Five-membered 2,3-dioxo heterocycles: XLVII. Reaction of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones with compounds containing C = N and C≡N bonds

Article abstract of DOI:10.1023/B:RUJO.0000045204.07277.72

Thermal decarbonylation of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones gives rise to intermediate aroyl(phenyl)ketenes which react with nonactivated Schiff bases, N,N'-dicyclohexylcarbodiimide, and p-di-methylaminobenzonitrile according to the [4 + 2]-cycloaddition pattern with formation of 6-aryl-5-phenyl-4H-1,3-oxazin-4-ones. Reactions of 5-aryl-4-phenyl-2,3- dihydrofuran-2,3-diones with activated Schiff bases at a temperature below the thermolysis temperature lead to 4-aroyl-4-phenyltetrahydropyrrole-2,3-diones.

Full text of DOI:10.1023/B:RUJO.0000045204.07277.72

Russian Journal of Organic Chemistry, Vol. 40, No. 7, 2004, pp. 1058–1061. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 7, 2004,
pp. 1099–1102.
Original Russian Text Copyright © 2004 by Vostrov, Leont’eva, Tarasova, Maslivets.
Five-Membered 2,3-Dioxo Heterocycles: XLVII.* Reaction
of 5-Aryl-4-phenyl-2,3-dihydrofuran-2,3-diones with Compounds
Containing C=N and C≡N Bonds
E. S. Vostrov, E. V. Leont’eva, O. P. Tarasova, and A. N. Maslivets
Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh@psu.ru
Received April 9, 2003
Abstract—Thermal decarbonylation of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones gives rise to intermediate
aroyl(phenyl)ketenes which react with nonactivated Schiff bases, N,N'-dicyclohexylcarbodiimide, and p-di-
methylaminobenzonitrile according to the [4+2]-cycloaddition pattern with formation of 6-aryl-5-phenyl-4H-
1,3-oxazin-4-ones. Reactions of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones with activated Schiff bases at
a temperature below the thermolysis temperature lead to 4-aroyl-4-phenyltetrahydropyrrole-2,3-diones.
5-Aryl-4-halo-2,3-dihydrofuran-2,3-diones and
their analogs containing no substituent at C4 undergo
thermal decarbonylation (80–110°C) to generate aroyl-
ketenes which act as dienes (through the conjugated
O=C–C=C bond system) in [4+2]-cycloadditions at
the C=N bond of nonactivated Schiff bases [2–4] and
carbodiimides [5] or at the C≡N bond of cyanamides
[6]. As a result, the corresponding 1,3-oxazin-4-one
derivatives are formed. Activated Schiff bases react
with 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones
under milder conditions (at room temperature), and
the reaction includes opening of the furan ring and
subsequent recyclization to substituted 3-hydroxy-
pyrrol-2-ones [4, 7].
Scheme 1.
O
O
Ph
Ar1CO
Ph
O
O
Ph
Ar3
Ar2
Ar4CH=NCH2Ph
Ar2CH=NAr3
N
Ar4
O
Ar1
O
N
O
Ar1
CH2Ph
IVa, IVb
Ia, Ib
IIIa–IIIc
Ar2CH=NAr3
∆
–CO
O
O
O
O
Ph
C6H11
Ph
C
O
Ph
(C6H11N)2C
Ar5CN
N
N
Ar1
NC6H11
Ar1
Ar1
O
Ar5
Va, Vb
IIa, IIb
VIa, VIb
I, II, Ar1 = Ph (a), 2,5-Me2C6H3 (b); III, Ar1 = Ph, Ar2 = p-BrC6H4, Ar3 = p-MeOC6H4 (a); Ar1 = Ar2 = Ph, Ar3 = 2,5-Me2C6H3 (b);
Ar1 = 2,5-Me2C6H3, Ar2 = p-BrC6H4, Ar3 = p-MeOC6H4 (c); IV, Ar1 = Ph, Ar4 = p-Me2NC6H4 (a); Ar1 = 2,5-Me2C6H3, Ar4 =
p-Et2NC6H4 (b); V, Ar1 = Ph (a), 2,5-Me2C6H3 (b); VI, Ar5 = p-Me2NC6H4, Ar1 = Ph (a), 2,5-Me2C6H3 (b).
* For communication XLVI, see [1].
1070-4280/04/4007-1058 © 2004 MAIK “Nauka/Interperiodica”

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XLVII.
1059
groups attached thereto, a doublet of doublets at
δ 3.80–5.04 ppm (AB system) from the CH2 protons of
the benzyl group, and a singlet from 5-H at δ 5.78–
5.98 ppm. Compound IVa showed the following
signals in the 13C NMR spectrum, δC, ppm: 119.58–
150.08 (Carom), 39.53 (Me2N), 45.84 (CH2), 62.49
(C4), 67.74 (C5), 156.86 (C2=O), 192.15 (PhC=O),
192.31 (C3=O).
In order to estimate the effect of a phenyl group
in position 4 of the furan ring on the above process,
we examined reactions of 5-aryl-4-phenyl-2,3-dihydro-
furan-2,3-diones Ia and Ib with some activated and
nonactivated Schiff bases, N,N'-dicyclohexylcarbodi-
imide, and p-dimethylaminobenzonitrile. Heating of
mixtures of compound Ia or Ib and N-benzylidene-
anilines in dry boiling 1,2,4-trimethylbenzene at 160–
165°C over a period of 30–40 min promoted thermal
decarbonylation of the former with generation of aroyl
(phenyl)ketenes IIa and IIb which reacted as dienes at
the C=N bond of Schiff bases according to the [4+2]-
cycloaddition pattern. As a result, the corresponding
2,3,6-triaryl-5-phenyl-3,4-dihydro-2H-1,3-oxazin-4-
ones IIIa–IIIc were obtained (Scheme 1).
Presumably, in the first stage, opening of the furan
ring in Ia and Ib as a result of nucleophilic attack by
the nitrogen atom of activated Schiff base gives
zwitterionic intermediate which then undergoes intra-
molecular cyclization to IVa and IVb [8].
Heating of furandiones Ia and Ib in boiling
1,2,4-trimethylbenzene (160–165°C, 30–40 min) in the
presence of N,N'-dicyclohexylcarbodiimide afforded
6-aryl-5-phenyl-3-cyclohexyl-2-cyclohexylimino-3,4-
dihydro-2H-1,3-oxazin-4-ones Va and Vb via [4+2]-
cycloaddition of intermediate aroylketenes IIa and IIb
at the C=N bond of carbodiimide. In the IR spectra
of oxazinones Va and Vb, absorption bands at 1700–
1702 and 1655–1660 cm–1 were present due to
stretching vibrations of the lactam carbonyl group
The IR spectra of products IIIa–IIIc contained
a strong absorption band at 1655–1678 cm–1 due to
stretching vibrations of the lactam carbonyl group
(C4=O). Its position is well consistent with the IR
spectra of their analogs containing a halogen atom or
1
no substituent at C5 [2–4]. In the H NMR spectra of
IIIa–IIIc we observed signals from aromatic protons,
a singlet at δ 6.85–6.87 ppm from 2-H, singlets at
δ 1.74–2.19 ppm from the methyl group protons
(IIIb, IIIc), and a singlet at δ 3.78–3.79 ppm from the
methoxy group proton (IIIa, IIIc). Compound IIIb
showed in the 13C NMR spectrum signals from
aromatic carbon atoms (δC 126.28–139.02 ppm),
methyl groups attached to the aromatic rings (δC 18.34,
20.27 ppm), and signals at δC 89.20, 160.39, 114.87,
and 162.16 ppm from the C2, C4, C5, and C6 atoms
of the 1,3-oxazine ring, respectively. These data are
consistent with the assumed structure. The mass
spectrum of IIIa contained the following ion peaks,
m/z (Irel, %): 289/291 (54/61) [p-BrC6H4CH=NC6H4-
OMe-p]+, 222 (35) [PhCO(Ph)C=C=O]+. This frag-
mentation pattern corresponds to the retro-Diels–Alder
decomposition.
1
(C4=O) and C=N bond, respectively. The H NMR
spectra of Va and Vb contained singlets from the
methyl group protons at δ 2.12 and 2.14 ppm (Vb),
a set of signals from ten CH2 groups in the two cyclo-
hexyl fragments in the regions δ 1.09–1.82 and 2.52–
2.62 ppm, two quintets from the CH protons in the
cyclohexyl fragments at 3.60–3.78 and 4.70–4.79 ppm,
and a set of aromatic proton signals in the region
δ 7.02–7.43 ppm. Compound Va showed the following
signals in the 13C NMR spectrum, δC, ppm: 127.73–
132.18 (Carom); 24.35–34.14, 53.47, 55.41 (cyclohexyl);
138.87 (C2), 162.06 (C4), 112.21 (C5), 156.79 (C6).
The reaction of furandiones Ia and Ib with p-di-
methylaminobenzonitrile in Dowtherm A [9] at 140–
145°C (20–30 min) gave 6-aryl-2-(p-dimethylamino-
phenyl)-5-phenyl-4H-1,3-oxazin-4-ones VIa and VIb,
respectively, as a result of [4+2]-cycloaddition of
aroyl(phenyl)ketenes IIa–IIc (generated by thermal
decarbonylation of Ia and Ib) at the C≡N bond of the
nitrile. The IR spectra of VIa and VIb contained
absorption bands belonging to stretching vibrations of
the lactam carbonyl group (C4=O) at 1660–1680 cm–1
and C=N bond in the oxazine ring at 1620–1621 cm–1;
their position is well consistent with the IR spectra of
structural analogs having no substituent at C5 [5].
Compound VIa showed the following ion peaks in the
mass spectrum, m/z (Irel, %): 368 (5) [M]+, 146 (100)
[p-Me2NC6H4C≡N]+.
By reaction of furandiones Ia and Ib with N-(ben-
zylidene)benzylamines in dry boiling chloroform (63–
64°C, 20–30 min) we obtained 4-aroyl-5-aryl-1-ben-
zyl-4-phenyl-2,3,4,5-tetrahydro-1H-pyrrole-2,3-diones
IVa and IVb, respectively [8]. In the IR spectra of
pyrrolediones IVa and IVb, stretching vibrations of
the lactam carbonyl group (C2=O) appeared at 1770–
1776 cm–1, and absorption bands due to ketone
carbonyl groups C3=O and 4-COAr were located at
1719–1725 and 1680–1695 cm–1, respectively. The
1H NMR spectra of pyrrolediones IVa and IVb con-
tained signals from protons in the aromatic rings and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

VOSTROV et al.
1060
7.60 m (16H, Harom). Found, %: C 68.90; H 4.87;
EXPERIMENTAL
Br 14.80; N 2.63. C31H26BrNO3. Calculated, %:
C 68.89; H 4.85; Br 14.78; N 2.59.
The IR spectra were recorded on a UR-20 spec-
trometer from samples dispersed in mineral oil. The
1H and 13C NMR spectra** were obtained on a Bruker
4-Benzoyl-1-benzyl-5-p-dimethylaminophenyl-
2,3,4,5-tetrahydro-1H-pyrrole-2,3-dione (IVa). A so-
lution of 5 mmol of furandione Ia and 5 mmol of
N-(p-dimethylaminobenzylidene)benzylamine in 15 ml
of dry chloroform was heated for 20–30 min under
reflux. The mixture was cooled, and the precipitate
was filtered off. Yield 1.95 g (80%), mp 197–198°C
(from isopropyl alcohol). IR spectrum, ν, cm–1: 1770
1
AM-400 instrument (400 MHz for H) from solutions
in DMSO-d6 or CDCl3 using tetramethylsilane as
internal reference. The mass spectra (electron impact,
70 eV) were recorded on an MKh-1310 mass spec-
trometer. The purity of the products was checked by
TLC on Silufol plates using ethyl acetate, ethyl
acetate–benzene (1:5), or benzene as eluent; develop-
ment with iodine vapor.
1
(C2=O), 1725 (C3=O), 1680 (PhC=O). H NMR spec-
trum (DMSO-d6), δ, ppm: 2.78 s (6H, Me2N), 3.80 d
(1H, CH2, AB system, J = 14.3 Hz), 5.04 d (1H, CH2,
AB system, J = 14.3 Hz), 5.98 s (1H, 5-H), 6.44–
7.47 m (19H, Harom). 13C NMR spectrum (100 MHz,
DMSO-d6), δC, ppm: 39.53 (Me2N), 45.84 (CH2),
62.49 (C4), 67.74 (C5), 119.58–150.08 (Carom), 156.86
(C2), 192.15 (PhCO), 192.31 (C3). Found, %: C 78.72;
H 5.78; N 5.70. C32H28N2O3. Calculated, %: C 78.67;
H 5.78; N 5.73.
2-p-Bromophenyl-3-p-methoxyphenyl-5,6-di-
phenyl-3,4-dihydro-2H-1,3-oxazin-4-one (IIIa). A so-
lution of 2.16 mmol of furandione Ia and 2.16 mmol
of N-(p-bromobenzylidene)-p-methoxyaniline in 5 ml
of dry 1,2,4-trimethylbenzene was heated for 30–
40 min under reflux. The mixture was cooled, and
the precipitate was filtered off. Yield 0.55 g (50%),
mp 144–146°C (decomp., from CCl4–hexane, 1:1).
IR spectrum, ν, cm–1: 1655 (C4=O). 1H NMR spectrum
(DMSO-d6), δ, ppm: 3.78 s (3H, OMe), 6.85 s (1H,
2-H), 6.89–7.65 m (18H, Harom). Mass spectrum, m/z
(Irel, %): 289/291 (54/61) [p-BrC6H4CH=NC6H4-
OMe-p]+, 222 (35) [Ph(PhCO)C=C=O]+, 105 (100)
[PhCO]+, 77 (88) [Ph]+. Found, %: C 67.99; H 4.31;
Br 15.65; N 2.75. C29H22BrNO3. Calculated, %:
C 67.98; H 4.33; Br 15.59; N 2.73.
1-Benzyl-5-p-diethylaminophenyl-4-(2,5-di-
methylbenzoyl)-2,3,4,5-tetrahydro-1H-pirrole-2,3-
dione (IVb) was synthesized in a similar way. Yield
71%, mp 182–183°C (from isopropyl alcohol). IR
spectrum, ν, cm–1: 1776 (C2=O), 1719 (C3=O), 1695
1
(C6H3C=O). H NMR spectrum (DMSO-d6), δ, ppm:
1.01 t (6H, CH3CH2, J = 7.0 Hz), 1.92 s (3H, Me),
1.96 s (3H, Me), 3.24 q (4H, CH3CH2, J = 7.0 Hz),
3.94 d (1H, CH2, AB system, J = 14.5 Hz), 4.93 d (1H,
CH2, AB system, J = 14.5 Hz), 5.78 s (1H, 5-H), 6.44–
7.28 m (17H, Harom). Found, %: C 79.42; H 6.70;
N 5.20. C36H36N2O3. Calculated, %: C 79.38; H 6.66;
N 5.14.
5-(2,5-Dimethylphenyl)-2,3,5-triphenyl-3,4-di-
hydro-2H-1,3-oxazin-4-one (IIIb) was synthesized in
a similar way. Yield 48%, mp 174–176°C (decomp.,
from benzene). IR spectrum, ν, cm–1: 1668 (C4=O).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.74 s
(3H, Me), 2.12 s (3H, Me), 6.87 s (1H, 2-H), 6.92–
7.60 m (18H, Harom). 13C NMR spectrum (100 MHz,
DMSO-d6), δC, ppm: 18.34 (Me), 20.27 (Me), 89.20
(C2), 114.87 (C5), 126.28–139.02 (Carom), 160.39 (C4),
162.16 (C6). Found, %: C 83.47; H 5.82; N 3.25.
C30H25NO2. Calculated, %: C 68.89; H 5.84; N 3.25.
3-Cyclohexyl-2-cyclohexylimino-5,6-diphenyl-
3,4-dihydro-2H-1,3-oxazin-4-one (Va). A solution of
2.16 mmol of furandione Ia and 2.16 mmol of
N,N'-dicyclohexylcarbodiimide in 5 ml of dry 1,2,4-tri-
methylbenzene was heated for 30–40 min under reflux.
The mixture was cooled, and the precipitate was
filtered off. Yield 0.88 g (95%), mp 166–168°C (from
hexane). IR spectrum, ν, cm–1: 1700 (C4=O), 1655
2-p-Bromophenyl-6-(2,5-dimethylphenyl)-3-
p-methoxyphenyl-5-phenyl-3,4-dihydro-2H-1,3-oxa-
zin-4-one (IIIc) was synthesized in a similar way.
Yield 47%, mp 195–197°C (decomp., from aceto-
1
(C=N). H NMR spectrum (DMSO-d6), δ, ppm: 1.17–
1.82 m, 2.52–2.62 m, 3.78 m, and 4.79 m (22H, C6H11-
cyclo); 7.18–7.43 m (10H, Harom). 13C NMR spectrum
(100 MHz, CDCl3), δ, ppm: 24.35–55.41 (C6H11-
cyclo), 112.21 (C5), 127.73–132.18 (Carom), 138.87
(C2), 156.79 (C6), 162.06 (C4). Found, %: C 78.45;
H 7.55; N 6.58. C28H32N2O2. Calculated, %: C 78.47;
H 7.53; N 6.54.
1
nitrile). IR spectrum, ν, cm–1: 1678 (C4=O). H NMR
spectrum (CDCl3), δ, ppm: 1.85 s (3H, Me), 2.19 s
(3H, Me), 3.79 s (3H, OMe), 6.68 s (1H, 2-H), 6.82–
** NMR studies were performed at the Ural-YaMR Center under
support by the Russian Foundation for Basic Research (project
no. 00-03-40139).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XLVII.
1061
%: C 78.75; H 6.12; N 7.10. C26H24N2O2. Calculated,
%: C 78.76; H 6.10; N 7.06.
3-Cyclohexyl-2-cyclohexylimino-6-(2,5-dimethyl-
phenyl)-5-phenyl-3,4-dihydro-2H-1,3-oxazin-4-one
(Vb) was synthesized in a similar way. Yield 87%,
mp 133–135°C (from hexane). IR spectrum, ν, cm–1:
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 04-03-33024 and 04-03-96033) and by the
Ministry of Education of the Russian Federation
(project no. A03-2.11-55).
1
1702 (C4=O), 1660 (C=N). H NMR spectrum
(DMSO-d6), δ, ppm: 2.12 s (3H, Me); 2.14 s (3H, Me);
1.09–1.81 m, 2.52–2.60 m, 3.60 m, and 4.70 m (22H,
C6H11-cyclo); 7.02–7.19 m (8H, Harom). Found, %:
C 78.94; H 7.98; N 6.15. C30H36N2O2. Calculated, %:
C 78.91; H 7.95; N 6.13.
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oxazin-4-one (VIa). A solution of 2 mmol of furan-
dione Ia and 2.00 mmol of p-dimethylaminobenzo-
nitrile in 3 ml of Dowtherm A was heated for 20–
30 min at 140–145°C. The mixture was cooled, and
the precipitate was filtered off. Yield 0.63 g (85%),
mp 243–245°C (from isopropyl alcohol). IR spectrum,
ν, cm–1: 1660 (C4=O), 1621 (C=N). 1H NMR spectrum
(DMSO-d6), δ, ppm: 3.12 s (6H, Me2N), 6.78–8.08 m
(14H, Harom). Mass spectrum, m/z (Irel, %): 368 (5)
[M]+, 146 (100) [p-Me2NC6H4C≡N]+, 105 (25) [PhCO]+,
77 (16) [Ph]+. Found, %: C 78.26; H 5.50; N 7.63.
C24H20N2O2. Calculated, %: C 78.24; H 5.47; N 7.60.
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2-p-Dimethylaminophenyl-6-(2,5-dimethyl-
phenyl)-6-phenyl-4H-1,3-oxazin-4-one (VIb) was
synthesized in a similar way. Yield 94%, mp 204–
206°C (from isopropyl alcohol). IR spectrum, ν, cm–1:
1
1665 (C4=O), 1620 (C=N). H NMR spectrum
(CDCl3), δ, ppm: 2.32 s (3H, Me), 2.42 s (3H, Me),
3.07 s (6H, Me2N), 6.60–7.79 m (12H, Harom). Found,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004