A domino amino-lactonisation of arylidene pyruvic acids (APAs) by amines in aqueous media

Article abstract of DOI:10.1016/j.tet.2013.02.036

The aqueous reaction of arylidene pyruvic acids (APAs) with arylamines or urea under refluxing conditions leading to the formation of 3-(amino)-5-aryl- furan-2(5H)-one, without catalyst, is described. Also (E)-4-(4-chlorophenyl)-2- oxobut-3-enoic acid reacts with 1,2-phenylenediamine to form (E)-3-(4-chlorostyryl)quinoxalin-2(1H)-one under the same conditions. Excellent yields were observed after filtration of the product and washing with brine solution.

Full text of DOI:10.1016/j.tet.2013.02.036

Tetrahedron 69 (2013) 3257e3263
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A domino amino-lactonisation of arylidene pyruvic acids (APAs)
by amines in aqueous media
,
a
,
a
b
Morteza Shiri a , Majid M. Heravi , Bita Soleymanifard , Hendrik G. Kruger ,
*
*
Mohammad Ali Zolfigol c
a Department of Chemistry, Faculty of Science, Alzahra University, Vanak, Tehran 1993893973, Iran
b Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa
c Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The aqueous reaction of arylidene pyruvic acids (APAs) with arylamines or urea under refluxing conditions
leading to the formation of 3-(amino)-5-aryl-furan-2(5H)-one, without catalyst, is described. Also (E)-4-(4-
chlorophenyl)-2-oxobut-3-enoic acid reacts with 1,2-phenylenediamine to form (E)-3-(4-chlorostyryl)
quinoxalin-2(1H)-one under the same conditions. Excellent yields were observed after filtration of the
product and washing with brine solution.
Received 4 November 2012
Received in revised form 23 January 2013
Accepted 11 February 2013
Available online 16 February 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Cascade reaction
arylidene pyruvic acids
Lactone
cyclisation
Aqueous media
1. Introduction
Arylidene pyruvic acids (APAs) 1 have a versatile structure and
have been used as starting materials for the synthesis of a large
Nowadays green and sustainable chemistry present huge chal-
lenges for the various branches of science.1 Green chemistry
involves the planning and execution of reactions with the aim to
reduce the use and production of harmful chemicals. Two major
sources of pollution in conventional reaction media for organic
reactions are solvents and catalysts. The drive for greener methods
has led to numerous exciting advances in the design of reactions
under solvent- and catalyst-free conditions or to introduce envi-
ronmentally benign solvents and catalysts.1
diversity of organic compounds.16 Although there are some erro-
neous reports17,18 on the identification of the main product isolated
from the reaction of amines and APAs, the correct structures,
namely 3-(amino)-5-aryl-furan-2(5H)-ones 2 have subsequently
been established by the same group (Scheme 1).19 Inspection of the
Water is the most suitable green solvent since it comes from the
heart of nature and it is safe, not to mention its cost-effectiveness.
In some cases it was reported that certain organic reactions in
water without any additives proceed better than in conventional
organic solvents. Sharpless named these ‘on water’ reactions.2,3 In
addition, certain reactions in water forms water-insoluble products,
which facilitate easier isolation and purification of the products.
g
-Lactone derivatives are important heterocyclic compounds
and they display a wide range of applications in medicinal chem-
istry.4e6 In particular, unsaturated
-lactones or butenolides
g
are known to exhibit significant biological and pharmacological
importance and are also present in many natural products.7e15
* Corresponding authors. Fax: þ98 21 88041344; e-mail addresses: mshiri@
Scheme 1.
alzahra.ac.ir (M. Shiri), mmh1331@yahoo.com (M.M. Heravi).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.036

3258
M. Shiri et al. / Tetrahedron 69 (2013) 3257e3263
reaction mechanism (see Scheme 1) suggests that the imine in-
termediate A and also product 2 are sensitive to water, therefore
the reaction was reported in absolute ethanol.17e19
1.5 h under reflux conditions and the precipitate was filtered and
washed with brine to give 2a as the sole product in 80% yield
without any further purification (Scheme 1 and Table 1, entry 1).
The reaction was repeated for other derivatives of aniline, which
also gave good yields for both electron-donating groups (such as
Me and OMe) and electron-withdrawing groups (such as Cl, Br, CF3
and NO2) (Table 1, entries 2e8).
Following our initial study on the chemistry of APAs,20 herein
we wish to report the reaction APAs with amines in water without
any additive leading to 3-amino-5-arylbutenolides.
Afterwards the scope of the reaction was evaluated using
methyl and methoxy derivatives of APAs (Scheme 1). To our delight,
all the aniline derivatives screened yielded the expected 3-amino-
5-arylbutenolides 2ie2u in good isolated yields (Table 1, entries
9e21).
2. Results and discussion
We first investigated the reaction of (E)-4-(4-chlorophenyl)-2-
oxobut-3-enoic acid (1a) and aniline in water. Although the re-
action did not proceed at room temperature, it was completed after
Table 1
Tandem amino-lactonisation of arylidene pyruvic acids (APAs) with different amines
Entry
APA
Amine
Aniline
Product
Isolated yield (%)
1
1a
80
2a
2b
2
1a
4-Methylaniline
75
3
4
1a
1a
4-Methoxyaniline
4-Bromoaniline
77
81
2c
2d
2e
5
6
1a
1a
4-Chloroaniline
83
80
2,4-Dichloroaniline
2f
7
8
1a
1a
3-(Trifluoromethyl) aniline
75
72
2g
2-Nitroaniline
2h

M. Shiri et al. / Tetrahedron 69 (2013) 3257e3263
3259
Table 1 (continued )
Entry
APA
Amine
Aniline
Product
Isolated yield (%)
9
1b
78
2i
10
1b
2,4-Dichloroaniline
82
2j
2k
2l
11
12
1b
1b
4-Chloroaniline
4-Bromoaniline
79
75
13
14
15
1b
1b
1b
3-(Trifluoromethyl)aniline
78
81
78
2m
2n
4-Nitroaniline
4-Methylaniline
2o
16
1c
4-Methoxyaniline
81
79
2p
2q
17
18
1c
1c
Aniline
4-Chloroaniline
78
(continued on next page)
2r

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M. Shiri et al. / Tetrahedron 69 (2013) 3257e3263
Table 1 (continued )
Entry
APA
Amine
Product
Isolated yield (%)
19
20
21
1c
3-(Trifluoromethyl)aniline
76
2s
2t
1c
1c
4-Bromoaniline
79
75
2,4-Dichloroaniline
2u
The reaction of the bromo- and chloro-aniline derivatives can
potentially be expanded by transition metal catalysed coupling to
the more complex structures similar to reports in the literature.21
Aliphatic amines did not produce the desired corresponding
products, but when urea was utilised as an alternative to anilines,
some interesting results were obtained. Unlike in the synthesis of
3,4-dihydropyrimidin-2-one C through the reaction of urea and
2(1H)-one (4) in 85% yield after 24 h of reflux in water without
catalyst (Scheme 3).
a,b-unsaturated carbonyl compounds, the reaction of 1 with urea
also gave butenolides 3ae3c in 63e67% when reacted at reflux in
water. The products form via tandem imination and lactonisation
reactions (Scheme 2). The yield of 3ae3c was increased to 80e87%
when heated at reflux 96% ethanol (Scheme 2).
Scheme 3.
In addition it was discovered that 1a undergoes cyclisation
with benzene-1,2-diamine to give (E)-3-(4-chlorostyryl)quinoxalin-
3. Conclusions
In summary, we have developed a green and direct entry to
3-amino-5-arylbutenolides through the reaction of arylidene pyr-
uvic acids and arylamines or urea with water as solvent and at
reflux temperature without any catalyst and/or additive. The
products were solely purified by filtration and washing with a brine
solution without using column chromatography.
4. Experimental section
4.1. General
Chemicals were purchased from Fluka, Merck and Aldrich
chemical companies. IR spectra were recorded on a Shimadzu Infra
Red Spectroscopy IR-435. Nuclear magnetic resonance (NMR)
spectra were recorded on a Bruker Avance 400 and 600 MHz
Spectrometers in CDCl3 and DMSO-d6 as solvent. High-resolution
mass spectrometric data were obtained using a Bruker micro TOF-Q
II instrument operating at ambient temperatures and a Leco CHNS,
model 932 was used for elemental analysis.
4.2. General procedure for the reaction of APAs and amines
To a stirring solution of arylidene pyruvic acids (0.5 mmol) in
H2O (5 mL), was added the amine (0.5 mmol). The aqueous solution
was heated at reflux and the reaction was monitored by TLC. After
the appropriate time, the reaction mixture was filtered when still
hot and the products were washed with brine. Usually the crude
material was pure, but in a few cases, for example, the urea
Scheme 2.

M. Shiri et al. / Tetrahedron 69 (2013) 3257e3263
3261
derivatives, it was necessary to wash filtrate with ethanol to obtain
94e96 ꢀC; nmax (KBr plate) 3337, 1753, 1659, 1618 cmꢁ1
(600 MHz, CDCl3)
(s, 1H, NH), 7.23 (d, J 8.1 Hz, 1H), 7.28e7.30 (m, 4H), 7.40 (d, J 8.6 Hz,
2H), 7.47 (t, J 7.9 Hz,1H); dC (150 MHz, CDCl3) 81.6,113.1,113.6,118.8,
; dH
pure products.
d
¼6.05 (d, J 1.9 Hz, 1H), 6.43 (d, J 2.2 Hz, 1H), 6.61
The copies of 1H NMR and 13C NMR spectra for the all products
are presented as Supplementary data.
120.0, 124.7, 128.2, 128.7, 129.2, 130.2, 132.0, 134.3, 135.4, 141.1,
35
4.3. Spectral data and physical properties
170.4; HRMS calculated for C17
found 376.0338.
H
ClF3NNaO2 [MþNa]þ 376.0353,
11
4.3.1. 5-(4-Chlorophenyl)-3-(phenylamino)furan-2(5H)-one
(2a). Yield 114 mg, 80% as a pale yellow powder; mp 144e146 ꢀC;
4.3.8. 5-(4-Chlorophenyl)-3-(2-nitrophenylamino)furan-2(5H)-one
nmax (KBr plate) 3339, 1741, 1661, 1601 cmꢁ1
;
dH (600 MHz, CDCl3)
(2h). Yield 118 mg, 72% as a yellow powder; mp 154e156 ꢀC; nmax
6.02 (d, J 2.2 Hz, 1H), 6.39 (d, J 2.2 Hz, 1H), 6.45 (s, NH, 1H),
7.03 (t, J 7.4 Hz, 1H), 7.08 (d, J 8.0 Hz, 2H), 7.28e7.31 (m, 2H),
7.34e7.40 (m, 4H); dC (150 MHz, CDCl3) 81.7, 112.5, 117.1, 122.4,
(KBr plate) 3442, 3323, 1765, 1661, 1613 cmꢁ1
; dH (600 MHz, CDCl3)
6.08 (d, J 2.1 Hz,1H), 6.68 (d, J 2.2 Hz,1H), 7.06e7.09 (m,1H), 7.30 (d, J
8.3 Hz, 2H), 7.41 (d, J 8.3 Hz, 2H), 7.45 (d, J 8.0 Hz, 1H), 7.62e7.65 (m,
1H), 9.93 (s, 1H, NH); dC (150 MHz, CDCl3) 81.3, 117.1, 118.2, 120.8,
128.5, 129.4, 129.8, 135.0, 135.4, 140.8, 171.0; HRMS calculated for
35
C16
H
ClNNaO2 [MþNa]þ 308.0450, found 308.0442.
127.2, 128.0, 128.1, 129.3, 130.6, 134.0, 135.5, 135.9, 169.7; HRMS
12
35
calculated for C16
H
ClN2NaO4 [MþNa]þ 353.0331, found 353.0315.
11
4.3.2. 5-(4-Chlorophenyl)-3-(p-tolylamino)furan-2(5H)-
one (2b). Yield 112 mg, 75% as a pale yellow powder; mp
4.3.9. 3-(Phenylamino)-5-p-tolylfuran-2(5H)-one (2i). Yield 103 mg,
78% as a yellow powder; mp 153e155 ꢀC; nmax (KBr plate) 3340,1739,
133e135 ꢀC; nmax (KBr plate) 3371, 1741, 1665, 1614 cmꢁ1
; dH
(600 MHz, CDCl3) 2.33 (s, 3H), 6.00 (d, J 2.2 Hz, 1H), 6.31 (d, J 2.2 Hz,
1H), 6.33 (s, 1H, NH), 6.98 (d, J 6.8 Hz, 2H), 7.15 (d, J 8.3 Hz, 2H),
7.28e7.30 (m, 2H), 7.37e7.39 (m, 2H); dC (150 MHz, CDCl3) 20.5,
1621, 1601 cmꢁ1
; dH (600 MHz, DMSO-d6) 2.32 (s, 3H), 6.16 (d, J
2.2 Hz,1H), 6.76 (d, J 2.3 Hz,1H), 6.90 (t, J 6.6 Hz, 1H), 7.22 (d, J 8.0 Hz,
2H), 7.26e7.30 (m, 6H), 8.35 (s,1H, NH); dC (150 MHz, DMSO-d6) 21.3,
81.7, 114.5, 117.3, 121.2, 127.3, 129.0, 129.8, 130.2, 134.5, 138.8, 142.3,
170.9; HRMS calculated for C17H15NNaO2 [MþNa]þ 288.1067, found
288.1052.
81.3, 111.3, 116.9, 128.1, 128.9, 129.3, 129.9, 131.6, 134.8, 134.9, 137.9,
35
170.6; HRMS calculated for C17
found 322.0613.
H
ClNNaO2 [MþNa]þ 322.0621,
14
4.3.3. 5-(4-Chlorophenyl)-3-(4-methoxyphenylamino)furan-2(5H)-
4.3.10. 3-(2,4-Dichlorophenylamino)-5-p-tolylfuran-2(5H)-one
one (2c). Yield 121 mg, 77% as a yellow powder; mp 129e131 ꢀC;
(2j). Yield 136 mg, 82% as a pale yellow powder; mp 151e153 ꢀC;
nmax (KBr plate) 3440, 1623, 1578, 1532 cmꢁ1
;
dH (600 MHz, DMSO-
nmax (KBr plate) 3367, 1744, 1664, 1597 cmꢁ1
; dH (600 MHz, CDCl3)
d6) 3.71 (s, 3H), 6.18 (d, J 2.3 Hz, 1H), 6.60 (d, J 2.3 Hz, 1H), 6.87
(d, J 6.9 Hz, 2H), 7.22 (d, J 6.9 Hz, 2H), 7.41(d, J 6.7 Hz, 2H), 7.48
(d, J 6.7 Hz, 2H), 8.19 (s, 1H, NH); dC (150 MHz, DMSO-d6) 55.7, 80.9,
2.34 (s, 3H), 5.98 (d, J 2.2 Hz, 1H), 6.38 (d, J 2.6 Hz, 1H), 6.88 (s, 1H,
NH), 7.13e7.23 (m, 6H), 7.39 (d, J 2.8 Hz, 1H); dC (150 MHz, CDCl3)
21.2, 82.3, 115.1, 116.4, 122.9, 126.5, 126.8, 127.8, 128.1, 129.7, 129.7,
132.7, 136.1, 139.5, 170.4; HRMS calculated for C17H15Cl2NO2
[MþH]þ 334.0426, found 334.0411.
112.9, 114.8, 119.1, 129.2, 129.2, 129.8, 133.8, 135.6, 136.8, 154.3, 170;
35
HRMS calculated for C17
338.0565.
H
ClNNaO3 [MþNa]þ 338.0576, found
14
4.3.11. 3-(4-Chlorophenylamino)-5-p-tolylfuran-2(5H)-one
4.3.4. 3-(4-Bromophenylamino)-5-(4-chlorophenyl)furan-2(5H)-one
(2k). Yield 118 mg, 79% as a pale yellow powder; mp 148e150 ꢀC;
(2d). Yield 146 mg, 81% as a pale yellow powder; mp 155e157 ꢀC;
nmax (KBr plate) 3338, 1735, 1659, 1597 cmꢁ1
; dH (600 MHz, CDCl3)
nmax (KBr plate) 3372, 1740, 1665, 1591 cmꢁ1
;
dH (400 MHz, CDCl3)
2.38 (s, 3H), 6.02 (d, J 2.2 Hz, 1H), 6.37 (d, J 2.2 Hz, 1H), 6.44 (s, 1H,
NH), 7.01 (d, J 6.9 Hz, 2H), 7.21e7.24 (m, 4H), 7.28e7.31 (m, 2H); dC
6.00 (d, J 1.6 Hz, 1H), 6.33 (d, J 1.9 Hz, 1H), 6.43 (s, 1H, NH), 6.94
(d, J 8.7 Hz, 2H), 7.26e7.28 (m, 2H), 7.37 (d, J 8.4 Hz, 2H), 7.43
(d, J 8.7 Hz, 2H); dC (100 MHz, CDCl3) 81.6, 112.9, 114.4, 118.4, 128.2,
(150 MHz, CDCl3) 21.2, 82.4, 113.6, 118.0, 126.9, 128.7, 129.5, 129.6,
35
133.0, 139.4, 170.8; HRMS calculated for C17
322.0613, found 322.0609.
H
ClNNaO2 [MþNa]þ
14
128.9, 129.2, 132.5, 134.5, 135.3, 139.6, 170.5; HRMS calculated for
81
C16
H
Br35ClNNaO2 [MþNa]þ 387.9557, found 387.9533.
11
4.3.12. 3-(4-Bromophenylamino)-5-p-tolylfuran-2(5H)-one
4.3.5. 5-(4-Chlorophenyl)-3-(4-chlorophenylamino)furan-2(5H)-one
(2l). Yield 128 mg, 75% as a pale yellow powder; mp 152e154 ꢀC;
(2e). Yield 133 mg, 83% as a pale yellow powder; mp 147e149 ꢀC;
nmax (KBr plate) 3339, 1735, 1660, 1592 cmꢁ1
; dH (600 MHz, CDCl3)
nmax (KBr plate) 3371, 1739, 1665, 1594 cmꢁ1
;
dH (600 MHz, CDCl3)
2.38 (s, 3H), 6.01 (d, J 2.2 Hz, 1H), 6.38 (d, J 2.2 Hz, 1H), 6.48 (s, 1H,
NH), 6.96 (d, J 7.1 Hz, 2H), 7.21e7.24 (m, 4H), 7.44 (d, J 7.0 Hz, 2H); dC
6.02 (d, J 2.2 Hz, 1H), 6.35 (d, J 2.2 Hz, 1H), 6.44 (s, 1H, NH), 7.01 (d, J
8.9 Hz, 2H), 7.29 (d, J 8.7 Hz, 2H), 7.31 (d, J 8.9 Hz, 2H), 7.39 (d, J
8.6 Hz, 2H); dC (150 MHz, CDCl3) 81.5, 112.7, 118.1, 127.1, 128.2, 129.0,
(150 MHz, CDCl3) 21.2, 82.4, 113.8, 114.1, 118.3, 126.9, 128.6, 129.6,
79
132.4, 132.9, 139.4, 139.9, 170.8; HRMS calculated for C17
H BrNO2
15
129.2, 129.6, 134.6, 135.3, 139.2, 170.5; HRMS calculated for
[MþH]þ 344.0430, found 344.0415.
35
C16
H
Cl2NO2 [MþH]þ 320.0432, found 320.0390.
12
4.3.13. 5-p-Tolyl-3-(3-(trifluoromethyl)phenylamino)furan-2(5H)-
one (2m). Yield 130 mg, 78% as a pale yellow powder; mp
4.3.6. 5-(4-Chlorophenyl)-3-(2,4-dichlorophenylamino)furan-2(5H)-
one (2f). Yield 141 mg, 80% a pale yellow powder; mp 162e164 ꢀC.
Found: C, 54.2; H, 2.8; N, 3.9. C16H10Cl3NO2 requires C, 53.9; H, 2.9;
133e135 ꢀC; nmax (KBr plate) 3347, 1751, 1659, 1609 cmꢁ1
; dH
(600 MHz, CDCl3) 2.39 (s, 3H), 6.05 (d, J 2.1 Hz, 1H), 6.45 (d, J 2.1 Hz,
1H), 6.59 (s, 1H, NH), 7.22e7.24 (m, 5H), 7.27e7.31 (m, 2H), 7.46 (t, J
7.92 Hz,1H); dC (150 MHz, CDCl3) 21.2, 82.4, 113.0,114.4,118.5,119.8,
126.9, 128.4, 129.7, 130.1, 132.1, 132.7, 139.5, 141.3, 170.9; HRMS
calculated for C18H14F3NNaO2 [MþNa]þ 356.0901, found 356.0885.
N, 3.7%. nmax (KBr plate) 3368, 1744, 1663, 1596 cmꢁ1
; dH (400 MHz,
CDCl3) 6.02 (d, J 1.3 Hz, 1H), 6.40 (d, J 1.7 Hz, 1H), 6.92 (s, 1H, NH),
7.17 (d, J 8.8 Hz, 1H), 7.23e7.25 (m, 1H), 7.28 (d, J 7.8 Hz, 2H), 7.39 (d,
J 8.4 Hz, 2H), 7.44 (d, J 2.0 Hz, 1H); dC (100 MHz, CDCl3) 81.4, 114.2,
116.6, 123.1, 126.8, 127.9, 128.2, 128.4, 129.2, 129.8, 134.3, 135.4,
135.9, 170.1.
4.3.14. 3-(4-Nitrophenylamino)-5-p-tolylfuran-2(5H)-one
(2n). Yield 125 mg, 81% as a yellow powder; mp 182e184 ꢀC.
Found: C, 65.8; H, 4.5; N, 9.0. C17H14N2O4 requires C, 56.1; H, 4.6; N,
4.3.7. 5-(4-Chlorophenyl)-3-(3-(trifluoromethyl)phenylamino)furan-
2(5H)-one (2g). Yield 132 mg, 75% as a pale yellow powder; mp
8.8%. nmax (KBr plate) 3327, 1747, 1714, 1607 cmꢁ1
; dH (600 MHz,

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M. Shiri et al. / Tetrahedron 69 (2013) 3257e3263
CDCl3) 2.39 (s, 3H), 6.08 (d, J 2.2 Hz, 1H), 6.63 (d, J 2.2 Hz, 1H), 6.95
(s, 1H, NH), 7.12 (d, J 9.1 Hz, 2H), 7.24 (m, 4H), 8.25 (d, J 9.2 Hz, 2H);
dC (150 MHz, CDCl3) 21.3, 82.5, 115.6, 117.5, 126.0, 126.9, 127.5, 129.8,
132.1, 139.7, 141.7, 146.3, 170.3.
128e130 ꢀC. Found: C, 58.3; H, 3.7; N, 4.0. C17H13Cl2NO3 requires C,
58.1; H, 3.5; N, 4.1%. nmax (KBr plate) 3369, 1745, 1664, 1607 cmꢁ1
dH
(600 MHz, CDCl3) 3.84 (s, 3H), 6.02 (d, J 2.1 Hz, 1H), 6.42 (d, J 2.2 Hz,
1H), 6.93 (d, J 8.8 Hz, 2H), 7.20 (d, J 8.5 Hz, 1H), 7.24e7.28 (m, 4H),
7.45 (d, J 2.8 Hz, 1H); dC (150 MHz, CDCl3) 55.4, 82.2, 114.4, 114.8,
116.4,123.0,126.5,127.5,127.8,128.3,128.5,129.7,136.2,160.5,170.3.
;
4.3.15. 5-p-Tolyl-3-(p-tolylamino)furan-2(5H)-one (2o). Yield 108 mg,
78% as a pale yellow powder; mp 132e134 ꢀC; nmax (KBr plate) 3343,
1737, 1658, 1614 cmꢁ1
;
dH (600 MHz, CDCl3) 2.28 (s, 3H), 2.33 (s, 3H),
4.3.22. 1-(5-(4-Chlorophenyl)-2-oxo-2,5-dihydrofuran-3-yl)urea
(3a). Yield 83 mg, 65% (in H2O) and 108 mg, 86% (in EtOH) as a pale
yellow powder; mp 210e212 ꢀC; nmax (KBr plate) 3460, 3369, 3270,
5.95 (d, J 2.1 Hz, 1H), 6.29 (d, J 2.3 Hz, 1H), 6.30 (s, 1H, NH), 6.93 (d, J
8.3 Hz, 2H), 7.09 (d, J 8.3 Hz, 2H), 7.16 (d, J 8.1 Hz, 2H), 7.20 (d, J 8.1 Hz,
2H); dC (150 MHz, CDCl3) 20.9, 21.4, 82.5, 112.6, 117.2, 127.1, 129.4,
129.7, 130.2, 131.7, 133.6, 138.5, 139.4, 171.3; HRMS calculated for
C18H17NNaO2 [MþNa]þ 302.1208, found 302.1180.
3221, 3069, 1751, 1660, 1624 cmꢁ1
; dH (600 MHz, CDCl3) 6.21 (d, J
2.0 Hz,1H), 6.37 (br s, 2H, NH2), 7.12 (d, J 1.9 Hz,1H), 7.39 (d, J 8.4 Hz,
2H), 7.50 (d, J 8.7 Hz, 2H), 8.63 (s, 1H, NH); dC (150 MHz, CDCl3) 81.4,
124.1, 127.0, 129.1, 129.3, 134.0, 135.9, 155.7, 170.2; HRMS calculated
for C11H395ClN2NaO3 [MþNa]þ 275.0301, found 275.0299.
4.3.16. 5-(4-Methoxyphenyl)-3-(4-methoxyphenylamino)furan-
2(5H)-one (2p). Yield 125 mg, 81% as a yellow powder; mp
143e145 ꢀC; nmax (KBr plate) 3441, 1597, 1569, 1511 cmꢁ1
;
dH
4.3.23. 1-(2-Oxo-5-p-tolyl-2,5-dihydrofuran-3-yl)urea (3b). Yield
74 mg, 63% (in H2O) and 101 mg, 87% (in EtOH) as a pale yellow
powder; mp 213e215 ꢀC; nmax (KBr plate) 3431, 3363, 3252, 3169,
(600 MHz, DMSO-d6) 3.71 (s, 3H), 3.77 (s, 3H), 6.11 (d, J 2.2 Hz, 1H),
6.55 (d, J 2.3 Hz, 1H), 6.86 (d, J 6.9 Hz, 2H), 6.96 (d, J 6.7 Hz, 2H), 7.22
(d, J 6.8 Hz, 2H), 7.29 (d, J 8.5 Hz, 2H), 8.14 (s, 1H, NH); dC (150 MHz,
DMSO-d6) 55.7, 55.8, 81.6, 113.2, 114.6, 114.9, 118.9, 122.6, 129.0,
129.8, 135.7, 154.2, 160.2, 170.9; HRMS calculated for C18H18NO4
[MþH]þ 312.1265, found 312.1248.
1750, 1725, 1656, 1629 cmꢁ1
; dH (400 MHz, CDCl3) 2.30 (s, 3H), 6.11
(d, J 1.6 Hz, 1H), 6.33 (br s, 2H, NH2), 7.05 (d, J 1.5 Hz, 1H), 7.21 (d, J
9.0 Hz, 4H), 8.56 (s, 1H, NH); dC (100 MHz, CDCl3) 21.2, 82.2, 124.4,
126.9, 127.2, 129.8, 133.8, 138.8, 155.7, 170.4; HRMS calculated for
C12H12N2NaO3 [MþNa]þ 255.0907, found 255.0863.
4.3.17. 5-(4-Methoxyphenyl)-3-(phenylamino)furan-2(5H)-one
(2q). Yield 111 mg, 79% as a pale yellow powder; mp 152e154 ꢀC;
4.3.24. 1-(5-(4-Methoxyphenyl)-2-oxo-2,5-dihydrofuran-3-yl)urea
(3c). Yield 83 mg, 67% (in H2O) and 99 mg, 80% (in EtOH) as a pale
yellow powder; mp 209e211 ꢀC; nmax (KBr plate) 3423, 3367, 3170,
nmax (KBr plate) 3334, 1742, 1661, 1603 cmꢁ1
; dH (600 MHz, CDCl3)
3.84 (s, 3H), 6.01 (d, J 2.2 Hz, 1H), 6.40 (d, J 2.2 Hz, 1H), 6.43 (s, 1H,
NH), 6.92 (d, J 6.7 Hz, 2H), 7.02 (t, J 7.5 Hz, 1H), 7.09 (d, J 7.74 Hz, 2H),
7.29 (d, J 6.4 Hz, 2H), 7.35 (t, J 7.9 Hz, 2H); dC (150 MHz, CDCl3) 55.4,
82.3, 112.9, 114.3, 116.8, 122.0, 128.1, 128.6, 129.0, 129.5, 140.8, 171.0;
HRMS calculated for C17H15NNaO3 [MþNa]þ 304.0985, found
304.0965.
1749, 1728, 1638, 1612 cmꢁ1
; dH (600 MHz, CDCl3) 3.77 (s, 3H), 6.11
(d, J 2.0 Hz, 1H), 6.34 (br s, 2H, NH2), 6.96 (d, J 8.5 Hz, 2H), 7.05 (d, J
2.2 Hz, 1H), 7.25 (d, J 8.8 Hz, 2H), 8.57 (s, 1H, NH); dC (150 MHz,
CDCl3) 55.7, 82.2, 114.6, 124.3, 127.0, 128.5, 128.9, 155.7, 160.2, 170.4;
HRMS calculated for C12H12N2NaO4 [MþNa]þ 271.0735, found
271.0713.
4.3.18. 3-(4-Chlorophenylamino)-5-(4-methoxyphenyl)furan-2(5H)-
one (2r). Yield 123 mg, 78% as a pale yellow powder; mp
4.3.25. (E)-3-(4-Chlorostyryl)quinoxalin-2(1H)-one
120 mg, 85% as a yellow powder; mp 260 ꢀC (dec); nmax (KBr plate)
3426, 1661, 1624, 1591 cmꢁ1
dH (600 MHz, CDCl3) 7.34e7.36 (m,
2H), 7.51e7.55 (m, 3H), 7.66 (d, J 16.3 Hz, 1H), 7.80e7.82 (m, 3H),
8.08 (d, J 16.3 Hz, 1H), 12.56 (s, 1H, NH); dC (150 MHz, CDCl3) 15.8,
(4). Yield
133e135 ꢀC; nmax (KBr plate) 3313, 1783, 1657, 1598 cmꢁ1
; dH
(600 MHz, CDCl3) 3.84 (s, 3H), 6.01 (d, J 2.2 Hz, 1H), 6.36 (d, J 2.2 Hz,
1H), 6.42 (s, 1H, NH), 6.93 (d, J 2.5 Hz, 2H), 7.02 (d, J 8.9 Hz, 2H), 7.28
(m, 2H), 7.31 (d, J 8.6 Hz, 2H); dC (150 MHz, CDCl3) 55.4, 82.3, 113.4,
;
114.3, 118.0, 126.9, 127.8, 128.5, 128.9, 129.5, 139.4, 160.5, 170.7;
123.3, 124.0, 128.9, 129.5, 129.8, 130.5, 132.2, 132.8, 134.2, 135.4,
35
35
HRMS calculated for C17
316.0742.
H
15
ClNO3 [MþH]þ 316.0749, found
136.1, 153.3, 155.2; HRMS calculated for C16
305.0412, found 305.0432.
H
11
ClN2NaO [MþNa]þ
4.3.19. 5-(4-Methoxyphenyl)-3-(3-(trifluoromethyl)phenylamino)fu-
ran-2(5H)-one (2s). Yield 133 mg, 76% as a pale yellow powder; mp
139e141 ꢀC. Found: C, 61.2; H, 4.0; N, 4.0. C18H14F3NO3 requires C,
Acknowledgements
We thank Alzahra University and National Elites Foundation
(Iran) for financial support to our research group. The Catalysis and
Peptide Research Unit, School of Health Sciences, UKZN, Durban,
South Africa is also greatly appreciated for supporting analytical
methods.
59.1; H, 4.2; N, 4.0%. nmax (KBr plate) 3348,1752,1659,1611 cmꢁ1
; dH
(600 MHz, CDCl3) 3.84 (s, 3H), 6.04 (d, J 2.0 Hz, 1H), 6.44 (d, J 2.2 Hz,
1H), 6.58 (s, 1H, NH), 6.94 (d, J 8.5 Hz, 2H), 7.24 (d, J 8.2 Hz, 1H),
7.27e7.31 (m, 4H), 7.46 (t, J 7.9 Hz, 1H); dC (150 MHz, CDCl3) 55.4,
82.4, 113.0, 114.2, 114.4, 118.5, 119.8, 127.6, 128.6, 130.1, 132.2, 141.3,
160.5, 170.6.
Supplementary data
4.3.20. 3-(4-Bromophenylamino)-5-(4-methoxyphenyl)furan-2(5H)-
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.02.036.
one (2t). Yield 142 mg, 79% as a pale yellow powder; mp
144e146 ꢀC; nmax (KBr plate) 3315, 1783, 1657, 1593 cmꢁ1
; dH
(600 MHz, CDCl3) 3.84 (s, 3H), 6.01 (d, J 2.2 Hz, 1H), 6.37 (d, J 2.2 Hz,
1H), 6.45 (s, 1H, NH), 6.94 (d, J 6.5 Hz, 2H), 6.97 (d, J 6.8 Hz, 2H), 7.28
(d, J 6.2 Hz, 2H), 7.44 (d, J 6.9 Hz, 2H); dC (150 MHz, CDCl3) 55.4, 82.3,
References and notes
1. Green Reaction Media in Organic Synthesis; Mikami, K., Ed.; Wiley-Blackwell:
Oxford, UK, 2005.
2. Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.; Sharpless, K. B.
113.6,114.1,114.3,118.3,127.8,128.5, 128.8,132.4,139.9, 160.5,170.8;
79
HRMS calculated for C17
360.0237.
H
BrNO3 [MþH]þ 360.0244, found
15
Angew. Chem., Int. Ed. 2005, 44, 3275e3279.
3. Chanda, A.; Fokin, V. V. Chem. Rev. 2009, 109, 725e748.
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4.3.21. 3-(2,4-Dichlorophenylamino)-5-(4-methoxyphenyl)furan-
2(5H)-one (2u). Yield 130 mg, 75% as a pale yellow powder; mp

M. Shiri et al. / Tetrahedron 69 (2013) 3257e3263
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