The reaction of (N-isocyanimino)triphenylphosphorane with biacetyl in the presence of aromatic carboxylic acids: Efficient one-pot three-component reaction for the synthesis of 3-(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2- one derivatives

Article abstract of DOI:10.1002/hlca.201000219

Reactions of biacetyl (=butane-2,3-dione) with (N-isocyanimino) triphenylphosphorane in the presence of aromatic carboxylic acids proceed smoothly at room temperature and under neutral conditions to afford 3-(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-

Full text of DOI:10.1002/hlca.201000219

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The Reaction of (N-Isocyanimino)triphenylphosphorane with Biacetyl in the
Presence of Aromatic Carboxylic Acids: Efficient One-Pot Three-Component
Reaction for the Synthesis of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-
2-one Derivatives
by Ali Ramazani*a), Morteza Rouhania), Aram Rezaeia), Nahid Shajaria), and Ali Souldozib)
a) Chemistry Department, Zanjan University, P.O. Box 45195-313, Zanjan, Iran
(fax: þ 982415283100; e-mail: aliramazani@gmail.com)
b) Chemistry Department, Islamic Azad University – Urmia Branch, P.O. Box 969, Urmia, Iran
Reactions of biacetyl (¼ butane-2,3-dione) with (N-isocyanimino)triphenylphosphorane in the
presence of aromatic carboxylic acids proceed smoothly at room temperature and under neutral
conditions to afford 3-(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-one derivatives in high yields.
Introduction. – Due to the atom economy, convergent character, and simplicity of
one-pot procedures, multi-component condensation reactions (MCRs) have an
advantageous position among other reactions. The development of novel MCRs is
receiving growing interest from industrial-chemistry research groups and represents a
challenge for organic chemists [1][2]. The drive toward the ideal synthesis embracing
step count, ideally just one, and yield, ideally 100%, has been pursued intensively since
scientists began to construct molecules. Of course, there are many other factors that
affect these two aspects of synthesis, including cost, starting material availability, safety,
environmental concerns, and overall ease of the process, including workup and
purification [3]. The nature of the synthesis project also plays a role. Complex-
molecule total synthesis is often driven by step count, while showcasing innovative
chemistry. Traditional structureꢀactivity relationship (SAR) evaluations in medicinal
chemistry typically involve the preparation of an advanced intermediate that can be
analogued readily to introduce the molecular diversity necessary to prepare a
collection, or library, of structurally related compounds. One strategy that potentially
meets the goals of total synthesis and library production is multicomponent reaction
(MCR) chemistry, in which three or more starting materials are brought together in a
highly convergent approach to rapidly build up molecular structure and complexity [4].
1,3,4-Oxadiazoles have attracted interest in medicinal chemistry as surrogates of
carboxylic acids, esters, and carboxamides. They are an important class of heterocyclic
compounds that have a wide range of pharmaceutical and biological activities including
antimicrobial, antifungal, anti-inflammatory, and antihypertensive properties [5 – 9].
Several methods have been reported in the literature for the synthesis of 1,3,4-
oxadiazoles. These protocols are multistep in nature [10 – 16]. The most general
method involves the cyclization of diacylhydrazides with a variety of reagents, such as
SOCl2, POCl3, or H2SO4, usually under harsh reaction conditions. Few reliable and
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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operationally simple examples have been reported for the one-pot synthesis of 1,3,4-
oxadiazoles, especially from readily available carboxylic acids and acid hydrazides [17 –
21].
In recent years, several synthetic methods have been reported for the preparation of
(N-isocyanimino)triphenylphosphorane (CNNPPh3; 3) [22][23]. There are several
reports on the use of 3 in the synthesis of metal complexes [22][23]. However,
application of 3 in the synthesis of organic compounds is rather rare [24 – 32]. As part
of our ongoing program to develop efficient and robust methods for the preparation of
heterocyclic compounds [25 – 35], we sought to develop a convenient preparation of 3-
(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-ones 4a – 4l. Here, we report a one-pot
three-component reaction, which, starting from readily available biacetyl (¼ butane-
2,3-dione; 2), affords 4a – 4l (Scheme 1). In the reaction, 2 is more reactive than
aldehyde derivatives (see [24]), and, therefore, the final products 4 (Scheme 1) were
formed under fairly mild and inexpensive reaction conditions (see [24] and Exper.
Part).
Scheme 1. Three-Component Synthesis of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-one Deriv-
atives 4 (see the Table). Electron-rich ketones such as acetone 6a and acetophenone 6b are not suitable
starting materials in the three-component synthesis of 4. We also used benzil ((PhCO)2) instead of
biacetyl (2) in this reaction, but no products corresponding to 4 were observed.
Results and Discussion. – The carboxylic acid derivative 1 with biacetyl (2) and (N-
isocyanimino)triphenylphosphorane (3) in CH2Cl2 react in a 1:1:1 ratio at room
temperature to produce 3-(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-ones 4 and
Ph3PO (5; Scheme 1 and Table). The reaction proceeds smoothly and cleanly under
mild conditions, and no side reactions were observed. We also used acetone (6a) and
acetophenone (6b) instead of biacetyl (2) in this reaction, but no corresponding
products of type 4 were observed. In both cases, 2-aryl-1,3,4-oxadiazoles 7 and Ph3P¼O
(5) were formed, as already reported in [26], and 6a and 6b were recovered unchanged
(Scheme 1). As indicated in the Table, the reactions proceeded efficiently with the
electron-poor ketone 2, but electron-rich ketones such as 6a and 6b are not suitable
starting materials in this reaction. We also used 1,2-diphenylethane-1,2-dione (benzil,

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(PhCO)2) instead of biacetyl (2) in this reaction, but no corresponding products 4 were
observed. In this case, 7 and 5 were observed as the sole products (see [26]), and 1,2-
diphenylethane-1,2-dione was recovered. The high steric hindrance in the case of benzil
relative to biacetyl (2) may be responsible for the reduction of the reactivity.
Table. Synthesis of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-one Derivatives 4 (see Scheme 1)
4
Ar
Yielda) [%]
4
Ar
Yielda) [%]
a
b
c
d
e
f
4-ClꢀC6H4
4-BrꢀC6H4
3-BrꢀC6H4
2-BrꢀC6H4
4-FꢀC6H4
3-FꢀC6H4
89
90
92
80
93
90
g
h
i
j
k
l
Ph
85
82
85
88
86
80
Thiophen-2-yl
4-MeꢀC6H4
3-MeꢀC6H4
Naphthalen-2-yl
Furan-2-yl
a) Yield of isolated products.
1
The structures of the products were deduced from their IR, MS, and H- and
13C-NMR data. The mass spectra of these compounds displayed molecular-ion peaks at
the appropriate m/z values. The 1H-NMR spectrum of 4a consisted of a singlet for Me
(d(H) 1.95), a singlet for MeCO (d(H) 2.37), a singlet for OH (d(H) 4.69),
exchangeable by D2O, and a AA’BB’ for the aromatic H-atoms (d(H) 7.49 and 7.99,
3J ¼ 8.5). The 1H-decoupled 13C-NMR spectrum of 4a showed ten distinct resonances,
1
partial assignment of these resonances is given in the Exper. Part. The H- and
13C-NMR spectra of compounds 4b – 4l were similar to those of 4a, except for the
aromatic moiety, which exhibited characteristic signals with appropriate chemical
shifts.
A mechanistic rationalization for this reaction is depicted in Scheme 2. On the basis
of the chemistry of isocyanides [4], it is reasonable to assume that the first step involves
nucleophilic addition of 3 to biacetyl (2), facilitated by its protonation with the acid 1,
leading to nitrilium intermediate 8. This intermediate may be attacked by the conjugate
base of the acid 9 to form the 1:1:1 adduct 10. This adduct may undergo an
intramolecular aza-Wittig [36] reaction of the iminophosphorane moiety with the ester
C¼O group to afford the isolated 3-(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-
ones 4 by removal of Ph3P¼O (5) from intermediate 11. In this reaction, the first two
reaction steps are analogous to the well-known Passerini reaction [4], and the final step
is analogous to the well-known intramolecular aza-Wittig reaction [36] (tandem
Passerini/intramolecular aza-Wittig sequence).
Conclusions. – The reported method offers a mild, simple, and efficient route for the
preparation of 3-(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-one derivatives via a
tandem Passerini/intramolecular aza-Wittig reaction. The ease of workup, high yields,
and fairly mild reaction conditions render this reaction as a useful addition to modern
synthetic methodologies [24]. In the reaction, biacetyl (2) is more reactive than
aldehyde derivatives (see [24]), and, therefore, the final products 4 (Scheme 1) were
formed under fairly mild and inexpensive reaction conditions (see [24] and Exper.
Part). Other aspects of this process are under investigation.

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Scheme 2. Proposed Mechanism for the Formation of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-
one Derivatives 4 via Tandem Passerini/Intramolecular Aza-Wittig Sequence
Experimental Part
General. Starting materials and solvents were obtained from Merck (Germany) and Fluka
(Switzerland) and were used without further purification. The methods used to follow the reactions
were TLC and NMR, which indicated that there was no side product. Flash column chromatography
(CC): Merck silica-gel powder (SiO2). M.p.: Electrothermal 9100 apparatus; uncorrected. IR Spectra:
Jasco 6300 FTIR spectrometer. 1H- and 13C-NMR spectra: in CDCl3; Bruker DRX-250 AVANCE
spectrometer at 250.0 and 62.5 MHz, resp. EI-MS: Finnigan-MAT 8430 mass spectrometer operating at
an ionization potential of 20 eV. Elemental analyses: Heraeus CHN-O-Rapid analyzer.
General Procedure. To a magnetically stirred soln. of (N-isocyanimino)triphenylphosphorane (3;
1 mmol) and biacetyl (¼ butane-2,3-dione; 2, 1 mmol) in CH2Cl2 (7 ml) was added dropwise of a soln. of
4-chlorobenzoic acid (1a; 1 mmol) in CH2Cl2 (5 ml) at r.t. within 15 min. The mixture was stirred for 12 h.
The solvent was removed under reduced pressure, and the viscous residue was purified by CC (SiO2;
petroleum ether/AcOEt 8 :1). The solvent was removed under reduced pressure to yield the crystalline
products.
3-[5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl]-3-hydroxybutan-2-one (4a). White crystals. M.p. 111.8 –
113.38. Yield: 237 mg (89%). IR (KBr): 3427 (OH), 2929, 2857, 2382, 2346, 1729, 1607, 1486, 1282, 1151,
838. 1H-NMR: 1.95 (s, Me); 2.37 (s, MeCO); 4.69 (s, OH, exchanged by D2O addition); 7.49, 7.99
(AA’BB’, J ¼ 8.5, 8.5, 4 arom. H). 13C-NMR: 23.30 (Me); 23.72 (MeCO); 75.75 (CꢀOH); 121.75 (arom.
C); 128.38, 129.50 (4 arom. CH); 138.50 (C(4) of Ar); 164.98, 165.54 (2 C of oxadiazole); 204.44 (C¼O).
EI-MS: 267 (12, Mþ), 226 (30), 223 (100), 180 (39), 167 (13), 149 (22), 137 (36), 75 (8), 57 (5). Anal.
calc. for C12H11ClN2O3 (266.60): C 54.05, H 4.16, N 10.50; found: C 54.00, H 4.10, N 10.45.
3-[5-(4-Bromophenyl)-1,3,4-oxadiazol-2-yl]-3-hydroxybutan-2-one (4b). White crystals. M.p. 117.9 –
120.18. Yield: 280 mg (90%). IR (KBr): 3433 (OH), 2926, 2857, 2361, 2343, 1727, 1603, 1405, 1274, 1152,
835. 1H-NMR: 1.95 (s, Me); 2.37 (s, MeCO); 4.68 (s, OH, exchanged by D2O addition); 7.65, 7.92
(AA’BB’, J ¼ 8.5, 8.3, 4 arom. H). 13C-NMR: 23.31 (Me); 23.70 (MeCO); 75.74 (CꢀOH); 122.20 (C(4) of
Ar); 126.95 (arom. C); 128.49, 132.46 (4 arom. CH); 165.07, 165.60 (2 C of oxadiazole); 204.40 (C¼O).
EI-MS: 311 (5, Mþ), 267 (100), 224 (30), 182 (67), 149 (15), 102 (9), 75 (10), 57 (5). Anal. calc. for
C12H11BrN2O3 (311.11): C 46.32, H 3.56, N 9.00; found: C 46.25, H 3.50, N 8.93.
3-[5-(3-Bromophenyl)-1,3,4-oxadiazol-2-yl]-3-hydroxybutan-2-one (4c). White crystals. M.p. 102.3 –
104.68. Yield: 286 mg (92%). IR (KBr): 3355 (OH), 2957, 2848, 2359, 2343, 1726, 1552, 1466, 1221, 1157,
1
805. H-NMR: 1.95 (s, Me); 2.37 (s, MeCO); 4.71 (s, OH, exchanged by D2O addition); 7.39 (t, J ¼ 7.7,

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HꢀC(5) of Ar); 7.68, 7.99 (2d, J ¼ 7.7, 8.0, HꢀC(4), HꢀC(6) of Ar); 8.19 (s, HꢀC(2) of Ar). 13C-NMR:
23.30 (Me); 23.72 (MeCO); 75.76 (CꢀOH); 123.12 (C(3) of Ar); 125.10 (arom. C); 125.64, 129.93,
130.66, 135.12 (4 arom. CH); 164.46, 165.76 (2 C of oxadiazole); 204.37 (C¼O). EI-MS: 311 (12, Mþ), 268
(100), 227 (22), 183 (22), 155 (13), 90 (6), 75 (10). Anal. calc. for C12H11BrN2O3 (311.11): C 46.32, H 3.56,
N 9.00; found: C 46.20, H 3.54, N 8.93.
3-[5-(2-Bromophenyl)-1,3,4-oxadiazol-2-yl]-3-hydroxybutan-2-one (4d). Colorless oil. Yield:
249 mg (80%). IR (neat): 3419 (OH), 2937, 2855, 2346, 2344, 1729, 1569, 1457, 1270, 1140, 768.
1H-NMR: 1.95 (s, Me); 2.37 (s, MeCO); 4.65 (s, OH, exchanged by D2O addition); 7.25 – 7.93 (m, 4 arom.
H). 13C-NMR: 23.14 (Me); 23.78 (MeCO); 75.69 (CꢀOH); 121.78 (C(2) of Ar); 127.23 (arom. C); 127.63,
131.78, 132.84, 134.51 (4 arom. CH); 164.71, 165.94 (2 C of oxadiazole); 204.29 (C¼O). EI-MS: 311 (3,
Mþ), 268 (33), 208 (67), 196 (50), 167 (30), 149 (60), 95 (20), 75 (15), 57 (23). Anal. calc. for
C12H11BrN2O3 (311.11): C 46.32, H 3.56, N 9.00; found: C 46.27, H 3.47, N 8.95.
3-[5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl]-3-hydroxybutan-2-one (4e). White crystals. M.p. 93.2 –
95.08. Yield: 233 mg (93%). IR (KBr): 3327 (OH), 2962, 2862, 2371, 2345, 1729, 1611, 1501, 1465,
1290. 1148, 850. 1H-NMR: 1.95 (s, Me); 2.37 (s, MeCO); 4.68 (s, OH, exchanged by D2O addition); 7.16 –
7.26 (m, 2 arom. H); 8.03 – 8.09 (m, 2 arom. H). 13C-NMR: 23.27 (Me); 23.71 (MeCO); 75.73 (CꢀOH);
116.47 (d, 2J(C,F) ¼ 22.0, arom. CH); 119.62 (d, 4J(C,F) ¼ 3.7, arom. CH); 129.45 (d, 3J(C,F) ¼ 9.4, arom.
CH); 165.00 (d, 1J(C,F) ¼ 249.9, arom. C); 164.97, 165.47 (2 C of oxadiazole); 204.51 (C¼O). EI-MS; 251
(3, Mþ), 208 (7), 167 (33), 148 (100), 104 (9), 91 (6), 70 (17), 57 (40). Anal. calc. for C12H11FN2O3
(250.23): C 57.60, H 4.43, N 11.20; found: C 57.57, H 4.40, N 11.18.
3-[5-(3-Fluorophenyl)-1,3,4-oxadiazol-2-yl]-3-hydroxybutan-2-one (4f). White crystals. M.p. 81.2 –
83.18. Yield: 225 mg (90%). IR (KBr): 3422 (OH), 2927, 2857, 2359, 2343, 1725, 1596, 1470, 1268,
1121, 869. 1H-NMR: 1.95 (s, Me); 2.37 (s, MeCO); 4.71 (s, OH, exchanged by D2O addition); 7.22 – 7.86
(m, 4 arom. H). 13C-NMR: 23.29 (Me); 23.70 (MeCO); 75.75 (CꢀOH); 114.17 (d, 2J(C,F) ¼ 24.3, arom.
CH); 119.27 (d, 2J(C,F) ¼ 21.3, arom. CH); 122.88 (d, 4J(C,F) ¼ 3.1, arom. CH); 125.14 (d, 3J(C,F) ¼ 8.2,
arom. CH); 130.96 (d, 3J(C,F) ¼ 8.2, arom. CH); 162.78 (d, 1J(C,F) ¼ 248.1, arom. C); 164.79, 165.73 (2 C
of oxadiazole); 204.37 (C¼O). EI-MS: 251 (9, Mþ), 207 (63), 167 (42), 149 (100), 121 (27), 95 (10), 70
(13), 57 (27). Anal. calc. for C12H11FN2O3 (250.23): C 57.60, H 4.43, N 11.20; found: C 57.55, H 4.41, N
11.15.
3-Hydroxy-3-(5-phenyl-1,3,4-oxadiazol-2-yl)butan-2-one (4g). White crystals. M.p. 104.1 – 106.08.
Yield: 274 mg (85%). IR (KBr): 3230 (OH), 2986, 2848, 2360, 2344, 1725, 1608, 1482, 1293, 1155, 782.
1H-NMR: 1.95 (s, Me); 2.36 (s, MeCO); 4.69 (s, OH, exchanged by D2O addition); 7.50 – 7.56 (m, 3 arom.
H); 8.05 (d, J ¼ 6.5, 3 arom. H). 13C-NMR: 23.25 (Me); 23.71 (MeCO); 75.73 (CꢀOH); 123.30 (arom.
C); 127.11, 129.08, 132.13 (5 arom. CH); 152.81, 152.84 (2 C of oxadiazole); 204.56 (C¼O). EI-MS: 233
(30, Mþ), 215 (4), 189 (100), 147 (32), 119 (4), 104 (35), 77 (17), 43 (24). Anal. calc. for C12H12N2O3
(232.24): C 62.06, H 5.21, N 12.06; found: C 62.00, H 5.18, N 12.01.
3-Hydroxy-3-[5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl]butan-2-one (4h). White crystals. M.p. 70.0 –
71.58. Yield: 195 (82%). IR (KBr): 3246 (OH), 2924, 1724, 1602, 1418, 1353, 727. 1H-NMR: 1.92 (s,
Me); 2.35 (s, MeCO); 4.80 (s, OH, exchanged by D2O addition); 7.11 – 7.19 (m, 1 H of thiophene); 7.56 (d,
J ¼ 4.7, 1 H of thiophene); 7.75 (d, J ¼ 3.2, 1 H of thiophene). 13C-NMR: 23.56, 24.08 (2 Me); 76.05
(CꢀOH); 124.68 (C of thiophene); 128.54, 130.85, 131.12 (3 CH of thiophene); 162.30, 165.20 (2 C¼N);
204.90 (C¼O). EI-MS: 238 (3, Mþ), 196 (72), 194 (38), 168 (4), 153 (62), 127 (23), 111 (55), 97 (5), 83
(13), 69 (14). Anal. calc. for C10H10N2O3S (238.26): C 50.41, H 4.23, N 11.76; found: C 50.29, H 4.19, N
11.70.
3-Hydroxy-3-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]butan-2-one (4i). White crystals. M.p. 97.5 –
1
98.58. Yield: 209 mg (85%). IR (KBr): 3422 (OH), 2921, 1728, 1612, 1498, 1362, 826. H-NMR: 1.92,
2.34, 2.39 (3s, 3 Me); 4.91 (s, OH; exchanged by D2O addition); 7.27 (d, J ¼ 8.0, 2 arom. H); 7.89 (d, J ¼
8.0, 2 arom. H). 13C-NMR: 21.93, 23.52, 24.10 (3 Me); 76.10 (CꢀOH); 120.71 (arom. C); 127.33, 130.05 (4
arom. CH); 143.07 (arom. C); 165.56, 166.17 (2 C¼N); 205.13 (C¼O). EI-MS: 246 (3, Mþ), 223 (5), 204
(50), 161 (45), 118 (43), 105 (5), 91 (50), 77 (9), 65 (18), 43 (100). Anal. calc. for C13H14N2O3 (246.26): C
63.40, H 5.73, N 11.38; found: C 63.37, H 5.69, N 11.33.
3-Hydroxy-3-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]butan-2-one (4j). White crystals. M.p. 75.0 –
76.58. Yield: 217 mg (88%). IR (KBr): 3421 (OH), 2926, 1728 (C¼O), 1609, 1458, 1377, 806.

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1H-NMR: 1.92, 2.35, 2.39 (3s, 3 Me); 4.92 (s, OH; exchanged by D2O addition); 7.26 – 7.38 (m, 2 arom. H);
7.75 – 7.89 (m, 2 arom. H). 13C-NMR: 21.53, 23.51, 24.10 (3 Me); 76.12 (CꢀOH); 123.34 (arom. C);
124.52, 127.83, 129.24, 133.23 (4 arom. CH); 139.26 (arom. C); 165.74, 166.16 (2 C¼N); 205.10 (C¼O).
Anal. calc. for C13H14N2O3 (246.26): C 63.40, H 5.73, N 11.38; found: C 63.37, H 5.66, N 11.30. EI-MS: 247
(2, Mþ), 204 (100), 161 (53), 133 (4), 118 (46), 91 (39), 77 (5), 65 (14), 43 (76), 41 (4).
3-Hydroxy-3-[5-(naphthalen-2-yl)-1,3,4-oxadiazol-2-yl]butan-2-one (4k). White crystals. M.p.
120.0 – 121.68. Yield: 243 mg (86%). IR (KBr): 3448 (OH), 2923, 1725 (C¼O), 1577, 1458, 1362, 755.
1H-NMR: 1.99, 2.40 (2s, 2 Me); 4.79 (s, OH; exchanged by D2O addition); 7.54 – 7.61 (m, 2 arom. H);
7.87 – 7.91 (m, 2 arom. H); 7.95 (d, J ¼ 8.6, 1 arom. H); 8.11 (d, J ¼ 8.6, 1 arom. H); 8.54 (s, 1 arom. H).
13C-NMR: 23.67, 24.13 (2 Me); 76.18 (CꢀOH); 120.82 (arom. C); 123.47, 127.55, 128.13, 128.31, 128.56,
129.24, 129.46 (7 arom. CH); 133.07, 135.19 (2 arom. C); 165.83, 166.30 (2 C¼N); 205.01 (C¼O). EI-MS:
282 (2, Mþ), 240 (100), 197 (67), 153 (72), 127 (47). Anal. calc. for C16H14N2O3 (282.29): C 68.07, H 5.00,
N 9.92; found: C 68.00, H 4.94, N 9.89.
3-[5-(Furan-2-yl)-1,3,4-oxadiazol-2-yl]-3-hydroxybutan-2-one (4l). White crystals. M.p. 100.68
(dec.). Yield: 178 mg (80%). IR (KBr): 3423 (OH), 2924, 1722 (C¼O), 1636, 1458, 1370, 752.
1H-NMR: 1.94, 2.35 (2s, 2 Me); 4.66 (s, OH, exchanged by D2O addition); 6.56 – 6.63 (m, 1 H of furan);
7.19 (d, J ¼ 3.2, 1 H of furan); 7.65 (s, 1 H of furan). 13C NMR: 23.64, 24.02 (2 Me); 76.02 (CꢀOH); 112.61,
115.28, 146.46 (3 CH of furan); 139.20 (C of furan); 163.01, 165.08 (2 C¼N); 204.62 (C¼O). EI-MS: 222
(2, Mþ), 196 (29), 180 (10), 153 (27), 127 (11), 111 (24), 95 (10), 83 (6), 43 (100), 41 (5). Anal. calc. for
C10H10N2O4 (222.20): C 54.05, H 4.54, N 12.61; found: C 54.00, H 4.49, N 12.58.
This work was supported by the ꢂZanjan Universityꢃ and the ꢂIran National Science Foundation:
INSFꢃ.
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Received June 3, 2010