[Hydroxy(tosyloxy)iodo]benzene in organic synthesis: A facile synthesis of furo[3,2-c]coumarins using-tosyloxyketones

Article abstract of DOI:10.1080/00397911.2011.570471

Facile synthesis of furo[3,2-c]coumarins (2a-g) via cyclocondensation of 4-hydroxycoumarin and-tosyloxyketones (1a-g) is described. A plausible mechanism involving C-C bond formation followed by 5-exo-tet cyclization is suggested.

Full text of DOI:10.1080/00397911.2011.570471

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[Hydroxy(tosyloxy)iodo]benzene in
Organic Synthesis: A Facile Synthesis
of Furo[3,2-c]coumarins Using α-
Tosyloxyketones
Om Prakash a , Deepak Wadhwa b , Khalid Hussain b & Ravi Kumar c
a Institute of Pharmaceutical Sciences, Kurukshetra Univesity,
Kurukshetra, Haryana, India
b Department of Chemistry, Kurukshetra University, Kurukshetra,
Haryana, India
c Department of Chemistry, Dyal Singh College, Karnal, Haryana,
India
Available online: 02 Jan 2012
To cite this article: Om Prakash, Deepak Wadhwa, Khalid Hussain & Ravi Kumar (2012):
[Hydroxy(tosyloxy)iodo]benzene in Organic Synthesis: A Facile Synthesis of Furo[3,2-c]coumarins Using
α-Tosyloxyketones, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 42:20, 2947-2951
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Synthetic Communications1, 42: 2947–2951, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.570471
[HYDROXY(TOSYLOXY)IODO]BENZENE IN
ORGANIC SYNTHESIS: A FACILE SYNTHESIS OF
FURO[3,2-c]COUMARINS USING
a-TOSYLOXYKETONES
Om Prakash,1 Deepak Wadhwa,2 Khalid Hussain,2 and
Ravi Kumar3
1Institute of Pharmaceutical Sciences, Kurukshetra Univesity, Kurukshetra,
Haryana, India
2Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana,
India
3Department of Chemistry, Dyal Singh College, Karnal, Haryana, India
GRAPHICAL ABSTRACT
Abstract Facile synthesis of furo[3,2-c]coumarins (2a–g) via cyclocondensation of
4-hydroxycoumarin and -tosyloxyketones (1a–g) is described. A plausible mechanism
involving C-C bond formation followed by 5-exo-tet cyclization is suggested.
Keywords Cyclocondensation; HTIB; 4-hydroxycoumarin; a-tosyloxyketones
INTRODUCTION
In view of the usefulness of 4-hydroxycoumarin derivatives such as rodenti-
cides,[1] oral anticoagulants,[2] and pesticides,[3] various 2,3- or 3,4-fused polycycles
or open-chain coumarin derivatives have been synthesized. However, a limited set
of studies have focused on the synthesis of linearly or angularly fused tricyclic
complex systems bearing coumarin systems. All the reported procedures referring
to this particular system require vigorous reaction conditions and laborious
preparation.[4] Moreover, these compounds are of significant importance in organic
synthesis because that the framework of these systems is present in a class of physio-
logically active natural products, 6H-benzofuro[3,2-c]benzopyran-6-ones.[5]
Received January 30, 2011.
Address correspondence to Om Prakash, Institute of Pharmaceutical Sciences, Kurukshetra
University, Kurukshetra 136 119, Haryana, India. E-mail: dromprakash50@rediffmail.com
2947

2948
O. PRAKASH ET AL.
a-Halocarbonyl compounds are versatile intermediates in organic synthesis.
The a-halocarbonyl compounds such as phenacyl bromides are well-known precur-
sors for the synthesis of a wide variety of heterocyclic compounds and a-functiona-
lized ketones.[6] In a report related to the utility of a-halocarbonyl compounds,
Risitano et al. reported the synthesis of furo[3,2-c]coumarin ring system via the tan-
dem O-alkylation=cyclisation of 4-hydroxycoumarin and a-haloketones.[7] Because of
the hazards associated with the halogenation of ketones and the unstability and tox-
icity of a-haloketones, it appeared attractive to find a suitable alternative to them.
Synthesis of a-tosyloxyketones can easily be achieved by treating a variety of
ketones with [hydroxy(tosyloxy)iodo]benzene (HTIB, Koser’s reagent).[8] These
compounds are stable, crystalline solids and provide a safe, ecofriendly alternative
route for synthesis of compounds conventionally prepared through a-haloketones.
We report in this article a facile synthesis of furo[3,2-c]coumarin derivatives (2) using
a-tosyloxyketones (1) and 4-hydroxycoumarin.
RESULTS AND DISCUSSION
Keeping in view that the a-haloketones and a-tosyloxyketones behave anal-
ogously in most of their reactions, it was anticipated that the reaction of a-tosyloxyke-
tones (1) with 4-hydroxycoumarin might afford furo[3,2-c]coumarins (2). To determine
the fate of the proposal, the a-tosyloxyacetophenone (1a) was refluxed in the presence of
acetic acid (AcOH) = ammonium acetate (NH4OAc). The usual workup followed by
purification afforded the cycloadduct, furo[3,2-c]coumarin (2a), in 82% yield. To
consider the generality of this reaction, various a-tosyloxyacetophenones (1b–g) were
treated with 4-hydroxycoumarin in a similar manner to afford 2b–g in good to excellent
yields (Scheme 1). Structures of the compounds were confirmed by analyzing their spec-
tral [infrared (IR), 1H NMR, 13C NMR] as well as elemental data. The clear assignments
come from IR carbonyl absorptions at 1728–1745 cmꢀ1 for the lactone group in
Scheme 1. Synthesis of furo[3,2-c]coumarins (2).

FACILE SYNTHESIS OF FURO[3,2-c]COUMARINS
2949
Scheme 2. Plausible mechanism for the formation of furo[3,2-c]coumarins (2).
compound 2. Structures of known compounds were confirmed by comparing their spec-
tral data and melting points with those reported in the literature.[7]
It should be noted that Risitano et al. suggested possibility of an O-alkylated or
C-alkylated intermediate in the formation of 2 from 4-hydroxycoumarin and a-halo-
ketone. Based on the reported work, two plausible pathways may be considered for
the mechanism of the present reaction (Scheme 2). 4-Hydroxycoumarin may undergo
O-alkylation with a-tosyloxyketones (1) followed by cyclization to give intermediate
3. The intermediate 3 finally loses a water molecule, leading to the formation of final
product 2 (route i). Alternatively, formation of the intermediate 3 may occur through
C-C bond formation followed by 5-exo-tet cyclization[9] (route ii).
Several experiments were carried out to determine the possible mechanism of the
reaction. During our attempts, we succeeded in isolating O-alkylated intermediate (4a;
Ar ¼ Ph), which did not undergo cyclization under similar conditions (heated for 3 h.
in ammonium acetate = acetic acid and a mixture of toluene=EtOH abs.). It is implied
that the reaction does not proceed through O-alkylation. Instead, C-C bond formation
followed by 5-exo-tet cyclization is a reasonable pathway for the synthesis of 2.
CONCLUSION
A facile synthesis of furo[3,2-c]coumarins (2a–g) via cyclocondensation of
4-hydroxycoumarin and a-tosyloxyketones (1a–g) is developed. It is suggested that
this reaction may proceed through C-C bond formation followed by 5-exo-tet
cyclization.
EXPERIMENTAL
Melting points were taken in open capillaries and are uncorrected. IR spectra
were recorded on a Perkin-Elmer 1800 Fourier transform (FT)–IR spectrophot-
1
ometer. H NMR and 13C NMR spectra were recorded on a Bruker 300-MHz
instrument using tetramethylsilane (TMS) as an internal standard. The chemical
shifts are expressed in parts per million (ppm) units downfield from an internal
TMS standard. a-Tosyloxyketones (1) were prepared according to the procedure
reported in the literature.[7]

2950
O. PRAKASH ET AL.
Synthesis of Furo[3,2-c]coumarins (2)
A toluene solution of the appropriate a-tosyloxyketone 1 (10 mmol) was added
to a solution of 4-hydroxycoumarin (10 mmol) and AcOH=NH4OAc (50 mmol) in
toluene=EtOH abs. (40:10). The solution was refluxed for 2–3 h and the solvent
was evaporated under reduced pressure. The residue was treated with cold water,
and the precipitates were filtered off, washed with water, and recrystallized from
ethanol to afford pure furo[3,2-c]coumarin (2).
Characterization Data of Furo[3,2-c]coumarins (2)
Compound 2a. Mp 176–177 ꢁc (lit.[7] mp 177ꢁc); yield 82%.
Compound 2b. Mp 144–146 ꢁC; yield 76%; IR (nmax, KBr, cmꢀ1): 1728 (C O
=
1
stretch), 1628, 1543, 1497, 1119, 1034, 964; H NMR (CDCl3, 300 MHz, d): 2.424
(s, 1H), 7.562–7.590 (dd, 1H, J1 ¼ 1.5 Hz, J2 ¼ 7.5 Hz), 7.304–7.557 (m, 4H),
7.664–7.691 (d, J ¼ 8.1 Hz), 7.763 (s, 1H), 7.923–7.954 (dd, 1H, J1 ¼ 1.5 Hz,
J2 ¼ 7.5 Hz); 13C NMR (CDCl3, d): 158.72, 157.87, 152.65, 140.95, 138.29, 130.86,
129.28, 128.58, 126.74, 126.13, 124.44, 120.95, 117.14, 112.87, 108.60, 21.28. Anal.
calcd. for C17H12O3: C, 77.27; H, 4.54. Found C, 78.25; H, 4.38.
Compound 2c. Mp 165–166ꢁc (lit.[7] mp 166 ꢁc); yield 77%.
Compound 2d. Mp 153–155 ꢁC; yield 81%; IR (nmax, KBr, cmꢀ1): 1744.32
(C O stretch), 1634, 1613.57, 1106, 1028; 1H NMR (CDCl3, 300 MHz, d):
=
7.377–7.503 (m, 4H), 7.557–7.581 (d, 1H, J ¼ 7.2 Hz), 7.728-7.756 (d, 2H,
J ¼ 8.4 Hz), 7.795 (s, 1H), 7.936–7.960 (d, 1H, J ¼ 7.2 Hz); 13CNMR (CDCl3, d):
158, 141.24, 131.14, 129.98, 128.81, 124.59, 121.03, 117.22. Anal. calcd. for
C16H9O3Cl: C, 67.48; H, 3.16. Found C, 68.82; H, 3.06.
Compound 2e. Mp 197–198 ꢁc (lit.[7] mp 198 ꢁc); yield 75%.
Compound 2f. Mp 203–205 ꢁC; yield 73%; IR (nmax, KBr, cmꢀ1): 1732.06
(C O stretch), 1629.91, 1597.22, 1519.59, 1343.88, 1110.98, 1074.20, 967.97;
=
1H NMR (CDCl3, 300 MHz, d): 7.408–7.644 (m, 3H), 7.930–8.028 (m, 4H),
8.329–8.358 (d, 2H, J ¼ 8.7 Hz); 13CNMR (CDCl3, d): 142.31, 135.79, 131.55,
129.43, 124.79, 123.87, 121.14, 117.31. Anal. calcd. for C16H9NO5: C, 65.08;
H, 3.05. Found C, 66.45; H, 2.95.
Compound 2g. Mp 183 ꢁC; Yield 74%; IR (nmax, KBr, cmꢀ1): 1740.23 (C O
=
1
stretch), 1642.17, 1613.57; H NMR (CDCl3, 300 MHz, d): 7.132–7.190 (m, 2H),
7.367–7.594 (m, 3H), 7.741–7.787 (m, 3H), 7.923–7.948 (d, 1H, J ¼ 7.5 Hz); 13CNMR
(CDCl3, d): 164.54, 161.25, 158.86, 157.88, 152.66, 141.02, 131.05, 130.54, 125.85,
125.16, 124.55, 121.01, 117.18, 115.72, 115.43, 112.75, 108.41. Anal. calcd. for
C16H9O3F: C, 71.64; H, 3.35. Found C, 72.86; H, 3.24.
Isolation of O-Alkyl Intermediate (4a)
An ethanolic solution of the a-tosyloxyacetophenone (1a, 5 mmol, 1.45 g) was
added to a solution of 4-hydroxy coumarin (5 mmol, 0.81 g) and AcOH=NH4OAc

FACILE SYNTHESIS OF FURO[3,2-c]COUMARINS
2951
(25 mmol). The solution was refluxed for 3 h, and the solvent was evaporated under
reduced pressure. The residue was treated with cold water, and the precipitates were
filtered off, washed with water, and recrystallized from ethanol to afford O-alkyl
intermediate (4a, 1.10 g). Mp 184–185 ꢁC; yield 78.5%; 1H NMR (CDCl3,
300 MHz, d): 5.502 (s, 2H), 5.611 (s, 1H), 7.312–7.377 (m, 2H), 7.548–7.628
(m, 3H), 7.678–7.727 (m, 1 H), 7.982–8.010 (m, 3H). Anal. calcd. for C17H12O4:
C, 72.85; H, 4.28. Found C, 73.27; H, 4.18.
ACKNOWLEDGMENTS
We are highly thankful to the Council of Scientific and Industrial Research
(CSIR), New Delhi (Grant No. CSIR 01(2186)= 07= EMR-II), and the Department
of Science and Technology, New Delhi (Grant No. SR=FTP=CS-125=2006), for pro-
viding financial assistance to accomplish this research work.
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