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[Hydroxy(tosyloxy)iodo]benzene inOrganic Synthesis: A Facile Synthesisof Furo[3,2-c]coumarins Using α-TosyloxyketonesOm Prakash a , Deepak Wadhwa b , Khalid Hussain b & Ravi Kumar ca Institute of Pharmaceutical Sciences, Kurukshetra Univesity,Kurukshetra, Haryana, Indiab Department of Chemistry, Kurukshetra University, Kurukshetra,Haryana, Indiac 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 Usingα-Tosyloxyketones, Synthetic Communications: An International Journal for Rapid Communication ofSynthetic Organic Chemistry, 42:20, 2947-2951

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[HYDROXY(TOSYLOXY)IODO]BENZENE INORGANIC SYNTHESIS: A FACILE SYNTHESIS OFFURO[3,2-c]COUMARINS USINGa-TOSYLOXYKETONES

Om Prakash,1 Deepak Wadhwa,2 Khalid Hussain,2 andRavi Kumar31Institute of Pharmaceutical Sciences, Kurukshetra Univesity, Kurukshetra,Haryana, India2Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana,India3Department 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 polycyclesor open-chain coumarin derivatives have been synthesized. However, a limited setof studies have focused on the synthesis of linearly or angularly fused tricycliccomplex systems bearing coumarin systems. All the reported procedures referringto this particular system require vigorous reaction conditions and laboriouspreparation.[4] Moreover, these compounds are of significant importance in organicsynthesis 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

Synthetic Communications1, 42: 2947–2951, 2012

Copyright # Taylor & Francis Group, LLC

ISSN: 0039-7911 print=1532-2432 online

DOI: 10.1080/00397911.2011.570471

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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-demO-alkylation=cyclisation of 4-hydroxycoumarin and a-haloketones.[7] Because ofthe 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 ofketones with [hydroxy(tosyloxy)iodo]benzene (HTIB, Koser’s reagent).[8] Thesecompounds are stable, crystalline solids and provide a safe, ecofriendly alternativeroute 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) usinga-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 determinethe fate of the proposal, the a-tosyloxyacetophenone (1a) was refluxed in the presence ofacetic acid (AcOH) = ammonium acetate (NH4OAc). The usual workup followed bypurification afforded the cycloadduct, furo[3,2-c]coumarin (2a), in 82% yield. Toconsider the generality of this reaction, various a-tosyloxyacetophenones (1b–g) weretreated with 4-hydroxycoumarin in a similar manner to afford 2b–g in good to excellentyields (Scheme 1). Structures of the compounds were confirmed by analyzing their spec-tral [infrared (IR), 1HNMR, 13CNMR] as well as elemental data. The clear assignmentscome from IR carbonyl absorptions at 1728–1745 cm�1 for the lactone group in

Scheme 1. Synthesis of furo[3,2-c]coumarins (2).

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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 orC-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 forthe mechanism of the present reaction (Scheme 2). 4-Hydroxycoumarin may undergoO-alkylation with a-tosyloxyketones (1) followed by cyclization to give intermediate3. The intermediate 3 finally loses a water molecule, leading to the formation of finalproduct 2 (route i). Alternatively, formation of the intermediate 3may occur throughC-C bond formation followed by 5-exo-tet cyclization[9] (route ii).

Several experiments were carried out to determine the possible mechanism of thereaction. During our attempts, we succeeded in isolating O-alkylated intermediate (4a;Ar¼Ph), 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 impliedthat the reaction does not proceed throughO-alkylation. Instead, C-C bond formationfollowed 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 of4-hydroxycoumarin and a-tosyloxyketones (1a–g) is developed. It is suggested thatthis reaction may proceed through C-C bond formation followed by 5-exo-tetcyclization.

EXPERIMENTAL

Melting points were taken in open capillaries and are uncorrected. IR spectrawere recorded on a Perkin-Elmer 1800 Fourier transform (FT)–IR spectrophot-ometer. 1H NMR and 13C NMR spectra were recorded on a Bruker 300-MHzinstrument using tetramethylsilane (TMS) as an internal standard. The chemicalshifts are expressed in parts per million (ppm) units downfield from an internalTMS standard. a-Tosyloxyketones (1) were prepared according to the procedurereported in the literature.[7]

Scheme 2. Plausible mechanism for the formation of furo[3,2-c]coumarins (2).

FACILE SYNTHESIS OF FURO[3,2-c]COUMARINS 2949

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Synthesis of Furo[3,2-c]coumarins (2)

A toluene solution of the appropriate a-tosyloxyketone 1 (10mmol) was addedto a solution of 4-hydroxycoumarin (10mmol) and AcOH=NH4OAc (50mmol) intoluene=EtOH abs. (40:10). The solution was refluxed for 2–3 h and the solventwas evaporated under reduced pressure. The residue was treated with cold water,and the precipitates were filtered off, washed with water, and recrystallized fromethanol 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 177�c); yield 82%.

Compound 2b. Mp 144–146 �C; yield 76%; IR (nmax, KBr, cm�1): 1728 (C=Ostretch), 1628, 1543, 1497, 1119, 1034, 964; 1H NMR (CDCl3, 300MHz, d): 2.424(s, 1H), 7.562–7.590 (dd, 1H, J1¼ 1.5Hz, J2¼ 7.5Hz), 7.304–7.557 (m, 4H),7.664–7.691 (d, J¼ 8.1Hz), 7.763 (s, 1H), 7.923–7.954 (dd, 1H, J1¼ 1.5Hz,J2¼ 7.5Hz); 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 165–166�c (lit.[7] mp 166 �c); yield 77%.

Compound 2d. Mp 153–155 �C; yield 81%; IR (nmax, KBr, cm�1): 1744.32(C=O stretch), 1634, 1613.57, 1106, 1028; 1H NMR (CDCl3, 300MHz, d):7.377–7.503 (m, 4H), 7.557–7.581 (d, 1H, J¼ 7.2Hz), 7.728-7.756 (d, 2H,J¼ 8.4Hz), 7.795 (s, 1H), 7.936–7.960 (d, 1H, J¼ 7.2Hz); 13CNMR (CDCl3, d):158, 141.24, 131.14, 129.98, 128.81, 124.59, 121.03, 117.22. Anal. calcd. forC16H9O3Cl: 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, cm�1): 1732.06(C=O stretch), 1629.91, 1597.22, 1519.59, 1343.88, 1110.98, 1074.20, 967.97;1H NMR (CDCl3, 300MHz, d): 7.408–7.644 (m, 3H), 7.930–8.028 (m, 4H),8.329–8.358 (d, 2H, J¼ 8.7Hz); 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, cm�1): 1740.23 (C=Ostretch), 1642.17, 1613.57; 1H NMR (CDCl3, 300MHz, 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, J¼ 7.5Hz); 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. forC16H9O3F: 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, 5mmol, 1.45 g) wasadded to a solution of 4-hydroxy coumarin (5mmol, 0.81 g) and AcOH=NH4OAc

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(25mmol). The solution was refluxed for 3 h, and the solvent was evaporated underreduced pressure. The residue was treated with cold water, and the precipitates werefiltered off, washed with water, and recrystallized from ethanol to afford O-alkylintermediate (4a, 1.10 g). Mp 184–185 �C; yield 78.5%; 1H NMR (CDCl3,300MHz, 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 Departmentof 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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