Download PDF
Synthesis 2014; 46(13): 1807-1814
DOI: 10.1055/s-0033-1341027
paper
© Georg Thieme Verlag Stuttgart · New York

Molecular Iodine Mediated Regioselective Synthesis of Pyranocoumarins and Bis-Fused Benzo-2H-pyran Derivatives

K. C. Majumdar*
a   Department of Chemistry, University of Kalyani, Kalyani 741235, W. B., India   Email: kcm@klyuniv.ac.in   Email: kcm_ku@yahoo.co.in
,
Biswajit Sinha
a   Department of Chemistry, University of Kalyani, Kalyani 741235, W. B., India   Email: kcm@klyuniv.ac.in   Email: kcm_ku@yahoo.co.in
,
Inul Ansary
a   Department of Chemistry, University of Kalyani, Kalyani 741235, W. B., India   Email: kcm@klyuniv.ac.in   Email: kcm_ku@yahoo.co.in
,
Sintu Ganai
a   Department of Chemistry, University of Kalyani, Kalyani 741235, W. B., India   Email: kcm@klyuniv.ac.in   Email: kcm_ku@yahoo.co.in
,
Debankan Ghosh
a   Department of Chemistry, University of Kalyani, Kalyani 741235, W. B., India   Email: kcm@klyuniv.ac.in   Email: kcm_ku@yahoo.co.in
,
B. Roy
a   Department of Chemistry, University of Kalyani, Kalyani 741235, W. B., India   Email: kcm@klyuniv.ac.in   Email: kcm_ku@yahoo.co.in
,
B. Sridhar
b   Laboratory of X-ray crystallography, IICT Hyderabad, Hyderabad 500007, India
› Author Affiliations
Further Information

Publication History

Received: 08 January 2014

Accepted after revision: 25 February 2014

Publication Date:
07 April 2014 (online)

 
 PDF Download Permissions and Reprints All articles of this category


Abstract

A simple and straightforward approach for the regioselective synthesis of pyranocoumarin and bis-fused benzo-2H-pyran derivatives using mild, easy to handle, and cheaper molecular iodine mediated heterocyclization is described.


#

Key words

molecular iodine - 6-endo-dig - electrophilic cylization - bis-fused benzo-2H-pyrans - pyranocoumarins

2H-Benzopyrans or 2H-chromenes represent the structural units of a variety of biologically important compounds.[2] Chroman derivatives are known to possess various useful biological activities, such as antioxidant,[3] anticonvulsion,[4] anti-estrogen,[5] and neuroprotection.[6] On the other hand, pyranocoumarin and pyranopyran derivatives are also important class of heterocycles. Their structural motif is found widely in natural products and in many synthetic molecules.[7] They exhibit biological activities including antifungal, anticancer, insecticidal, anti-inflammatory, anti-HIV, and antibacterial activities (Figure [1]).[8]

Because of their biological and pharmaceutical importance much attention has been paid to the isolation and synthesis of 2H-pyrans fused with both benzene and coumarin rings.[9] It is surprising that only few examples of bis-fused benzopyran derivatives are known. Different research groups have utilized either metal-catalyzed intramolecular cyclization strategies using AuCl3, Pd(OAc)2 as catalysts or iodocyclization reaction using IPy2BF4-HBF4 catalytic system.[10] On the other hand, pyranocoumarins and pyranopyran derivatives have been synthesized by using gold(III)-catalyzed tandem conjugate addition/annulation reaction, ytterbium triflate-catalyzed reactions, and multicomponent reactions (Scheme [1]).[11]

Zoom Image
Scheme 1 Literature reports on 2H-pyrans fused with both benzene and coumarin rings
Zoom Image
Figure 1 Some biologically active 2H-benzopyran, pyranopyran, and pyranocoumarin derivatives

Therefore, it is apparent that synthesis of pyranocoumarins, pyranopyrans, and benzo-2H-pyran derivatives are very important. Thus, search for an alternative protocol that is easy to handle and also uses a cheaper reagent is always welcome. In this respect, molecular iodine-mediated heterocyclization can be a useful alternative for the synthesis of benzo-2H-pyran derivatives. This is because iodocyclization offers an easy access to the complex molecules that are not always accessible by the usual organometallic reagents.[12] [13] A few attempts were made to synthesize 2H-benzopyran derivatives[14] utilizing molecular iodine-mediated heterocyclization, but the synthesis of bis-fused 2H-benzopyrans is rare. Moreover, the growing importance of pyranocoumarin derivatives also demands an easy route for their effective syntheses. Therefore, all these findings inspired us to undertake a detailed study on the molecular iodine-mediated intramolecular heterocyclization to access pyranocoumarin and bis-fused 2H-benzopyran derivatives. Herein we report our results.

Zoom Image
Scheme 2 Preparation of propargyl ethers. Reagents and conditions: (i) propargyl bromide, acetone, K2CO3, NaI, reflux; (ii) p-substituted iodobenzene, Pd(PPh3)2Cl2, CuI, DMF–Et3N, r.t.

The required precursors 13a–c for this study were synthesized in 72–77% yields from the substrates 12 by the reaction with various p-substituted iodobenzenes. The reactions were carried out in the presence of Pd(PPh3)2Cl2 as catalyst and copper(I) iodide as co-catalyst in anhydrous triethylamine–DMF (1:4) as mixed solvent at room temperature for three hours. The O-propargylated compound 12 was in turn prepared by refluxing resorcinol 11 with propargyl bromide in acetone in the presence of anhydrous K2CO3. Other precursors 14, 15, and 16a,b were prepared accordingly starting from hydroquinone, catechol, and 2,7-dihydroxynaphthol, respectively (Scheme [2]).

The iodocyclization reaction was performed with the compound 13a, molecular iodine (2 equiv), and NaHCO3 (2 equiv) at room temperature in anhydrous acetonitrile for six hours to give the bis-fused benzo-2H-pyran derivative 17a in 65% yield. The reaction occurred by a 6-endo-dig mode of cyclization. The 5-exo-dig cyclized product was not obtained (Scheme [3]).

Zoom Image
Scheme 3 Preparation of 17a. Reagents and conditions: (i) I2, NaHCO3, MeCN, r.t.

The product 17a was characterized by its spectral analysis. The structure was confirmed from the analysis of its single crystal X-ray diffraction[15] data (Figure [2]). It is interesting to note that the reaction is regioselective and gave only the linearly cyclized product 17a.

Optimization experiments were carried out with a view to improve the yield of the products. By varying the amounts of both the iodine and base it was found that 3 equivalents of iodine and 3 equivalents of NaHCO3 were optimum and the yield of 17a was unexpectedly increased to 90%. Further increase of the amount of NaHCO3 (4 equiv) and iodine (4 equiv) did not give any better result. NaHCO3 was found to be more effective compared to other bases like K2CO3, Na2CO3, etc. for the completion of the reaction. Dichloromethane or methanol gave lower yields of the product. On the basis of our observations, the optimized conditions for the above reaction is I2 (3 equiv), NaHCO3 (3 equiv), MeCN, r.t., six hours, and the results are summarized in Table [1].

Table 1 Optimization of I2-Mediated Reactions

Entry

Electrophile (equiv)

Base (equiv)

Solvent

Product

Yield (%)a

1

I2 (2)

NaHCO3 (2)

MeCN

17a

65

2b

I2 (3)

NaHCO3 (3)

MeCN

17a

90

3

I2 (4)

NaHCO3 (4)

MeCN

17a

90

4

I2 (3)

K2CO3 (3)

MeCN

17a

35

5

I2 (3)

NaHCO3 (3)

CH2Cl2

17a

25

6

I2 (3)

Na2CO3 (3)

MeCN

17a

50

7

I2 (3)

NaHCO3 (3)

MeOH

17a

45

a Isolated yields.

b Optimized reaction conditions.

With the optimized reaction conditions in hand, the other substrates 13b,c, 14, 15, and 16a,b were treated similarly to afford the bis-fused 2H-benzopyran and naphthopyran derivatives 17b,c, 18, 19, and 20a,b in 68–85% and 62, 80% yield, respectively (Table [2]).

Table 2 Synthesis of Bis-Fused Benzo-2H-pyran Derivatives

Starting material

R

Producta

Yield (%)

13b

4-MeC6H4

17b

85

13c

4-MeOC6H4

17c

80

14

4-MeOC6H4

18

70

15

4-MeOC6H4

19

68

16a

4-MeC6H4

20a

80

16b

4-ClC6H4

20b

62

a Reaction conditions: I2 (3 equiv), NaHCO3 (3 equiv), MeCN, r.t.

Zoom Image
Figure 2 ORTEP diagram of the compound 17a

After achieving the synthesis of the bis-fused iodocyclized products, the reaction was extended to the readily available starting material, 4-hydroxycoumarin to accomplish the synthesis of pyranocoumarin derivatives.

Table 3 Synthesis of Pyranocoumarin and Pyranopyran Derivatives

Starting material

Producta

Yield (%)

22b

23b

68

22c

23c

72

22d

23d

55

a Reaction conditions: I2 (3 equiv), NaHCO3 (3 equiv), MeCN, r.t.

For this purpose, a number of starting materials 22a–d were prepared in moderate to good yields by the Sonogashira coupling reaction of 21 with iodobenzene derivatives. The reactions were performed in the presence of Pd(PPh3)2Cl2 as catalyst and copper(I) iodide as co-catalyst in a mixture of anhydrous triethylamine and DMF (1:4) as mixed solvent at room temperature for five hours. The substrate 22a was treated under the optimized reaction conditions (Table [1]) to give the pyranocoumarin derivative 23a in 65% yield (Scheme [4]).

Zoom Image
Scheme 4 Preparation of pyranocoumarin derivative 23a. Reaction conditions: (i) p-substituted iodobenzene, Pd(PPh3)2Cl2, CuI, DMF–Et3N, reflux; (ii) I2, NaHCO3, MeCN, r.t., 6 h.

Detailed experiments were carried out by changing solvents and bases. It was found that the optimized reaction conditions stated in Table [1] is also suitable for the above reaction (Scheme [4]). The other substrates 22b–d were also subjected to react under the optimized conditions to afford the cyclized products 23b–d in 55–72% yields (Table [3]).

Here it should be noted that iodobenzenes containing Me, Cl, and NO2 substituents do not undergo iodocyclization reaction. In these cases, only iodine-addition products were obtained as the only isolable products. In contrast, the iodobenzenes containing p-methoxy and p-ethoxy groups, that is, strong electron-donating groups, reacted efficiently to give the desired cyclized products.

From the above discussion it is clear that the reaction conditions described above are simple and convenient compared to other available methods. They avoid the use of complex and relatively costlier reagents like palladium, ytterbium, gold, etc. and the reactions are carried out at ambient temperature.

In conclusion, the protocol reported here provides an operationally simple method for effective iodocyclization reaction. These reactions are cost effective and proceed under very mild conditions to give a number of important heterocyclic motifs including pyranocoumarins and bis-fused 2H-benzopyrans expeditiously from readily accessible starting materials. Moreover, during the reaction the iodine atom is incorporated in the cyclized products that offers scope for further modification.

Melting points were determined in an open capillary and are uncorrected. IR spectra were recorded on a Perkin-Elmer L 120-000A spectrometer on KBr disks. 1H NMR and 13C NMR spectra were recorded on a Bruker DPX-400 spectrometer in CDCl3 with TMS as internal standard. CHN analyses were recorded on a 2400 series II CHN analyzer (Perkin-Elmer). DMF was sequentially dried (3 ×) over freshly activated 4 Å molecular sieves and Et3N was dried by keeping overnight over anhydrous CaH2 and then distilled after 2 h at reflux. Silica gel (60–120 mesh and 230–400 mesh, Spectrochem, India) were used for chromatographic separation. Silica gel G and silica gel GF-254 (Spectrochem, India) were used for TLC analyses. Petroleum ether (PE) refers to the fraction boiling between 60–80 °C.


#

Propargyl Ethers 13a–c, 14, 15, and 16a,b; Compound 13a; Typical Procedure

A mixture of compound 12 (300 mg, 1.6 mmol), p-chloroiodobenzene (920 mg, 3.9 mmol), anhydrous Et3N (2 mL), Pd(PPh3)2Cl2 (34 mg, 3 mol%), and CuI (9 mg, 3 mol%) was stirred in anhydrous DMF (8 mL) at r.t. for 3 h. Then, the reaction mixture was diluted to 30 mL with CH2Cl2. The organic phase was washed successively with H2O (3 × 15 mL) and brine (15 mL), and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product was purified by silica gel (60–120 mesh) column chromatography using EtOAc–PE (1:19) as an eluent to give the solid compound 13a; yield: 505 mg (77%); colorless solid; mp 118–119 °C.

IR (KBr): 1608, 2237, 2845 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.88 (s, 4 H, OCH2), 6.66–6.70 (m, 3 H, ArH), 7.22–7.28 (m, 5 H, ArH), 7.35 (d, J = 8.4 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 56.7, 84.7, 86.1, 102.5, 107.9, 120.7, 128.7, 130.0, 133.1, 134.8, 159.0.

MS (ESI): m/z = 428.92 [M + Na]+, 430.90 [M + Na + 2]+, 432.90 [M + Na + 4]+.

Anal. Calcd for C24H16Cl2O2: C, 70.77; H, 3.96. Found: C, 70.72; H, 3.88.


#

13b

Yield: 445 mg (75%); colorless solid; mp 112–114 °C.

IR (KBr): 1614, 2230, 2860 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 6 H, CH3), 4.89 (s, 4 H, OCH2), 6.67 (dd, J = 8.4, 2.4 Hz, 2 H, ArH), 6.72 (d, J = 2.0 Hz, 1 H, ArH), 7.09 (d, J = 8.0 Hz, 4 H, ArH), 7.22 (t, J = 8.4 Hz, 1 H, ArH), 7.33 (d, J = 8.0 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 21.5, 56.9, 83.1, 87.4, 102.5, 107.9, 119.2, 129.0, 129.9, 131.8, 138.8, 159.1.

HRMS (ESI): m/z calcd for C26H22O2: 389.1517 [M + Na]+; found: 389.1518 [M + Na]+.


#

13c

Yield: 460 mg (72%); colorless solid; mp 100–101 °C.

IR (KBr): 1604, 2227, 2840 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.79 (s, 6 H, OCH3), 4.88 (s, 4 H, OCH2), 6.66 (dd, J = 8.4 Hz, 2.0 Hz, 2 H, ArH), 6.72 (d, J = 2.0 Hz, 1 H, ArH), 6.80 (d, J = 8.8 Hz, 4 H, ArH), 7.23 (t, J = 8.4 Hz, 1 H, ArH), 7.37 (d, J = 8.8 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.3, 56.9, 82.4, 87.2, 102.5, 107.8, 113.9, 114.3, 129.9, 133.4, 159.1, 159.9.

Anal. Calcd for C26H22O4: C, 78.37; H, 5.57. Found: C, 78.49; H, 5.39.


#

14

Yield: 405 mg (63%); colorless solid; mp 130–131 °C.

IR (KBr): 1602, 2230, 2855 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.80 (s, 6 H, OCH3), 4.85 (s, 4 H, OCH2), 6.81 (d, J = 8.8 Hz, 4 H, ArH), 6.99 (s, 4 H, ArH), 7.37 (d, J = 8.8 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.3, 57.5, 57.6, 82.8, 87.1, 113.9, 114.4, 116.0, 116.1, 116.4, 133.3, 152.0, 152.6, 159.8.

Anal. Calcd for C26H22O4: C, 78.37; H, 5.57. Found: C, 78.51; H, 5.42.


#

15

Yield: 450 mg (70%); colorless solid; mp 92–93 °C.

IR (KBr): 1604, 2224, 2836 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.79 (s, 6 H, OCH3), 4.98 (s, 4 H, OCH2), 6.80 (d, J = 8.8 Hz, 4 H, ArH), 6.97 (dd, J = 6.0, 4.0 Hz, 2 H, ArH), 7.14 (dd, J = 6.0, 3.6 Hz, 2 H, ArH), 7.34 (d, J = 8.8 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.3, 57.8, 82.7, 87.4, 113.9, 114.0, 114.5, 115.0, 121.9, 133.3, 147.9, 159.8.

Anal. Calcd for C26H22O4: C, 78.37; H, 5.57. Found: C, 78.29; H, 5.68.


#

16a

Yield: 290 mg (55%); yellow solid; mp 132–134 °C.

IR (KBr): 1625, 2233, 2921 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 6 H, CH3), 5.01 (s, 4 H, OCH2), 7.07–7.11 (m, 6 H, ArH), 7.25 (s, 2 H, ArH), 7.32 (d, J = 7.6 Hz, 4 H, ArH), 7.69 (d, J = 8.8 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 21.5, 56.8, 83.1, 87.5, 107.1, 116.6, 119.2, 124.9, 129.1, 129.2, 131.7, 135.6, 138.8, 156.4.

Anal. Calcd for C30H24O2: C, 86.51; H, 5.81. Found: C, 86.79; H, 5.88.


#

16b

Yield: 320 mg (55%); yellow solid; mp 71–72 °C.

IR (KBr): 1629, 2228, 2923 cm–1.

1H NMR (400 MHz, CDCl3):δ = 5.01 (s, 4 H, OCH2), 7.10 (dd, J = 8.8, 2.4 Hz, 2 H, ArH), 7.22–7.24 (m, 6 H, ArH), 7.35 (d, J = 8.4 Hz, 4 H, ArH), 7.70 (d, J = 8.8 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 56.6, 84.8, 86.2, 107.0, 116.6, 120.7, 125.0, 128.7, 129.4, 133.0, 134.8, 135.5, 156.3.

Anal. Calcd for C28H18Cl2O2: C, 73.53; H, 3.97. Found: C, 73.37; H, 3.88.


#

Bis-Fused Benzo-2H-pyran Derivatives 17a–c, 18, 19, and 20a,b; Compound 17a; Typical Procedure

A mixture of compound 13a (100 mg, 0.24 mmol), molecular iodine (183 mg, 0.72 mmol), and anhydrous NaHCO3 (60 mg, 0.72 mmol) was stirred in anhydrous MeCN (10 mL) at r.t. for 6 h. Then, CH2Cl2 (50 mL) was added to the reaction mixture. The organic phase was washed successively with 10% aq Na2S2O3 (15 mL), H2O (15 mL), and brine (15 mL), and dried (Na2CO3). The solvent was removed under reduced pressure and the crude product was purified by silica gel (230–400 mesh) column chromatography using PE–EtOAc (9.7:0.3) as eluent to give the solid product 17a; yield: 145 mg (90%); colorless solid; mp 176–177 °C.

IR (KBr): 1612, 2831 cm–1.

1H NMR (400 MHz, CDCl3): δ = 5.00 (s, 4 H, OCH2), 5.70 (s, 1 H, ArH), 6.36 (s, 1 H, ArH), 6.90 (d, J = 8.4 Hz, 4 H, ArH), 7.25 (d, J = 8.4 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 75.4, 92.1, 113.8, 118.9, 125.4, 130.6, 131.8, 140.9, 141.4, 159.3.

MS (ESI): m/z = 658.62 [M + H]+, 660.71 [M + H + 2]+.

HRMS (ESI): m/z calcd for C24H14Cl2I2O2: 658.8538 [M + H]+; found: 658.8500 [M + H]+.


#

17b

Yield: 145 mg (85%); colorless solid; mp 192–193 °C.

IR (KBr): 1609, 2838 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.32 (s, 6 H, CH3), 5.00 (s, 4 H, OCH2), 5.80 (s, 1 H, ArH), 6.34 (s, 1 H, ArH), 6.84 (d, J = 8.0 Hz, 4 H, ArH), 7.03 (d, J = 8.0 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 21.2, 75.1, 86.4, 103.3, 118.0, 125.2, 128.7, 128.9, 136.2, 137.4, 141.2, 154.6.

MS (ESI): m/z = 640.73 [M + Na]+.

Anal. Calcd for C26H20I2O2: C, 50.51; H, 3.26. Found: C, 50.68; H, 3.18.


#

17c

Yield: 130 mg (80%); colorless solid; mp 168–170 °C.

IR (KBr): 1602, 2847 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.85 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 4.35 (s, 2 H, OCH2), 4.93 (s, 2 H, OCH2), 6.38 (d, J = 8.4 Hz, 1 H, ArH), 6.52 (d, J = 8.4 Hz, 1 H, ArH), 6.91–6.95 (m, 4 H, ArH), 7.05 (d, J = 8.0 Hz, 2 H, ArH), 7.12 (d, J = 8.0 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.2, 74.1, 75.6, 87.9, 90.0, 109.1, 113.0, 113.8, 114.1, 120.2, 127.6, 129.6, 130.6, 132.1, 135.2, 139.3, 141.2, 149.2, 155.8, 158.7, 159.3.

Anal. Calcd for C26H20I2O4: C, 48.02; H, 3.10. Found: C, 48.17; H, 2.96.


#

18

Yield: 115 mg (70%); colorless solid; mp 188–189 °C.

IR (KBr): 1602, 2837 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.85 (s, 6 H, OCH3), 4.69 (d, J = 12.8 Hz, 2 H, OCHaHb), 4.94 (d, J = 12.8 Hz, 2 H, OCHaHb), 6.57 (d, J = 8.8 Hz, 4 H, ArH), 6.64 (d, J = 8.8 Hz, 4 H, ArH), 6.97 (s, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.3, 75.1, 92.6, 113.5, 114.0, 125.0, 130.5, 131.7, 141.2, 147.6, 159.4.

MS (ESI): m/z = 650.73 [M + H]+.

Anal. Calcd for C26H20I2O4: C, 48.02; H, 3.10. Found: C, 48.21; H, 3.01.


#

19

Yield: 110 mg (68%); yellow solid; mp 158–159 °C.

IR (KBr): 1608, 2831 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.83 (s, 6 H, OCH3), 5.12 (s, 4 H, OCH2), 6.09 (s, 2 H, ArH), 6.91 (d, J = 8.4 Hz, 4 H, ArH), 7.07 (d, J = 8.4 Hz, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.2, 75.4, 92.1, 113.8, 118.9, 125.4, 130.6, 131.8, 140.9, 141.4, 159.3.

MS (ESI): m/z = 672.71 [M + Na]+.

Anal. Calcd for C26H20I2O4: C, 48.02; H, 3.10. Found: C, 48.16; H, 3.13.


#

20a

Yield: 130 mg (80%); yellow solid; mp 162–163 °C.

IR (KBr): 1615, 2932 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.31 (s, 6 H, CH3), 3.57 (d, J = 12.4 Hz, 2 H, OCHaHb), 4.65 (d, J = 12.4 Hz, 2 H, OCHaHb), 6.93 (d, J = 8.8 Hz, 2 H, ArH), 7.64 (d, J = 8.4 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 21.2, 76.9, 79.5, 113.9, 120.8, 125.8, 127.4, 130.0, 131.2, 136.8, 137.1, 142.4, 156.7.

MS (ESI): m/z = 669.07 [M + H]+, 691.07 [M + Na]+.

Anal. Calcd for C30H22I2O2: C, 53.92; H, 3.32. Found: C, 54.01; H, 3.41.


#

20b

Yield: 95 mg (62%); yellow solid; mp 194–195 °C.

IR (KBr): 1603, 2962 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.57 (d, J = 12.4 Hz, 2 H, OCHaHb), 4.67 (d, J = 12.8 Hz, 2 H, OCHaHb), 6.89 (d, J = 8.8 Hz, 2 H, ArH), 7.60 (d, J = 8.8 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 29.7, 76.9, 80.6, 114.3, 120.1, 125.8, 127.0, 129.4, 131.8, 133.4, 138.0, 141.3, 157.0.

HRMS (ESI): m/z calcd for C28H16Cl2I2O2: 708.8695 [M + H]+, 710.8695 [M + H + 2]+; found: 708.8687 [M + H]+, 710.8807 [M + H + 2]+.


#

Propargyl Ethers 22a–d; Compound 22a; Typical Procedure

A mixture of compound 21 (300 mg, 1.50 mmol), p-methoxyiodobenzene (1.80 mmol), anhydrous Et3N (2 mL), Pd(PPh3)2Cl2 (3 mol%), and CuI (3 mol%) was stirred in anhydrous DMF (8 mL) at r.t. for 5 h. Then, the reaction mixture was diluted to 70 mL with CH2Cl2. The organic phase was washed successively with H2O (3 × 25 mL) and brine (25 mL), and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product was purified by silica gel (60–120 mesh) column chromatography using EtOAc–PE (1:19) as eluent to give compound 22a; yield: 350 mg (76%); yellow solid; mp 120–122 °C.

IR (KBr): 1728, 2232, 2931 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.82 (s, 3 H, OCH3), 5.09 (s, 2 H, OCH2), 5.93 (s, 1 H, ArH), 6.84 (d, J = 8.4 Hz, 2 H, ArH), 7.29–7.34 (m, 2 H, ArH), 7.40 (d, J = 8.4 Hz, 2 H, ArH), 7.56 (t, J = 8.4 Hz, 2 H, ArH), 7.87 (d, J = 7.6 Hz, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.3, 58.0, 79.6, 89.5, 91.6, 114.1, 115.6, 116.8, 123.2, 123.9, 132.5, 133.6, 153.4, 160.3, 162.7, 164.8.

MS (ESI): m/z = 321.12 [M + H]+.

Anal. Calcd for C19H14O4: C, 74.50; H, 4.61. Found: C, 74.38; H, 4.73.


#

22b

Yield: 365 mg (72%); brown solid; mp 108–109 °C.

IR (KBr): 1733, 2224, 2931 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.41 (s, 3 H, CH3), 3.82 (s, 3 H, OCH3), 5.07 (s, 2 H, OCH2), 5.89 (s, 1 H, ArH), 6.84 (d, J = 7.8 Hz, 2 H, ArH), 7.21 (d, J = 8.4 Hz, 1 H, ArH), 7.35 (d, J = 8.4 Hz, 1 H, ArH), 7.40 (d, J = 8.4 Hz, 1 H, ArH), 7.66 (s, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 20.9, 55.3, 57.9, 79.7, 89.4, 91.5, 113.4, 114.0, 115.2, 116.5, 122.8, 133.5, 133.6, 133.7, 151.5, 160.3, 163.0, 164.6.

Anal. Calcd for C20H16O4: C, 74.99; H, 5.03. Found: C, 75.23; H, 4.85.


#

22c

Yield: 275 mg (58%); brown solid; mp 126–127 °C.

IR (KBr): 1725, 2221, 2945 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.40 (t, J = 6.8 Hz, 3 H, CH3), 4.01 (q, J = 6.8 Hz, 2 H, OCH2), 5.09 (s, 2 H, OCH2), 5.93 (s, 1 H, =CH), 6.83 (d, J = 7.6 Hz, 2 H, ArH), 7.29–7.34 (m, 1 H, ArH), 7.39 (d, J = 7.6 Hz, 3 H, ArH), 7.56 (t, J = 8.0 Hz, 1 H, ArH), 7.87 (d, J = 8.0 Hz, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 14.7, 58.0, 63.6, 79.5, 89.5, 91.7, 113.2, 114.5, 116.8, 123.2, 124.0, 132.5, 133.6, 153.4, 159.7, 162.7, 164.8.

Anal. Calcd for C20H16O4: C, 74.99; H, 5.03. Found: C, 74.73; H, 4.88.


#

22d

Yield: 295 mg (73%); brown solid; mp 110–111 °C.

IR (KBr): 1734, 2229, 2931 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.21 (s, 3 H, CH3), 3.82 (s, 3 H, OCH3), 4.87 (s, 2 H, OCH2), 5.62 (s, 1 H, ArH), 5.83 (s, 1 H, ArH), 6.83 (d, J = 8.4 Hz, 2 H, ArH), 7.38 (d, J = 8.4 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 20.1, 20.6, 29.2, 89.4, 95.1, 95.7, 99.8, 114.1, 160.1, 160.9, 163.8, 166.0, 170.0.

Anal. Calcd for C16H14O4: C, 71.10; H, 5.22. Found: C, 71.03; H, 5.32.


#

Pyranocoumarin and Pyranopyran Derivatives 23a–d; Compound 23a; Typical Procedure

A mixture of compound 22a (100 mg, 0.24 mmol), molecular iodine (183 mg, 0.72 mmol), anhydrous NaHCO3 (60 mg, 0.72 mmol) was stirred in anhydrous MeCN (10 mL) at r.t. for 6 h and then CH2Cl2 (50 mL) was added to the reaction mixture. The organic phase was washed successively with 10% aq Na2S2O3 (15 mL), H2O (15 mL) and brine (15 mL), and dried (Na2CO3). The solvent was removed under reduced pressure and the crude product was purified by silica gel (230–400 mesh) column chromatography using PE–EtOAc (9.7:0.3) as eluent to give the solid product 23a; yield: 90 mg (65%); yellow solid; mp 142–143 °C.

IR (KBr): 1732, 2931 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.84 (s, 3 H, OCH3), 5.29 (s, 2 H, OCH2), 6.91 (d, J = 8.8 Hz, 2 H, ArH), 7.11 (d, J = 8.4 Hz, 2 H, ArH), 7.26–7.31 (m, 2 H, ArH), 7.56 (t, J = 7.6 Hz, 1 H, ArH), 7.82 (d, J = 7.6 Hz, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 55.1, 76.6, 84.8, 101.4, 113.4, 114.5, 116.7, 123.1, 124.1, 129.6, 132.2, 132.9, 139.0, 153.4, 157.7, 159.2, 161.4.

MS (ESI): m/z = 432.87 [M + H]+.

Anal. Calcd for C19H13IO4: C, 52.80; H, 3.03. Found: C, 52.97; H, 3.23.


#

23b

Yield: 95 mg (68%); yellow solid; mp 136–138 °C.

IR (KBr): 1727, 2924 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.43 (s, 3 H, CH3), 3.84 (s, 3 H, OCH3), 5.27 (s, 2 H, OCH2), 6.91 (d, J = 8.8 Hz, 2 H, ArH), 7.10 (d, J = 8.4 Hz, 2 H, ArH), 7.16 (d, J = 8.4 Hz, 1 H, ArH), 7.35 (d, J = 8.4 Hz, 1 H, ArH), 7.62 (s, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 20.9, 55.1, 76.5, 84.6, 104.3, 113.4, 114.2, 116.5, 122.7, 129.6, 132.3, 133.8, 134.0, 139.1, 151.6, 157.9, 159.1, 161.5.

MS (ESI): m/z = 672.71 [M + Na]+.

Anal. Calcd for C20H15IO4: C, 53.83; H, 3.39. Found: C, 53.78; H, 3.13.


#

23c

Yield: 100 mg (72%); yellow solid; mp 146–148 °C.

IR (KBr): 1730, 2922 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.43 (t, J = 7.2 Hz, 3 H, CH3), 4.04 (q, J = 7.2 Hz, 2 H, OCH2), 5.28 (s, 2 H, OCH2), 6.90 (d, J = 8.4 Hz, 2 H, ArH), 7.09 (d, J = 8.8 Hz, 2 H, ArH), 7.27–7.31 (m, 2 H, ArH), 7.54 (dt, J = 8.8, 1.2 Hz, 1 H, ArH), 7.82 (d, J = 8.8 Hz, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 14.9, 63.3, 76.6, 84.8, 104.4, 113.9, 114.5, 116.7, 123.1, 124.1, 129.6, 132.0, 132.9, 139.0, 153.4, 157.7, 158.6, 161.4.

MS (ESI): m/z = 432.87 [M + H]+.

Anal. Calcd for C20H15IO4: C, 53.83; H, 3.39. Found: C, 54.01; H, 3.26.


#

23d

Yield: 80 mg (55%); yellow solid; mp 135–137 °C.

IR (KBr): 1729, 2925 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.20 (s, 3 H, CH3), 3.83 (s, 3 H, OCH3), 5.01 (s, 2 H, OCH2), 5.87 (s, 1 H, ArH), 6.89 (d, J = 8.4 Hz, 2 H, ArH), 7.07 (d, J = 8.4 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 20.4, 55.1, 76.2, 82.8, 99.3, 101.6, 113.3, 129.6, 132.1, 138.5, 159.1, 164.1, 166.4.

MS (ESI): m/z = 396.88 [M + H]+.

Anal. Calcd for C16H13IO4: C, 48.51; H, 3.31. Found: C, 48.47; H, 3.13.


#
#

Acknowledgment

K.C.M. is thankful to UGC (New Delhi) for an Emeritus Fellowship. B.S., S.G., and D.G. are grateful to CSIR (New Delhi) for Senior Research fellowships. I.A. is grateful to UGC (New Delhi) for a Senior Research fellowship. We also thank DST (New Delhi) for providing Perkin-Elmer L 120-000A IR spectrometer, Bruker DPX-400 NMR spectrometer, and 2400 series II CHN analyzer under its FIST program.

Supporting Information

    for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis.
  • Supporting Information


   Permissions and Reprints All articles of this category
Zoom Image
Scheme 1 Literature reports on 2H-pyrans fused with both benzene and coumarin rings
Zoom Image
Figure 1 Some biologically active 2H-benzopyran, pyranopyran, and pyranocoumarin derivatives
Zoom Image
Scheme 2 Preparation of propargyl ethers. Reagents and conditions: (i) propargyl bromide, acetone, K2CO3, NaI, reflux; (ii) p-substituted iodobenzene, Pd(PPh3)2Cl2, CuI, DMF–Et3N, r.t.
Zoom Image
Scheme 3 Preparation of 17a. Reagents and conditions: (i) I2, NaHCO3, MeCN, r.t.
Zoom Image
Figure 2 ORTEP diagram of the compound 17a
Zoom Image
Scheme 4 Preparation of pyranocoumarin derivative 23a. Reaction conditions: (i) p-substituted iodobenzene, Pd(PPh3)2Cl2, CuI, DMF–Et3N, reflux; (ii) I2, NaHCO3, MeCN, r.t., 6 h.