Simple, convenient method for the synthesis of substituted furan-2(5 H)-one derivatives using tin(II) chloride

Article abstract of DOI:10.1080/00397911.2011.554062

Furan-2(5H)-one derivatives have been synthesized by a simple, efficient, one-pot, three-component condensation of anilines, dimethylacetylenedicarboxylate, and aromatic aldehydes in the presence of a catalytic amount of tin(II) chloride in excellent yields.

Full text of DOI:10.1080/00397911.2011.554062

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Simple, Convenient Method for the
Synthesis of Substituted Furan-2(5H)-one
Derivatives Using Tin(II) Chloride
Lingaiah Nagarapu a , U. Nikhil Kumar a , P. Upendra a & Rajashaker
Bantu a
a Organic Chemistry Division II, Indian Institute of Chemical
Technology, Hyderabad, India
Available online: 07 Dec 2011
To cite this article: Lingaiah Nagarapu, U. Nikhil Kumar, P. Upendra & Rajashaker Bantu (2012):
Simple, Convenient Method for the Synthesis of Substituted Furan-2(5H)-one Derivatives Using Tin(II)
Chloride, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 42:14, 2139-2148
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Synthetic Communications1, 42: 2139–2148, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.554062
SIMPLE, CONVENIENT METHOD FOR THE SYNTHESIS
OF SUBSTITUTED FURAN-2(5H)-ONE DERIVATIVES
USING TIN(II) CHLORIDE
Lingaiah Nagarapu, U. Nikhil Kumar, P. Upendra, and
Rajashaker Bantu
Organic Chemistry Division II, Indian Institute of Chemical Technology,
Hyderabad, India
GRAPHICAL ABSTRACT
Abstract Furan-2(5H)-one derivatives have been synthesized by a simple, efficient, one-pot,
three-component condensation of anilines, dimethylacetylenedicarboxylate, and aromatic
aldehydes in the presence of a catalytic amount of tin(II) chloride in excellent yields.
Keywords Dimethylacetylenedicarboxylate; furan-2(5H)-ones; three-component conden-
sation; tin(II) chloride
INDRODUCTION
2(5H)-Furanones are versatile synthetic modules in organic synthesis and are
key structural elements present in many biologically active natural products.[1] They
occur widely in nature and have recently attracted considerable attention as
plant-growth regulators, antiulcer agents, and fish-growth promoters.[2] The devel-
opment of new synthetic methods for the efficient preparation of natural products
containing furanone ring fragments (Fig. 1; freelingyne 1, tetrenoline 2, and sarco-
phine 3) is ongoing because they have biological activities such as antibacterial,
antifungal, antimicrobial, antiviral, anticancer, anti-inflamatory, antipsoriasis, and
anti–phospholipase A2 activities.[3] The unusual range of usefulness of compounds
Received November 10, 2010.
Address correspondence to Lingaiah Nagarapu, Organic Chemistry Division II, Indian Institute
of Chemical Technology, Hyderabad 500 607, India. E-mail: nagarapu@iict.res.in; lnagarapuiict@
yahoo.com
2139

2140
L. NAGARAPU ET AL.
Figure 1. Natural products containing furanone ring fragment.
containing the basic butenolide ring has stimulated considerable research on the
synthesis of these valuable compounds. In recent years, development of newer meth-
ods for the synthesis of natural products is gaining interest in the chemical community.
In view of these biological activities, the chemists have developed a number of
methodologies[4–6] for the synthesis of 2(5H)-furanones.[4] However, these methods
suffer from poor yields and practical utility in organic synthesis because of harsh
reaction conditions, long reaction times, and use of expensive, toxic, and moisture-
sensitive reagents. Therefore, development of a practical and economical method for
the synthesis of substituted furan-2(5H)-ones is highly desirable.
Recently, SnCl2 ꢀ 2H2O has emerged as a medium and catalyst in various
organic transformations such as synthesis of quinoline derivatives,[7] conjugate
addition of indoles to a,b-unsaturated ketones,[8] synthesis of bisindolylmethanes,[9]
the Paul–Knorr synthesis of pyrroles,[10] and the Fisher indole synthesis.[11] In view
of its properties such as environmental compatibility, reusability, greater selectivity,
operational simplicity, noncorrosiveness, low cost, and ease of isolation of products,
we planned use it in developing newer synthetic applications. We here describe our
results of SnCl2 ꢀ 2H2O-catalyzed, one-pot condensation of aniline, dimethylacetyle-
nedicarboxylate, and aromatic aldehydes under ethanolic media at reflux tempera-
ture to give substituted furan-2(5H)-ones (Scheme 1).
In continuation of our studies[12] of the synthesis of novel compounds as useful
biologically active compounds, we report in this communication an efficient synthesis
of substituted furan-2(5H)-one derivatives. To the best of our knowledge, in literature
there appears no report for the synthesis and screening of 4,5-substituted furan-2(5-
H)-one derivatives using SnCl2 ꢀ 2H2O. This fact has prompted us to investigate in
depth the utility of SnCl2 ꢀ 2H2O for the synthesis of substituted furan-2(5H)-ones.
Scheme 1. Synthesis of substituted methyl 2,5-dihydro-5-oxo-2-phenyl-4-(phenyl amino)furan-3-carboxy-
late derivatives.

FURAN-2(5H)-ONE DERIVATIVES
2141
Initially, a pilot reaction was attempted using aniline 1, dimethylacetylenedi-
carboxylate 2, and benzaldehyde 3 in the presence of SnCl2 ꢀ 2H2O (0.03 mmol)
and in the absence of solvent. This reaction (10 h) resulted in the isolation of the
required product, namely methyl 2,5-dihydro-5-oxo-2-phenyl-4-(phenylamino)-
furan-3-carboxylate 4a, in poor yield (45%). Increasing the amount of SnCl2 ꢀ 2H2O
O to 1 mol equivalent did not improve the product yield by a considerable amount.
Subsequently, we investigated the use of different catalysts and solvents for the pur-
pose. In chlorinated solvents such as dichloromethane and chloroform, the reaction
was very slow and resulted in lower product yield. Similar results were obtained in
coordinating solvents such as tetrahydrofuran (THF) and diethyl- and dimethyl
ethers. Conducting the reaction in protic solvents such as MeOH or EtOH improved
the reaction rates as well as product yields. After screening different solvents, EtOH
was the solvent of choice, which not only afforded the products in good yield but
also with faster reaction rates (90% yield in 6.5 h) (Table 1). The condensation using
SnCl2 ꢀ 2H2O proceeds rapidly and is superior with respect to reaction time, tempera-
ture, and yield. This claim is justified through the representative examples, illustrated
in Table 1, in which the efficiency of SnCl2 ꢀ 2H2O is compared with those of different
Lewis and protic acid catalysts (Table 1). The formation of compound 4a was evi-
dent from the appearance of the [M þ H]þ peak at m=z 310 in mass spectrum
ꢁ1
=
(ESI), -C O stretching at 1710 cm
in infrared (IR), and the appearance of
methoxy proton as singlet at d 3.70 and the characteristic proton of furanone at d
5.70 in H NMR.
1
To extend the scope of this catalytic transformation and find the general appli-
cability of this method, a reaction of aniline (1) and dimethylacetylenedicarboxylate
(2) with benzaldehyde (3) was verified. No observable ortho- and para-substituent
effect was noted for various anilines used in the reaction (entry 4k). This was one
of the drawbacks of the earlier methods. Anilines 1a–m, dimethylacetylenedicar-
boxylate 2, and aromatic aldehydes 3a–m in the presence of SnCl2 ꢀ 2H2O undergo
a fast 1:1:1 addition reaction at reflux temperature in ethanol (6.5–7.5 h) to produce
substituted furan-2(5H)-ones derivatives 4a–m (Scheme 1) (Table 2). The results were
excellent in terms of yields and product purity, and compounds 4a–m are stable
1
solids whose structures are fully supported by IR, H NMR, 13C NMR, and mass
spectrometric analyses.
Table 1. Effect of different reagents and solvents in the condensation of
benzaldehyde, aniline, and dimethylacetylenedicarboxylate
Entrya
Catalyst
Solvent
Condition
Time (h)
Yield (%)b
1
2
3
4
5
6
BF3 ꢀ Et2O
TBAB
TBAB
CH3CN
Neat
Reflux
Reflux
Reflux
Reflux
RT
14.0
11.0
10.0
9.0
36
42
EtOH
Neat
48
45
SnCl2 ꢀ H2O
SnCl2 ꢀ 2H2O
SnCl2 ꢀ 2H2O
EtOH
EtOH
11.09
6.5
65
990
Reflux
aAll reactions were performed using benzaldehyde (1.0 mmol), aniline
(1.0 mmol), and dimethylacetylenedicarboxylate (1.0 mmol).
bCombined isolated yields.

2142
L. NAGARAPU ET AL.
Table 2. SnCl2 ꢀ 2H2O-catalyzed synthesis of substituted furan-2(5H)-ones
Entry
Aldehydes
Antines
Product
Time(h) Yield (%)a
a
6.5
7.0
7.0
90
89
88
b
c
d
e
7.0
7.0
88
85
f
7.0
7.0
7.0
7.0
86
87
88
g
h
i
89
(Continued )

FURAN-2(5H)-ONE DERIVATIVES
Table 2. Continued
2143
Entry
Aldehydes
Antines
Product
Time(h) Yield (%)a
j
7.0
7.0
87
86
k
l
7.0
7.0
87
88
m
aIsolated yields.
Tin(II) chloride (SnCl2 ꢀ 2H2O) showed remarkable reactivity as a ‘‘hard–soft’’
reagent and considerably accelerated the reactions. On the basis of all our experi-
mental results, together with literature reports, we propose a plausible mechanism
for the formation of furan-2(5H)-one derivatives 4a–m in the presence of
SnCl2 ꢀ 2H2O (Scheme 2). The hypothesis is supported by the fact that the reaction
Scheme 2. Plausible mechanism for the formation of methyl 2,5-dihydro-5-oxo-2-phenyl-4-
(phenylamino)furan-3-carboxylate 4a.

2144
L. NAGARAPU ET AL.
proceeds via the formation of enamine (X) of aniline=dimethylacetylenedicarboxy-
late carbanion and subsequent reaction of aldehyde and cyclodehydration gives
furan-2(5H)-one as indicated in Scheme 2. The simplicity, together with the use of
inexpensive and environmentally benign SnCl2 ꢀ 2H2O catalyst under ethanol media,
are other remarkable features of the procedure. The reaction mixture cooled to room
temperature; the precipitate formed was filtered and dried to give crude residue,
which was crystallized in ethanol to give pure 4a–m in excellent yields.
In conclusion, we have successfully synthesized and characterized derivatives of
substituted furan-2(5H)-one using a catalytic amount of tin(II) chloride. This simple
procedure is efficient and can be applied to a wide variety of aromatic aldehydes and
anilines. Shorter reaction times and excellent product yields make this catalytic sys-
tem an alternative method for the synthesis of substituted furan-2(5H)-ones deriva-
tives. Further application to explore this simple catalytic system for construction of
biological molecules is under way. The remarkable catalytic activity of SnCl2 ꢀ 2H2O
is convincingly superior to other recently reported catalytic methods with respect to
reaction time and amount of catalyst used. Easy workup and ready availability of
the catalyst make the procedure superior to the existing methods. Furthermore,
the present protocol is readily amenable to parallel synthesis and generation of
combinatorial substituted furan libraries.
EXPERIMENTAL
Melting points were determined using Fisher John’s melting-point apparatus
and are uncorrected. IR spectra were recorded on a Thermo Nicolet Nexus 670
Fourier transform (FT)–IR spectrometer. Accurate mass measurement was perfor-
med on a Q STAR mass spectrometer (Applied Biosystems USA). 1H NMR spectra
and 13C NMR were recorded at 300 MHz on a Bruker Avance NMR spectrometer
with tetramethylsilane (TMS) as an internal standard (chemical shifts in d, ppm).
Optical rotations were measured with a Jasco DIP-370 instrument. For column
chromatography, silica gel (60–120 mesh) was used. For thin-layer chromatography
(TLC), silica gel 60 F254 (Merck) was used.
General Procedure for Synthesis of 4a–m
To a solution of aniline (1a, 1.0 mmol), dimethylacetylenedicarboxylate (2a,
1.0 mmol), and benzaldehyde (3a, 1.0 mmol) was added SnCl2 ꢀ 2H2O (0.3 mmol).
The mixture was refluxed for 2–6 h in 2.0 mL of ethanol (progress of the reaction
was monitored by TLC). After completion, the reaction mass was cooled to room
temperature, and the solid products were obtained filtered through a Buchner funnel,
washed with ethanol (2 ꢂ 5 mL), and dried. The crude product was recrystallized in
ethanol.
Methyl-2,5-dihydro-5-oxo-2-phenyl-4-(phenylamino)furan-3-
carboxylate (4a)
Yield 90%; mp 160–163 ꢃC; IR (KBr): nmax 3209, 2953, 1680, 1596, 1233,
1132 cmꢁ1 1H NMR (300 MHz, DMSO-d6): d 3.75 (s, 3H, CH3), 5.68 (s, 1H,
.

FURAN-2(5H)-ONE DERIVATIVES
2145
benzylic), 7.07–7.45 (m, 10H, Ar-H). 13C NMR (75 MHz, DMSO-d6): d 50.71,
122.36, 125.56, 127.59, 127.74, 128.12, 128.67, 128.85, 135.91, 136.79, 162.83. HRMS
(ESI) m=z calcd. for C18H16NO4 310.1074; found 310.1066.
Methyl-2-(4-methylphenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-
furan-3-carboxylate (4b)
Yield 89%; mp 180–183 ꢃC; IR (KBr): nmax 3292, 3053, 2954, 1686, 1595, 1195,
1127 cmꢁ1. H NMR (300 MHz, DMSO-d6) d 2.56 (s, 3H, CH3), 3.60 (s, 3H, CH3),
6.18 (s, 1H, benzylic), 7.05–7.40 (m, 9H, Ar-H); 13C NMR (75 MHz, DMSO-d6) d
18.99, 51.08, 122.77, 124.74, 125.65, 126.08, 127.48, 128.70, 130.33, 136.32, 137.28,
162.56; MS- ESI: m=z ¼ 324 ([M þ H]þ).
Methyl-2-(4-methoxyphenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-
furan-3-carboxylate (4c)
Yield 88%; mp 240–243 ꢃC; IR (KBr) nmax 2954, 1667, 1607, 1202, 1121 cmꢁ1
;
1H NMR (300 MHz, DMSO-d6) d 3.64 (s, 3H, CH3), 3.70 (s, 3H, CH3), 5.80 (s, 1H,
benzylic), 6.71–7.49 (m, 9H, Ar-H); 13C NMR (75 MHz, DMSO-d6) d 54.89, 113.98,
122.50, 128.85, 158.63. HRMS (ESI) m=z calcd. for C19H18NO5 340.1184; found
340.1074.
Methyl-2-(3-methoxyphenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-
furan-3-carboxylate (4d)
1
Yield 88%; IR (KBr) nmax 2950, 2837, 1705, 1637, 1597, 1227, 1025 cmꢁ1; H
NMR (300 MHz, DMSO-d6) d 3.66 (s, 3H, CH3), 3.71 (s, 3H, CH3), 5.80 (s, 1H,
benzylic), 6.71–7.49 (m, 9H, Ar-H); MS-ESI: m=z ¼ 340 ([M þ H]þ).
Methyl-2-(2,4-dimethoxyphenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-
furan-3-carboxylate (4e)
Yield 85%; mp > 300 ꢃC; IR (KBr) nmax 2949, 1662, 1608, 1207, 1159 cmꢁ1; 1H
NMR (300 MHz, DMSO-d6) d 3.60 (s, 3H, CH3), 3.69 (s, 3H, CH3) 3.81 (s, 3H,
CH3), 6.12 (s, 1H, benzylic), 7.05–7.50 (m, 8H, Ar-H); MS-ESI: m=z ¼ 370
([M þ H]þ).
Methyl-2-(2-chlorophenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-
furan-3-carboxylate (4f)
Yield 86%; mp 274–276 ꢃC; IR (KBr) nmax 3062, 2949, 1668, 1602, 1249,
1197 cmꢁ1 1H NMR (300 MHz, DMSO-d6) d 3.66 (s, 3H, CH3), 5.86 (s, 1H,
;
benzylic), 7.07–7.54 (m, 9H, Ar-H); 13C NMR (75 MHz, DMSO-d6) d 50.59,
122.34, 126.03, 128.17, 128.87, 129.51, 132.29, 135.51, 136.26, 163.12. HRMS
(ESI) m=z calcd. for C18H15NClO4 344.0689; found 344.0678.

2146
L. NAGARAPU ET AL.
Methyl-2-(4-chlorophenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-
furan-3-carboxylate (4g)
Yield 87%; mp 148–151 ꢃC; IR (KBr) nmax 3216, 2951, 1687, 1637, 1231,
1130 cmꢁ1 1H NMR (300 MHz, DMSO-d6) d 3.67 (s, 3H, CH3), 5.83 (s, 1H,
;
benzylic), 7.07–7.48 (m, 9H, Ar-H); MS-ESI: m=z ¼ 344 ([M þ H]þ).
Methyl-2-(2,4-dichlorophenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-
furan-3-carboxylate (4h)
Yield 88%; mp 272–274 ꢃC; IR (KBr) nmax 2947, 1669, 1601, 1243, 1196 cmꢁ1
;
1H NMR (300 MHz, DMSO-d6) d 3.61 (s, 3H, CH3), 6.35 (s, 1H, benzylic), 7.11–7.44
(m, 8H, Ar-H); 13C NMR (75 MHz, DMSO-d6) d 50.62, 58.06, 122.07, 126.34,
127.71, 128.67, 128.79, 129.02, 132.98, 134.08, 135.30, 162.97; MS-ESI: m=z ¼ 378
([M þ H]þ).
Methyl-2-(4-isopropylphenylamino)-2,5-dihydro-5-oxo-2-
phenylfuran-3-carboxylate (4i)
Yield 89%; mp > 300 ꢃC; IR (KBr) nmax 3197, 2958, 1682, 1513, 1230, 1131 cmꢁ1
;
1H NMR (300 MHz, DMSO-d6) d 1.12 [d, 6H, J ¼ 6.98 Hz, CH(CH3)2], 2.79 (m, 1H,
CH), 3.58 (s, 3H, CH3), 6.02 (s, 1H, benzylic), 7.15–7.47 (m, 9H, Ar-H); 13C NMR
(75 MHz, DMSO-d6) d 23.56, 23.65, 32.73, 50.99, 60.83, 112.06, 122.39, 126.43,
127.57, 128.86, 128.23, 133.94, 162.68, 164.14; MS-ESI: m=z ¼ 352 ([M þ H]þ).
Methyl-2-(4-trifluoromethoxyphenylamino)-2,5-dihydro-5-oxo-2-
phenylfuran-3-carboxylate (4j)
Yield 87%; mp 188–191 ꢃC; IR (KBr) nmax 3317, 3125, 3027, 2963, 1714, 1655,
1
1207, 1138 cmꢁ1; H NMR (300 MHz, DMSO-d6) d 3.62 (s, 3H, CH3), 5.98 (s, 1H,
benzylic), 7.18–7.68 (m, 9H, Ar-H); 13C NMR (300 MHz, DMSO-d6) d 51.06,
121.32, 123.88, 127.60, 127.98, 128.31, 128.84, 135.27, 136.12, 162.36, 164.11. HRMS
(ESI) m=z calcd. for C19H15NF3O5 394.0902; found 394.0890.
Methyl-2-(2-fluorophenylamino)-2,5-dihydro-5-oxo-2-phenylfuran-3-
carboxylate (4k)
Yield 86%; mp > 300 ꢃC; IR (KBr) nmax 3312, 3062, 2954, 1707, 1633, 1261,
1145 cmꢁ1 1H NMR (300 MHz, DMSO-d6) d 3.44 (s, 3H, CH3), 5.77 (s, 1H,
;
benzylic), 7.09–7.35 (m, 9H, Ar-H); MS-ESI: m=z ¼ 328 ([M þ H]þ).
Methyl-2-(4-fluorophenylamino)-2,5-dihydro-5-oxo-2-phenylfuran-3-
carboxylate (4l)
Yield 87%; mp 295–297 ꢃC; IR (KBr) nmax 3313, 3062, 2924, 1708, 1632, 1257,
1096 cmꢁ1 1H NMR (300 MHz, DMSO-d6) d 3.34 (s, 3H, CH3), 5.91 (s, 1H,
;
benzylic), 7.15–7.46 (m, 9H, Ar-H); 13C NMR (75 MHz, DMSO-d6) d 50.73,

FURAN-2(5H)-ONE DERIVATIVES
2147
63.13, 114.94, 115.2, 116.04, 116.31, 123.78, 124.53, 125.87, 127.381, 128.23, 140.56,
155.17, 157.69, 163.16, 163.38; MS-ESI: m=z ¼ 328 ([M þ H]þ).
Methyl-2-(4-methylphenylamino)-2,5-dihydro-5-oxo-2-phenylfuran-
3-carboxylate (4m)
Yield 88%; mp 285–288 ꢃC; IR (KBr) nmax 3029, 2923, 1709, 1640, 1249,
1137 cmꢁ1 1H NMR (300 MHz, DMSO-d6) d 2.22 (s, 3H, CH3), 3.60 (s, 3H,
;
CH3), 5.90 (s, 1H, benzylic), 7.04–7.39 (m, 9H, Ar-H); MS-ESI: m=z ¼ 324
([M þ H]þ).
ACKNOWLEDGMENTS
The authors are thankful to the director and head, Organic Chemistry Division
II, Indian Institute for Chemical Technology (IICT), Hyderabad, for their constant
encouragement and support. N. K. U. and U. P. thank the Council for Scientific and
Industrial Research, New Delhi, for financial support.
REFERENCES
1. Rao, Y. S. Recent advances in the chemistry of unsaturated lactones. Chem. Rev. 1976, 76,
625–694.
2. (a) Nemchenko, V. V.; Ivanova, N. P. Humic substances in terrestrial ecosystems. Khim.
Sel’sk. Khoz. 1991, 1, 91–93; Chem. Abrstr. 1991, 115, 44136; (b) Aihara, H.; Muramatsu,
M.; Arai, I. Jpn Kokai Tokkyo Koho 1988, 225315, 1988; Chem. Abs. 1989, 110, 63776; (c)
Tsen, L. N.; Suleimanyan, V. S. A convenient synthesis of 2(5H)-furanone. Rybn. Khoz
(Moscow) 1982, 5, 37–42; Chem. Abs. 1979, 90, 54751.
3. (a) Massy-Westropp, R. A.; Reynolds, G. D.; Spotswood, T. M. Freelingyne, an acetylenic
sequiterpenoid. Tetrahedron Lett. 1966, 7, 1939–1946; (b) Khalid, A.; Sayed, E.; Khaled,
Y.; Orabi, D.; Dunbar, C.; Hamann, M. T.; Mitchell, A. A.; Yogesh, A. S.; Jaber, S.
M.; El-Feraly, Farouk S. Transformation of lactone to lactam in sarcopine and antimalar-
ial activity of the resulting N-substituted azasarcophines. Tetrahedron 2002, 58, 3699–3708;
(c) Ma, S. Shi, Z. Pd(O)=Agþ-cocatalyzed cyclization reaction of 1,2-allenic carboxylic
acids with aryl=alkenyl halides: An efficient synthesis of butenolides. J. Org. Chem.
1998, 63, 6387–6389; (d) Alaa, A.; El-Tombary, Y.; Abdel-Ghany, A. S. F. B.; Shams,
A.; El-Dine, S.; Farid, S. G. S. Synthesis of some substituted furan-2(5H)-ones and derived
quinoxalinones as potential anti-microbial and anticancer agents. Med. Chem. Res. 2011,
20, 865–876.
4. (a) Domschike, G. Z. Chem. 1976, 16, 13; (b) Cao, R.; Liu, C.; Liu, L. A convenient
synthesis of 2(5H)-furanone. Org. Prep. Proced. Int. 1996, 28, 215–216; (c) Fu, C.; Ma, S.
Efficient preparation of 4-iodofuran-2(5H)-ones by indolactonisation of 2,3-allenoates with
I2. Eur. J. Org. Chem. 2005, 3942–3945.
5. Bassetti, M.; D’Annibale, A.; Fanfoni, A.; Minissi, F. Synthesis of a,b-unsaturated 4,5-
disubstituted c-lactones via ring-closing metathesis catalyzed by the first-generation
Grubb’s catalyst. Org. Lett. 2005, 7, 1805–1808.
6. Narayana Murthy, S.; Madhav, B.; Vijay Kumar, A.; Rama Rao, K.; Nageswar, Y. V. D.
Facile and efficient synthesis of 3,4,5-substituted furan-2(5H)-ones by using b-cyclodextrin
as reusable catalyst. Tetrahedron 2009, 65, 5251–5256.

2148
L. NAGARAPU ET AL.
7. Arumugam, P.; Karthikeyan, G.; Atchutan, R.; Muralidharan, D.; Perumal, P. T. A
simple, efficient, and solvent-free protocol for the Friedlander synthesis of quinolines
by using SnCl2 ꢀ 2H2O. Chem. Lett. 2005, 34, 314–315.
8. Yadav, J. S.; Reddy, B. V. S.; Baishya, G.; Reddy, K. V.; Narsaiah, V. Conjugate addition
of indoles to a,b-unsaturated ketones using Cu(OTf)2 immobilized in ionic liquids.
Tetrahedron 2005, 61, 9541–9544.
9. Da-Gong, G.; Shun-Jun, J.; Zhao-Qin, J.; Min-Feng, Z.; Teck-Peng, L. An efficient
synthesis of bis(indolyl) methanes catalyzed by recycled acidic ionic liquid. Synlett.
2005, 959–962.
10. Wang, B., Gu, Y., Luo, C., Yang, T., Yang, L., Suo, J. Pyrrole synthesis in ionic liquids by
Pall-Knorr condensation under mild conditions. Tetrahedron Lett. 2004, 45, 3417–3419.
11. Rebeiro, G. L.; Khadilkar, B. M. Chloroaluminate ionic liquid for Fischer indole
synthesis. Synthesis 2001, 370–372.
12. (a) Nagarapu, L.; Satyender, A.; Rajashakar, B.; Srinivas, K.; Rupa Rani, P.; Radhika,
K.; Subhashini, G. Synthesis and antimicrobial activity of novel C-linked imidazole
glycoconjugates. Bioorg. Med. Chem. Lett. 2008, 18, 1167–1171; (b) Nagarapu, L.;
Venkateswarlu, P.; Satyender, A. Synthesis of novel analogeues of (þ)-varitriol via olefin
cross-metathesis reaction. Bioorg. Med. Chem. Lett. 2008, 18, 2351–2354; (c) Nagarapu,
L.; Chary, M. V.; Satyender, A.; Supriya, B.; Rajashakar, B. Iron(III) chloride in
ethanol–water: Highly efficient catalytic system for the synthesis of Garcia Gonzalez poly-
hydroxyalkyl- and C-glycosylfurans. Synthesis 2009, 2278–2282; (d) Nagarapu, L.;
Narsimhaji, C.; Shukla Chary, K.; Rajashakar, B. Synthesis of annulated pyrroles: Con-
densation of aldose sugars, arylamines, and 1,3-diones using TBAB. Synthesis 2010, 3374–
3378; (e) Nagarapu, L.; Shukla Chary, K.; Rajashakar, B. An efficient, high-yield protocol
for the one-pot synthesis of benzopyran derivatives catalyzed by p-TSA in aqueous media.
Synth. Commun. 2012, 42, 967–974; (f) Mereyala, H. B.; Pathuri, G.; Nagarapu, L. Syn-
thesis of (2S,4S)-4-hydroxyproline from D-glucose. Synth. Commun. 2012, 42, 1278–1287.