Mild and Convenient Synthesis of Benzodithiazoles by Oxidative Cyclization of Bis(thiobenzanilides)

Zahid Hassan; Peter Langer

doi:10.1055/s-0032-1317510

Synlett, Table of Contents

Synlett 2012; 23(19): 2811-2813
DOI: 10.1055/s-0032-1317510

letter

Mild and Convenient Synthesis of Benzodithiazoles by Oxidative Cyclization of Bis(thiobenzanilides)

Zahid Hassan

^aInstitut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany Fax: +49(381)4986412 Email: peter.langer@uni-rostock.de

,

Peter Langer*

^aInstitut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany Fax: +49(381)4986412 Email: peter.langer@uni-rostock.de

^bLeibniz-Institut für Katalyse an der Universität Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany

› Author Affiliations

Abstract

All articles of this category

Abstract

Benzodithiazoles were prepared by oxidative cyclization of bis(thiobenzanilides). The reactions were performed at room temperature under mild conditions and rely on the use of N-benzyl-DABCO tribromide.

Key words

benzodithiazoles - thioamides - organic ammonium tribromides - cyclization - C–S bond formation

Full Text

References

References and Notes

1a Pena P, Perez D, Guitián E, Castedo L. J. Org. Chem. 2000; 65: 6944
1b Damani A. Sulfur-containing Drugs and Related Organic Compounds – Chemistry, Biochemistry, and Toxicology. Ellis Harwood; Chichester: 1989
1c Cremlyn RJ. An Introduction to Organosulfur Chemistry . John Wiley; New York: 1996
1d Polshettiwar V, Kaushik MP. J. Sulfur Chem. 2006; 27: 353

For selected reviews on the synthesis of benzothiazole ring systems, see:

2a Yadav PS, Devprakash Senthilkumar GP. Int. J. Pharm. Sci. Drug Res. 2011; 3: 1
2b Weekes AA, Westwell AD. Curr. Med. Chem. 2009; 16: 2430
2c Gupta A, Rawat SJ. Curr. Pharm. Res. 2010; 3: 13

3a Bradshaw TD, Westwell AD. Curr. Med. Chem. 2004; 11: 1241
3b Su X, Vicker N, Ganeshapillai D, Smith A, Purohit A, Reed MJ, Potter BV. L. Mol. Cell. Endocrinol. 2006; 248: 214

4a Chakraborti AK, Rudrawar S, Kaur G, Sharma L. Synlett 2004; 1533
4b Shirke VG, Bobade AS, Bhamaria RP, Khadse BG, Sengupta SR. Indian Drugs 1990; 27: 350
4c Das J, Moquin RV, Liu C, Doweyko AM, Defex HF, Fang Q, Pang S, Pitt S, Shen DR, Schieven GL, Barrish JC. J. Bioorg. Med. Chem. Lett. 2003; 13: 2587
4d Hays SJ, Rice MJ, Ortwine DF, Johnson G, Schwarz RD, Boyd DK, Copeland LF, Vartanian MG, Boxer PA. J. Pharm. Sci. 1994; 83: 1425
4e Paget CJ, Kisner K, Stone RL, Delong DC. J. Med. Chem. 1969; 12: 1016
4f Bergman JM, Coleman PJ, Cox C, Hartman GD, Lindsley C, Mercer SP, Roecker AJ, Whitman DB. WO 2006127550, 2006
4g Yoshino K, Kohno T, Uno T, Morita T, Tsukamoto G. J. Med. Chem. 1986; 29: 820

5a Mylari BL, Larson ER, Beyer TA, Zembrowski WJ, Aldinger CE, Dee MF, Siegel TW, Singleton DH. J. Med. Chem. 1991; 34: 108
5b Sato G, Chimoto T, Aoki T, Hosokawa S, Sumigama S, Tsukidate K, Sagami F. J. Toxicol. Sci. 1999; 24: 165

6 Kulkarni SS, Newman AH. Bioorg. Med. Chem. Lett. 2007; 17: 2987
7 Sheng Y, Hyo YA, Xuhua W, Jie F, Van Stryland EW, Hagan DJ, Belfield KD. J. Org. Chem. 2010; 75: 3965

8a Alloum AB, Bakkas S, Soufiaoui M. Tetrahedron Lett. 1997; 38: 6395
8b Seijas JA, Vazquez MP. T, Reboredo MR, Campo JC, Lopez LR. Synlett 2007; 313

9a Hungerschoff H. Ber. Dtsch. Chem. Ges. 1901; 34: 3130
9b Hungerschoff H. Ber. Dtsch. Chem. Ges. 1903; 36: 3121

10 Moghaddam FM, Boeini HZ. Synlett 2005; 1612
11 Jordan AD, Luo C, Reitz AB. J. Org. Chem. 2003; 68: 8693

12a Pierron P. Ann. Chim. Phys. 1908; 15: 269
12b Hutchison KA, Sraganov G, Hicks R, Yudl H, Strassner T, Nendel M, Houk KN. J. Am. Chem. Soc. 1998; 120: 2989

13 Dongho C, Jiyoung A, Kathlia AC, Hyunseok A, Hakjune R. Tetrahedron 2010; 66: 5583
14 General Procedure A for the Synthesis of 6a–f To a cold suspension of 1,3-benzenediamine 4 (1.0 equiv, 18.5 mmol) and Et₃N (5.1 mL, 37 mmol, 2.0 equiv) in dry CH₂Cl₂ (50 mL), a CH₂Cl₂ solution (10 mL) of benzoyl chloride 5a–g (2.0 equiv) was added dropwise. The reaction mixture was stirred at 20 °C for 12 h and subsequently poured into 100 mL of H₂O. The organic layer was separated, washed with an aq solution of NaHCO₃ and with H₂O (30 mL), and dried by Mg₂SO₄. The solution was filtered and concentrated under reduced pressure.
15 N,N′-(1,3-Phenylene)bis(4-methylbenzamide) (6a) Starting with 4 (2.00 g, 18.5 mmol, 1.0 equiv), Et₃N (5.1 mL, 37 mmol, 2.0 equiv), 4-methylbenzoyl chloride (4.8 mg, 37 mmol, 2.0 equiv), CH₂Cl₂ (25 mL), following General Procedure A, 6a was isolated (3.5 g, 55%); mp 257–259 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 3.37 (s, 6 H, CH₃), 7.29–7.37 (m, 5 H), 7.51 (dd, J = 7.9, 1.8 Hz, 2 H), 7.92 (d, J = 8.2 Hz, 4 H), 8.34 (t, J = 3.2 Hz, 1 H), 10.2 (s, 2 H, NH). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 20.7 (2-CH₃), 112.9, 115.9, 127.7, 128.4, 128.8 (CH), 132.0, 139.3, 141.5 (C), 165.3 (CO). GC–MS (EI, 70 eV): m/z (%) = 344 (67) [M⁺], 119 (99), 91 (44), 65 (13). HRMS (EI, 70 eV): m/z calcd for C₂₂H₂₀N₂O₂ [M]⁺: 344.1519; found: 344.1522.
16 General Procedure B for the Synthesis of 7a–f The amide starting material (0.5 mmol) and Lawesson’s reagent (0.5 mmol) were refluxed in toluene (30 mL) for 1 h. Upon cooling, the solvent was evaporated using a rotary evaporator. The crude mixture was purified by column chromatography (silica gel, CH₂Cl₂–hexane = 1:1) to obtain the deep yellow colored compounds 7a–f in high yields (76–82%).
17 N,N′-(1,3-Phenylene)bis(4-methylbenzothioamide) (7a) Starting with 6a (1.00 g, 1.0 equiv), Lawesson’s reagent (0.80 g, 1.0 equiv), toluene (25 mL), following General Procedure B, 7a was isolated (1.34 g, 92%). ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.39 (s, 6 H, CH₃), 7.29 (d, J = 8.1 Hz, 4 H), 7.49 (t, 3 H), 7.69 (d, J = 7.6 Hz, 4 H), 8.35 (s, 1 H), 11.74 (s, 2 H, NH). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 20.8 (2-CH₃), 120.1, 122.2, 127.5, 128.3, 128.5 (CH), 139.4, 140.1, 140.9 (C), 197.4 (CS). GC–MS (EI, 70 eV): m/z (%) = 377 (76) [M⁺], 343 (67), 240 (43), 226 (93), 135 (70); HRMS (EI, 70 eV): m/z calcd for C₂₂H₂₀N₂S₂ [M]⁺: 377.1140; found: 377.1138.
18 General Procedure C for the Oxidative Cyclization of Thiobenzanilides To a stirred solution of thiobenzanilide 7a–f (1.0 equiv) in CH₂Cl₂–CCl₄ (1:1, 10 mL), N-benzyl-DABCO tribromide (2.0 equiv) was added. The reaction mixture was stirred for 30–90 min at 20 °C (TLC control). The solvent was removed under reduced pressure, and the residue was subjected to column chromatography (CH₂Cl₂–hexane, 1:1) to obtain products 8a–f.
19 1,4-Bis[4-methylphenyl]benzo[1,2-d:4,5-d]bisdithiazole (8a) Starting with 7a (200 mg, 1.0 equiv), N-benzyl-DABCO tribromide (450 mg, 2.0 equiv), CH₂Cl₂–CCl₄ (1:1, 10 mL), following General Procedure C, 8a was isolated as a yellow solid (138 mg, 70%); mp 221–223 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.38 (s, 6 H, CH₃), 7.31 (d, J = 8.1 Hz, 4 H), 7.98 (d, J = 8.4 Hz, 5 H), 8.03 (s, 1 H). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 26.3 (CH₃), 124.8, 125.1, 132.2, 134.8 (CH), 135.3, 141.4, 146.6, 158.6, 172.2 (C). GC–MS (EI, 70 eV): m/z (%) = 372 (100) [M⁺], 186 (16), 138 (43). HRMS (EI, 70 eV): m/z calcd for C₂₂H₁₆N₂S₂ [M]⁺: 372.0749; found: 372.0751.