Efficient Synthesis of Imidazo[2,1-b][1,3]benzothiazoles and 9H-Imidazo-[1,2-a][1,3]benzimidazoles under Solvent-Free Conditions

Abstract

An efficient synthesis of imidazo[2,1-b][1,3]benzothiazoles and 9H-imidazo[1,2-a][1,3]benzimidazoles is described from a novel multicomponent reaction between 2-aminobenzothiazoles or 2-aminobenzimidazole, benzaldehydes, and imidazoline-2,4,5-trione under solvent-free conditions.

Key words

imidazo[2,1-b][1,3]benzothiazoles - 9H-imidazo[1,2-a][1,3]benzimidazoles - imidazoline-2,4,5-trione - multicomponent reactions - solvent-free synthesis - heterocycles

References and Notes

• 1a Multicomponent Reactions   Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005. 
• 1b Basso A. Banfi L. Riva R. Guanti G. J. Org. Chem.  2005,  70:  575 
• 1c Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2005,  44:  1602 
• 1d Dömling A. Chem. Rev.  2006,  106:  17 
• 2a Solvent-free Organic Synthesis   1st reprint:  Tanaka K. Wiley-VCH; Weinheim: 2004. 
• 2b Tanaka K. Toda F. Chem. Rev.  2000,  100:  1025 
• 3 Calderwood DJ. Jones CGP. In Comprehensive Heterocyclic Chemistry II   Vol. 8:  Katritzky AR. Rees CW. Scriven EVF. Pergamon; London: 1996.  Chap. 4. p.95-122  ; and references therein
• 4 Mahesh R. Perumal RV. Pandi PV. Pharmazie  2005,  60:  411 
• 5 Amino N. Ideyama Y. Yamano M. Kuromitsu S. Tajinda K. Samizu K. Matsuhisa A. Kudoh M. Shibasaki M. Cancer Lett.  2006,  238:  119 
• 6 Anisimova VA. Spasov AA. Kovalev YG. Kovalev SG. Dudchenko GP. Khim.-Farm. Zh.  2004,  38:  16 
• 7 Anisimova VA. Spasov AA. Ostrovskii OV. Dudchenko GP. Kosolapov VA. Kucheryavenko AF. Parionov NP. Kovalev SG. Khim.-Farm. Zh.  2002,  36:  3 
• 8 Anisimova VA. Spasov AA. Kucheryavenko AF. Panchenko TI. Ostrovskii OV. Kosolapov VA. Larionov NP. Khim.-Farm. Zh.  2002,  36:  12 
• 9 Nawrocka W. Sztuba B. Liszkiewicz H. Kowalska MW. Wietrzyk J. Nevozhai D. Opolski A. Pol. J. Chem.  2005,  79:  709 
• 10 George P, De Peretti D, Roy J, Schmitt JP, and Sevrin M. inventors; EP  607076A1.  ; Chem. Abstr. 1994, 121, 157646e
• 11 Anisimova V. Spasov A. Kosolapov V. Chernikov M. Stukovina A. El’tsova L. Larionov N. Libinzon R. Vatolkina O. Pharm. Chem. J.  2006,  40:  521 
• 12 Han XJ. Pin SS. Burris K. Fung LK. Huang S. Taber MT. Zhang J. Dubowchik GM. Bioorg. Med. Chem. Lett.  2005,  15:  4029 
• 13 Blake AJ. Clark BAJ. McNab H. Sommerville CC. J. Chem. Soc., Perkin Trans. 1  1997,  1605 
• 14 Shiokawa Y. Ohki S. Chem. Pharm. Bull.  1973,  21:  981 
• 15 Anisimova VA. Levchenko MV. Pozharskii AF. Khim. Geterstsikl. Soedin.  1986,  22:  918 
• 16 Ogura H. Takayanagi H. Yamazaki Y. Yonezawa S. Takagi H. Kobayashi S. Kamioka T. Kamoshita K. J. Med. Chem.  1972,  15:  923 
• 17a Adib M. Mohammadi B. Bijanzadeh HR. Synlett  2008,  177 
• 17b Adib M. Aali Koloogani S. Abbasi A. Bijanzadeh HR. Synthesis  2007,  3056 
• 17c Adib M. Nosrati M. Mahdavi M. Zhu LG. Mirzaei P. Synlett  2007,  2703 
• 17d Adib M. Sheibani E. Abbasi A. Bijanzadeh HR. Tetrahedron Lett.  2007,  48:  1179 
• 17e Adib M. Sheibani E. Mostofi M. Ghanbary K. Bijanzadeh HR. Tetrahedron  2006,  62:  3435 
• 17f Adib M. Mahdavi M. Mahmoodi N. Pirelahi H. Bijanzadeh HR. Synlett  2006,  1765 
• 17g Adib M. Ghanbary K. Mostofi M. Bijanzadeh HR. Tetrahedron  2005,  61:  2645 
• 17h Adib M. Mollahosseini M. Yavari H. Sayahi MH. Bijanzadeh HR. Synlett  2004,  1086 

18

Procedure for the Preparation of 2-(4-Methylphenyl)- N ^³ -[( E )-1-(4-methylphenyl)methylidene]imidazo[2,1- b ]-[1,3]benzothiazol-3-amine (6a)
A mixture of 2-aminobenzothiazole (0.30 g, 2 mmol),
4-methylbenzaldehyde (0.60 g, 5 mmol), and imidazoline-2,4,5-trione (0.34 g, 3 mmol) was stirred at 200 ˚C for 5 min. Then, the reaction mixture was cooled to r.t. and the residue was purified by column chromatography using n-hexane-EtOAc (1:3) as eluent. The solvent was removed and the product was recrystallized from n-hexane-EtOAc (1:1). The product 6a was obtained as yellow crystals; yield 0.70 g (92%, relative to 2-aminobenzothiazole). IR (KBr): 1603, 1495, 1479, 1379, 1352, 1315, 1175, 1146, 1109, 820, 748 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 2.37, 2.45 (2 × s, 6 H, 2 × CH₃), 7.19 (d, J = 7.4 Hz, 2 H, 2 × CH), 7.29-7.32 (m, 3 H, 3 × CH), 7.42 (dd, J = 7.9, 7.4 Hz, 1 H, CH), 7.64-7.68 (m, 3 H, 3 × CH), 7.76 (d, J = 7.4 Hz, 2 H, 2 × CH), 8.27 (d, J = 8.0 Hz, 1 H, CH), 8.74 (s, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 21.30, 21.70 (2 × CH₃), 115.03, 123.79, 124.45, 126.18, 127.32, 128.60, 129.52, 129.70 (8 × CH), 130.27, 131.88, 133.25, 133.36, 133.61, 135.18, 137.10, 142.32, 144.98 (9 × C), 159.89 (CH). MS: m/z (%) = 381 (100) [M⁺], 366 (10), 289 (4), 251 (85), 134 (16), 103 (7), 91 (14), 77 (7), 65 (5). Anal. Calcd (%) for C₂₄H₁₉N₃S (381.50): C, 75.56; H, 5.02; N, 11.01. Found: C, 75.5; H, 5.2; N, 10.9.
Compound 6d: yellow crystals; yield 0.75 g (97%). IR (KBr): 1603, 1589, 1528, 1500, 1491, 1454, 1379, 1290, 1225, 1192, 1148, 1092, 845, 752 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 7.09 (dd, ^³ J _FH = 8.6 Hz, ^³ J _HH = 8.7 Hz, 2 H, 2 × CH), 7.20 (dd, ^³ J _FH = 8.6 Hz, ^³ J _HH = 8.7 Hz, 2 H,
2 × CH), 7.35 (dd, J = 8.1, 7.2 Hz, 1 H, CH), 7.45 (dd, J = 8.1, 7.2 Hz, 1 H, CH), 7.69 (d, J = 7.2 Hz, 1 H, CH), 7.72 (dd, ⁴ J _FH = 5.4 Hz, ^³ J _HH = 8.7 Hz, 2 H, 2 × CH), 7.86 (dd, ⁴ J _FH = 5.5 Hz, ^³ J _HH = 8.7 Hz, 2 H, 2 × CH), 8.24 (d, J = 8.1 Hz, 1 H, CH), 8.67 (s, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 114.94 (CH), 115.87 (d, ^² J _FC = 21.5 Hz, CH), 116.27 (d, ^² J _FC = 22.1 Hz, CH), 123.93, 124.71, 126.29 (3 × CH), 129.34 (d, ^³ J _FC = 7.9 Hz, CH), 130.30 (C), 130.56 (d, ^³ J _FC = 8.8 Hz, CH), 130.82 (d, ⁴ J _FC = 3.3 Hz, C), 132.30 (d, ⁴ J _FC = 3.2 Hz, C), 132.56, 133.21, 134.89, 145.43 (4 × C), 158.47 (CH), 162.20 (d, ^¹ J _FC = 247.3 Hz, CF), 165.05 (d, ^¹ J _FC = 253.7 Hz, CF). MS: m/z (%) = 389 (98) [M⁺], 350 (32), 326 (8), 255 (100), 229 (27), 201 (13), 134 (37), 107 (15), 90 (9). Anal. Calcd (%) for C₂₂H₁₃F₂N₃S (389.43): C, 67.85; H, 3.36; N, 10.79. Found: C, 67.8; H, 3.4; N, 10.7.
Compound 6g: yellow crystals; yield: 0.68 g (92%). IR (KBr): 3290 (NH), 1601, 1585, 1528, 1510, 1493, 1450, 1339, 1232, 1225, 1196, 1150, 1094, 839, 768 cm^-¹. ^¹H NMR (500.1 MHz, DMSO-d ₆): δ = 7.19 (dd, J = 7.8, 7.6 Hz, 1 H, CH), 7.25 (dd, ^³ J _FH = 8.6 Hz, ^³ J _HH = 8.7 Hz, 2 H,
2 × CH), 7.31 (dd, J = 7.8, 7.6 Hz, 1 H, CH), 7.37 (dd, ^³ J _FH = 8.6 Hz, ^³ J _HH = 8.7 Hz, 2 H, 2 × CH), 7.43 (d, J = 7.8 Hz, 1 H, CH), 7.71 (d, J = 8.0 Hz, 1 H, CH), 8.04 (dd, ⁴ J _FH = 5.3 Hz, ^³ J _HH = 8.7 Hz, 2 H, 2 × CH), 8.19 (dd, ⁴ J _FH = 5.4 Hz, ^³ J _HH = 8.7 Hz, 2 H, 2 × CH), 8.86 (s, 1 H, CH), 12.00 (br, 1 H, NH). ^¹³C NMR (125.8 MHz, DMSO-d ₆): δ = 112.04, 112.36 (2 × CH), 115.04 (d, ^² J _FC = 21.4 Hz, CH), 116.00 (d, ^² J _FC = 22.0 Hz, CH), 119.84, 123.61 (2 × CH), 124.98, 127.37 (2 × C), 129.18 (d, ^³ J _FC = 7.9 Hz, CH), 130.03 (d, ^³ J _FC = 8.7 Hz, CH), 131.22 (d, ⁴ J _FC = 3.3 Hz, C), 133.29 (d, ⁴ J _FC = 3.2 Hz, C), 136.45, 138.98, 148.09 (3 × C), 150.49 (CH), 162.41 (d, ^¹ J _FC = 247.9 Hz, CF), 164.95 (d, ^¹ J _FC = 252.5 Hz, CF). MS: m/z (%) = 372 (19) [M⁺], 360 (15), 326 (97), 238 (91), 229 (23), 196 (100), 133 (33), 118 (43), 107 (19), 95 (35), 79 (44), 69 (16). Anal. Calcd (%) for C₂₂H₁₄F₂N₄ (372.38): C, 70.96; H, 3.79; N, 15.05. Found: C, 71.0; H, 3.8; N, 14.9.

19

Selected X-ray Crystallographic Data for Compound 6a
C₂₄H₁₉N₃S, monoclinic, space group = P2₁/n, a = 12.7579 (12) Å, b = 7.5112 (7) Å, c = 21.2243 (20) Å, β = 91.626 (2)˚, V = 2033.03 (3) Å^³, T = 295 (2) K, Z = 4, D _calcd = 1.25 g cm^-³, µ = 0.173 mm^-¹, 2245 observed reflections, final R ₁ = 0.079, wR ₂ = 0.149 and for all data R ₁ = 0.137, wR ₂ = 0.172. CCDC 671151 contains the supplementary crystallographic data for the structure reported in this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.