum, ν, cm–1:
1705, 1630, 3240. Found, %: C 57.34; H 4.03; N 8.07.
C17H13BrN2O2. Calculated, %: C 57.16; H 3.66; N 7.84.
1700 (C=O), 3145 (NH). H NMR spectrum
(DMSO-d6), δ, ppm: 6.90 s (1H, C=CH), 7.30–8.32 m
(10H, Harom), 11.88 s (1H, NH). The ether solution was
evaporated to obtain 0.22 g of a mixture of imidazo-
lone XXV (Rf 0.71) and oxazolone II (Rf 0.88) at
a ratio of 9:1 (according to the 1H NMR data).
Reaction of 2-benzoylamino-3-phenylprop-2-en-
amide (XV) with hexamethyldisilazane. A mixture of
1.0 g (3.76 mmol) of amide XV and 1.78 g (2.3 ml,
1.13 mmol) of HMDS in 10 ml of DMF was heated for
1 h under reflux. The mixture was diluted with 50 ml
of water, and the yellow precipitate was filtered off,
dried in air, and purified by recrystallization. Yield
0.69 g (74%). The product was identical to imidazo-
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1
lone XXV in physical constants and IR and H NMR
spectra.
Reaction of 2-benzoylamino-3-phenylprop-2-en-
amide (XV) with chlorotrimethylsilane. a. A mixture
of 1.0 g (3.7 mmol) of amide XV and 1.2 g (1.4 ml,
11 mmol) of chlorotrimethylsilane in 10 ml of aceto-
nitrile was heated for 1 h under reflux. After cooling,
the precipitate was filtered off and treated with 10 ml
of diethyl ether. The solution was separated by decant-
ing from the undissolved tarry material and evaporat-
ed. The residue was a yellow crystalline substance
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007