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Synlett 2016; 27(04): 631-639
DOI: 10.1055/s-0035-1560808
letter
© Georg Thieme Verlag Stuttgart · New York

An Unexpected C–C Bond Cleavage of Acetophenones: Synthesis of Bis(heteroaryl)arylmethanes and Triarylmethanes via SeO2/Lanthanide Chloride Catalyzed Friedel–Crafts Arylation

G. Santosh Kumar
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Telangana 500007, India   Email: hmmeshram@yahoo.com
,
A. Sanjeeva Kumar
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Telangana 500007, India   Email: hmmeshram@yahoo.com
,
A. Swetha
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Telangana 500007, India   Email: hmmeshram@yahoo.com
,
B. Madhu Babu
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Telangana 500007, India   Email: hmmeshram@yahoo.com
,
H. M. Meshram*
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Telangana 500007, India   Email: hmmeshram@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 15 June 2015

Accepted after revision: 28 September 2015

Publication Date:
30 November 2015 (online)

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Abstract

A novel synthesis of bisheteroarylaryl methanes and triarylmethanes is described by the selective C–C bond cleavage of acetophenones in the presence of SeO2/lanthanide chlorides. The present strategy provides an in situ generation of aldehydes from acetophenones followed by a double Friedel–Crafts reaction of electron-rich arenes. Natural product 1,1,1-tris(3-indolyl)methane is synthesized in a single step following the same protocol.

Key words

acetophenones - C–C bond cleavage - double Friedel–Crafts reaction

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560808.
  • Supporting Information
 

  • References and Notes

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  • 31 General Procedure for the Synthesis of Compounds 4 or 5 A solution of acetophenone 1 (1 mmol), SeO2 (2 mmol), and YbCl3 (0.3 mmol) in DMSO–H2O (9:1, 3 mL) was well stirred at 110 °C for 15 h. Then the 2-methylfuran (2) or 2-methylthiophene (3) was added to the reaction mixture at r.t. and stirred again for 10 min at 70 °C. After completion of the reaction, the reaction mixture brought to r.t., and it was filtered through a short pad of Celite, excess SeO2, and other selenium-containing byproducts were removed by adsorption on Celite. Water was added to the filtrate, and the mixture was extracted with CH2Cl2. The combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo, and purified by chromatography on silica gel to afford required products 4 or 5. The recovered catalyst was obtained from the aqueous layer after removing water. 1H NMR, 13C NMR, MS, and IR spectral data for the new products are given below. 2-[Bis(5-methylfuran-2-yl)methyl]-6-methoxyphenol (4c, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.23 (s, 6 H), 3.86 (s, 3 H), 4.01 (s, 1 H), 5.86 (s, 4 H), 6.73–6.83 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.6, 37.6, 55.9, 105.9, 107.9, 109.1, 119.2, 121.3, 123.3, 125.6, 142.9, 146.3, 151.1, 152.4, ppm. IR (KBr): ν = 731, 790, 1023, 1232 1290, 1481, 1608, 3521 cm–1. ESI-MS: m/z = 321 [M + Na]+. ESI-HRMS: m/z calcd for C18H18O4Na [M + Na]+: 321.1098; found: 321.1092. 4-[Bis(5-methylfuran-2-yl)methyl]benzene-1,2-diol (4d, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.24 (s, 6 H), 5.21 (s, 1 H), 5.83–5.88 (m, 4 H), 6.68 (dd, J = 1.88, 8.12 Hz, 1 H), 6.75 (d, J = 1.88 Hz, 1 H), 6.80 (d, J = 8.30 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.5, 44.3, 106.0, 107.9, 115.2, 115.4, 120.9, 132.9, 142.5, 143.3, 151.3, 152.9 ppm. IR (KBr): ν = 750, 801, 1107, 1269, 1519, 1603, 3387cm–1. ESI-MS: m/z = 307 [M + Na]+. ESI-HRMS: m/z calcd for C17H16O4Na [M + Na]+: 307.0945; found: 307.0939. 2-[Bis(5-methylfuran-2-yl)methyl]-4,6-dichlorophenol (4e, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.24 (s, 6 H), 5.73–5.76 (m, 1 H), 5.87–5.93 (m, 4 H), 7.01–7.04 (m, 1 H), 7.22 (d, J = 2.13 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.5, 38.4, 106.1, 108.6, 120.4, 125.2, 127.1, 128.3, 128.9, 147.6, 150.8, 151.7 ppm. IR (KBr): ν = 735, 811, 1051, 1182, 1240, 1321, 1465, 1679, 3509 cm–1. ESI-MS: m/z = 360 [M + Na]+. ESI-HRMS: m/z calcd for C17H14Cl2O3Na [M + Na]+: 360.0214; found: 360.0210. 2-[Bis(5-methylthiophen-2-yl)methyl]phenol (5a, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.40 (s, 6 H), 5.94 (s, 1 H), 6.56–6.58 (m, 2 H), 6.63 (d, J = 3.35 Hz, 2 H), 6.77 (dd, J = 1.22, 8.54 Hz, 1 H), 6.88 (td, J = 1.22, 7.47 Hz, 1 H), 7.12–7.16 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.3, 41.6, 116.2, 120.8, 124.6, 125.8, 128.3, 129.3, 130.1, 139.3, 143.7, 153.0 ppm. IR (KBr): ν = 754, 810, 1042, 1227, 1270, 1455, 1593, 3504 cm–1. ESI-MS: m/z = 301 [M + H]+. ESI-HRMS: m/z calcd for C17H17OS2 [M + H]+: 301.0719; found: 301.0714. 2-[Bis(5-methylthiophen-2-yl)methyl]-4-nitrophenol (5b, Scheme 3) White solid; mp 196–198 °C. 1H NMR (300 MHz, CDCl3): δ = 2.44 (s, 6 H), 5.94 (s, 1 H), 6.61 (dd, J = 0.94, 3.39 Hz, 2 H), 6.65 (d, J = 3.39 Hz, 2 H), 6.90 (q, J = 6.04 Hz, 1 H), 8.07–8.12 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.3, 41.6, 116.5, 124.7, 124.9, 125.5, 126.4, 131.0, 140.2, 141.7, 158.8 ppm. IR (KBr): ν = 639, 1071, 1278, 1327, 1486, 1588, 3317 cm–1. ESI-MS: m/z = 368 [M + Na]+. ESI-HRMS: m/z calcd for C17H16NO3S2 [M + Na]+: 368.0390; found: 368.0387. 4-[Bis(5-methylthiophen-2-yl)methyl]benzene-1,2-diol (5c, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.40 (s, 6 H), 5.55 (s, 1 H), 6.53–6.60 (m, 4 H), 6.72–6.82 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.3, 47.0, 115.1, 115.4, 120.9, 124.4, 125.5, 136.9, 138.9, 142.4, 143.2, 145.3 ppm. IR (KBr): ν = 765, 806, 1111, 1282, 1518, 1607, 3392 cm–1. ESI-MS: m/z = 317 [M + H]+. ESI-HRMS: m/z calcd for C17H17O2S2 [M + H]+: 317.0668; found: 317.0666. 2-[Bis(5-methylthiophen-2-yl)methyl]-4,6-dichlorophenol (5d, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.42 (s, 6 H), 5.71 (s, 1 H), 6.04 (br s, 1 H), 6.57 (s, 4 H), 7.09 (d, J = 2.45 Hz, 1 H), 7.24 (d, J = 2.45 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.3, 40.7, 120.4, 124.6, 125.2, 126.0, 127.1, 128.0, 133.0, 139.3, 142.9, 147.2 ppm. IR (KBr): ν = 757, 800, 1039, 1161, 1227, 1321, 1460, 1667, 3521 cm–1. ESI-MS: m/z = 370 [M + H]+. ESI-HRMS: m/z calcd for C17H18Cl2OS2 [M + H]+: 370.3362; found: 370.3358. 5,5′-[(3-Nitrophenyl)methylene]bis(2-methylthiophene) (5e, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.40 (s, 6 H), 5.77 (s, 1 H), 6.54–6.62 (m, 4 H), 7.44 (t, J = 8.30 Hz, 1 H), 7.64 (d, J = 7.55 Hz, 1 H), 8.08 (d, J = 8.30 Hz, 1 H), 8.16 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.1, 47.0, 121.9, 123.0, 124.6, 126.0, 129.1, 134.2, 139.6, 143.2, 145.7, 148.1 ppm. IR (KBr): ν = 730, 800, 1229, 1350, 1530 cm–1. ESI-MS: m/z = 352 [M + Na]+. ESI-HRMS: m/z calcd for C17H15NO2S2Na [M + Na]+: 352.0347; found: 352.0342. 3-[Bis(5-methylthiophen-2-yl)methyl]phenol (5f, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.39 (s, 6 H), 5.25 (br s, 1 H), 5.60 (s, 1 H), 6.49–6.61 (m, 4 H), 6.63–6.77 (m, 2 H), 6.82–6.89 (m, 1 H), 7.09–7.18 (m, 1 H) ppm. IR (KBr): ν = 703, 754, 803, 1040, 1227, 1263, 1451, 1598, 3393 cm–1. ESI-MS: m/z = 301 [M + H]+. ESI-HRMS: m/z calcd for C17H17O2S2 [M + H]+: 301.0717; found: 301.0712. 5,5′-[(4-Fluorophenyl)methylene]bis(2-methylthiophene) (5h, Scheme 3) Dark-brown viscous oil. 1H NMR (300 MHz, CDCl3): δ = 2.40 (s, 6 H), 5.64 (s, 1 H), 6.56 (s, 4 H), 6.97 (t, J = 3.50 Hz, 2 H), 7.22–7.28 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.0, 46.8, 115.1, 124.4, 125.5, 129.6, 138.9, 144.8, 159.9, 163.1 ppm. IR (KBr): ν = 537, 803, 842, 1158, 1227, 1505, 1603 cm–1. ESI-MS: m/z = 303 [M + H]+. ESI-HRMS: m/z calcd for C17H16FS2 [M + H]+: 303.0673; found: 303.0670. 5,5′-[(3,4-Dimethoxyphenyl)methylene]bis(2-methylthiophene) (5j, Scheme 3) Brown solid; mp 112–114 °C. 1H NMR (300 MHz, CDCl3): δ = 2.40 (s, 6 H), 3.81 (s, 3 H), 3.84 (s, 3 H), 5.61 (s, 1 H), 6.55 (dd, J = 0.94, 3.39 Hz, 2 H), 6.59 (d, J = 3.21 Hz, 2 H), 6.80–6.86 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.2, 47.3, 55.7, 110.8, 111.6, 120.2, 124.3, 125.4, 136.3, 138.8, 145.4, 147.9, 148.7 ppm. IR (KBr): ν = 721, 759, 1038, 1251, 1302, 1491, 1572, 1692 cm–1. ESI-MS: m/z = 367 [M + Na]+. ESI-HRMS: m/z calcd for C19H20O2S2Na [M + H]+: 367.0899; found: 367.0894.