Synlett 2019; 30(16): 1904-1908
DOI: 10.1055/s-0039-1690201
letter
© Georg Thieme Verlag Stuttgart · New York

Acid-Catalyzed Synthesis of Aryl[4,5]isothiazoles through a Sulfenic Acid Pathway

Hong Yuan
,
Zhihua Sun
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China   Email: sungaris@gmail.com
› Author Affiliations
We gratefully thank the financial support from the Science and Technology Commission of Shanghai Municipality (17ZR1412000).
Further Information

Publication History

Received: 03 August 2019

Accepted after revision: 22 August 2019

Publication Date:
05 September 2019 (online)

Abstract

A new method to efficiently prepare 3-substituted aryl[4,5]isothiazoles by simply heating the starting materials with a catalytic amount of p-toluenesulfonic acid in toluene is reported. This simple procedure is well suitable for a variety of substrates that can tolerate substitution changes in the fusing aromatic ring, as well as at the 3-position. Substituted aryl rings of varying electronic properties and alkyl substitution eventually afford aryl[4,5]isothiazoles in high yields.

Supporting Information

 
  • References and Notes

    • 1a Busch FR, Rose CA. Patent US6110918, 1995
    • 1b Stahl SM, Shayegan DK. J. Clin. Psychiatry 2003; 64: Suppl. 19: 6-12
    • 2a George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA. Eur. J. Clin. Pharmacol. 2013; 69: 1497
    • 2b Osaka MN, Osaka MO, Osaka SS. Patent US9174975, 2003
  • 3 Huebl D, Pieroh E. Patent DE 3837578 A1, 1990
    • 4a Clarksville JK. A. Patent US8609840 B2, 2008
    • 4b Nielsen M, Liljefors T, Nilsson J, Sterner O. Patent WO 2009123536 A1, 2009
    • 4c Dejonghe S, Herdewyn P, Bekerman E, Einav S, Neveu G. Patent WO 2016012536 A1, 2016
  • 5 Ana DO. S, James M, Michal S. Adv. Synth. Catal. 2019; 361: 3050
  • 6 McKinnon DM, Lee KR. Can. J. Chem. 1988; 66: 1405
  • 7 Devarie-Baez NO, Xian M. Org. Lett. 2010; 12: 752
  • 8 Xu F, Chen Y, Fan E, Sun Z. Org. Lett. 2016; 18: 2777
  • 9 Wei JH, Sun Z. Org. Lett. 2015; 17: 5396
  • 10 Wu S, Lei X, Fan E, Sun Z. Org. Lett. 2018; 20: 522
  • 11 Zhang X, Nirschl AA, Zou Y, Priestley ES. PCT Int. Appl 2007002313, 2007
  • 12 To a solution of 7 (1 equiv) in toluene (3 mL) TsOH (0.2 equiv) in toluene (2 mL) was added. The mixture was stirred at 60 °C for 1 h. Then the reaction mixture was cooled to room temperature and concentrated. The residue was loaded on a silica gel using petroleum ether/ethyl acetate (20:1) to afford the desired product 9.
  • 13 Characterization data of new compounds (2-Methyl-propane-2-sulfinyl)-benzylamine (7a): eluent CH2Cl2/MeOH (10:1, v/v), yellow oil; yield: 645 mg (61%). 1H NMR (400 MHz, CDCl3): δ = 7.81–7.79 (m, 1 H), 7.50–7.38 (m, 3 H), 4.18 (d, J = 14.5 Hz, 1 H), 3.74 (d, J = 14.5 Hz, 1 H), 1.72 (s, 2 H), 1.16 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 142.9, 138.0, 131.5, 128.1, 127.3, 126.4, 57.4, 42.7, 23.0.[2-(tert-Butylsulfinyl)phenyl](4-trifluoromethylphenyl)methanamine (7d): eluent PE/EtOAc (1:9, v/v), colorless oil; yield: 255 mg (72%). 1H NMR (400 MHz, CDCl3): δ = 7.87−7.84 (m, 1 H), 7.65−7.62 (m, 1 H), 7.60−7.53 (m, 4 H), 7.50−7.42 (m, 2 H), 5.82 (s, 1 H), 1.82 (s, 2 H), 1.31 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 147.0, 145.6, 138.6, 131.9, 129.7, 129.4, 128.0, 127.3, 125.3 (q, J = 3.7 Hz), 122.7, 57.5, 53.9, 23.3. 19F NMR (376 MHz, CDCl3): δ = –62.42 (s). HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H20NF3SH: 356.4072; found: 356.4069.[2-(tert-Butylsulfinyl)phenyl](1-methyl-1H-pyrrol-2-yl)methanamine (7g): eluent PE/EtOAc (1:9, v/v), purple red oil; yield: 230 mg (84%). 1H NMR (400 MHz, CDCl3): δ = 7.90−7.87 (m, 1 H), 7.53−7.46 (m, 3 H), 6.55−6.54 (m, 1 H), 6.07−6.02 (m, 2 H), 5.62 (s, 1 H), 3.52 (s, 3 H), 1.93 (s, 2 H), 1.32 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 144.2, 138.0, 136.1, 131.7, 127.7, 127.4, 126.4, 123.0, 106.7 (d, J = 2.2 Hz), 57.0, 48.2, 34.3, 23.4. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H22N2OSNa: 313.1345; found: 313.1341.[2-(tert-Butylsulfinyl)-4-methoxyphenyl](phenyl)methan­amine (7i): eluent PE/EtOAc (1:9, v/v), white solid; yield: 236 mg (83%). 1H NMR (400 MHz, CDCl3): δ = 7.58−7.56 (m, 1 H), 7.44 (t, J = 8.1 Hz, 1 H), 7.37 (d, J = 7.9 Hz, 2 H), 7.29−7.26 (m, 2 H), 7.19 (d, J = 7.3 Hz, 1 H), 6.97 (d, J = 7.9 Hz, 1 H), 5.57 (s, 1 H), 3.62 (s, 3 H), 2.27 (s, 3 H), 1.33 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 157.7, 144.3, 139.8, 133.5, 128.6, 128.3, 127.9, 127.6, 126.3 (d, J = 8.5 Hz), 125.9 (d, J = 19.4 Hz), 118.6, 114.8, 57.3, 55.7, 53.6, 23.3. HRMS (ESI-TOF): m/z [M + Na] + calcd for C18H23NO2SNa: 340.1342; found: 340.1340.[2-(tert-Butylsulfinyl)-5-methoxyphenyl](furan-2-yl)methanamine (7l): eluent PE/EtOAc (1:9, v/v), white solid; yield: 265 mg (80%). 1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J  =  8.8 Hz, 1 H), 7.33 (d, J = 2.6 Hz, 1 H), 7.16−7.15 (m, 1 H), 6.70−6.97 (m, 1 H), 6.27−6.26 (m, 1 H), 6.03 (d, J = 3.2 Hz, 1 H), 3.84 (s, 3 H), 3.17 (s, 2 H), 2.01 (s, 1 H), 1.25 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 162.3, 156.2, 144.4, 142.2, 128.7, 128.5, 113.8, 112.4, 110.3, 106.5, 56.9, 55.5, 49.2, 23.1. HRMS (ESI-TOF): m/z [M + Na] + calcd for C16H21NO3SNa: 330.1134; found: 330.1133.[2-(tert-Butylsulfinyl)-5-methoxyphenyl](4-trifluoromethyl-phenyl)methanamine (7m): eluent PE/EtOAc (1:9, v/v), colorless oil; yield: 288 mg (83%). 1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 8.8 Hz, 1 H), 7.61−7.54 (m, 4 H), 7.17 (d, J = 2.6 Hz, 1 H), 6.98−6.95 (m, 1 H), 5.81 (s, 1 H), 3.83 (s, 3 H), 1.94 (s, 2 H), 1.29 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 162.5, 158.3, 147.0, 138.8, 134.8, 128.9, 125.8 (q, J = 3.8 Hz), 120.7, 119.3, 104.8, 55.7. 19F NMR (376 MHz, CDCl3): δ = −62.49 (s). HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H22F3NO2SNa: 408.1216; found: 408.1214.1-[2-(2-Methyl-propane-2-sulfinyl)-phenyl]-allylamine (7r): eluent PE/EtOAc (1:9, v/v), colorless liquid; yield: 226 mg (65%). 1H NMR (400 MHz, CDCl3): δ = 7.80−7.78 (m, 1 H), 7.53−7.51 (m, 1 H), 7.48−7.45 (m, 1 H), 7.44−7.37 (m, 1 H), 5.96−5.88 (m, 1 H), 5.17 (d, J = 17.1 Hz, 1 H), 5.06−5.03 (m, 2 H), 1.74 (s, 2 H), 1.22 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 144.3, 141.2, 137.5, 131.6, 127.5, 126.4 (d, J = 19.7 Hz), 114.2, 56.9, 53.2, 23.1. HRMS (ESI-TOF): m/z [M + Na] + calcd for C13H19NOSNa: 260.1080; found: 260.1076.3-Naphthalen-2-yl-benzo[d]isothiazole (9f): eluent PE/EtOAc (20:1, v/v), colorless oil; yield: 132 mg (85%). 1H NMR (400 MHz, CDCl3): δ = 8.39 (s, 1 H), 8.32 (d, J = 8.2 Hz, 1 H), 8.06 (d, J = 7.7 Hz, 3 H), 8.02−7.92 (m, 2 H), 7.60 (m, 3 H), 7.53 (m, 1 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 164.3, 153.7, 134.0, 133.7, 133.3, 132.7, 128.6 (d, J = 3.2 Hz), 128.2, 127.8, 127.5, 126.9, 126.6, 126.2, 125.0 (d, J = 18.6 Hz), 120.0. HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H11NSH: 262.0685; found: 262.0683.3-(1-Methyl-1H-pyrrol-3-yl)-benzo[d]isothiazole (9g): eluent PE/EtOAc (20:1, v/v), colorless oil; yield: 127 mg (86%). 1H NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 8.3 Hz, 1 H), 7.98 (d, J = 8.1 Hz, 1 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.52−7.46 (m, 1 H), 6.87 (s, 1 H), 6.80−6.74 (m, 1 H), 6.36−6.26 (m, 1 H), 3.98 (s, 3 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 164.1, 160.6, 153.4, 133.8, 130.0, 127.9, 127.5, 125.0, 124.9, 120.0, 114.3, 55.4. HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H10N2SH: 215.0634; found: 215.0637.3-Furan-2-yl-benzo[d]isothiazole (9h): eluent PE/EtOAc (20:1, v/v), yellow oil; yield: 118 mg (81%). 1H NMR (400 MHz, CDCl3): δ = 8.68−8.61 (m, 1 H), 8.02−7.93 (m, 1 H), 7.72−7.64 (m, 1 H), 7.55 (m, 2 H), 7.22 (m, 1 H), 6.64 (m, 1 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 153.9, 153.2, 150.7, 143.3, 132.8, 127.7, 125.3, 125.2, 119.7, 111.8, 110.4. HRMS (ESI-TOF): m/z [M + H]+ calcd for C11H7NOSH: 202.0322; found: 202.0321.6-Methoxy-3-phenyl-benzo[d]isothiazole (9i): eluent PE/EtOAc (20:1, v/v), light yellow oil; yield: 111 mg (73%). 1H NMR (400 MHz, CDCl3): δ = 7.77−7.66 (m, 2 H), 7.57−7.49 (m, 2 H), 7.46 (m, 3 H), 6.80 (d, J = 7.1 Hz, 1 H), 3.81 (s, 3 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 129.6, 129.3, 128.8, 128.5, 127.3, 112.0, 104.9, 55.2, 29.7. HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H11NOSH: 242.0637; found: 242.0634.3-Furan-2-yl-5-methoxy-benzo[d]isothiazole (9l): eluent PE/EtOAc (20:1, v/v), colorless oil; yield: 122 mg (81%). 1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 2.3 Hz, 1 H), 7.82 (d, J = 8.9 Hz, 1 H), 7.67 (d, J = 1.1 Hz, 1 H), 7.24 (m, 1 H), 7.18 (m, 1 H), 6.64 (m, 1 H), 3.98 (s, 3 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 158.2, 153.3, 150.9, 146.5, 143.1, 134.0, 120.3, 119.3, 111.8, 110.2, 105.7, 55.7. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C12H9NO2SNa: 254.0246; found: 254.0245.5-Methoxy-3-(4-trifluoromethyl-phenyl)-benzo[d]isothiazole (9m): eluent PE/EtOAc (20:1, v/v), yellow oil; yield: 125 mg (78%). 1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.1 Hz, 2 H), 7.90 (d, J = 8.9 Hz, 1 H), 7.84 (d, J = 8.2 Hz, 2 H), 7.50 (d, J = 2.2 Hz, 1 H), 7.28 (m, 1 H), 3.91 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ = 162.0, 158.3, 147.0, 138.8, 134.8, 128.9, 125.3 (q, J = 3.8 Hz), 120.7, 119.3, 104.8, 55.7. 19F NMR (376 MHz, CDCl3): δ = −62.64 (s). HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H10F3NOSNa: 332.0327; found: 332.0325.