Synthesis and characterization of novel indanone-based spiro-dihydrobenzofuran derivatives

Article abstract of DOI:10.3906/kim-1904-13

In this study, the synthesis and characterization of novel indanone-based spiro-dihydrobenzofuran derivatives were examined. Firstly, chalcone-like compounds 4a–k, (E) -2-benzylidene-2,3-dihydro-1 H -inden-1-one derivatives, were synthesized by the base-c

Full text of DOI:10.3906/kim-1904-13

Turk J Chem
Turkish Journal of Chemistry
(2019) 43: 1445 – 1457
© TÜBİTAK
http://journals.tubitak.gov.tr/chem/
doi:10.3906/kim-1904-13
Research Article
Synthesis and characterization of novel indanone-based spiro-dihydrobenzofuran
derivatives
Meliha Burcu GÜDERE,, Neşe DÜRÜ,, Yakup BUDAK,, Mustafa CEYLAN∗,
Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpaşa University, Tokat, Turkey
Received: 09.04.2019
•
Accepted/Published Online: 11.09.2019
•
Final Version: 07.10.2019
Abstract: In this study, the synthesis and characterization of novel indanone-based spiro-dihydrobenzofuran deriva-
tives were examined. Firstly, chalcone-like compounds 4a–k, (E)-2-benzylidene-2,3-dihydro-1H -inden-1-one deriva-
tives, were synthesized by the base-catalyzed addition of benzaldehyde derivatives to 2,3-dihydro-1H -inden-1-one. Then
Mn(OAc)3 -mediated addition of dimedone (2) to the chalcone-like compounds gave two novel spiro-dihydrobenzofuran
isomers: (3S)-6,6-dimethyl-3-aryl-6,7-dihydro-3H -spiro [benzofuran-2,2’-indene]-1’,4(3’H ,5H)-dione (5a–k) and (2’S)-
6,6-dimethyl-2-aryl-6,7-dihydro-2H -spiro[benzofuran-3,2’-indene]-1’,4(3’H ,5H)-dione (6a–k) in good yields. The iso-
mers were separated by column chromatography and their structures were elucidated on the basis of spectral data (NMR,
IR) and elemental analysis.
Key words: Indanone, spirobenzofuran, chalcone-like compound, Mn(OAc)3 , dimedone
1. Introduction
Benzofuran derivatives are an important class of heterocyclic compounds having biological activity, such as
dihydrofuran [1,2]. Benzofuran [3] and spiro-benzofuran [4] derivatives have advantageous structural skeletons
in medicinal chemistry for drug discovery [5]. They are found in the structures of many natural and signif-
icant pharmaceuticals [6–10]. Moreover, they have a wide spectrum of biological activity such as antifungal
[11], antibacterial [12], antitumor [13,14], antimicrobial [15–18], antiinflammatory [19,20], antihyperglycemic,
analgesic, antiparasitic, and kinase inhibitory [21–26].
The synthesis, characterization, and isolation of spiro-benzofuran derivatives are of interest to chemists
due to the wide range of biological activity and many methods have been used for their synthesis [27–30].
Among these methods, manganese(III) acetate-catalyzed oxidative free radical addition of 1,3-dicarbonyls to
related olefins is one of the most useful [20,31–35].
In addition, indanones are also an important group amongst the compounds exhibiting pharmacological
properties and are often used as starting materials in synthesis [36], drug intermediates, ligands of olefinic
polymerization catalysts, and discotic liquid crystals [37].
In our previous study, we reported the Mn(OAc)3 -mediated oxidative free radical addition of dimedone
(2) to (E)-2-(benzylidene)-3,4-dihydronaphthalen-1(2H)-one derivatives (1). From this reaction, tetralone-
based spirodihydrobenzofuran derivatives (3) were obtained by regioselective addition of dimedone to the β -
carbon atom of the α,β -unsaturated unit following oxidative cyclization in good yields [38].
∗Correspondence: mustafa.ceylan@gop.edu.tr
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This work is licensed under a Creative Commons Attribution 4.0 International License.

GÜDERE et al./Turk J Chem
As part of our previous work, the current study reports the oxidative free radical addition of dimedone
(2) to (E)-2-benzylidene-2,3-dihydro-1H-inden-1-one derivatives (4a–k) mediated by Mn(OAc)3 .
2. Materials and methods
2.1. General
All chemicals were purchased from Sigma-Aldrich and Fluka. Melting points were measured on an Electrother-
1
13
mal 9100 apparatus. IR spectra (KBr disc) were recorded on a Jasco FT/IR-430 spectrometer. H and
C
1
NMR spectra were recorded on a Bruker Avance DPX-400 instrument. TMS ( H NMR, δ (0.00)) and CDCl3 (δ
(77.0)) served as internal standards for C NMR spectroscopy, J values are given in Hz. Elemental analyses
13
were conducted using a LECO CHNS 932 Elemental Analyzer.
2.2. Synthesis
2.2.1. General procedure for the synthesis of (E)-2-benzylidene-2, 3-dihydro-1H-inden-1-one
(chalcone-like compounds) derivatives (4a–k)
The chalcone-like compounds, (E)-2-benzylidene-2,3-dihydro-1H -inden-1-one derivatives (4a–k), were synthe-
sized using our previously published procedure [39].
2.2.2. General procedure for the synthesis of indano-based spiro-didyhrobenzofuran derivatives
(5a–k and 6a–k) [38]
A solution of Mn(OAc)3 (10 mmol) in AcOH (10 mL) was heated for 2 h at 80 ◦ C under N2 atmosphere. After
the temperature had dropped to 60 ◦ C, to this solution was added solution of 4a–k (1 mmol) and dimedone
(2) (3 mmol) in AcOH (10 mL) dropwise over 25 min. The mixture was refluxed for 3 h under N2 atmosphere.
The reaction mixture was extracted with CH2 Cl2 , dried over anhydrous Na2 SO4 , and concentrated under
reduced pressure. The crude products were separated on a silica gel column eluting with ethyl acetate/hexane
(3:7). The first product was the isomer 3.
2.3. Spectral characterization of the synthesized compounds (5a–k and 6a–k)
2.3.1. (3S)-3-(4-bromophenyl)-6, 6-dimethyl-6, 7-dihydro-3H-spiro[benzofuran-2, 2’- indene]-1’, 4
(3’H,5H)-dione (5a)
Yield 45%, mp: 167–170 ◦ C. IR (KBr, cm−1 ): 3404, 2959, 2870, 2310, 2246, 1724, 1644, 1487, 1466, 1389,
1348, 1300, 1218, 1010. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.84 (d, J = 7.6 Hz, 1H), 7.61 (d, J =
7.6 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 7.6 Hz, 1H), 6.88 (d, J = 8.4 Hz,
2H), 4.43 (bs, 1H), 3.10 (d, J = 17.6 Hz, 1H), 2.80 (d, J = 17.6 Hz, 1H), 2.54–2.51 (m, 2H), 2.36 (d, J = 16.0
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Hz, 1H), 2.27 (d, J = 16.4 Hz, 1H), 1.23 (bs, 6H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 199.9, 193.4,
176.2, 150.3, 137.3, 136.2, 133.1, 131.9 (4C), 129.8, 128.4, 126.3, 125.4, 121.6, 115.0, 95.3, 51.1, 49.6, 37.7, 35.8,
34.2, 28.8. Anal. calc. for C24 H21 BrO3 : C, 65.91; H, 4.84. Found: C, 65.86; H, 4.77.
2.3.2. (2’S)-2-(4-bromophenyl)-6, 6-dimethyl-6, 7-dihydro-2H-spiro[benzofuran-3, 2’-indene]-1’, 4
(3’H,5H)-dione (6a)
Yield: 40%, mp: 178–181 ◦ C. IR (KBr, cm−1 ): 3404, 2960, 2868, 2348, 1702, 1650, 1628, 1490, 1464, 1396,
1284, 1226, 1151, 1071, 1015. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.56 (t, J = 7.4 Hz, 1H), 7.44 (d,
J = 7.6 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.28 (d, J = 9.2 Hz, 2H), 7.26 (d, J = 7.6 Hz, 1H), 6.98 (d, J
= 8.4 Hz, 2H), 5.69 (bs, 1H), 4.13 (d, J = 17.2 Hz, 1H), 3.21 (d, J = 17.6 Hz, 1H), 2.59 (m, 2H), 2.34 (d, J
= 16.0 Hz, 1H), 2.22 (d, J = 16.0 Hz, 1H), 1.27 (bs,3H), 1.22 (bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ
(ppm): 202.6, 193.9, 178.0, 151.5, 135.8, 135.0, 133.8, 131.2 (2C), 127.6, 127.5 (2C), 125.8, 124.1, 122.4, 115.3,
94.4, 61.7, 51.1, 39.1, 38.0, 34.7, 29.4, 27.7. Anal. calc. for C24 H21 BrO3 : C, 65.91; H, 4.84. Found: C, 65.83;
H, 4.80.
2.3.3. (3S)-3-(4-chlorophenyl)-6, 6-dimethyl-6, 7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-1’, 4
(3’H,5H)-dione(5b)
Yield: 40%, mp: 161–164 ◦ C. IR (KBr, cm−1 ): 3432, 2959, 2871, 2361, 1724, 1635 1604, 1541, 1490, 1468,
1389, 1300, 1218, 1090. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.85 (d, J = 7.6 Hz, 1H), 7.63 (t, J =
7.6 Hz, 1H), 7.43 (t, J = 7.4 Hz, 1H), 7.28 (d, J = 8.4 Hz, 3H), 6.94 (d, J = 8.4 Hz, 2H), 4.44 (bs, 1H), 3.10
(d, J = 17.6 Hz, 1H), 2.80 (d, J = 17.6 Hz, 1H), 2.54–2.51 (m, 2H), 2.36 (d, J = 16.0 Hz, 1H), 2.27 (d, J
= 16.4 Hz, 1H), 1.23 (bs, 6H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 200.0, 193.4, 176.1, 150.3, 136.8,
136.2, 133.4, 133.1, 129.5 (2C), 129.0 (2C), 128.4, 126.3, 125.4, 115.0, 95.4, 51.2, 49.5, 37.7, 35.8, 34.2, 28.8,
28.7. Anal. calc. for C24 H21 ClO3 : C, 73.37; H, 5.39. Found: C, 73.24; H, 5.18.
2.3.4. (2’S)-2-(4-chlorophenyl)-6, 6-dimethyl-6, 7-dihydro-2H-spiro[benzofuran-3, 2’-indene]-1’, 4
(3’H,5H)-dione (6b)
Yield: 40%, mp: 172–175 ◦ C. IR (KBr, cm−1 ): 3434, 2960, 2893, 2345, 1703, 1653, 1632, 1606, 1495, 1465,
1397, 1227, 1194, 1151, 1093, 1071. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.56 (t, J = 7.4 Hz, 1H),
7.44 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 8.4 Hz, 2H), 7.04 (d,
J = 8.4 Hz, 2H), 5.70 (bs, 1H), 4.13 (d, J = 17.2 Hz, 1H), 3.21 (d, J = 17.2 Hz, 1H), 2.59 (m, 2H), 2.34 (d, J
= 16.0 Hz, 1H), 2.23 (d, J = 16.4 Hz, 1H), 1.27 (bs, 3H), 1.22 (bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ
(ppm): 202.6, 193.9, 178.0, 151.5, 135.8, 135.0, 134.2, 133.2, 128.2 (2C), 127.6, 127.3 (2C), 125.8, 124.0, 115.3,
94.4, 61.8, 51.1, 39.1, 38.0, 34.7, 29.4, 27.7. Anal. calc. for C24 H21 ClO3 : C, 73.37; H, 5.39. Found: C, 73.28;
H, 5.27.
2.3.5. (3S)-3-(4-methoxyphenyl)-6, 6-dimethyl-6, 7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-1’,
4 (3’H,5H)-dione (5c)
Yield: 50%, mp: 146–149 ◦ C. IR (KBr, cm−1 ): 3404, 2955, 2884, 2347, 1703, 1655, 1632, 1517, 1460, 1422,
1391, 1396, 1348, 1303, 1252, 1232, 1178, 1052, 1027. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.84 (d, J
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= 9.6 Hz, 1H), 7.55 (t, J = 10 Hz, 1H), 7.46–7.36 (m, 4H), 6.68 (d, J = 12 Hz, 2H), 4.41 (bs, 1H), 3.72 (bs,
3H), 3.08 (d, J = 23.2 Hz, 1H), 2.84 (d, J = 23.2 Hz, 1H), 2.58 (bs, 2H), 2.51 (bs, 2H), 1.28 (bs, 3H), 1.22 (bs,
3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 200.5, 193.3, 175.6, 150.9, 136.5, 136.3, 136.2, 133.0, 130.6,
128.3, 127.4, 127.3, 126.3 (2C), 125.3, 115.5, 97.4, 55.4, 45.5, 37.7, 36.1, 34.2, 28.9, 28.8, 19.6. Anal. calc. for
C25 H24 O4 : C, 77.30; H, 6.23. Found: C, 77.15; H, 6.17.
2.3.6. (2’S)-2-(4-methoxyphenyl)-6, 6-dimethyl-6, 7-dihydro-2H-spiro[benzofuran-3, 2’-indene]-
1’, 4 (3’H,5H)-dione (6c)
Yield: 45%, mp: 157–160 ◦ C. IR (KBr, cm−1 ): 3609, 3407, 3962, 2893, 2347, 1725, 1712, 1632, 1609, 1512,
1466, 1421, 1388, 1348, 1302, 1267, 1243, 1221, 1143, 1026, 1000. 1 H NMR (400 MHz, CDCl3 ) δ (ppm):
7.53 (t, J = 9.8 Hz, 1H), 7.37 (d, J = 10.0 Hz, 1H), 7.24 (d, J = 8.8 Hz, 1H), 7.04 (d, J = 11.2 Hz, 1H),
6.91 (d, J = 11.6 Hz, 2H), 6.83 (d, J = 12.0 Hz, 2H), 5.68 (bs, 1H), 4.11 (d, J = 22.8 Hz, 1H), 3.79 (bs. 3H),
3.18 (d, J = 23.2 Hz, 1H), 2.58 (bs. 2H), 2.51 (bs. 2H), 1.24 (bs. 3H), 1.23 (bs. 3H). 13 C NMR (100 MHz,
CDCl3 ) δ (ppm): 200.3, 193.9, 177.9, 153.3, 135.8, 134.7, 134.0, 133.3, 129.9, 128.1, 127.6, 127.5, 125.7,
125.6, 123.9, 114.9, 91.0, 62.2, 55.1, 40.5, 38.0, 34.7, 29.1, 28.1, 19.2. Anal. calc. for C25 H24 O4 : C, 77.30; H,
6.23. Found: C, 77.20; H, 6.13.
2.3.7. (3S)-6, 6-dimethyl-3-(p-tolyl)-6, 7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-1’, 4 (3’H,5H)-
dione (5d)
Yield: 45%, mp: 145–147 ◦ C. IR (KBr, cm−1): 3432, 3037, 2955, 2869, 2348, 1726, 1634, 1509, 1468, 1394,
1299, 1218, 1143, 1113, 1001. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.84 (d, J = 10.0 Hz, 1H), 7.60
(d, J = 11.0 Hz, 1H), 7.43 (t, J = 10.6 Hz, 1H), 7.24 (d, J = 10.4 Hz, 1H), 7.10 (d, J = 10.4 Hz, 2H), 6.87
(d, J = 10.8 Hz, 2H), 4.42 (bs, 1H), 3.74 (d, J = 9.6 Hz, 1H), 3.08 (d, J = 23.6 Hz, 1H), 2.84 (d, J = 23.6
Hz, 1H), 2.53 (d, J = 9.6 Hz, 2H), 2.29 (bs, 1H), 2.19 (bs, 3H), 1.24 (bs, 3H), 1.23 (bs, 3H). 13 C NMR (100
MHz, CDCl3 ) δ (ppm): 199.6, 193.4, 180.2, 147.0, 141.0, 139.8, 139.2, 136.0, 133.1, 129.4 (2C), 128.0 (3C),
126.3, 106.2, 97.6, 51.2, 44.9, 34.7, 32.9, 30.1, 28.8, 28.7, 26.3. Anal. calc. for C25 H24 O3 : C, 80.62; H, 6.49.
Found: C, 80.54; H, 6.39.
2.3.8. (2’S)-6, 6-dimethyl-2-(p-tolyl)-6, 7-dihydro-2H-spiro[benzofuran-3,2’-indene]-1’, 4 (3’H,5H)-
dione (6d)
Yield: 45%, mp: 152–155 ◦ C. IR (KBr, cm−1 ): 3433, 3030, 2958, 2929, 2869, 2348, 1703, 1654, 1643, 1607,
1515, 1463, 1428, 1395, 1273, 1229, 1188, 1147, 1070. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.53 (d, J
= 9.8 Hz, 1H), 7.43 (d, J = 10.0 Hz, 1H), 7.37 (d, J = 10.0 Hz, 1H), 7.20 (d, J = 9.8 Hz, 1H), 6.98 (d, J =
4.8 Hz, 4H), 5.71 (bs, 1H), 4.11 (d, J = 22.8 Hz, 1H), 3.22 (d, J = 23.2 Hz, 1H), 2.59 (d, J = 1.6 Hz, 2H),
2.32 (d, J = 6.0 Hz, 1H), 2.23 (bs, 3H), 2.19 (bs, 1H), 1.27 (bs, 3H), 1.22 (bs, 3H). 13 C NMR (100 MHz,
CDCl3 ) δ (ppm): 202.9, 194.0, 178.3, 157.8, 151.5, 138.1, 136.0, 134.7, 131.6, 128.7, 127.3, 125.8, 123.9,
118.3, 115.4, 113.0, 95.4, 61.7, 51.2, 39.1, 38.0, 34.7, 29.4, 27.8, 21.1. Anal. calc. for C25 H24 O3 : C, 80.62; H,
6.49. Found: C, 80.56; H, 6.34.
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2.3.9. (3S)-3-(3-chlorophenyl)-6,6-dimethyl-6,7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-1’, 4
(3’H,5H)-dione (5e)
Yield: 41%, mp: 136–139 ◦ C. IR (KBr, cm−1 ): 3405, 2959, 2879, 2344, 1735, 1639, 1470, 1433, 1393, 1300,
1226, 1214, 1116, 1004. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.85 (d, J = 7.6 Hz, 1H), 7.63 (t, J =
7.4 Hz, 1H), 7.45 (t, J = 7.4 Hz, 1H), 7.26–7.23 (m, 3H), 6.99 (bs, 1H), 6.90 (d, J = 6.4 Hz, 1H), 4.43 (bs,1H),
3.12 (d, J = 17.6 Hz, 1H), 2.79 (d, J = 17.6 Hz, 1H), 2.53 (m, 2H), 2.36 (d, J = 16.4 Hz, 1H), 2.29 (d, J = 16.0
Hz, 1H), 1.24 (bs, 3H), 1.23 (bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 199.8, 193.3, 176.2, 150.3,
140.4, 136.2, 134.7, 133.0, 130.0, 128.4, 128.2, 127.9, 126.4, 126.3, 125.4, 115.0, 95.4, 51.2, 49.6, 37.7, 38.8, 34.3,
28.7 (2C). Anal. calc. for C24 H21 ClO3 : C, 73.37; H, 5.39. Found: C, 73.25; H, 5.30.
2.3.10. (2’S)-2-(3-chlorophenyl)-6, 6-dimethyl-6, 7-dihydro-2H-spiro[benzofuran-3, 2’-indene]-1’,
4(3’H,5H)-dione (6e)
Yield: 40%, mp: 143-147 ◦ C. IR (KBr, cm−1 ): 3444, 2954, 2348, 1700, 1654, 1633, 1600, 1475, 1427, 1398,
1273, 1227, 1145, 1077. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.59–7.55 (td, J = 7.4 Hz, 1.2 Hz, 1H),
7.46 (d, J = 7.6 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.10
(bs, 1H), 7.07 (d, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 5.70 (bs, 1H), 4.15 (d, J = 17.2 Hz, 1H), 3.23 (d,
J = 17.2 Hz, 1H), 2.60–2.55 (m, 2H), 2.34 (d, J = 16.0 Hz, 1H), 2.22 (d, J = 16.0 Hz, 1H), 1.27 (bs, 3H), 1.23
(bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 202.4, 193.9, 177.9, 157.5, 151.4, 136.8, 135.0, 134.1,
129.2, 128.5, 127.6, 126.1, 125.9, 124.0, 123.8, 115.3, 94.2, 61.8, 51.2, 39.1, 37.9, 34.7, 29.4, 27.8. Anal. calc. for
C24 H21 ClO3 : C, 73.37; H, 5.39. Found: C, 73.27; H, 5.27.
2.3.11. (3S)-3-(3-methoxyphenyl)-6,6-dimethyl-6,7-dihydro-3H-spiro[benzofuran-2,2’-indene]-1’,
4(3’H,5H)-dione (5f)
Yield: 80%, mp: 155–158 ◦ C. IR (KBr, cm−1 ): 3449, 2994, 2958, 2928, 2830, 2347, 1715, 1642, 1605, 1581,
1465, 1420, 1390, 1348, 1300, 1267, 1221, 1154, 1140, 1051. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.85
(d, J = 7.6 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.44 (d, J = 7.4 Hz, 1H), 7.25 (d, J = 7.6 Hz, 1H), 7.21 (d,
J = 8.0 Hz, 1H), 6.81 (d, J = 7.6 Hz, 1H), 6.59 (d, J = 7.6 Hz, 1H), 6.51 (bs, 1H), 4.43 (bs, 1H), 3.73 (bs,
3H), 3.08 (d, J = 17.6 Hz, 1H), 2.83 (d, J = 17.6 Hz, 1H), 2.54–2.53 (m, 2H), 2.37 (d, J = 16.0 Hz, 1H), 2.29
(d, J = 16.4 Hz, 1H), 1.25 (bs, 3H), 1.23 (bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 200.3, 193.4,
176.0, 159.8, 150.7, 139.8, 136.0, 133.2, 129.8, 128.3, 126.3, 125.3, 120.5, 115.1, 113.9, 112.9, 95.6, 55.1, 51.2,
50.1, 37.7, 35.8, 34.2, 28.9, 28.7. Anal. calc. for C25 H24 O4 : C, 77.30; H, 6.23. Found: C, 77.25; H, 6.09.
2.3.12. (3S)-6, 6-dimethyl-3-(m-tolyl)-6, 7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-1’,
4 (3’H,5H)-dione (5g)
Yield: 75%, mp: 157–160 ◦ C. IR (KBr, cm−1 ): 3457, 3018, 2957, 2867, 2347, 1716, 1659, 1641, 1603, 1464,
1423, 1391, 1349, 1298, 1236, 1219, 1154, 1110, 1046. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.75 (d, J
= 10.0 Hz, 1H), 7.51 (d, J = 10.0 Hz, 1H), 7.34 (d, J = 10.0 Hz, 1H), 7.14 (d, J = 10.4 Hz, 1H), 7.08 (d, J
= 10.0 Hz, 1H), 6.97 (dd, J = 10.4 Hz, 1H), 6.70 (d, J = 11.2 Hz, 1H), 4.32 (bs, 1H), 2.98 (d, J = 23.6 Hz,
1H), 2.71 (d, J = 23.2 Hz, 1H), 2.47 (d, J = 23.6 Hz, 1H), 2.40 (d, J = 23.6 Hz, 2H), 2.27 (d, J = 21.6 Hz,
1H), 2.19 (bs, 3H), 2.18 (d, J = 21.6 Hz, 1H), 1.57 (bs, 3H), 1.14 (bs, 3H). 13 C NMR (100 MHz, CDCl3 )
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δ (ppm): 200.3, 193.4, 175.8, 150.7, 138.3, 1348.1, 136.0, 128.6, 128.4, 128 (2C), 126.3 (2C), 125.3 (2C), 115.4,
95.7, 51.2, 50.0, 37.7, 35.8, 34.7, 28.9, 28.7, 21.4. Anal. calc. for C25 H24 O3 : C, 80.62; H, 6.49. Found: C,
80.49; H, 6.37.
2.3.13. (3S)-6, 6-dimethyl-3-(o-tolyl)-6, 7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-1’,
4 (3’H,5H)-dione (5h)
Yield: 38%, mp: 163–166 ◦ C. IR (KBr, cm−1 ): 3438, 3047, 2953, 2928, 2346, 1725, 1649, 1608, 1465, 1422,
1383, 1342, 1299, 1230, 1133, 1050. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.85 (d, J = 7.6 Hz, 1H),
7.61 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.4 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H), 7.20–7.14 (m, 2H), 7.09 (d, J
= 7.2 Hz, 1H), 7.04 (d, J = 7.4 Hz, 1H), 4.78 (bs,1H), 3.05 (d, J = 17.6 Hz, 1H), 2.75 (d, J = 18.0 Hz, 1H),
2.52 (m, 2H), 2.36 (d, J = 16.0 Hz, 1H), 2.30 (d, J = 16.4 Hz, 1H), 1.93 (bs, 3H), 1.26 (bs, 3H), 1.24 (bs,
3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 200.5, 193.3, 175.6, 150.9, 136.5, 136.3, 136.2, 133.0, 130.6,
128.3, 127.4, 127.3, 126.3 [5(2C)], 125.3, 115.5, 95.4, 51.3, 45.5, 37.7, 36.1, 34.2, 28.9, 28.8, 19.6. Anal. calc. for
C25 H24 O3 : C, 80.62; H, 6.49. Found: C, 80.56; H, 6.33.
2.3.14. (2’S)-6, 6-dimethyl-2-(o-tolyl)-6, 7-dihydro-2H-spiro[benzofuran-3, 2’-indene]-1’,
4 (3’H,5H)-dione (6h)
Yield: 35%, mp: 178–181 ◦ C. IR (KBr, cm−1 ): 3416, 3029, 2961, 2946, 2929, 2867, 2348, 1717, 1645, 1604,
1492, 1466, 1420, 1395, 1368, 1340, 1291, 1266, 1227, 1191, 1143, 1071, 1013. 1 H NMR (400 MHz, CDCl3 )
δ (ppm): 7.53 (t, J = 7.4 Hz, 1H), 7.42 (d, J = 7.4 Hz, 1H), 7.34 (d, J = 7.4 Hz, 1H), 7.32 (d, J = 8.8 Hz,
1H), 7.23 (d, J = 7.4 Hz, 1H), 7.20 (d, J = 7.4 Hz, 1H), 7.08 (t, J = 7.4 Hz, 1.2 Hz, 1H), 6.86 (d, J = 7.2 Hz,
1H), 6.04 (bs, 1H), 4.07 (d, J = 16.8 Hz, 1H), 3.34 (d, J = 17.2 Hz, 1H), 2.63 (d, J = 17.6 Hz, 1H), 2.56 (d,
J = 17.6 Hz, 1H), 2.31 (m, 2H), 1.90 (bs, 3H), 1.31 (bs, 3H), 1.23 (bs, 3H). 13 C NMR (100 MHz, CDCl3 )
δ (ppm): 202.3, 193.9, 177.9, 151.3, 135.8, 134.7, 134.0, 133.3, 129.9, 128.1, 127.6, 127.5, 125.7, 125.6, 123.9,
114.9, 92.8, 62.2, 51.1, 40.5, 38.0, 34.7, 29.1, 28.1, 19.2. Anal. calc. for C25 H24 O3 : C, 80.62; H, 6.49. Found:
C, 80.59; H, 6.38.
2.3.15. (3R)-3-(2-chloro-5-nitrophenyl)-6, 6-dimethyl-6, 7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-
1’, 4 (3’H, 5H)-dione (5i)
Yield: 43%, mp: 210–213 ◦ C. IR (KBr, cm−1 ): 3441, 3079, 2348, 1708, 1604, 1527, 1464, 1347, 1268, 1095,
1048. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 8.21 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 12.0 Hz, 1H), 7.82
(d, J = 12.0 Hz, 1H), 7.69 (d, J = 11.6 Hz, 1H), 7.56 (d, J = 9.6 Hz, 1H), 7.50 (d, J = 10.4 Hz, 1H), 7.16
(d, J = 10.4 Hz, 1H), 6.98 (d, J = 9.6 Hz, 1H), 4.57 (bs, 1H), 3.74 (d, J = 9.6 Hz, 1H), 3.34 (m, 2H), 2.19
(m, 2H), 1.57 (bs, 6H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 200.7, 198.2, 173.6, 149.2, 146.8, 139.1,
137.8, 137.5, 133.2, 131.2, 128.1, 127.2, 126.3 (2C), 124.4, 105.0, 97.7, 51.7, 39.7, 36.7, 34.7, 33.7, 27.5 (2C).
Anal. calc. for C24 H20 ClNO5 : C, 65.83; H, 4.60; N, 3.20. Found: C, 65.79; H, 4.51; N, 3.14.
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2.3.16. (2’S)-2-(2-chloro-5-nitrophenyl)-6, 6-dimethyl-6, 7-dihydro-2H-spiro[benzofuran-3, 2’-indene]-
1’, 4 (3’H,5H)-dione (6i)
Yield: 38%, mp: 220–223 ◦ C. IR (KBr, cm−1 ): 3433, 2960, 2873, 2347, 1592, 1527, 1468, 1451, 1403, 1239,
1046. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 8.02 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 10.4 Hz, 1H), 7.56
(d, J = 10.0 Hz, 1H), 7.55 (d, J = 10.0 Hz, 1H), 7.43 (d, J = 11.6 Hz, 1H), 7.38 (d, J = 9.6 Hz, 1H), 7.22
(d, J = 10.4 Hz, 1H), 5.05 (bs, 1H), 3.01 (d, J = 23.6 Hz, 1H), 2.62 (d, J = 23.6 Hz, 1H), 2.46 (m, 2H), 2.30
(m, 2H), 1.23 (bs, 3H), 1.16 (bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 199.1, 193.3, 177.0, 150.4,
146.9, 141.3, 138.2, 136.4, 132.8, 130.6, 128.5, 126.3, 125.5, 123.7, 113.1, 94.6, 51.1, 46.2, 37.8, 36.3, 34.3, 28.8,
28.7, 27.5. Anal. calc. for C24 H20 ClNO5 : C, 65.83; H, 4.60; N, 3.20. Found: C, 65.75; H, 4.54; N, 3.08.
2.3.17. (3S)-3-(2, 4-dimethoxyphenyl)-6, 6-dimethyl-6, 7-dihydro-3H-spiro[benzofuran-2, 2’-indene]-
1’, 4 (3’H,5H)-dione (5j)
Yield: 45%, mp: 170–173 ◦ C. IR (KBr, cm−1 ): 3423, 2950, 2839, 2345, 1716, 1643, 1588, 1507, 1467, 1386,
1274, 1228, 1209, 1152, 1124, 1036. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.52 (t, J = 9.8 Hz, 1H),
7.37 (t, J = 10.0 Hz, 2H), 7.23 (d, J = 9.6 Hz, 2H), 6.75 (d, J = 11.2 Hz, 1H), 6.32 (dd, J = 11.2 Hz, 3.2
Hz, 1H), 5.97 (d, J = 3.2 Hz, 1H), 4.81 (bs, 1H), 3.98–3.81 (m, 1H), 3.72–3.69 (m, 1 H), 3.64 (bs, 3H), 3.48
(d, J = 22.4 Hz, 1H), 2.92 (bs, 3H) 2. 58 (d, J = 23.6 Hz, 1H), 2.36 (d, J = 22.4 Hz, 1H), 2.24 (d, J = 21.6
Hz, 1H), 1.23 (bs, 3H), 1.12 (bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 200.3, 193.9, 177.2, 159.9,
156.6, 150.1, 135.2, 134.6, 129.2, 126.3, 125.7, 123.6, 125.7, 116.8,112.9, 103.5, 97.8, 96.18, 55.2, 51.6, 49.8, 43.3,
39.7, 34.4, 34.2, 27.8. Anal. calc. for C26 H26 O5 : C, 74.62; H, 6.26. Found: C, 74.53; H, 6.11.
2.3.18. (2’S)-2-(2, 4-dimethoxyphenyl)-6, 6-dimethyl-6, 7-dihydro-2H-spiro [benzofuran-3, 2’-
indene]-1’, 4(3’H,5H)-dione (6j)
Yield: 40%, mp: 162–165 ◦ C. IR (KBr, cm−1 ): 3439, 3057, 2958, 2874, 2348, 1689, 1631, 1596, 1580, 1507,
1464, 1409, 1327, 1298, 1272, 1231, 1181, 1160, 1153, 1116, 1094, 1083. 1 H NMR (400 MHz, CDCl3 ) δ
(ppm): 7.84 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 8.4 Hz,
1H), 7.20 (d, J = 7.6 Hz, 1H), 6.54 (d, J = 8.4 Hz, 1H), 6.23 (bs, 1H), 6.12 (bs, 1H), 3.81 (bs, 3H), 2.99 (m,
4H), 2.70–2.51 (m, 3H), 2.28 (d, J = 16.0 Hz, 1H), 2.15 (d, J = 16.0 Hz, 1H), 1.20 (bs, 3H), 1.25 (bs, 3H).
13 C NMR (100 MHz, CDCl3 ) δ (ppm): 206.9, 193.2, 176.4, 160.8, 156.8, 152.8, 136.1, 134.4, 126.9, 126.5,
125.7, 123.7, 117.4, 117.4, 104.0, 97.7, 90.4, 60.8, 55.3, 53.8, 51.0, 37.9, 35.7, 34.3, 29.1, 28.2. Anal. calc. for
C26 H26 O5 : C, 74.62; H, 6.26. Found: C, 74.51; H, 6.18.
2.3.19. (3S)-3-(2, 5- dimethoxyphenyl)-6, 6-dimethyl-6, 7-dihydro-3H-spiro [benzofuran-2, 2’-
indene]-1’, 4 (3’H,5H)-dione (5k)
Yield: 40%, mp: 137–140 ◦ C. IR (KBr, cm−1 ): 3440, 2956, 2867, 2839, 2347, 1731, 1628, 1501, 1465, 1420,
1402, 1352, 1329, 1298, 1225, 1042. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.77 (d, J = 10.0 Hz, 1H),
7.50 (t, J = 9.8 Hz, 1H), 7.33 (t, J = 9.8 Hz, 1H), 7.14 (d, J = 10.0 Hz, 1H), 6.65 (dd, J = 6.2 Hz, 4.2 Hz,
1H), 6.53 (d, J = 12.0 Hz, 1H), 6.48 (d, J = 4.0 Hz, 1H), 4.85 (bs, 1H), 3.66 (bs, 3H), 3.04 (bs, 3H), 2.88 (d,
J = 24.0 Hz, 1H), 2.70 (d, J = 24.0 Hz, 1H), 2.40 (m, 2H), 2.29 (bs, 2H), 1.19 (bs, 3H), 1.14 (bs, 3H). 13 C
NMR (100 MHz, CDCl3 ) δ (ppm): 201.1, 193.5, 176.5, 153.5, 151.3, 151.2, 135.6, 133.5, 127.8, 127.2,
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125.9, 125.0, 115.3, 112.9, 112.1, 110.4, 95.2, 55.6, 54.6, 51.4, 44.3, 37.9, 36.4, 34.1, 28.9, 28.8. Anal. calc. for
C26 H26 O5 : C, 74.62; H, 6.26. Found: C, 74.58; H, 6.20.
2.3.20. (2’S)-2-(2, 5-dimethoxyphenyl)-6, 6-dimethyl-6, 7-dihydro-2H-spiro[benzo-furan-3,2’-indene]-
1’, 4 (3’H,5H)-dione (6k)
Yield: 38%, mp: 147–150 ◦ C. IR (KBr, cm−1 ): 3440, 3014, 2956, 2867, 2347, 1731, 1628, 1502, 1646, 1420,
1402, 1352, 1329, 1298, 1225, 1120, 1042. 1 H NMR (400 MHz, CDCl3 ) δ (ppm): 7.86 (d, J = 10 Hz,
1H), 7.52 (d, J = 9.6 Hz, 1H), 7.23 (d, J = 10 Hz, 2H), 6.62 (d, J = 12 Hz, 1H), 6.57 (d, J = 4 Hz, 2H), 6.04
(bs, 1H), 3.88 (d, J = 22 Hz, 1H), 3.79 (bs, 3H), 3.50 (d, J = 22.4 Hz, 1H), 3.02 (bs, 3H), 2.38 (bs, 2H), 2.25
(bs, 2H), 1.24 (bs, 3H), 1.23 (bs, 3H). 13 C NMR (100 MHz, CDCl3 ) δ (ppm): 202.3, 193.9, 177.9, 151.3,
135.8, 134.7, 134.0, 133.3, 129.9, 128.1, 127.6, 127.5, 125.7, 125.6, 123.9, 114.9, 92.8, 62.2, 51.1, 40.5, 38.0, 34.7,
29.1, 28.1, 19.2, 19.0. Anal. calc. for C26 H26 O5 : C, 74.62; H, 6.26. Found: C, 74.49; H, 6.23.
3. Results and discussion
Firstly, the starting materials, chalcone-like derivatives, 2-(benzylidene)-2,3-dihydro-1H -inden-1-one (4a–k),
were synthesized from the Claisen–Schmidt condensation of 2,3-dihydro-1H -inden-1-one (1-indanone) with
benzaldehyde derivatives according to our recently published procedure [39]. The structures of compounds
4a–k were elucidated by spectroscopic data (NMR, IR, and elemental analysis) and comparison with authentic
samples of them [39].
Then the compounds (4a–k) were reacted with the dimedone (2) in the presence of Mn(OAc)3 in acetic
acid at 60 ◦ C for 2 h. The reaction resulted in the formation of two isomeric spirobenzofuran derivatives (5a–k
and 6a–k) in a ratio of almost 1:1 (Table). In the case of compounds 4f and 4g, the single isomers 5f and 5g
were formed, respectively, in both reactions. The isomers 5a–k and 6a–k were separated by silica gel column
chromatography eluting with ethyl acetate/hexane (3:7). The structures of the compounds were explained on
the basis of spectral data (NMR and IR) and elemental analysis. All spectral data were in good agreement with
the proposed structures of the compounds.
In our previous study [38], we investigated the Mn(OAc)3 -mediated oxidative free radical addition of
dimedone to 2-(benzylidene)-3,4-dihydronaphthalen-1(2H)-one derivatives. We determined that the dimedone
was regioselectively added to the β -carbon atom of the α,β -unit of the starting materials and the tetralone-
based spirodihydrobezofuran derivatives occurred by oxidative cyclization as a single isomer in good yield. In
the present study, the addition of dimedone to 2-(benzyliden)-2,3-dihydro-1H -inden-1-one (4a–k) gave the two
isomeric indanone-based spirodihydrobenzofuran derivatives. Formation of the two isomers can be explained
by the addition of dimedon to the β - and α-carbon atoms of the α,β -unsaturated unit in the structure of
2-(benzyliden)-2,3-dihydro-1H -inden-1-one (4a–k), respectively. A distinction between these structures has
1
been made on the basis of H NMR spectral studies. The benzylic proton C1-H of isomers 5 and 6 resonated in
the upfield region at δ 4.32–4.85 ppm and in the downfield region at δ 5.05–6.12 ppm as expected, respectively,
1
in their H NMR spectra.
4. Conclusion
Two novel series of isomeric indanone-based spirodihydrobenzofuran derivatives, (3S)-6,6-dimethyl-3-aryl-6,7-
dihydro-3H -spiro[benzofuran-2,2’-indene]-1’,4(3’H ,5H)-dione (5a–k) and (2’S)-6,6-dimethyl-2-aryl-6,7-dihydro-
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2H -spiro[benzofuran-3,2’-indene]-1’,4(3’H ,5H)-dione (6a–k), were synthesized using Mn(OAc)3 -mediated ox-
idative free radical additions between indanone-based chalcone-like compounds 4a–k and dimedone (2) in a
ratio of almost 1:1.
Table. Synthesis of spirobenzodihydrofurane derivatives.
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Acknowledgments
The authors are indebted to the Gaziosmanpaşa University Scientific Research Projects Commission (Project
No: BAP-2015/42) and the Scientific and Technological Research Council of Turkey (TÜBİTAK; BİDEP-2210-
C) for their financial support.
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